6 15 672 Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 204 Folder The folder containing the original item. 5754 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource 1979 Title A name given to the resource Letter: To General Garth B. Dettinger, Deputy Surgeon General, USAF, from Colonel J.W. Thiessen, U.S. Army Environmental Hygiene Agency, Department of the Army, regarding VA Advisory Committee on Health-Related Effects of Herbicides, dated July 19, 1979 w ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 204 Folder The folder containing the original item. 5753 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource 1979 Title A name given to the resource Letters, memoranda, reports, charter, agenda, membership list, and other documents related to VA Advisory Committee on Health-Related Effects of Herbicides, 1979 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/db67395466b108c0f6ba55df980eb8a8.pdf 99887b351ce7b7b783ca7b4135b84060 PDF Text Text Item D Number 05752 G MScanned Author Corporate Author Roport/Artiolo TltlO Agenda, membership list, memorandum and committee questions related to VA Advisory Committee on HealthRelated Effects of Herbicides, June 1979 Journal/Book Title Year 1979 Month/Day Color Number of Images D 7 Descriptor! Notes Thursday, March 28, 2002 Page 5752 of 5780 �5^5 & <jr+~e ~J< INQ /WD TRANSMITTAl • SLIP • • ' 'f0{ (Name, office symbol, room number, building Agency/Post) Initials Date 2, 8. /^f»f*3^- /}#&yc> /ffl ^ u '-^--^ ff^ LJ v >: Action File For Clearance For Correction >< '•for Your Information Investigate Justify Approval As Requested Circulate Comment Coordination REMARKS Note and Return Per Conversation Prepare Reply See Me Signature DO NOT use this form as a RECORD of approvals, concurrences, disposals, clearances, and similar actions PROM: (Name, org. symbol, Agency/Post) Room No.—Bldg. Phone No. 6041-102 *U.S. OPO: 1»7(—261-647/332* 41 (Rev. 7-76) 01-11.206 �AGENDA VA Advisory Committee on Health-Related Effects'of Herbicides June 11, 1979 VA Central Office 810 Vermont Ave., N.W. Washington, D.C. 20420 Room 119 10:00 A.M. Welcome - James C. Crutcher, M.D. Chief Medical Director 10:05 A.M. Review of Advisory Committee's Functions and Relationships - Paul A. L. Haber, M.D., Chairman 10:15 A.M. Summary of VA Steering Committee's Activities by Steering Committee Chairman and Members 10:45 A.M. Herbicide Research - Lawrence B. Hobson, M.D. Deputy ACMD for Research and Development 11:00 A.M. Individual Reports by Advisory Committee Members on Their Activities Related to Herbicides 12:00 noon L U N C H 1:30 P.M. Continuation of Individual Reports 2:30 P.M. Presentation and Discussion of Written Questions from VA Steering Committee to Advisory Committee 3:00 P.M. Written Questions from the Floor 3:25 P.M. Future Meetings 3:30 P.M. Adjournment �ADVISORY COMMITTEE ON HEALTH-RELATED EFFECTS OF HERBICIDES MEMBERSHIP - JUNE 1979 Paul A. L. Haber. M. D. - CHAIRMAN Assistant Chief Medical Director for Professional Services Veterans Administration Central Office 810 Vermont Avenue, N. W. Washington, D. C. 20420 202/389-2214 Gerrit W. H. Schepers. M. D. - VICE-CHAIRMAN Medical Service Veterans Administration Central Office 810 Vermont Avenue, N. W. Washington, D. C. 20420 202/389-2550 James R. Allen. Jr.. Ph.D. Professor of Pathology The University of Wisconsin Medical School Department of Pathology 470 North Charter Street Madison, Wisconsin 53706 608/263-3524 Irving B. Brick. M. D. Senior Medical Consultant National Veterans Affairs and Rehabilitation Commission The American Legion 1608 K Street, N. W. Washington, D. C. 20006 202/389-2603 J. David Erickson, D.D.S., Ph.D. Center for Disease Control Birth Defects Branch Atlanta, Georgia 30333 404/236-3967 Jack Griffith. Ph.D. Acting Director Hazard Evaluation Division, TS-769 U. S. Environmental Protection Agency 401 M Street, S. W. Washington, D. C. 20460 703/557-7490 Page 1 of 3 Pages �ADVISORY COMMITTEE ON HEALTH-RELATED EFFECTS OF HERBICIDES MEMBERSHIP - JUNE 1979 (Continued) Philip C. Kearney. Ph.D. Chief, Pesticide Degradation Laboratory Department of Agriculture .--•• Building 050 • BARC West Beltsville, Maryland 20705 301/344-3533 or 3082 Richard A. Lemen Assistant Chief Industrywide Studies Branch Robert A. Taft Laboratories 4676 Columbia Parkway Cincinnati, Ohio 45226 513/684-3593 Robert H. Lenham Special Projects Officer National Service and Legislative Headquarters Disabled American Veterans 807 Maine Avenue, S. W. Washington, D. C. 20024 202/554-3501 Carolyn H. Lingeman. M. D. Carcinogenesis Testing Program National Cancer Institute Room 402, Delray Building National Institutes of Health Bethesda, Maryland 20205 301/576-2434 Walter W. Melvin. Jr.. M. P.. Sc.D. Professor, Environmental Health Sciences Colorado State University Fort Collins, Colorado 80523 303/491-6115 or 6136 Page 2 of 3 Pages �ADVISORY COMMITTEE ON HEALTH-RELATED EFFECTS OF HERBICIDES MEMBERSHIP - JUNE 1979 (Continued) John A. Moore. D.V.M. Associate Director for Research Resources Program National Institute of Environmental Health Sciences P. 0. Box 12333 Research Triangle Park, North Carolina 919/629-3267 27709 SheIdon D.Murphy. Ph. D. Department of Pharmacology University of Texas Medical School Houston, Texas 77025 713/792-5977 Colonel J. W. Thiessen. MC USA U. S. Army Environmental Hygiene Agency Aberdeen Proving Ground, Maryland 21010 301/671-2304 Page 3 of 3 Pages �• JON i 1 PROPOSED QUESTIONS TO BE ADDRESSED TO THE ADVISORY COMMITTEE ON THE TOXIC EFFECTS OF HERBICIDES. 1. Do the a v a i l a b l e d a t a on exposure of V i e t n a m v e t e r a n s to h e r b i c i d e s p e r m i t t h e performance o f s c i e n t i f i c a l l y v a l i d e p i d e m i o l o g i c a 1 studies on the long-term health effects of h e r b i c i d e s in this group? 2. What are the best human p o p u l a t i o n groups in which to s t u d y the long-term e f f e c t s of h e r b i c i d e s on h e a l t h , and how may these s t u d i e s b e s t be conducted? 3. Of what d i a g n o s t i c v a l u e are the following procedures in assessing p o s s i b l e h e r b i c i d e t o x i c i t y : levels of d i o x i n in fat pad b i o p s i e s ; study of immune f a c t o r s ; study of chromosonal p a t t e r n s ; and s t u d y of l i v e r m i c r o s o m a l enzymes? What a d d i t i o n a l d i a g n o s t i c p r o c e d u r e s should be c o n s i d e r e d ? 4. Is it p o s s i b l e for h e r b i c i d e s to have long-term adverse e f f e c t s on the male r e p r o d u c t i v e system? 5. What t o p i c s should be included in the e d u c a t i o n a l c u r r i c u l a b e i n g d e v e l o p e d to u p g r a d e knowledge of p o t e n t i a l h e r b i c i d e t o x i c i t y among VA Staff members? 6. What sorts of a n i m a l s t u d i e s would make the most important c o n t r i b u t i o n s to u n d e r s t a n d i n g the p o t e n t i a l l y toxic effects of h e r b i c i d e s in humans? 7. What a d d i t i o n a l data should be included in the VA's h e r b i c i d e r e g i s t r y over that being c u r r e n t l y c o l l e c t e d ? 8. What are the known facts on the p e r s i s t e n c e of dioxin and the h e r b i c i d e s used d u r i n g the Vietnam War in w a t e r , soil and the a t m o s p h e r e ? Can these m e d i a serve as a source of human exposure to d i o x i n and h e r b i c i d e s ? 9. What m e d i c a l tests should be utilized to help establish a d i a g n o s i s of c h r o n i c h e r b i c i d e - i n d u c e d t o x i c i t y among Vietnam veterans? 10. Can c r i t e r i a be e s t a b l i s h e d for d e t e r m i n i n g the l e v e l of e x p o s u r e of m i l i t a r y p e r s o n n e l to d i o x i n d u r i n g the V i e t n a m war based on s p r a y i n g tapes and unit h i s t o r i e s . 11. W i l l it be possible to.develop standards and criteria w h i c h define the p r e c i s e r e l a t i o n s h i p between h e r b i d i d e s and d i o x i n with chronic a d v e r s e effects in humans? Can these c r i t e r i a also specify the reasonable limits between the time of exposure to h e r b i c i d e s and the d e v e l o p m e n t of disease? �VETERANS ADMINISTRATION ADVISORY COMMITTEE ON HEALTH-RELATED EFFECTS OF HERBICIDES June 11, 1979 DR. HABER Chairman VA STENOGRAPHER :?<*/' DR. SCHEPERS Vice-Chairman VA / 1 MR. LEMEN NIOSH DR. KEARNEY USDA <.> A DR. GRIFFITH EPA MR. LENHAM DAV DR. ERICKSON CDC DR. LINGEMAN NCI ~ C,,,r DR. MOORE, ^NIEHS DR. BRICK ^ 'eslsyj I f:/.f f^t>~^ 'S'"it DR. ALLEN NACV DR. MURPHY NAS COL. THIESSEN DOD I ' � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 204 Folder The folder containing the original item. 5752 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource 1979 Title A name given to the resource Agenda, membership list, memorandum and committee questions related to VA Advisory Committee on Health-Related Effects of Herbicides, June 1979 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/29d6223f81754b0830cf6b6eae46c356.pdf f2e92fcab1b3aa7f5f2be97b5ce40af8 PDF Text Text Item D) Number 05749 LJ ^ scanned Author Corporate Author ROpOPt/APtiClB Tltto Tables anc) Calculations Regarding 2,4,5-T Exposed Forest Workers Journal/Book Title Yggp Month/Day Color Number of Images 1979 March 21 n ° Descrlpton Notes Thursday, March 28, 2002 Page 5749 of 5780 �TABLE 1. Worker No. Sex Weight kg Daily and Total Amounts of 2,4,5-T Excreted in the Urine of Forest Workers Following Application of ESTERON® 245a Job Description Day 0 Day 1 Day 2 mg 2,4,5-T Excreted Day 4 Day 3 Day 5 Day 6 Total Total mg/kg 1 Backpack Application Study 1A B M 72.6 Mixer/ Supervisor 0.119 0.039 0.182 0.169 0.210 0.122 0.127 0.167 0.155 0.203 0.085 0.198 0.075 0.834 0.859 0.011 0.012 2A B M 68.1 Sprayer 0.398 0.784 0.611 2.067 1.458 0.911 1.460 0.978 0.723 0.646 0.422 0.464 1.212 5.886 5.066 0.086 0.074 F 49.9 Sprayer nd 0.246 0.472 1.142 1.100 0.237 1.648 0.515 0.618 0.549 0.218 0.214 0.267 4.323 2.657 3A B . • 0.087 0.053 4A B M 95.3 Sprayer 0.146 0.749 0.254 0.402 0.913 1.101 0.421 0.584 0.495 0.506 0.279 0.597 0.494 2.856 3.190 0.030 0.033 5A B F 52.2 Sprayer 0.033 0.098 0.133 0.193 0.772 0.367 0.251 0.126 0.222 0.122 0.101 0.074 0.142 1.621 0.882 0.031 0.017 6A M 65.8 Sprayer 0.373 0.572 1.027 0.458 0.235 0.214 - 2.506 0.038 7A B M 74.9 Sprayer 0.796 0.314 0.211 0.931 3.701 0.708 0.856 0.368 0.876 0.422 0.760 0.334 0.566 6.970 2.763 0.093 0.037 Continued �TABLE 1. Worker Sex Weight kg Daily and Total Amounts of 2,4,5-T Excreted in the Urine of Forest Workers Following Application of ESTERON® 245a - Continued. Job Description Day 0 Day 1 Day 2 mg 2,4,5-T Excreted Day 3 Day 4 Day 5 Day 6 •j Total" Total mg/kg Tractor Mounted Mist Blower Application Study 8A B M 95.3 Supervisor 0.088 0.698 0.858 0.277 0.579 0.196 0.380 0.146 0.259 0.134 2.775 0.753 0.029 0.008 9A B M 84.0 Driver 0.103 0.097 0.343 0.644 1.500 0.716 0.687 0.548 0.599 0.478 0.372 0.278 3.501 2.664 0.042 0.032 10A B M 106.7 Driver 0.690 0.953 0.709 0.889 0.748 1.068 0.773 0.539 0.761 0.892 0.498 0.893 3.489 4.281 0.033 0.040 11A B M 79.5 Mixer 0.037 1.246 2.272 1.632 1.653 1.204 0.629 0.283 0.408 0.279 6.208 ' 3.398 0.078 0.043 nd nd nd 0.230 nd 0.310 0.041 0.267 nd 0.097 nd ' 0.084 0.069 0.041 1.057 0.001 0.011 1.894 1.362 2.430 1.470 1.409 1.397 1.827 1.344 1.386 0.964 1.136 0.737 0.773 8.188 6.685 0.075 0.061 nd 0.012 nd 0.099 0.029 0.060 0.109 0.038 0.155 0.010 0.032 0.081 0.031 0.325 0.319 0.004 0.004 0.020 nd 0.008 nd 0.035 nd 0.026 nd 0.007 0.005 0.008 0.003 0.005 0.084 0.013 0.001 0.001 0.026 nd 0.008 0.020 0.053 0.037 0.107 0.014 nd nd nd nd nd 0.168 0.071 0.002 0.001 Helicopter (Microfoil Boom) Application Study 12A B M 13A _B M 14A B M 15A B M 16A B M Continued 95.3 109.0 84.0 61.3 74.9 Pilot Mixer Supervisor Flagman Flagman �TABLE 1. Workei: No. Sex Weight kg Daily and Total Amounts of 2,4,5-T Excreted in the Urine of Forest Workers Following Application of ESTERON® 245a - Continued. Job Description Day 0 Day 1 Day 2 mg 2,4,5-T Excreted Day 3 Day 5 Day 4 Day 6 Total" Total mg/kg J Helicopter (Raindrop Nozzle) Application Study 17A B M 72.6 Pilot 0.288 0.324 0.467 0.370 0. 602 0. 812 0.383 0.600 0.409 0.602 0. 365 0. 455 0.255 2.481 2.839 0.034 0.039 ISA B M 86.3 Mixer 0.715 0.960 1.610 1.112 1. 229 3. 536 0.883 2.229 0.916 2.428 0. 804 1. 650 0.465 5.907 10.955 0.068 0.127 19A B M 81.7 Supervisor nd 0.047 0.014 0.018 0. 158 0. 057 0.113 0.032 0.073 nd 0.067 nd 0.116 0.541 0.107 0.007 0.001 20A B M 86.3 Flagman nd nd 0.070 nd 0. 079 0. 022 0.064 nd 0.016 nd nd nd nd nd 0.229 0.022 0.003 0.001 21A B M 95.3 Flagman nd nd nd nd 0. 029 0. 016 0.033 0.022 0.032 0.011 nd 0. 089 0.022 0.116 0.138 0.001 0.001 Data taken from Lavy ( ) 1. A and B refer to the first and second exposure, respectively. c The beginning of day 1 is designated as the beginning of the exposure. Excluding the 2,4,5-T excreted on day 0 (the "pre-exposure" sample). £ - means no data available; nd means 2,4,5-T below detection limit in urine. �L HEALTH AND ENVIRONMENTAL 4 : MARGUERITE L. LENG FROM: 9008 Building Phone (517) 636-3720 �TABLE 2. Worker No a Calculated vs. Observed Amount of 2,4,5-T Absorbed by Forest Workers During Application of ESTERON® 245. Method A Calculated mg 2,4,5-T Absorbed Method B Method Cb Total mg 2,4,5-T Excreted0 Backpack Application Study 1A B 0.898 0.875 0.943 1. 040 ± 0.408 (6) 1. 221 ± 0.833 (5) 0.834 0.859 2A B 5.153 6.175 5 .564 9. 016 ± 9.539 (6) 5. 804 ± 2 .840 ( ) 5 5 .886 5 .066 3A B 4.262 4.535 2.918 4. 585 ± 2.030 ( ) 6 3. 173 ± 1.884 (5) 4.323 2 .657 4A B 2.755 2.996 3 .504 4. 206 ± 3 .720 ( ) 6 4. 003 ± 2 .175 (5) 2.856 3 .190 5A B 1.561 0.947 1.701 0.969 1. 800 ± 1.005 ( ) 6 0.941 ± 0.248 (5) 1.621 0.882 6A 2.644 2 .752 2. 624 ± 0.719 (5) 2 .506 7A B - 7 .312 3 .035 6. 842 ± 4.667 ( ) 6 3. 270 ± 1.260 (5) 6.970 2 .763 Continued. - �TABLE 2. Worker No.a Calculated vs. Observed Amount of 2,4,5-T Absorbed by Forest Workers During Application of ESTERON® 245 - Continued. Method A Calculated nig 2,4,5-T Absorbed Method B Method C Total mg 2,4,5-T Excreted*" Tractor Mounted Mist Blower Application Study 8A B 3.086 3.048 3.077 ± 0.365 (5) 1.169 ± 0.373 (4) 2.775 0.753 9A B 3.844 3.085 3.845 2.926 3.877 ± 1.410 (5) 3.088 ± 0.527 (5) 3.501 2.664 3.832 4.702 4.369 ± 1.574 (5) 5.766 ± 3.513 (5) ,489 .281 6.818 6.373 ± 1.449 (5) 4.240 ± 1.732 (4) 6.208 3.398 0.059 1.109 0.190 (1) 1.151 ± 0.290 (6) 0.041 1.057 13A B 8.993 7.013 10.130 ± 3.704 (5) 8.882 ± 4.750 (6) 8.188 6.685 14A B 0.357 0.335 0.541 ± 0.439 (4) 0.455 ± 0.374 (6) 0.325 0.319 15A B 0.092 0.014 0.088 ± 0.039 (5) 0.064 ± 0.046 (3) 0.084 0.013 16A B 0.241 0.102 0.241 ± 0.233 (3) 0.099 ± 0.032 (3) 0.168 0.071 10A B 11A B 6.450 Helicopter (Microfoil Boom) Application Study 12A B Continued. 1.063 �TABLE 2. Worker No. Calculated vs. Observed Amount of 2,4,5-T Absorbed by Forest Workers During Application of ESTERON® 245 - Continued. Method A Calculated mg 2,4,5-T Absorbed Method B Method C Total mg 2,4,5-T ExcretedC Helicopter (Raindrop Nozzle) Application Study 17A B 2.603 3.118 3.323 ± 1.653 (6) 3.560 ± 1.572 (5) 2.481 2.839 ISA B 6.197 12.032 7.431 ± 2.905 (6) 13.501 ± 6.143 (5) 5.907 10.955 19A B 0.568 0.153 0.877 ± 0.934 (6) 0.147 ± 0.054 (3) 0.541 0.107 20A B 0.275 0.112 0.262 ± 0.102 (4) 0.077 (1) 0.229 0.022 21A B 0.113 0.152 0.251 ± 0.184 (4) 0.345 ± 0.532 (4) 0.116 0.138 A and B refer to the first and second exposure, respectively. The number of individual determinations of D "From Table 1. by Method C is shown in parentheses. �TABLE 4. CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: BACKPACK SPRAYER APPLICATION WORKER (sex) BODY WEIGHT (kg) 1 (M) 72.6 JOB DESCRIPTION EXPOSURE MAXIMUM CALCULATED DOSE OF 2,4,5-T (mg/kg) Mixer/Supervisor First Second 0.014 0.017 0.011 OBSER EXCRE1 2,4,5 n k !is./0.012 2 (M) 68.1 Sprayer First Second 0.132 0.085 0.086 0.074 3 (F) 49.9 Sprayer First Second 0.092 0.064 0.087 0.053 4 (M) 95.3 Sprayer First Second 0.044 0.042 0.030 0.033 5 (F) 52.2 Sprayer First Second 0.034 0.031 0.019 0.017 6 (M) 65.8 Sprayer First 0.042 0.038 7 (M) 74.9 Sprayer First Second 0.098 0.044 0.093 0.037 �TABLE 5. CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: TRACTOR MOUNTED MIST BLOWER APPLICATION WORKER i£LexL. 8 (M) BODY WEIGHT _&&>__ 95.3 JOB MAXIMUM CALCULATED DOSE OF OBSERVED 2,4,5-T rag /kg EXCRETED DISCRETION EXPp_SURE isBZK&J... Supervisor First Second 0.032 0.012 0.029 0.008 9 (M) 84.0 Driver First Second ' 0.046 0.037 0.042 0.032 10 (M) 106.7 Driver First Second 0.041 0.054 0.033 First Second 0.086 0.053 0.078 0.043 11 (M) 79.5 Mixer 0.040 �TABLE 6. CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: HELICOPTER BODY WEIGHT (MICROFQIL BOOM) APPLICATION MAXIMUM CALCULATED DOSE OF 2,4,5-T WORKER Isc*>.. _(k&L_ PA^QMLTJLQN JEXPp_suRE iss/_Ha)_. OBSERVED mg/kg EXCRETED 12 (M) 95.3 Pilot First Second 0.002 0.012 0.001 0.011 13 (M) 109.0 Mixer First Second 0.092 0.081 0.075 0.061 14 (M) 84.0 Supervisor First Second 0.006 0.005 0.004 0.004 15 (M) 61.3 Flagman First Second 0.002 0.001 0.001 0.001 16 (M) 74.9 Flagman First Second 0.003 0.001 0.002 0.001 JOB �TABLE 7. CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: EXPOSURE MAXIMUM CALCULATED DOSE OF 2,4,5-T (m&/kgj) OBSERVED mg/kg EXCRETED WORKER (sex) BODY WEIGHT (kg) JOB DESCRIPTION 17 (M) 72.6 Pilot First Second 0.046 0 . 049 0.034 0.039 18 (M) 86.3 Mixer First Second 0.086 0.156 0.068 0.127 19 (M) 81.7 Supervisor First Second 0.011 0.002 0.007 0.001 20 (M) 86.3 Flagman First Second 0.003 0.001 0.003 0.001 21 (M) 95.3 Flagman First Second 0.001 0.002 0.001 0.001 �Q QS r o si $5 s/ � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 203 Folder The folder containing the original item. 5749 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource March 21 1979 Title A name given to the resource Tables and Calculations Regarding 2,4,5-T Exposed Forest Workers ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5747 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource Corporate Author: Ocean County College, Office of Veterans Affairs Title A name given to the resource Vietnam Veterans Forum: Agent Orange, December 6, 1978 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/aaebddbb9cd89b8f06cea10d6b3d3e64.pdf e9e1a2e7911e8de5787ee24d910e65c4 PDF Text Text Item D Number °5746 U Not Scanned Author Corporate Author Report/Article Title Charter of New Veterans Administration Advisory Committee Journal/Book Title Year Month/Day Color Number of Images September 20 n ° Descriptor) Notes Thursday, March 28, 2002 Page 5746 of 5780 �CKAP.TF.K OF KCW VETERAlir. ADMINISTRATION ADVISORY COMMITTEE A, O F F I C I A L DESIGNATION: ADVISORY COfiMITTf/.P. O?? I1EALTH-RFI.ATED ~.......'. . . " * ...... "**" EFFECTS OF liEKP.ICIDEfi B. OEJ CCTI VT.S JWD SC_OPJj OP ..ACTIVITY t It has teco.rttly b^c-n biounhi. to 1 Icht that enormous q u a n t i t i e s ol h f v b i c i r l a l chenicnls wctt» used tfuri.no the Vietnam Wat and that thorn* i*i a p o s s i b i l i t y t b u t lame nunbets of Americans, rrary of vhorr- now f j u a i i t y as v e t e r a n s , I'-.ny have encountered these c h e m i c a l s to en extent that Icnu ran«e r.icnif iconl h p n l t h er,i^ nay hAvc hecn i n i l i A t e d . Thocc ic consider chlf 1 - cyntto* in tb^ p u b i i r » h e r l l i t o t a t x i r c ano it is ptohaMo that ruch infof.rs.tiop, i:f.Hiatr.s ar.put J ir.bccl. The V e t e r a n s Adr..inictration ti«;- r.ot M «' vio:u~ Iy br-«»n l o c ' u i t u d to r-r-uolve tor icoloT icfll i'jauos of such A corpiox fncl hinh.lv conttover v.ial n ^ t i u e . Thy corutittee w i l l , Uuuofotf:, (Sr.F.frrjblo and <^n«lys;e the information v>-hich th<? Vet'-'itn:-; jV.ninistiation r.recE in or-ler to f o r r u i a t f appto;;i - i a t < r . O f ' i c f l l policy an.; r-toc^c'ui oa in the i n t o r o a t j ; of the? ir.volva vc ts?ta:\s . Thf; Corr-. i tt»><* w i i i h&ve an o n t i t c l y i",;,ct~f inr". ino ^r.c ncjviijoi y i.olo «n«:l w i l l not be f-2-ouit^d to develop policy, Tho Cor.nittoo w i l J a-lhoic to fill Uio provir,ions of U, S. 1'ublic f.r.v * 0 2 - 4 r « 3 , T, U . i i . C . An p. I r r.y^cut ive Ctdet <?li769 anfi P f r s i f ^ n t l A l C i t c u l c s t 4A-63, of Katch 27, 1974 «ncl subf.pqucnt It ifi ont loioflt.i*d ti;.'it tho Cor.fr itt^o nay achieve its v / i t h i n t v e l v calender nonths. If an txtonsion of tiir.e ic oc'i, t h i s w i l l bo properly negotiated. D. A';?;t:CY PJTICIAL 10 WHG^ Tnr. C'OK/aTTFJf.1 REPORTS : The Corrr.tt tee w i l l report to the thi«9f Hedical Diiectot through t h o AEC i f i t o n t C h i e f .".odicai Kirectoi for Profpr.sionol Service?., V*- 1 f t ami A r f r n i n i f l t t a t ion Dopaitp-icnt of r.^dicinc and C u t c o t y . r. nrr-cRip'rioi; or FH-C The c o m i t t n c h o l d o o u o r t c i l y sosr>lonn at the V c t o t a n s Aclntnist r a t i o n C o n t i f t l Q l i f i r e in accord arc-? v.-ith an fjpptcnt Utt*J r>cJH;<5~ u i ^ of da toe set, at pioCf-rJin'o r,e£t ir,t;3, A K t t u c t u t e c l ar;cnca ic f o l l o w e d . J-^rbcj s a t e aekotJ to prepuce special ptcsontatione �and gather categories of data uniquely accessible to them. Ml members state their views fully and explicitly and support those with documentation as needed. The views of individuals with differlno opinions are recorded. Testimony is obtained from knowledgeable persons. Meetings are open to the public except when, in the discretion of the Chairman, the privacy of individuals, who may cor.e under discussion, nay be infringed. Members of the public may direct questions to the chairman in writing and submit prepared stftensents for review by the committee. At the discretion of the Chairman, ftuch members of the public may be asked to clarify such submitted iTtatetiai prior to consideration by the committee. The committee maintains summary minutes of: its findings and develops conclur, ions and interim reports for consideration by the staff of the Veterans M'iminis tration. The committee maintains liai~ son with a l l other federal agencies which have knowledge of and expertise in toxicology of chemical substances which may be pertinent to the herbicide issue. G. MVT.nCUSillP: MeiT.be rs of the committee include experts delegated by the other federal agencies, non-federal experts including toxicologists and physicians from industry, universities, end chartered veterans groups. Selected staff of the Veterans Administration Central 01. f. ice serve ex officio on the committee. The Chairman is a lexicologist stf.fr member of the Wedical Service. It. ESTIMATED OPRPA.TIFG COSTS: *> " ..... ...... •"" "* """" ""*"" ' .«.«-——— - Dollars: $5000.00 Man days: 300 co" : ; x. t-re r.":t.i£. q :-.L tex lv for cr.£ half day per session. : 0. TKkfllUATICl^ JW'.'iT: (me- year f'roi- the date of the first meeting, unless there is tea son to extend the life of the committee on a quarterly basis, K - - Federal Employees: Others : Volunteers i None Consulting Fees and Expenses per 5 U.S.C". 5703 Service on the committee sana remuneration is acceptable. �L. September 20, 1978. kWROVBO, —'" «* DATE. DATI-' U1/G«rU W. H. Sch^r., M,B,/«* 9/M/78 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5746 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource September 20 1978 Title A name given to the resource Charter of New Veterans Administration Advisory Committee ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/ded626526163d1197f0e760af15de9f5.pdf afd5a354ed1a2f73bf44f57ff4ec4fea PDF Text Text Item D Number °5745 D Rot Scanned Author Corporate Author Report/Article TKIB Walter W. Melvin's Comments on the Draft Minutes of the July 7, 1978 Meeting of the Ad Hoc Advisory Committee on Herbicides Journal/Book Title Year Month/Day Color Number of Images DeSCrlptOU NOtBS n ° Also includes tne draft and notes by others. See item 5744 for final version of minutes. Thursday, March 28, 2002 Page 5745 of 5780 �VETER A N'S AD,v11N!STRATION DfCF'AR TMT.NT OF- Mt OICiNE AND SURGERY WASHINGTON, D.C. 20420 July 14, 1978 IN REPLY REFKHTO: r SchCpCM" 1 MEM EERS OF ADVISORY COMMITTEE ON HERBICIDES Please review the attached draft of the minutes of the meeting which we held on July 7. Please return your copy with suggested changes marked on it, We did not have a column for your degrees and your title on our sign in sheet. Please accent our apologies if we have accorded you the wrong degree or title and supply the correct information. After the comments have been received from you we shall prepare a formal version incorporating your suggestions and corrpctions. I may have missed scvre points while performing my dunl role of chairman and Gc.'iba. Please also indicate your preference for the date of the next meeting by circling the appropriate day in September on page 7. The appendices ,irc not included at this time. They will be atr.achf.d to the final ve:sion of the minutes. Gerrit Schepcrs ,Kd'. "To care for him who shall have b.-'nc ;hc / > . • / / / / < , mid for /.'.'i vA'i-.-v,. cn;l l:;r ,.>!plia:i. " - - A U K A M ^^l L I N C O L N (IT �\'f.: cr.i A,. ,\<TT:> rr.,;/,;/. '_/-,,//-••, • J.' • • MINUTES OF MEETING OF THE VACO ADVISOURY COMMITTEE ON HERBICIDES July 7, 1978 810 Vermont Ave, NW WASHINGTON, DC 1, Attendance: Mom berr:: Gcrrit V.'.H. Schcpers, MD, Sc.D. , Medical Service,VACO, Chairman Richard Levinson, MD, Deputy AC1-3) for Professional Services V/iUi/im J Jacoby, MD, Director, Medical Service, VACO John J. Castellot, ID, Deputy Director, Medical Service, VACO Lawrence Hobson, M.D. Ph.D., Deputy Director for Research and Development, VACO Charles Pcckarsky, J.D., Director, Compensation and Pension Service, VACO Abraham Dury, Ph.D, Consultant to Medical Service, VACO Ben B. Holder, MD, Medical Director, DOW Chemical Company Midland, MI Philip C Kearney, Ph.D, Office of the Secretary for US Department of Agricu"cure. Walter W. Melvin, M.D. Sc.D., Professor of Environemental Health, Coloado S:c£. Unl\ Carolyn Offutt , Dioxin Project Manager, Environmental Protection Apc-ncy Donna Kurocla, Ph.D. , Environmental Protection Agency / -rnpnta 1 Health £: '.one/;: Hans Falk, Ph.D., Director, Pesticides Division, National Institute of Environ- / Ciprisno Cueto, Ph.D., Director, Pesticides Program, National Cancer Institute. Joseph A Thornasino, MD, Aberdeen Proving Grounds, US Array , Major, MC Marjorie Williams, MD, Director, Pathology Service, VACO Johan Bayer, United States Airforce, Office oT 'Surgeon General, Colonel. Visitors: Hank Spring, Representing Congressman S.B. McKirmey Jim Michi? , Representing Senator E. Kennedy 2. Dr Schepers introduced the mem_bers of the committee and explained the manner in which it came into being. In authorizing the conujnittee the Chief Medical Director required it to explore the following: a) The potential adycrr:r:c££ectf! 01 defoliants on the •.ecith oi' Vj'.etnatR Veterrms. including the rymptqi?.3 aiid signs as^ocisted with thoae effect.s. b) Methods for diagnosing and treating the adverse health effects of defoliants. c) Approaches through which the VA might attempt to discover the prevalencco£ the adverse effects of the dqfoli^ntc; on its patient population, The CKD furtiier expected the Committee to accomplish its task v/itnin one year , to prepare interim reports; and a final report Dr Schepers outlined the manner in which VACO became involved with tho. herbicide problem since March 1978 and the steps which have, been taken. About 500 claims have been lodged with the regional offices of the department of veterans lenefitc. An almost equal nu'rioar of Vietnam Vcti,---anj. h^v'i also applied tor radical cxnrir'mticrr u Since only r nlnor:'..y of VA health care specialiPts it- converar.nt v/ith tuo discipline of toxicology a brief brochure ( Appendix A ) war. prepared and sent to all health csro �2 HERBICIDE COMMITTEE Mii;;;tn Interim facilities/telephonic and written orientation also was provided for these HOPS concerning the administrative aspects of managing veterans who claim exposure, to potentially toxic chemicals. A final version of this directive is currently being reviewed by VACO departmental chiefs. A copy will be mailed to the mem__bers of the committee. Because of the many inter-service problems which have arisen the ClID also created a VACO Steering Committee. The steering committee sent the questions listed in Appendix B. 3. Dr Levinson reviewed the perspectives of the Office of the ACMD for Professional Services concerning the herbicide issue. He pointed out that the VA has traditionally managed only disear.es of biological origin and that it has only recently become involved with diseases of environmental etiology such as radiation effects, asbestos exposure and now herbicides. Since VA professionals are relatively poorly informed concerning these environmental health problems( although not necessarily more so than is the general health care system in the USA ) the need for education of the staff is apparent. Education of patients is equally important, the more particularly because environmental diseases are to a large extent preventable. Thercmay be specific areas which will require more research, and perhaps research which the VA should sponsor or accomplish. The deliberations of the committee should address these issues. 4. Dr Dury provided highlights of his reviews of the literature on herbicjc'-£.nd promised to provide a written suiTiiiiary. He. referred to the work Captain A. Young of the USAF has done to summarize the numar. ous publication;;. This report still is being evaluated by thf; USAF prior to its release. Dr Dury reported that in both experiments with animals rrtd experience with human subjects accidentally exposed to herbicides short term toxicity of fectr, are on record. There is considerable disagreement concerning long tern or delayed adver^ohealch effects. Both the <nos ;.£».' snd the duration oi exposure influence' the severity and type of health effects elicited in animal experiments. Little is known about i:hc adjuvant orrvstralir.ing action of mixtures of herbicides. Health effects have been recorded for aninals and man with respect to symptoms, gross pathology , biochemical responses, hictologic-.nl changes. The best infom\at.ion about human subject.1 derive? from the DOM experiences with inn avert en!; c-r-fosuitt-.s. Other 'Lnx'oru •.-•_. .JL; is suggested by thcP'St: Louis horse. _f«rm acci.nonl ;?nd the fc3obe. Arizoi.a event. There is slight cv_ iclrr.ee thac dioxin and perhaps 2,4,5-T niny indue-; tei*atoge:nesis and carcinogcnesis in experimental subjects of a limited variety. There, may be receptor site inhibition sothat delayed indirect effects may become possible. There is no receded evidence of this for man. 5. Dr Holder pointed out that it is important to distinguish between the health effects of individual herbicides. Chemicals with closely similar ncraes are not necessarily cpajble of the same biological action. This is selectively true for the dioxins. of which ther<;.nrc many variants. The higher chlorinate! dior.in." appear to be morr: t< ic than tho 'J oncer chlor.intf..l inoietiep. Some*, of the mi r.unc'.ers tending a brut Hi'- roxir^ty of dioxin stem from failure tc differentiate one dioxin typo frorr, another, l-'or tht; Victnc-- �HERBICIDE COMMUTE]] MINUTES War herbicide issue only TCDD proper ( 2,5,7,8 tctrachlorodibonzo-para -dicxln^ is of relevance. It also is important to realize that not all herbicides contain dioxins a:»d when prcsentthe dioxin is i.ot always in the same amount. For 2,4,5-T supplied by DOW to the military during the Vietnam War the concentration of TCDD varied from zero to about 50 parts per million. No 2,4,5 - T was made specially for the war effort. The herbicide was standard grade agricultural production. Since the war., chemical maufncturing techniques have improved sothat current batches of herbicides tend to have very much less dioxin than was originally likely. Most of UO^'s/experience with humar subjects and much of the" toxicology work on animal s'(^dycrse) gOos back m"-,y years. DOT has been studying these herbicides for the past 36 years since the chemicals have been produced for agriculture since the early 1940's. The main human experience involving serious exposure leading to symptom production commenced during 1965 when about 60 employees received excessiveexposure at one point in their factory. These all developed chloracne. JThere was no lost time. All recovered completely, except that two individualE tatistIcaL'k'deve 1 opg_d gome depression, not necessarily attributable to the chemical .excessive/exposure. No/carcinogenesis has been observed, but; the. company is still adopting a guarded position on this issue since the embryonating period for chemically induced cancers may be longer than ten years. The acne may have resulted as much from oils and inadequate hygiene an from direct chemical action of dioxin. The embryonfitinr; period for chloracne ranged from 6 to 8 weeks after exposure. Not all employe'••?. developed this symptom. Other s vtr.pl ?-r.s were not_pbsery_ed__imless thcrre _ y_?__3 concurrent _ch_l_oracrtc. For this reason i': seems doubtful whc thcr Victr.r.r.'. \.'ar veterans who never developed chloracne t.;. the time ofexposure in_Vietnam wil'l,,.now ^evi-'lop^ _sy;nTjt:orns, Dr Holder also expressed doubt about whether there waf err* TCIM; exposure in tha Globe AZ, St Loutf.-.VO c:r the Sevesn . T-V;-,. ,- . <;r'>pnpr:, vnich are so often quoted GS <.:.;..:.>!..;; oi" the Vu..ic.i:ul consequences of dioxin exposure. In response t,; a question by Dr Cueto, Dr Holder affdvmpd that* DO'.' if? looking into ths possibility of delayed effects on fertility and teratogenesis, . K- aryqypir.;studies and reproductivit)' studies are being conducted. "• 6. Dr FaIk has had considerable experience with animal experimentation , lu: no direct involvement with human subjects. The chcr.ical fonnulation of types of herbicides dctcmrir.es to r. larj,e extent vri-.c-ther they sre more or less toxic. The position o;': the- chlorine ".torn affcctr toxicity and so doer: vhether one dcnlr. v?ith the acid or the ester forr.n>j.-':tion of the herbicic'y. Some of the experiments v?ith animals which yielded terato'_f;cnic and carcinogenic results were conducted with ester.1.;. Similar results have not been produced by means of the £>cid. formulations. In the A;;cnf Orange the 2,4-D £-d 2,4,5 -T wete aci^s. The rate of biodegrad_at:icn of t'.ie herbicides is HI.PO affected by whether the herbicic'c is an acid or ester. Dr Faik attributed some: of this information to Dr Dianne Courtney. He- ^7ill nummarizc hir, obscr.-ation: and send these as a supplement to the minutes, Ou 7.Dr Melvin said that mention frequently is made of the Qlgfyg .>-u-J, jat_ Loviir -episodes, about which there ir. some doubt/with rcsnect to tlir. roin of dio::iii\ vmereas a much bi-uter documented evenr .tcci'^rcct irr>w.'"r:t' Virftiy.ir1 durj.r.g 19''-!0 in which 228 persons were relatively r;rors]y exposed to htrbici::1.! chcnicais. This included factory workers and their families. Much of the �A -...HERBICIDE COMMUTE MINUTES material was carried home on the clothes of the workers sothat their wives and children also were exposed. Most bec_amo seriously ill, vith significant; neurological symptoms and chloracne. There were no deaths . All recovered symptomatically e::cept for the chloracne scarti. Although this group has survived for more than thirty years , cpidemiological data have never been derived from their individual health experiences. Since the poj Ration of West Virginia is relatively stable, it may be possible to traci ^nany if not most of these individuals They would constitute a valuable source. of guidance concerning the remote effects of herbicides on human health. Dr Melvin also dscribed {some aspects of an industrial accident in Rotterdam, Netherlands, during 1963 involving the exposure of a t least 10 individuals. Since the Dutch government maintains relatively good public, health records it may be possible to trace the heaV h histories of these individuals. Dr Melvin also worked vith the Ua/.T during; 1970 in connection with the disposal of millions of gallons ox AgctiL" Orange. About 200 AF employees were involved with the de-drumming process.6 Some If not all probably made significant .contact wi*:h the chemicals. It in ay be worthwhile following _up ' ' 5 . . . " o f these indiyiduals , Dr Melvin further stated ^ thaV it is his impression that* the acute biological observations reported after ' .QgangG_ J^Janinal and huinanj^ri c due_to thfc__.2J.4r.D..and the 2,4.5-T themselves and not to the dioxin. Xiie occur eric c of ^symptom" slibrtn'y' ~aTt' eV exposure TcTTigent Orange therefore does not signify thr.t ;^^ but only tliat there had 'been; " exposure ; p.Q..R»Asft..-gA.. or ...2, j:;j-T. The cutaneous reaction "(' e precisely \riLth _ the intensity or ' duration of ex~'"" ' ' posure to th? hcridcs f ftcri' j.riclividuals vhc- ho-vs had raini:ns e::p6."U'.rc vrili show more chloracne than others known to have had si^iiificrntly more exposure. Individual susceptibility, personal l.ygiens and other factor? may be significant determinants of health effects. 8» Dr Kearney described the involvcrasnt of the department of agriculture; t*'it:h the same herbicide? 1 which were used in Ageit Orcnge. They of couroc have regulator^7 responsibility for otlier herMcictes too. Locentlv tlu: department has h?.d a flood of letters of inquiry, prote&c. and" complaint. Much concerns the fear of residents ., in forret-tod area of the US uiiat the u«e of herbicj.des and pesticides spryed from low fly?.u^ aircraft may exert health e f f e c t s o£ r.\ undesirsbic'kind eltrii^r throvgh direct exposure or throtif'li the hcrbicicer. enterinr. the ccosyf;tt-u;. AHhou;:li Ll'.e urcsrni. assessraent of the USDA ir. that thcf.>e fears ar» proimulesi., Oiiseu on th-known information concerning the biological actions of herbicides and pesticides, th& departr.inr has never-the-less created a medical team which will systematically exanin persons who claim that they may have been significantJ.y exposed to these chemiciilc. Dr She J. 1cm Wagner, a dcrrr.r'toic'uctis heading this investigation. I'r Kearney has had an opportunity to remain in touch vith the authcrites who axe raoaivoring the outcor.i-3 of Llie Seveso industrial chemical accident in Italy. One death has been reported. Jl'iiis was an elclcrly vomnn who dj.ed tron cancer siigrtl.y af ter tha incident. It ic " general ly~helG""ttia't: thi.sTancer developed "too r.oo;rcf uer the chemical craur.c. to have been caused by the chemicals. 9. DH Kurod". outlined the rcbattcble prcsut.vptioii c-ocuwenl v?hich the L^'A has f i l e d £gaiust 2,4,5-T which is published ir. the- Friday 21, 1078, I'art II icfiue of the i"ederal i ; -c' r :istcr. ( /.ppendix C ). 'J"hf principa.] concern:: of EPA is that there are lirora'cure _ci.tcitions cun;gcr;tjnf. that ai.c"3.n:; "ay r.avc. �5 HERBICIDE COMMITTEE MINUTES ytuta;;cnlc and carcinogenic properties, Dr Kuroda desired to know what evidence there is thnt mutapienicity raay not be an effect which may be mediated independently from chloracne. She also discussed the influence of individual species used as test animals on thu type of biological action which chemicals my elicit. Thus animals vjhich do not possess sebaceous glands may not be able to produce a chloiacne symptom, yet be able to produce other lesions. This 01 course does not change the fact that human subjects do have sebaceous glands and may therefore be expected to register the chloracne response. 10, Dr Cueto discussed the effects of mixtures of herbicides versus the effects of the individual ingredients. He could ncu recall any research which has specifically been dcue with the actual Agent Grange used in Vietnam. He is aware of only one paper incriminating 2,4,5-T is being capable of producing excess tunoors in experimental aniroals. There was however no specific tumor type produced- only total tumor counts were slightly increased as compared with the. natural incidence of tumors in the control animals. Until more research has been don.? he believes that carcinogenicity can be neither ruled out nor accepted as a vclid effect. He knows of no literature showing that 2,4 -D can prcKice a similar effect. The KCI has sponsored several investigations. The results of th^se are still unreported and thus not yet analysed by the institute staff. His institute may bo x^illinp: to sponsor additional necdiid research. However he cannot make a firm contnitiaant at thie time since the institute i? currently undergoing reorganization sotliat conttaand lines ana action centers nay change, 11. Col. Bayer stated, in response to various tpacLi.ca«, that the DOD never contracted with cheiaicai companies to have the con/poncntt. of Agent Oranp.e specially made for DOD^tThc available production of chemical industry in the USA ( apprpxiuatcly 18 " companies) w&s up?.d, Ac.ont "Orange therefore possibly varied, by lot according to the sources cf the component. IX)D has kept, records of inaividufd lot numbers eothat the conposi tion of each lot can perhaps be traced if the clicmical co:..y^.'iies kept similar records y^tl'J.Q during 1?7'0. However, it should be possible to reconstitut the lorKjlaioris of inaividufil Iocs if the acticr, of precise Eiixtures is deerned relevant to the inqxiiry concerriiug Agent Orange. TO the present nothing has bacn publit.'ucd to fho\! t:iu; t tue coK'-aination r>I 2,4-D and 2,4,5-T in itself produces eriects di.ffc.ix.nt from the biological action ascribable to the individual co&ipoiienLs separately. 12. Dr Williams described the current plan of the. VA to test about 100 fat biopsy specimen? for dioxin. >his moy cost ai:oi.j(- ^80. OOP <• The biopsies Viotiig!n War Veterans with undoubted _ tp_ Apojit_ Or^^^ vi. th___r.yn'n Corns, others witKoutT^y'iptoms." ^oTs^' bly a''^o^ciinT:rpJLLr:.pc'c:!.'^3n.'> wi,ljl bo~ obtained f_rcm veterans who have not had, any exposure to Ar .••?!< vranpic^ Trie tests will be done by a contracting laboratory', vj.f.i1. known cvpsrtir-e and suitable equipment and s t a f fD< VJyic.ht ~ Pattcrso_n_ A^rforcr I'-.; c~, has t>ucn a laboratory'. , ..... _ ..... 3.3, tr Thomnsino queried tho value of tlvir proposed biopcy entlfrr.vor by the VA, Kir; main concern is thrt thcix*e if. no kn.r-wn body of _l^ci»lodf t c lir.kiii", ns of dioxin to any__ effects. He compared the vork done at f h o Kottcri.r..- ^r.borp.tor)'1 in Cincinnjit: on �HEUBICID2 C01M1TTEE MINUTES tissue lead levels versus clinical evidence of. lead poisoning. It took many years of exper-' mentation and clinical invest: I gat ion before tho threshold for toxic tissue burdens of lead could be arrived at. In the < case of lead one has a specific atomic moiety to tnsasurc. Hatters arc much more vague for dio::ins. If dioxin it: found in any of the fat samples obtninec' faom yctortmn, it would be iinposfilbl c^ ffi ascribe any; msRnin^ to such finding r. since there is no' defined disease^ Kypdrome vlth TJhich the dioxin tissue burden can be correlated. _ Likewise, _ if no aio-p.n is f:ound in any of. Juhg specimens, it would still, be impossible to say _ what. _thi_a signifies n __since the ciloxin could have been in the' t i saaor or in JCTJVC- other j/i ta'i organ ' lorraarly , may or may riot have irickrcedjb]^!^ leached ut ci.t_hc_tjlssuj&V Until there" are; biornonitor data with which to . correlate tissue dioxin levels, iu ia?y not be worth the enormous expense to start this biopsy program. 13. Dr Hobson outlined the political overtone B which have relevance to this biopsy issue. In the CJiS presentation of Agent Orange-., there was a scenario showing a physician extracting a fat sample from a patient and the physician ' stated emphatically that he hap been obtaining confirmation of dioxin poinonir,through finding (Uoxin levels in such biopsy ?pcjcir;.evis. Veterans, and action grouon speaking for the veterans arc firmly convinced that the VA must test tht'-in for dio;;iu, A populist scj sntiflc epokcunsn • also said in the CBS progrr.ri that diozin accursulaccc iu fat and may later be reieaficci to re-exert: toxic actions on vital organ? during: periods of stress x;hen the rnetabolista riay be deranged. I-iany veuerans tlsercfort bejjWe rj.ni-.ly that they may be walking around with such a chemical *'cin'2 bomb* in their tissues. Tiit VA essehti«ly has no option but to check whether there is any proof that dioxin even is stored in fat eight years after the lust exposure in VS.etr.aic.. If no dioia.n is found in themcn who are IcnoiTn. to .isve had significant exposur. to Agent Orange or who way evw have had specific eyn>t.o:as,. this will be meaningful infomatf.on.. If as much diojcin it. found in persons who have never been in Vietnam as xs deterstilneu for veterans who were decisively exposed to Agent Orange, this alf,o would be- meaningful information. If the dcteririinatio, for dioxin proves exceedingly difficult: or erratic , as suggested by Dr i;o?d':;-, confirmation o^ this through the; VA endeavor, wc'UJ d -r.^.ain bo nic;:ni7if,f:ul, :-5ir , if no rslicblc. dstr. can be obtained in cva-.i the bsrrt: Icborauory, t'tr- vclidif of the CBS ctatOLirr.t cf:n be challenged* i)r Cut- to supported this approach. 14. Dr Schepers mentioned the current review o£ cancer incidence ftnvisticr. which can be derived from the VA's enorroou^ data fil; which is compiled frorthe diagnor.cs reported for each hospitalised veto-ran ( Patient lraatn;cr.it 1'il; -"IT 1"he annual incidence of liver cancer has recently brier, reviewed, Records aro available for the period 196 Z thru 1977. Thtrc is no indication that liver cancer has incrc.isod in the age categories representative of veterans v:ho served in the Vietnam V/ar. On the contrary, the incidence of liver cancer in the cohort of vetc.--.-ans aged less rnnn 2b yenrs, tht? cotiort af,r?;i 25 to 3^ ye::-,, and the chort aged 35 thru 4A years has actually declined over the past fifteen ycr.rs. For i::rr.'plc. in 1969 the, incidences J.cr there three cohorts r:-~ renpectivoiy 0 . 37 '/,, 0 , '/^t '/.-. r.nd 3,. '>0 V... counfln;- al? cases and all fvp^s QJ. neoplasm, tia liver cancer ox any kind occurred in ti;.£: Ico" tlir.n 2~j yc--"r cohcr". since 1970. No liver cancer has "k^cn re'corcad in thir coiiort arid In lac ne>:: ~ (25"'-34 years) since 1^/4. '" '"Sl'nct; iU/ / no 'c/xnc^rf; \\,-:--<: DC:. a r o r ^ v l i r J ' • f .the te^T-eo cohrvrr.Eftn hP.lnw :^ yftgrs JJirou^h �7 15. " HEKMCiDE ADVISORY COMMITTEE MINUTES sharply with increases in liver cancer in veterans nf the riW.A and 65 and over age groupjgQbortF-..p.ycr the s.umc .£iftc.cn..yp^r pprinrl. These older veterans pc.liaps obviously were not in Vietnam during the time when Agent Orange was being used. More detailed statistical data are to be found in Appendix I). Dr Schepers also inquired whether it would be possible for the VA to obtain biopsy ^•.pccimc-rasi'rom theJ7c;jt group .dexnc_rlhi?_d by_5r"lie_lvin./i'ia"'Of~fuiI ">>tr.t'cd" tlu':'tT 't'he_EFA__c~_ a'SSif;t"X7ltir"£lTc""TtI'cnTir£cat'jon" 6T "fhe.;c 7.r.dividualD.She described' the pollution ot' _ t i'd rb i c f3 c s" "an d p e ;>' t i ci (Ie"s7 *"T i i c" ire'b u'tft a bT(T~p r c s utii p t i on to V7hich Or ICuroda had reierred is an illustration of the posture1, the EPA may adopt on these matters. She clarified that if as a result of the evidence which may be offered during hearings concerning this rebuttable presumtion, the hypotheses on which it is based are destroyed, the EPA will withdraw the presumtion. Until such retraction occurs, the presumptior. reflects the persuasions of the EPA concerning herbicide 2,4,5-T. The EPA has a voluminous collection of literr.ture on herbicides, end Ms Offutt invited members of the committee to consult their library rather than attempting to start all over again. 16. The meeting wcs adjourned at 4 pm. Themernbert., all expressed preferenccfor a morning meeting. The next session of the cor.-..uif.tte will be called for September 8, 11,22 or 23. i I Gerrit V.'.H. Schepers ,1-JD,C: .D. Appendix A : VA brochure, on Herbicides B: Steering Committee request to advisorory committee C: Rebuttable presumption of EPA regarding 2,4,5-T D: Livccr.,; cancer in Veterans E: Tocity daua on herl)iciac.:; :: re pi: red byL'SArtny r,nvj.ro:in'.entr.lllygj. •..• F: VA administrative instructions to Field Health Cure Faciliti:" �• II 0 fiO �r t-~^-Av^j~^-zxr "/^jy '^ �DEPARTMENT OF THE AIR FOf USAF OCCUPATIONAL AND ENVIRONMENTAL HEALTH1 LABORATORY (AFSC) BROOKS AIR FORCE BASE, TEXAS 78235 Memorandum from the Commander VB He\uiws �tic Colorado State University Fort Collins, Colorado 80523 College of Veterinary Medicine and Biomedical Sciences Institute of Rural Environmental Health Microbiology Building Gerrit W. H. Schepers, M.D., Sc.D. Ref. (Ill) Chairman VACO Advisory Cornmittee on Herbicides Department of Medicine and Surgery Veterans Administration Washington, D. C. 20420 Dear Doctor Schepers: I have carefully reviewed the draft minutes of the July 7, 1978, meeting of the ad hoc advisory coirmittee on herbicides and have a number of \comments which I feel obligated to make. It is not my intent to be hypercritical but considering the nature and alleged magnitude of the problem as envisioned by the Veterans Adminis-' tration, all statements made and opinions expressed must be as carefully, accurately and objectively presented as is possible. There are a number of errors and misrepresentations to which I must call attention. My corrments are attached. I have indicated the paragraph by number, e.g., 4, and the phrase, clause sentence or section to which the conment is directed has been underlined in red. Where two or more comments have been made, these are indicated by the paragraph number followed by a small letter, e.g., 7b, etc. I trust that the attached comments will be of some assistance in the preparation of the final minutes. Sincerely, txff ^aTEer W. Melvin, Jr., . o . , Sc.D. Professor Environmental Health Sciences WWW:jbw Enclosures �2a. The only known, documented adverse effects in man have followed industrial accidents or incidents in the production of 2,4,5-txicfrLorophenoxyacetic acid derived herbicides from 2,4,5-trichlorophenol which contained 1 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a contaminant. Another source of possible TCDD exposure in industry is to pentachlorophenol which may contain TCDD as a contaminant introduced during primary production. The adverse effects are the residual scars of chloracne in some persons who were exposed to and absorbed TCDD. The experiences at the Monsanto Chemical Company 2,4,5,-trichlorophenol (2,4,5-TCP) plant accident at Nitro, WV in 1949/ at BASF Ludwigshafen-am-Rhein (Fed. Repub. of Germany) in 1953, Phillips Duphars Ltd. plant, near Amsterdam, The Netherlands, in 1963, and more recently, on July 10, 1976 at the ICMESA (Industrie Chimice Meda Societa Anonyma) plant in Meda, near Seveso, Italy, clearly point to this conclusion. Similar accidents have occurred in a plant operated by Coalite and Chemical Products Ltd., Bolsover, Derbyshire, England, in 1968, in Czechoslovakia in somewhat different types of accidents from 1965-1969 and in France on at least three occasions. Any other long term, adverse effects are unknown and are, currently, undetectable. 2b. To the best of my knowledge there are no known diagnostic laboratory methods which are specific, either singly or in combination, for the detection of tissue or organ damage due to TCDD exposure and absorption. For example, none of the following laboratory determinations, some of which are rather sophisticated and difficult to interpret, specifically indicate cellular or subcellular damage from the action of dioxins, including TCDD, at cellular levels: fructose-1,6-diphosphate aldolase (AID), d-hydroxybutyrate dehydrogenase (d-HBD) , alkaline phosphatase �(ALP), creatine phosphokinase (CPK), gamma-glutamyl transpeptidase (GGTP), glutamate dehydrogenase (GLDII), glutamate oxal acetate transaminase (SOOT), glutamate pyruvate transaminase (SGPT), leucine aminopeptidase *, (LAP) and lactate dehydrogenase (LDH). However, an enzyme of particular interest would be aryl hydrocarbon hydroxylase (AHH) with associated cytochrome PI-450. Another enzyme which might also be of interest is 6-aminolevulinic acid synthetase. It would be possible to expand this list but one would cone to the same conclusion. These are valuable tools which can be and have been used in experimental animal studies of TCDD but they are of no value in the evaluation of cellular damage in man when the last exposure—in the case defined by the Veterans Administration— occurred in Vietnam over eight years ago. 2c. Retrospective epidemiologies! studies offer a faint and difficult hope. Prospective epidemiological studies may be of value if a true and reasonable population at risk is defined. For this purpose, I would suggest concentration on former members of the "Ranch Hands." These were personnel who were assigned to the aerial application flights who serviced and flew the aircraft from which the Herbicide Orange was applied to limited areas in South Vietnam. But first, adverse effects must be medically and scientifically—not emotionally and politically—defined. Secondly, a population at risk of reasonable size and composed of persons who can be identified must be established. The following information may be of value in estimating the population at risk in Vietnam. About 3.58 million acres or only about 8.6% of the total area of South Vietnam were sprayed with herbicides one or more times. Only 10.3% (2.67 million acres) of inland forest were sprayed while 36.1% (0.26 million acres) of mangrove forest were sprayed and 3.2% (0.26 million acres) of cultivated �land were sprayed. For this purpose, Herbicide Blue (hydroxymethylarsine oxide) was used. Herbicide Orange was not intentionally used on cultivated land. The total area of South Vietnam was approximately 41.6 *, million acres. Many acres were sprayed only once. For example, one treatment with either Herbicide Orange or Herbicide White killed essentially all of the mangrove species. Thus, it is apparent that not all members of the U.S. military forces who served in Vietnam were exposed to 2,4,5-T and to TCDD. The population actually exposed is far less than the 3-4 million persons estimated by the Veterans Administration. I have talked with many Air Force veterans and others who were in South Vietnam, were not exposed to Herbicide Orange and were completely unaware of the defoliation program. The source of the above data is: National Academy of Sciences, 1974, "The effects of herbicides in South Vietnam. Part A, Summary and Conclusions." MAS. Wash. D.C. 4a. Again accuracy and careful, truthful statements are vitally necessary. Until reading these draft minutes, I had never hear of a "...St. Louis horse farm accident" because there was no St. Louis horse farm accident. The incident referred to occurred at the Shenandoah Horse Farm, near Moscow Mills, MO which is approximately 59 miles northwest of St. Louis, MO. The farm was operated by Judy Piatt and Frank Hampel. The child who was most severely involved was Andrea Piatt, who was six years old on May 21, 1971, when approximately 2000 gallons of waste oil were applied as a dust control measure. I should also like to point out that the causative compound was not identified until 1974 at the Center for Disease Control (CDC) by Dr. Renate Kimbrough. In 1977, six years after the exposure, the Piatt family was examined by physicians at the Washington University School of Medicine in St. Louis. Andrea Piatt had grown normally and �both her height and weight were abouve the 75th percentile. Detailed physical/ chemical and neurological examinations were also conducted and found to be normal. The examining physicians concluded: "Our experience demonstrates that people exposed to dioxin can recover completely with no apparent sequelae from the toxin. It remains to be determined whether the exposure to dioxin in these children will result in abnormal pregnancies or affect their offspring." [Beale, M. G., W. T. Shearer, M. M. Karl, and A. M. Robson. 1977. Long Term Effects of Dioxin Exposure, lancet 1 (8014) :748] (see Atch. 1). The Nitro, WV and the more recent ICMESA accidents confirm the abouve conclusion. 4b. I agree that the events occuring during several years, i.e., 1965, 1966, 1968 and 1969 of aerial application of herbicide in the Final Mountains in Arizona are oatironly referred to as the "Globe event" or the "Globe cases." Herbicide Orange formulation was not used in this area. The formulations used, the manufacturers names, USDA Registration numbers, pounds acid equivalent per gal. applied and application rates as pounds acid equivalent per acre are available. This event is still under study. 5. I am in general agreement with the Garments made by Dr. Holder. I do believe, however, that even more emphasis should be placed on the importance of chloracne. The presence of chloracne is central to making the diagnosis of TCDD intoxication in man. The latent period for the development of clinically apparent chloracne in man is, at a minimum, about two weeks, and usually four to eight weeks. To the best of my knowledge no cases of chloracne were diagnosed among United States personnel stationed in Vietnam during the period of 19621970. While TCDD has been shown to be the causative agent of chloracne, its role in the development of porphyria cutanea tarda is less clear. However, again to the best of �my knowledge, no cases of this condition were diagnosed in Vietnam. There are residual scars following chloracne but porphyria cutanea tarda appears to be reversible. There is another point to be made. Very few <; physicians in the United States and, of course, those serving in Vietnam, have seen cases of chloracne and fewer still would be aware of the acquired condition of porphyria cutanea tarda. (After all, you cannot make a diagnosis unless you have knowledge of the disease and think of it at the time!) Again, as I did at the meeting on July 7, 1978, I strongly recommend that Raymond R. Suskind, M.D., Director, Institute of Environmental Health, College of Medicine, University of Cincinnati (telephone: 513-872-5701) be asked to join the ad hoc committee. He examined and followed for some period of time patients from the Nitro, WV plant accident in 1949 (see paragraph 7). 6. Generally, I aggree with the comments of Dr. Falk. However, the sentence (underlined in red) is completely incorrect. The 2,4-D and 2,4,5-T used in Herbicide (Agent) Orange were not acids but were esters and in all but a few thousands of gallons of herbicide, they were the normal butyl esters of both 2,4-D and 2,4,5-T referred to as Orange I. Some formulations contained the isooctyl esters and were known as Orange II. Procurement Specifications are listed in Atch. 2. Data on the physical properties of 2,4-D, 2,4,5-T, TCDD, Orange I and Orange II are provided in Atch. 3. 7a. See Comment 4 relative to the Globe and St Louis episodes. 7b. This industrial accident occurred in 1949 not 1940. It occurred in a 2,4,5-trichlorophenol (2,4,5-TCP) reaction vessel in a plant operated by Monsanto in Nitro, WV (see Comment 5, relative to Dr. Raymond R. Suskind). �7c. The words "...many if not most..." should road "—an unknown number of these people." 7d. I was the scientific director for the United States Air Force in its « efforts to dispose of Herbicide Orange from April 1970 to December 1977. 7e. The sentence beginning "Some if not all..." is completely incorrect as are the following sentences. First, the contact with the herbicide was not significant; it was itiinimal. The personnel were selected after reasonable medical evaluation and worked under very complete industrial hygiene surveillance. Air and water samples were collected based on a carefully determined sampling protocol. Analyses were performed for the herbicides and TCDD. Biological monitors, e.g. rapidly growing 4"-6" high, tomato plants were also used. The concentrations of TCDD in air and water were determined in and adjacent to dedrum facilities at NCBC, Gulfport, MS and on Johnston Island. These environmental data should be available from Air Force sources. Within the limitations of the Privacy Act, copies of physical examinations might also be available. 7f. The sentence beginning "Dr. Melvin further stated..." must be completely rewritten. I stated that the immediate effects on man, animals, birds, reptiles, insects and vegetations were due to process products from reaction vessels which had undergone process malfunction, i.e., temperature buildup and pressure overload with discharge of the reaction products into the plant and, in the case of the ICMESA accident ("Seveso incident"), drift of the cloud into adjacent environmental (neighborhood) areas. The reaction products include 2,4,5-trichlorophenol, other chlorinated phenols, chlorphenates, NaOH or KOH and, in some accidents, ethylene glycol and, of course, TCDD. The production of 2,4,5-T requires additional chemical reactions and 2,4,5-T was not present in the reaction �products in these accidents. 2,4-D is not present for the simple reason that it is produced by an entirely different direct chlorination process. 2,4-D does not contain TCDD as a contaminant. In the case of man and other animals, the iimiediate effects (24-48 hours) are the result of the direct caustic (burn) action of the polychlorinated phenols and resemble, at certain stages, burns resulting from other phenols or cresols. Chloracne, caused by TCDD, does not appear for a minimum of two weeks and, most comrnonly, four to eight weeks following exposure. In this sense, TCDD does not have an iirmediate or acute toxic action. This is verified by animal experimentation. I might further add that direct skin contact with TCDD is not necessary for the development of chloracne. It has occurred after exposure by the inhalation route alone. 8. At the request of Italian medical and paramedical authorities, Captain Alvin L. Young and I visited Meda-Seveso and adjacent areas in Italy and Zurich-Dubendorf, Switzerland in November 1977. We have remained in contact with many of these authorities since that time. The death mentioned by Dr. Kearney was that of an elderly woman who died of carcinoma of the head of the pancreas with widespread metastases. While in Italy and since then, I have received official documents from Italian and Swiss authorities. Some of these documents have been translated and are attached (see Atch's 4 and 5). Note that the report form the Mario Negri Institute of Pharmacological Research, signed by Dr. Roberto Fanelli and dated November 7, 1977 contains data on the concentrations of TCDD in the liver and mesenteric fat from the necropsy on Mrs. Colombo. The sensitivity of the analytic method used was 0.25 nanograms per gram of tissue (see Atch. 4 and 5). �9. There arc probably just as many literature citations which provide evidence that TCDD is not rnutagenic. 10. No comient. lla. There were 8 not 18 manufacturers of Herbicide Orange. The herbicide did not possibly vary by the source and lot number, it varied significantly and the extent of these variations has been documented and the data are available (see Atch. 6). lib. Destruction of Herbicide Orange occurred in a 10,000 sq. mi. EPA designated "burn" area approximately 120 nautical miles west of Johnston Island, Central Pacific Ocean during July-September, 1977. 12a. I must seriously question the value of this costly program. The detection of TCDD in a biopsy specimen from a veteran who served in Vietnam as long as eight years ago does not a priori estalish that exposure, absorption and storage occurred while the person was in Vietnam, especially with a study population of only 100 subjects. One of the most difficult problems that we face in the Institute of Rural Environmental Health, Epidemiologic Pesticide Studies Center at Colorado State University in studies of chemicals in the environment, including an on-going study of TCDD in human milk, is the identification of suitable control groups. Again (see comment number 2c), I strongly reconmend that if a study of this general type is to be conducted that the "Ranch Hands" be considered as the exposed cohort with a control group consisting of crews assigned to the same type of aircraft but not engaged in the aerial application of chemicals, at least not Herbicide Orange, and not assigned to Vietnam. Having been involved for seven years in studies of TCDD concentrations in the tissues of mammals, birds, reptiles and fish with known—sometimes semiquantified—exposure data to 2,4,5-T and TCDD, I can only state that �this will be an extremely costly program and may well be completely nonproductive. 13. (Dr. Thomasino) In general I agree with the continents. r, 13. (Dr. Hobson) Based upon my seven year involvement with Herbicide Orange while in the Air Force and my many encounters with political officials including members of the Congress, governors, the media, environmentalists, etc., I can well apprecite the position in which the Veterans Administration finds itself. It is indeed an appalling position to be in. 15. No comment relative to Herbicide Orange or TCDD. However, I must wonder if these data may possibly reflect an aging population, nitrosamines in man, his food chain and the long latent period of these and other carcinogens prior to the development of malignant tumors. 16. My opinion is that there is a reasonable possibility that much useful data could be derived from a study of those persons who were involved in the MDnsanto plant accident at Nitro, WV in 1949 and are still living and can be identified and located. The causes of death of those now deceased might also be of interest though probably difficult to evaluate. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5745 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Walter W. Melvin's Comments on the Draft Minutes of the July 7, 1978 Meeting of the Ad Hoc Advisory Committee on Herbicides ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/d28c0f9379ec9efd34ce7d68b4682343.pdf a32f2aee1ca4413db607c9019b152260 PDF Text Text ItonDNumbor 05744 Author Corporate Author Roport/Artlclo TltlO Minutes °f tne AdHoc VACO Advisory Committee on Herbicides Meeting of July 7, 1978 Journal/Book Title Yoar Month/Day Color I-J Number of Images ° Doscrlpton Notos See item 5745 for draft and comments Thursday, March 28, 2002 - Page 5744 of 5780 �MINUTES OF TI1K ADIiOC VACO ADVISORY COMMITTEE ON HERBICIDES MEETING OF JULV 7, 1978 810 VERMONT AVE. N.W. WASHINGTON, D.C. .1. A I. ton donee Members: Gen it w.ll. Schepers, M..D., Sc,i.K, Medical Service, VACO, Chairman Richard Lcvinson, M.D., Deputy ACMD for Professional Sorvices W i l l i a m J. Jacoby, Jr., M.D., Director, Medical Service VACO John J. Castellot, M.D., Deputy Director, Medical Service, VACO Lawrence Hobson, M.D.f Ph.D, Deputy Director for Research and Development, VACO Abraham Dury, Ph.D, Consultant to Medical Service, VACO P h i l i p C. Kearney, Ph.D, Office of the Secretary for U.S. Dcpt. of: Agriculture. Carolyn Offutt, M.S., Dioxin Project Manager, Environmental Protection Agency Donna Kuroda, Ph.D., Ecological Effects Division, Environmental Protection Agency Hans Falk, Ph.D., Associate Director, Health Hazarad Assessment, National Institute of. Environmental Health Sciences Cipriano Cueto, Ph.D., Director, Pesticides Program, National Cancer Institute. Joseph A. Thomasino, M.D., Aberdeen Proving Grounds, Major, Me, U.S. Army Char Ies Peckar. sky, L.L, B., DirecLor, Compensation and Pension Service, VACO Marjorie Williams, M.D., Director, Pathology Service, VACO Johan Bayer, Office of Surgeon General';" Colonel, MC U.S. Ai r force. ., ,; Consul tanL_s: Ben B. Holder, M.D., Medical Director, DOW Chemical Conipany, Mid 1 and, MI Walter W. M e l v i n , M.D., Sc. D.>- Professor of Environmental Health Sciences, Colorado State University V i s it o r s : Hank Spring, Represent ig Congresman S. S3. McKinnoy J Lin Michie, Representing Senator: B. Kennedy �2. Dr.. Schepers introduced the members of the committee and explained the marmot in which it came into being. Inauthorizing th committee the Chief Medical Director required it to explore the following: a.) The potential adverse effects on veterans of defoliants used in Vietnam and to assess the symptoms and signs associated with those effects. b.) Methods for diagnosing and treating adverse health effects of: defoliants. c.} Approaches through which the VA might discover the prevalence of adverse effects o£ defoliants used in Vietnam on its patient population. The CMD further expected the Committee to accomplish its task within one year, to preare interim reports and a final report. Dr. Schepers outlined the manner in which VACO became involved with the herbicide problem since March 1978 and the steps which have been taken. About 500 claims have been lodged with regional offices of the Department of Veterans Benefits. An almost equal number of Vietnam Veterans have also applied for medical examinations. Since only a minority of VA health care specialists is skillful in the discipline of toxicology a brief brochure (Appendix A) was prepared and sent to all health care facilities. Interim telephonic and w r i t t e n orientation also was provided for these HCFs concerning administrative aspects of managing veterans who claim exposure to potentially toxic chemicals. A final version of this directive is currently being reviewed by VACO departmental chiefs. A copy will be mailed to members of the committee. The CMD also created a VACO Steering Committe e to deal w i th i n t cr -- s er vi ce i s s u e s on this problem. The steering committee submitted the questions listed.in Appendix B. 3. Dr. Levinson reviewed the perspectives of the Office of the ACMD for Professional Services concerning the herbicide issue. He pointed out that the VA has traditionally managed only disease of biological origin and that it has only recently become involved with diseases of environmental etiology such as radiation effects, asbestos exposure and now herbicides. The need for education of the HCF staff is apparent. Education of patients is equally important, �p a r t i c u l a r l y because e n v i r o n m e n t a l l y caused diseases are p o t e n t i a l l y preventable. There may be specific areas which will require more research, and perhaps research which the VA should sponsor or accomplish. The deliberations of the committee should address these issues. 4. Dr. Dury provided highlights of his reviews of the literature on herbicides and promised to provide a written summary. He referred to the work of: Captain A. Young of the USAF who has .summarized numerous publications. This report still is being evaluated by the USAF prior to its release. Dr. Dury reported that in both experiments with animals and experience with human subjects accidentally exposed to herbicides short term toxicity effects are on record. There is considerable disagreement concerning long term or delayed adverse health effects. Both the dosage and the duration of exposure influence the severity and type of health effects elicited in animal experiments. Little is known about any adjuvant or n e u t r a l i z i n g action of mixtures of herbicides. H e a l t h effects have been recorded for animals and man with respect to symptoms, gross pathology, biochemical responses, a n d h i s t o .1 o g :. c a I. c h a n g e s. T h e b e s t information about h u rn a n subjects derives from the DOW experiences with inadvertent ox p o suios. 01h e r i n for ma t i on i s s u g g e s te d by the M i s s o u r i horse farm accident and the Globe Arizona event. There is evidence that di.ox.in at the 1.0 ng/kg level and 2,4,5-T at 500 ppt may induce f e totoxic i ty, tera togenes is arid care inogenesis in e x p e r i m e n t a l rodents. There may be receptor site inhibition so that delayed indirect effects may become possible. There is no recoided evidence of this for man. f>. Dr. Holder pointed out that it is important to distinguish b e t w i > e n t. h e h e a j. t h e f f e c t s of i n d i v i d u a 1 her b i c i d e s and the i r contaminant:.:;. These c h e m i c a l s are not necessarily capable of the same biological action. This is especially true for the d i o x i n s , of which there arc many v a r i a n t s . The 2,3,7,8te 1. t act) lorocl ibenzo-para-d iox in (TCDD) appears to be the most toxic. Some of the misunderstanding about the foxicity of d iox in sterns from f a i l u r e to d i f f e r e n t i a t e one d iox in type from anot.her. For the V i e t n a m War herbicide issue, the proper d i o x i n (TCDD) is of relevance. It also is important to realize that not all. herbicides contain dioxins and, when present, the dioxin is not always in the same amount. The 2,4,5-T supplied to the military during the Vietnam War had concentrations of TCDD varying ft'om one part-per-mil 1 ion (ppm) to about 50 ppni. The phenoxy herbicide was a standard grade a g r i c u l t u r a l product. Since the war, chemical manufacturing techniques have improved so that current batches of phenoxy herbicides tend to have much less dioxin cantamination. Most �of Dow's experience with human subjects and rnueh of their toxicology work on animals goes back many years. Dow has been studying these phenoxy herbicides for the past 36 years. Their main human experience involving over-exposure to TCDD leading to symptoms commenced during 1965 when about 60 employees received excessive exposure to TCDD in a Irichlorophenol plant. No 2,4,5-T was involved. These 60 employees developed chloracne. Two individuals developed some depression, but all recovered. There was no lost time. It is the concensus of world experts that symptoms from TCDD toxicity does not occur in the absence of chloracne. For this reason, it seems doubtful whether: Vietnam War veterans, who never developed chloracne at the time of exposure in Vietnam, did or will show signs of other disease. L i t t l e TCDD in Globe and no 2,4,5-T in Missouri or Seveso again remind that one must not group chemicals, but must relate to specific materials. In a response to a question by Dr. Queto, Dr. Holder affirmed that Dow is studying possible human reproductive effects from TCDD and has completed some karyotyping on a 2,4,5-T population. 6. Dr. Fa Ik has had considerable experience with animal experimentation, but no direct involvement with human .subjects. The chemical structure of herbid ides may determine the toxicity depending, in case of the esters of 2,4,5-T, on the ease with which they can be metabolized. The position of the chlorine atoms also may alter toxicity. This applies similarly to the impurities in 2,4,5-T and its esters which have different potencies depending on whether the chlorine atoms on the dibenzop-dioxins are located in critical positions. Early experiments were carried out with the acid which was contaminated with neatly 30 ppra of the tetrachlorodibenzodioxin, giving rise to teratogenicity in mice and rats. When purified 2,4,5-T was used, the teratogenicity with regard to the kidney disappeared, which was largely due to the dioxins but remained noticeable regarding cleft palates in mice. With regard to rats, teratogenic potency declined considerably. This susceptibility of the mou.se to 2,4,5-T (pure) in producing malformed offspring appears to be unique because subsequent studies in other species like the rabbit, the sheep, as well as, the rat produced little evidence of teratogenici.ty. Agent Orange consists of the n-butyl esters of 2,4-D and 2,4,5-T in equal amounts and was also studied for teratogenicity in mice. It did not produce as much toxicity as its two components when tested separately although this finding is hard to interpret. It suggests that the two agents together are not showing enhanced tox ic i. ty. 4. �The teratogenic activity of 2,4,5-T was first observed by Dr. Courtney, who had obtained a sample of 2,4,5-T which was contaminated with 2 , 3, 7, 8™ tettachioro-~p--d.ioxin. When it was pointed out that the impurity was not present in most of the s a rnp 1 c s of 2,4,5 -T a n d w a s i t. s e 1 f h i g h 1 y toxic, add i t, i o n a 1. studies were carried out to evaluate 2,4,5-T as distinct from its impurities for teratogenicity. It turned out that the "dtoxin" impurity was teratogenic and that the purified 2,4,5~T was without effect in the rat but was still producing malformations in the mouse. The dioxin, however, produced kidney anomalies in the rat and the mouse. Because of the difference in response of mice and rats to 2,4,5-T in the absence of dioxins, it is of importance to learn that in other laboratories 2,4,5-T produces no malformations in the rabbit arid in sheep. In a study by Collins and Williams impure 2,4,5-T was teratogenic in the Syrian hamster which seemed to be a function of the impurity present in the sample. King, et al. confirmed that purified 2,4,5-T and 2,4-D did not produce malformations in the rat and studies in the chick embryo did not produce evidence of icra tog en i c.i ty that was clear cut. The teratogenic effect of 2,4,5-T in mice when the content of the dioxin was Less than 0.1 ppm was reported by Roil confirming that in the mouse indeed the pure 2,4,5-T was active. Khera and McKinley studied 2,4,5-T and 2,4-D as well as certain esters of these herbicides in rats.and observed malformations at comparatively high dose levels. Similar studies on esters were also carried out by Courtney in CD-I mice and fetotoxicity as well as tera logonicity was observed for each one of the compounds. The solvent seemed to make a contribution in altering the toxicity. Courtney also carried out several studies to dermine the distribution of 2,4,5-T between the pregnant animal and its fetuses in the mouse as well as the rat, to clarify the d i f f ere n ce i n t ox i. c i t y. 7. Dr. Melvin said that mention frequently is made of the Globe and Missouri episodes, about which there is some doubt with respect to the role of dioxin. A much better documented event occurred at Natro, West Virginia, during 1949 in which 282 persons were grossly exposed to 2,4,5-TCP. This included factory workers and their families. Much of the material was carried home on the clothes of the workers so that their wives and children also were exposed. Most became seriously ill, with significant neurological symptoms and chloracne. There were no deaths. All recovered symptomatically except for chloracne scars. Although this group has survived for more than thirty years, epidemic Log Leal data have never been derived from their individual health experiences. Since the population of West �Virginia is relatively stable, it may be possible to trace some of these Individuals. They would constitute a valuable source of guidance concerning the long term or delayed effects of herbicides on human h e a l t h . Dr. Melvin also described some aspects of an industrial accident in Rotterdam, Netherlands, during 1963, involving exposure of at least 10 individuals. Since the Dutch government maintains relatively good public health records it may be possible to trace the health histories of these individuals. Dr. M e l v i n was the Scientific Director of the USAF from 1970 thru 1.977 and thus is familiar with the disposal of millions of gallons of Agent Orange. About 200 AF employees were involved w i t h the dedrumming process. Some ~pr<5b~ably made contact with the chemicals. However, there was strict, biological, m e d i c a l : a n d industrial hygienic monitoring of the operation so that contact was minimized. Agent Orange was fully studied for its chemical characteristics at this time (Appendix G), It may be worthwhile following up the health histories of these individuals. Or, M e l v i n further stated that it is his impression that the acute biological observations reported after exposure to Agent Orange (animal and human) are due to the 2,4~D and the 2,4,5-T themselves and not to the dioxin. The occurence of symptoms shortly after exposure to Agent Orange therefore does not signify that dioxin exposure necessarily had.occurred, but only that there had been exposure to 2,4-D and or 2,4,5-T. By contrast, Dioxin has not manifested an immediate toxic symptomatic response. It. does evoke chloracne about 4 to 8 weeks later both after cutaneous and after inhalation exposure. This cutaneous reaction (chloracne) does not correlate precisely with the intensity or duration of exposure to the dioxin. Individuals who have had m i n i m a l exposure will show more chloracne than others known to have had significantly more exposure. Individual susceptibility, personal hygiene arid other factors may be significant determinants of health effects. 8. Dr. Kearney described the involvement of: the Department of A g r i c u l t u r e with the same herbicides which were used in Agent Orange, Although the EPA has the principal regulatory responsibility for perticides, USDA has some additonal control over herbicides in general. Recently, the Department has had a flood of letters of inquiry, protest and complaint. Much concerns the fear of residents in forested areas of the US that the use of herbicides and pesticides sprayed from low flying aircraft may exert health effects of an undesirable kind, either through direct exposure or through the herbicides entering the ecosystem. Although the present assessment of the USDA is that these fears are groundless, based on the known information concerning the biological actions of herbicides and pesticides, �the Department has nevertheless created a medical team which will systematically examine persons who claim 'that they may have been significantly esposed to these chemicals. Dr. Sheldon Wagner, a dermatologist is heading this investigation. Drs. Kearney and Meivin have remained in touch with the Italian and Swiss authorities who are monitoring the outcome of. the Seveso industrial chemical accident in Italy. One death has been reported. This was an elderly woman who died from metastasising pancreatic cancer shortly after the incident. It is generally held that this cancer developed too soon after the chemical trauma to have been caused by chemicals released in that incident. No TCDD was found in liver or snesenteric fat samples analysed to a tolerance of 0,25 nanograms per gram. 9. "Dr. Kuroda outlined the Rebuttable Presumption Against Registration with EPA filed against 2,4,5—T and its contaminant 2, 3,7, 8-tetracholordibenzo-p-dioxin. This document was published in the Federal REgistor for Friday, April 21, 1978. The Agency is concerned about the carcinogenic and t.eratogenic effects found in laboratory animals when exposed to either 2,4,5-T or the dioxin. TCDD is a potent teratogen in almost every laboratory animal tested and 2,4,5-T containing low levels of TCDD (.05 ppm) is ter-atogen ic in several strains of laboratory rodents. Even Dow*r studies have determined that levels of TCDD as low as lOng/day cause adverse reproductive effects in laboratory rats. Laboratory studies have shown statistically significant increases in the number of tumors in rats fed levels of TCDD as low as 5 ppt. One laboratory study has shown 2,4,5-T containing 0.05 ppm TCDD to be carcinogenic in mice. Although the evidence for mutagenic effects of TCDD did not meet the multi-test criteria for issuing the RPAR, the Agency is continually reviewing all new data especially any forthcoming from the Seveso incident. Dr. Kuroda raised the question of whether TCDD can cause effects, especially chronic effects, without causing chloracne in exposed i n d i v i d u a l s . Although there are animal species that do exhibit. adverse effects w i t h o u t chloracne when administered TCDD, these species may not have sebaceous glands. Dr, Kuroda suggested that we look at individuals living around forested areas such as Oregon that may have been sprayed by 2,4,5-T for possible adverse effects. This population may exhibit some of the same effects supposedly seen by the Vietnam veterans since the type of exposure is similiar, although the levels may be lower. She believed the Agency has received some data on people exposed {sprayed) to 2,4,5,-T that would be of interest and would try to make it available to the committee. She commented that the "Zero" content for d i o x i n in some military tests are not absolute '/eros but reflect the limited analytical sensitivity of chemicaltests a v a i l a b l e ten years ago. Dr. Meivin commented that there 7. �is an equal number of publications which provide evidence that TCDD is not iiKiUKj 10. Dr. Cuoto discussed the effects, of mixtures of versus the effects oE the individual ingredients. He could not recall any research which has specifically been done with the actual Agent Orange used in Vietnam. He is aware of only one paper incriminating 2,4,5-T as being capable of producing excess tumors in experimental animals. There was however no specific turaoi. type produc^d-only total tumor counts were slightly increased as compared with the natural incidence of tumors in the control animals. Until more research has been done, he believes that carcinogen.icity can be neither ruled out nor accepted as a valid effect. He knows of no literature showing that 2,4-D can produce a similar effect. The NCI has sponsored several investigations of which the results are still unreported arid thus not yet analysed by the Institute staff, FJis Institute may be willing to sponsor additional needed research. However, he cannot make a firm commitment at this time since the Institute is currently undergoing reorganization so that, command lines and a c t i o n cent e r s in a y c h a n g e . 1 J . Col. Bayer stated, in response to various questions, that the DOD never contracted with chemical companies to have the components of Agent Orange specially made for DOD. The available production of the chemcial industry in the USA (eight (8) companies) was used. Agent Orange therefore varied '—" q u a n t i t a t i v e l y by lot according to the source of manufacture. DOD has kept records of individual lot numbers so that the composition of each lot can perhaps be traced if the chemical companies kept similar records. DOD destroyed ail its stock of Agent Orange during 1977 by burning it at sea in an EPA designated area. However, it should be possible to reconstitute the formulations of individual lots if the action of precise mixtuir-s is deemed relevant to the inquiry concerning Agent Orange. To the present, nothing has been published to show that the combination of 2,4-D and 2,4,5-T in itself produces effects different, from the biological action ascribable to the individual c o mp o n e n t s s e p a r a t e 1 y . 12. Dr. Williams described steps that had been taken to ascertain a v a i l a b i l i t y of sources for analysis of dioxin levels in body fat. Dr. W i l l i a m s noted that, they have identified two individuals at academic institutions who have experience with the analysis and are w i l l i n g to accept specimens from the VA. The costs per analysis are in the range of $600-800 but are volume dependent. Both individuals need some reasonably firm estimates of likely number of specimens requiring analysis over a given 8. �time period such as one year, Dr. W i l l i a m s noted that in-house experience in VA Laboratory Services with dioxin analysis does riot exist. However, it could be developed if there were to develop a continued demand over years for a 100 or more analyses per year. 13. Dr. Thomasino queried the value of this proposed biopsy endeavor by the VA, His main concern is that there is no known body of. knowledge Linking tissue concentrations of dioxin to any specific syndrome of biological effects. Pie compared the work done at. the Kettering Laboratory in Cincinnati on tissue lead .levels versus c l i n i c a l evidence of lead poisoning. He pointed out that it took many years of experimentation and clinical i n v e s t i g a t i o n before th<& threshold for toxic tissue burdens of lead could bo arrived at. In the case of lead, one has a specific atomic moiety to measure. Matters are much more vague for dioxins. If d i o x i n is found in any of the fat samples obtained from veterans, it would be impossible to ascribe any meaning to such f i n d i n g s since there is no defined diseases yndroine w i t h which the d i o x i n tissue burden can be correlated. Likewise, if no dioxin is found in any of the specimens, it would s t i l l be impossible to say what this signifies, since the dioxin could have been in the tissues or in some other vital organ formerly, may or may not have induced biological responses, and subsequently may hve leached out of the tissue. Until there are biomonitor data with which to correlate tissue dioxin levels, it may not be worth the enormous expense to start this biopsy program. Dr. Melvin concurred with this critique. 14. Dr. Hobson outlined the political overtones which have relevance to this biopsy issue. In the CBS presentation of Agent Orange, there was a scenario showing a physician extracting a fat sample from a patient and the physician stated emphatically that he could obtain confirmation of dioxin poisoning through such biopsy specimens. Veterans, and action groups speaking for the veterans are firmly convinced that the VA must test them for dioxin. A populist scientific spokesman also said in the CBS program that d i o x i n accumulates in fat and may later be released to re-exert toxic actions on vital organs, during periods of weight loss. Many veterans therefore believe firmly that they may be walking around with such a chemical "time bomb" in their tissues. The VA essentially has no option but to check whether there is any proof that dioxin remains in fat eight years after the last exposure in Vietnam. If no dioxin is found in the men men who are known to have had significant exposure to Agent Orange or who may even have had specific symptoms, this will be meaningful information. If as much dioxin is found in persons who have never been in Vietnam as in those who were decisively 9. �exposed to Agent Orange, this .also would be meaningful information. 1C the determination for dioxin proves exceedingly difficult or erratic, as suggested by Dr. Holder, confirmation of this through the VA endeavor, would again be meaningful, since, if no reliable data can be obtained in even the best laboratory, the v a l i d i t y of the CBS statement can be challenged. Dr. Cueto s u p p o r t e d t h .1 s a p p r o a c h . 15. Dr. Sehcpers mentioned the current review of cancer incidence statistics which can be derived from the VA's enormous data file which is compiled from the diagnoses reported for each hosptia.lizat.ion veteran (Patient Treatment Fiie-PTF). The annual incidence of liver cancer has recently been reviewed. Records are available for the period 1963 thru 1977. There is no conclusive indication that liver cancer has increased in the age categories representative of veterans who served in the Vietnam War. For veterans below the age 25 years, there have been 32 cases over the period 1967 thru 1977. This represents an average of about 3.0 cases per year. However, during 1974 there were 7 cases and in 1976 5 cases occurred. In between these two years there were none. (Appendix D-l) When these cancers are averaged out over three year periods (Appendix D-2) there does appear to be a slight increase of cases between 1969 and 1974. For the age group 25 years thru 34 years there were 63 cases with an average of about 5.6 per year. However, spurts of cancer increase also occurred in 1973 and 1976, These spurts yielded higher values for the final six years of this review period. There is no explanation yet for thir.. The records have been called for to determine whether any of these cases represented Vietnam War veterans. The tables do however show that liver cancer has all along been relatively prevalent in the older age group veterans, none of whom may be expected to include Vietnam War veterans, 16. Ms. Offutt stated that the EPA can probably assist with the .identification of these individuals. She described the serious concerns of he?; agency with the question of pollution of the ecosystem by herbicides and pesticides. The rebuttable presumption injunction to which Dr..Kuroda had referred is an illustration of the posture the EPA may adopt, on these matters. She clarified that if as a result of the evidence which may be offered during hearings concerning this rebuttable presumption, the hypotheses on which it is based are destroyed, the EPA will withdraw the presumption. Until such retraction occurs, the presumption reflects the persuasions of the EPA concerning herbicide 2,4,'j-T. The EPA has. a voluminous collection of l i t e r a t u r e on herbicides 1 -, and Ms. Offutt invited members of the commit Leo to consult their library rather than attempting to at or t. all ov e r a g a i n. 10. �17. The meeting was adjourned at 4 PH. The members all expressed preference for a morning meeting. The next session of the committee will be called Cor September 8, 11, 22 or 25, 1978. GERRIT W . H . SCIIEPERS, M . D . Chairman Appendix A; B; C: D. E. F. G. VA brochure on Herbicides Steering Committee request to Advisory Committee Re b u t table P r e s u rap t i o n of E PA Re g a r d i n g 2,4,5 -T L i v e r C a n ce r i n V e te r an s 1963 t hr u 197 7 Toxicity Data on Herbicides Prepared by US Array Environmental Hygiene Agency VA Administrative Instructions to Field Health Care F a c i1i ties Chemical Characterization of Agent Orange 11. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5744 Series The series number of the original item. Series VIII Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Minutes of the AdHoc VACO Advisory Committee on Herbicides Meeting of July 7, 1978 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/19be58d7228c34820e124375ae9cd031.pdf 9c1dee5882ebf49e71d1a30c54c9fb47 PDF Text Text Item D Number °5742 U |fot scanned Author Corporate Author Report/Article Title Chronology of Changes in the Agent Orange Study Journal/Book Title Year 000 ° Month/Day Color Number of Images n o Descrlpton Notes Tuesday, March 26,2002 Page 5742 of 5743 �January 1985 23 Battalions tracked. Report to Office of Technology Assessment shows changes Four major changes: a. Battalions rather than companies to be used. b. Ranking of unit exposure likelyhood will not determine selection of men. v» c. Personnel Records and Morning Reports will be used to verify vets period of service. d. Infantry - Artillery units only. March 1985 Three modifications: a. New coding. b. More location recording. c. Reabstract battalion H, 27, 28 March 1985 Now use gazeteer and maps. 18 November 1985 Interim Report number 2 CDC proposed more changes: a. Reviewing 6,000 201 Files will increase to 8,670. At a subsequent meeting on 20 November 1985 figures changed to 6,600. b. Will require additional tracking time periods (1966 and 1969). c. Will eliminate approximately 70% of vets already qualified. 21 November 1985 40 Battalions tracked. �CHRONOLOGY OF CHANGES IN THE AGENT ORANGE STUDY January 1983 Transfer of study to Centers for Disease Control (CDC). February 1983 Assisted with military input to the original protocol. * June 1983 - Jan 1984 ESG pilot study of 10 companies. 16 November 1983 Identified 122 Combat Battalions and Combat Support units. Initiated Vietnam Experience Study. - completed April 1985. 18 M~"ember 1983 50 Battalions now required. 1400 individuals per month. 13 January Initiation of ESG support for CDC Agent Orange Study. Automation delay in arrival of CDC PCs. Constant changes in the rules for use of worksheets. 1984 01 February 1984 Extract all coordinate and locations/- 15 June 1984 Did away with KAYPROS and back to manual mode. 24 July 1984 Telecon about most recent version of time table which now moves up ESG time schedule. 26 July 1984 14 point ESG briefing paper raises questions about procedures. 08 November 1984 20_ Battalions tracked. 09 November 1984 Major changes to protocol given to ESG. 21 December 1984 Major changes to protocol given to ESG. The requirement for 50 Battalion increased to 65. Shorter time lines. Quality Control Plan implemented 11 months into study. • Personnel Data Abstractions increased from 1433 subjects to 2500 per month. Original protocol called for 26 data elements. Vietnam Experience change to 73 data elements. Agent Orange - 143 Data Elements. Back page added, which required additional research. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5742 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Chronology of Changes in the Agent Orange Study ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/ed0ea1c4feabbddcbf716254c75344b3.pdf 31e5d48de211e8411d668a0fbf649906 PDF Text Text itoinD Number °5741 n ^t Scanned Author Corporate Author Report/Article TltlO Historical Sketch of the Agent Orange Working Group Journal/Book Title Year 000 ° Month/Day Color Number of Images n ° Descriptor Notes Tuesday, March 26, 2002 Page 5741 of 5743 �The Cabinet Council Agent Orange Working Group established by President Reagan had its genesis in the Interagency Work Group (IWG) to study the possible long-term effects of ph^eoxy herbicides and contaminants. The IWG had been chartered by the White House on December 11, 1979. jL/ Its mission was to monitor, coordinate and set priorities among Federal Government research activities, to design a research agenda, and to organize the means to assure that the research agenda are carried out. In response to the concerns of veterans1 groups that exposure to herbicides in Vietnam could be presenting health problems, President Reagan on July 17, 1981 expanded the membership of the IWG, renamed it the Agent Orange Working Group (AOWG) and raised its status to Cabinet Council working group level. 2Y The IWG's mandate was a reaffirmed with stated emphasis on research relating to Agent Orange exposure. 3/ In addition, the AOWG was charged with guiding the Congressionally mandated epidemiological study of Vietman Veterans exposed to Agent Orange. 4/ The Congress in authorizing this study directed the President to assure that the study be fully coordinated with other on-going or future studies. 5/ The legislative history of the Act relative to this presidential responsibility states: "The Committees also JL/ Memorandum for Secretary of Defense, Secretary of Health, Education and Welfare, Administrator of Veterans Affairs from Stuart E. Eizenstat, Assistant to the President for Domestic Affairs and Policy, Subject: Interagency Group to Study the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants, December 11, 1979. 2/ Memorandum for Secretary Richard Schweiker, Chairman Pro-Tern, Cabinet Council on Human Resources from Robert Carleson, Executive Secretary of Human Resources Cabinet Council, Subject: Agent Orange Working Group, July 17, 1981. _3/ Memorandum for Secretary of Defense, et al from Secretary Richard Schweiker, Chairman Pro-Tern, Cabinet Council on Human Resources, Subject: Agent Orange Working Group, August 21, 1981. 4/ Veterans Health Programs Extension and Improvement Act of 1979, Sec. 307 (a), 93 Stat. 1097, P.L. 96-151. 5/ Ibid., Sec. 307 (c), 38 U.S.C. 219 note. �Page 2 i stress the importance of the provision directing the President to assure (preferably through an interageney task force) that the mandated study be fully coordinated with on-going or future governmental studies . . " 6>y .. The Act was later amended to authorize an expansion of the scope of the epidemiological study to include an evaluation of the adverse health effects which may have occurred as a result of other factors that may have been present in Vietnam. 7_/ The amendment did not disturb the direction given to the president regarding coordination of the study nor was the delegation of this presidential responsibility to the AOWG affected. Consequently, the AOWG is charged, in this one instance only, to oversee and coordinate the Vietnam Experience component of the Congressionally authorized study even though the study component is not concerned with the health effects of exposure to Agent Orange. 6/ 125 Cong. Rec. 34992, December 6, 1979. 7/ Veterans' Health Care, Training, and Small Business Loan Act of 1981, Sec. 401, 95 Stat. 1061, P.L. 97-62, 38 U.S.C. 219 note. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5741 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Historical Sketch of the Agent Orange Working Group ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/383e26d869b763c6fe79f928eb67a883.pdf f60fd95545fb9def96bd1cfd2de65b22 PDF Text Text item D Number 05740 a Author Corporate Author Report/Article Title Compilation of Information on the Federal Government and Agent Orange Journal/Book Title Year 000 ° Month/Day Color D Number of Images ° DBSOrlptOn NOtBS 13 sections . including a history of the AOWG, studies of note, and Congressional committees. Tuesday, March 26, 2002 Page 5740 of 5743 �I N D E X Section I Executive Summary Section II Statement of President Reagan Section III Agent Orange A. Fact Sheet B. Expenditures (circle charts) Section IV Use of Agent Orange in Vietnam A. White House Primer on Agent Orange - 10/27/83 Section V Background of the Agent Orange Working Group A. White House memo - 12/11/79 B. White House memo 07/17/81 C. White House memo 08/21/81 D. Secretary Margaret Heckler's Press Release - 6/6/83 E. Charter Section VI Agent Orange Working Group Organization A. Membership and staff Section VII Advisory Committee on Special Studies A. White House memos - 09/16/80 B. Charter C. Members Section VIII Congressionally Authorized Epidemiological Study Section IX Scientific Studies of Note A. CDC Birth Defects B. International Soft Tissue Sarcoma Studies C. National Cancer Institute Ongoing Studies D. Air Force Ranch Hand Studies E. Proposed Studies Section X Science Panel Report A. Executive Summary B. Brief History C. D. Rationale for Research Efforts from a. What is known b. What is not known Federal Research 1981-1987 a. Effects in animals b. Effects in humans c. Others E. Evaluation F. Future Directions 1980 �Index (cont'd) Section XI Additional Information A. Exposure Opportunity Index B. Agent Orange Litigation C. VA Advisory Committee created by P.L. 98-5A2 Section XII Congressional Veterans Committees A. Senate Committee B. House Committee Section XIII Appendix - Literature Review �EXECUTIVE SUMMARY The Agent Orange Issue A legacy of the Vietnam conflict is the concern of many Vietnam veterans that they may be at risk of a spectrum of adverse health effects as a result of their service in Vietnam. These concerns focus largely on Agent Orange, a herbicide used for defoliating areas of enemy troop concentration and staging. History In late 1979, the White House established an Interagency Work Group to bring together knowledgeable government scientists to oversee the research, develop areas where scientific study is needed, and report the results as soon as they become available to the Congress and the public. On August 21, 1981, President Reagan established an Agent Orange Working Group (AOWG) as part of the Cabinet Council on Human Resources, elevating and enlarging the scope of the prior group. Secretary Margaret Heckler, as Chair pro tempore of this Cabinet Council, named John (Jack) Svahn, at that time Under Secretary, to chair the AOWG and in a Press Release dated June 6, 1983 stated her well known concern for veterans and her particular concern in the Agent Orange question "By designating the second highest official of my department as Chairman, I am reaffirming this administration's commitment to the prompt and scientifically responsible resolution of the health concerns of Vietnam veterans who were exposed to Agent Orange and other environmental factors during their service to their country in that conflict. His leadership of this vital working group will help us get the answers we need " the Secretary said. Subsequent chairpersons have been Assistant Secretary for Health, Dr. Edward Brandt September 1983 - December 1984, Under Secretary Charles N. Baker, December 1984 * August 1985. On April 11, 1985 the eight Cabinet Councils, including Human Resources were combined into two, the Council on Economic Policy Council and the Council on Domestic Policy to which the AOWG now reports. Organization The Agent Orange Working Group is under the leadership of the Department of Health and Human Services and includes scientific, legal and policy representatives from that Department, the Departments of Defense and State, the Veterans Administration, the Environmental Protection Agency, the Department of Agriculture, the Occupational Safety and Health Administration of the Labor Department, the White House Offices of Policy Development and of �the Science and Technology Policy, Office of Management and Budget, Council of Economic Advisors, ACTION, and Congress' Office of Technology Assessment (observer status). The Science The issue of possible adverse health effects in humans as a consequence of exposure to Agent Orange in Vietnam has attracted and maintained the attention of the nation for nearly a decade. For the past four years, the AOWG has been evaluating the direction and extent of the government's scientific research in Agent Orange and related issues. When the AOWG was formed in 1981, it was clear from animal studies and the limited human studies that the toxic contaminant of Agent Orange (TCDD) has the potential to cause a broad range of deleterious effects. The extent to which these effects were likely to appear in humans exposed to Agent Orange in Vietnam, however, was unknown. Between 1981 and 1987, AOWG member agencies will have expended $150 million in Agent Orange-related research with over one hundred and fifty (150) studies. The majority of these funds has been directed at closing the largest gap in our knowledge on Agent Orange: the effects of Agent Orange on humans. Ten major epidemiological studies scheduled for completion by 1990, and five ongoing health surveillance projects should provide information on whether exposure to Agent Orange has affected the health of Vietnam veterans and for framing hypotheses which can be tested in follow*up studies if necessary. Additional resources have been expended to better characterize known toxic properties of 2,3 ,7 ,8*TCDD and Agent Orange. The Public The Agent Orange Working Group has received support from veterans organizations and members of Congress and its recommendations have been accorded significant weight. The President In a July 17, 1981 meeting with veterans leaders, President Reagan indicated that the Administration took seriously the concerns of Vietnam veterans and their families about their health status as a result of their actual or presumed exposure to Agent Orange in Vietnam and was firmly committed to con* tinuing and according the highest priority to the current scientific research studies now being conducted and planned by Federal agencies. �-3* The President cautioned that the scientific research may never yield definitive answers to the question of whether Agent Orange i»» or any other single factor ^* has adversely affected the health of an individual veteran but that we can learn whether Vietnam veterans as a group are suffering any chronic health effects not present in a comparable population that did not serve in Vietnam. The Results The results of the scientific research will prove useful in helping to formulate sound public policy regarding health care and compensation for Vietnam veterans. Some studies are completed and are inconclusive; the major Epidemiologic studies underway by the Centers for Disease Control, mandated by Congress is the most comprehensive but will not be completed until late 1989. Based on the growing body of information in hand, the worst case scenarios envisioned by some as a consequence of exposure to Agent Orange are not being realized. Populations known or possibly exposed to Agent Orange which are being studied have not so far exhibited increased incidences of cancer, or death from other causes, or abnormally high rates of birth defects in their offspring. This optimism is tempered by the knowledge that other, less*well characterized effects of concern may by associated with 2,3,7.8TTCDD ( e . g . , immunotoxicity). Some effects (e.g., cancer) may not become manifest for several more years, due to a longer latency period. The consensus of the Science Panel is that initiation of any new, major epidemiological study should await and be built upon the results of studies already underway. A large number of ongoing research projects designed to characterize the toxicity and mechanisms of action of 2,3,7,8-TCDD in laboratory animals will also help to identify possible adverse human health effects and will assist in the interpretation of epidemiologic study results. �AGENT O R A N G E D I O X I N EXPENDITURE AGENCY EXPENDITURES BY STUDY TYPE $152,455,000 TOTAL EXPENDITURES ANIMAL (12.8%) ANALYT (1 .6%) ENVIR (6.2%) UT (1 .2%) STUDY TYPE EXPENDITURES HUMAN ANIMAL ENVIRONMENT ANALYTICAL LITERATURE TOTAL $119,293,500 19,522,000 9,382,000 2,368,000 1,890,000 $152,455,000 ,X HUMAN (78.2%) �AGENT O R A N G E D I O X IN EXPENDITURES $152,455,000 TOTAL COST IJSDA (Q.4%) $594,000 N DOD (22.O%)$33,605,000 \ Jk VA (53.3%) $81,286,000 EPA (9.5%) $ 1 4 , 4 6 7 , 0 0 0 y X X HHS (14.8%)$22,503,000 �HHS A.O./DIOXIN EXPENDITURES $22,50.3,000 TOTAL EXPENDITURES ANALYT (2.5%) $556,000 HUMAN (41 .1%) $9,244,000 ANIMAL (56.5%) $12,703,000 �DOD A.O./DIOXIM EXPENDITURES $33,605,500 TOTZVL EXPENDITURES ANIMAL (0.9%) $288,000 HUMAN (99.1%) $33,317,500 �USDA A.O./DIOXIN EXPENDITURES $594,000 TOTAL EXPENDITURES LIT (1O.8%) $64,000 HUMAN (89.2%) $530,000 �EPA A.O./DIOXIN EXPENDITURES $14,467,000 TOTAL EXPENDITURES $2,146,000 ANIMAL (14.8%) LIT (7.3%) $1,052,000 ANALYT (12.5%) $1,812,000 HUMAN (G.5%) $75,000 ENVIR (64.9%) $9,382,000 �V.A. A.O./DIOXIN EXPENDITUREIS $81 .286.OOO TOTAL EXPENDITURES $774,000 $4,385,000 \ r ( 4 O ) $76,127,OOU 9 . % �HHS U.S. DEPARTMENT Of HEALTH AND HUMAN SERVICES FOR IMMEDIATE RELEASE DRAFT Contact: Telephone HHS Secretary Margaret M. Heckler today forwarded to the Cabinet Council on Domestic Policy an updated report from the Agent Orange Working Group suggesting no new major studies are needed on the subject until evaluations have been done on those already completed or continuing through 1987 at a cost of more than $150 million. Terming results of the studies thus far as "reassuring," Secretary Heckler said, "Completed studies show no increase in birth defects among children of Vietnam veterans or higher mortality due to Agent Orange exposure. "However, careful and intensive epidemiological studies in other areas are going on and we must await their findings." The advisory science panel formed by the AOWG says in the report that the numerous research projects completed or already underway are the ones it considers both essential and feasible. It recommends "that any additional major research efforts involving Vietnam veterans' exposure to Agent Orange should await evaluation of the results of studies which are currently in progress." Created in 1979 as a small interagency work group, the AOWG was enlarged and elevated to cabinet council status in July 1981 by President Reagan to show his concern over the fears of Vietnam veterans that they may suffer ill effects from exposure to phenoxy acid herbicides, principally Agent Orange. The herbicides were sprayed to defoliate dense jungle areas from which enemy troops operated. - MORE - �- 2- Veterans groups have maintained they were endangered by an increase in cancers and liver disorders, and expressed fears that their children might be born with defects. They called for scientific research, compensation and treatment. In forwarding the new AOWG report to the Cabinet Council on Domestic Policy, Secretary Heckler, a long-time advocate of veterans' rights, said, "The president's promise to support any research necessary to learn whether Vietnam veterans as a group are suffering any chronic health effects not i present in a comparable population that did not serve in Vietnam, will be kept." Twelve federal departments or independent agencies are represented on the Agent Orange Working Group. It sets priorities, coordinates and overses federal research into the possibility of long-term adverse health effects resulting from exposure to the herbicides used in Vietnam. The science panel's report says HHS, the departments of Defense and Agriculture; the Environmental Protection Agency; and the Veterans Administration are conducting ongoing studies with the other AOWG members providing advice and guidance. The others are the Department of State; Department of Labor; ACTION; the White House Offices of Policy Development, Science and Technology Policy; Office of Management and Budget; Council of Economic Advisors; and the Congressional Office of Technology Assessment, the latter as an observer. #### �STATEMENT OF PRESIDENT REAGAN JULY 17, 1981 "One of the most unfortunate legacies of the Vietnam conflict is the continuing concern of many Vietnam veterans that they are, or may be, at increased risk of a broad spectrum of adverse health effects as a result of their service in Vietnam. These concerns have largely focused on Agent Orange, a herbicide used for defoliating areas of enemy ground troop concentrations and staging. Agent Orange was made by combining two herbicides that were in widespread use in forestry and agriculture. Unfortunately, despite much discussion in the media and among scientists, there are still few definitive answers to the difficult scientific issues involved. Indeed, we may never be able to determine with certainty whether Agent Orange — or any other single factor •*- has adversely affected the health of an individual veteran. The scientists working on this problem are hopeful, however, that we can learn whether Vietnam veterans as a group are suffering any chronic health effects not present in a comparable population that did not serve in Vietnam. In addition, several studies —» including an epidemiological study of the Air Force Personnel who sprayed Agent Orange *•*• are directly examining the Agent Orange issue. The results of these and other studies, including a congressionally mandated VA epidemiological study of the health status of Vietnam veterans, should be extremely useful in helping to formulate sound public policy regarding health care and compensation for Vietnam veterans. I believe that .the Federal Government has made significant progress in the past year in organizing and beginning a serious scientific inquiry into the Agent Orange issue. Much, however, remains to be done and I share the deep and abiding concern of Vietnam veterans about their health and that of their children. I am committed to assuring that the important scientific research now under way and being planned under the overall guidance and coordination of the White House Inter agency Work Group continue to completion in an efficient, expeditious manner, consistent with sound scientific principles. Accordingly, I am hereby reaffirming the mandate of the Work Group and making its work a major priority of my Administration." �Agent Orange The terra "Agent Orange" is derived from the orange color code painted on the barrels of herbicide shipped to Vietnam. Other herbicides used in Vietnam carried various other color codes depending on the nature of the herbicide. Agent Orange was a 50/50 mixture of the herbicide 2,4,-D and 2,4,5*7. The product was provided on contract with the Department of Defense by a number of chemical companies. A by-product created in extremely small amounts during the manufacture of 2,4,5~T was the chemical, dioxin. The average contamination amount of dioxin was, according to the Veterans Administration, two parts per million. Dioxin has caused lethal and toxicological effects in some laboratory animals at lower levels than any other man-made chemical. However, both the lethal dose levels and the toxicological effects vary considerably among different animal species. The toxicological effect upon humans remains under study and additional work must be done before an authorized view of the risks can be made. �A a n j, s Nv w n H ana, �CABINET COUNCIL ON DOMESTIC POLICY AGENT ORANGE WORKING GROUP FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE TYPE OF STUDY AGENCY STUDY TITLE Mortality ReproMorbidity Cancer duction Analytical STATUS Estimated Completed Ongoing Completion Date DEPARTMENT OF HEALTH AND HUMAN SERVICES NIOSH Investigation of Leukemia Cluster in Madison County, Kentucky Allegedly Associated with Pentachlorophenol Treated Ammunition Boxes Published NTIS 1984 NIOSH Dioxin Registry X Late 1985 NIOSH Soft Tissue Sarcome Investigation X Published Scan. J. Work Environ Health 1984 NIOSH NJ/Missouri plant worker and worker's spouse reproductive outcome study Reproductive outcomes in persons possibly exposed to 2,3,7,8 RDP Measurement of TCDD levels in adipose tissue from potentially exposed persons in Missouri. X (begins 1985) �Page 2 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE TYPE OF STUDY AGENCY STUDY TITLE Mortality ReproMorbidity Cancer duction Analytical STATUS Completed Ongoing Estimated Completion Date DEPARTMENT OF HEALTH AND HUMAN SERVICES cont'd NIEHS Establishment and Maintenance of an International Register of Persons Exposed to Phenoxy Acid Herbicides and Contaminants X NIEHS Effects on Intestinal Cells UNC-CU Grad student X Indefinite X 1984 X 1984 Lipid Assimilation NRSA Membrane/LP Receptor NRSA X X 1986 NIEHS Pesticides and transport across bilayer Lipid membranes (toxicology) X X 1987 NIEHS Occupational and Environmental Health Center Grant (toxicology) X 1987 NIEHS - Dioxin Environmental Health Sciences Center Grant Clinical Studies X 1987 NIEHS Dioxin Mechanism(s) for toxicity of chlorinated dibenzodioxins (toxicology) X 1987 �Page 3 FEDERALLY SPONSORED HIMAN STUDIES RELATED TO AGENT ORANGE TYPE OP STUDY STUDY TITLE Mortality Repro* Morbidity Cancer duction Analytical Estimated Completed Ongoing Completion Date NIEHS Dioxtn Environmental pollutants and toxicology of the liver X X 1986 NIEHS Dioxin XenobiotLc induction of pleiotropic responses in liver X X 1986 NIEHS Dioxin molecular toxicology of TODD X X 1986 NIEHS Dioxin chlorinated dibenzoisp-dioxins; mechanisms of toxicity X X 1987 NIEHS Dioxin » Toxic halogenated wastes: In vitro bioassay development X X 1986 NIEHS Dioxin * Atomic emission spectrometry for dioxin trace anlaysis (detection) X X 1986 NCI Study of Mortality Among Pesticide Applicators from Florida Publications in Press NCI Case Control Study of Lymphoma and Soft Tissue Sarcoma Indefinite �Page 4 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE AGENCY STLDY TITLE TYPE Mortality OF b 1 UDY Repro* Morbidity Cancer duction CDC Birth Defects and Military Service in Vietnam Study STATUS Analytical Estimated Completed Ongoing Completion Date X Published Aug. 1984 *CDC Epidemiologic Study of Ground Troops Exposed to Agent Orange during the Vietnam Conflict Sept 1989 CDC Study for Body Burden for Dioxin in the General Population Late 1988 VETERANS ADMINISTRATION Vietnam Veteran Mortality Studies December 1985 Vietnam Veteran Identical TWin Studies Under Review by OTA and AOWG VA/AFIP Case Control Study of Soft Tissue Sarcoma *Mandated to the VA by P.L. 9&S-151 Sec. 307. 1983. X July 1986 Transferred from VA to CDCunder Interagency Agreement January 14, �Page 5 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT GRANGE Or AGEUOf STUDY TITLE Mortality b l U U Y Repro*Morbidity Cancer diction Analytical STAIUS Estimated Completed Ongoing Completion Date VETERANS ADMINISTRATION cont'd Survey of Patient Treat-!ment File for Vietnam Veteran In-Patient Care X Sarcoma Study in Patient Treatment File Agent Orange Registry Examinations X December 1985 X X Review of Soft Tissue Initial 1983 Survey Indefinite X TCDD in Body Fat of Vietnam Veterans and Other Man Published X Retrospective Study of Dioxins and Furans in Adipose Tissue of Vietnam-Era Veterans 18 96 DEPARTMENT OF DEFENSE Epidemiologic Investiga'tion of Health Effects in Air Force Personnel Following Exposure to Herbicide Orange (Air Force Health Study) Armed Forces Institute of Pathology Agent Orange Registry of Vietnam Veteran Biopsy Tissues X Baseline 1983 Complete 1999 Indefinite �Page 6 FEDERALLY SPONSORED WMAN STIDIES REIATED TO AGENT ORAN<£ AGENCY STUDY TITLE TYPE OF Mortality STUDY Repro* Morbidity Cancer duction Analytical STATUS Estimated Completed Ongoing Completion Date ENVROEMENTAL PROTECTIDN AGENCY Report of Assessment of a Field Investigation of Six^Year Spontaneous Abonr tion Rates in Three Oregon Areas of Relation to Forest 2,4,5*T Spray Practices (Published) National Pesticide Monitor* ing Project of Human Adipose Tissue Indefinite (Annual Reports) DEPARTMENT OF AGRICULTURE A Case Control Study of the Relationship Between Exposure to 2,4*D and Spontaneous Abortions in Humans Exposure Measurements of Mixers, Loaders and Appli^ cators of 2,4*D on Wheat 1982 Exposure of Forest Workers to Ground Applications of 1983 �THE ANIMAL STUDY �Page 7 FEDERALLY SPONSORED LABORATORY STUDIES AM) LITERATURE SURVEYS RELATED ID AGENT ORANGE AGEHCr STUDY EFECRT 1 i r E OX Animal Environmental b l U D Y Analytical STATUS Literature Completed Ongoing Estimated Completion Date DEPARTMENT OF HEALTH AN) HUMAN SERVICES NIEHS Bioassay of Octachlorodiben*zo-^p^dioxin Indefinite Carcinogenesis Bioassay of 2,3,7,8rTetrachlorodibenzoi-pr dioxln in Swiss Webster Mice Indefinite Carcinogenesis Bioassay of 2,3,7,8*-Tetradilorodibenzo-»p» dioxln in Osbornei-Mendel Rats and B6C3F1 Mice Bioassay of a Mixture of 1,2,3,6,7,8* and a Mixture of 1,2,3,6,7,8-rHexachloror dibenzo*prdioxins for Possible Carcinogenicity Comparative species Evalur ation of Chemical Disposition and Metabolism of 2,3,7,8r Tetrachlorodibenzofuran (TCDF) in Rat, Monkey, Guinea Pig and Two Strains of Mice Neurotoxicity of 2,4,-H) in Rodents Indefinite �Pagp 8 FEDERALLY SPObECRED LABORATORY STUDIES AN) LITERATIRE SURVEYS RELATED TO AGENT ORANGE AGENCY STUDY EFFORT l Y F b OF S 1 U D Y Animal Environmental Analytical Literature STATUS Completed Ongoing Estimated Completion Date DEPARTMENTOF HEALTH AN) HUMAN SERVICES cent 'd Studies of the Chemical Disposition and Metabolism of Octachlorodibenzodioxln (OCDD) Indefinite Effects of Agent Orange Compor nents on Male Fertility and Reproduction Mutagenicity Studies of TCDD, 2,4-4); 2,4,5~T and Esters of 2,4~D and 2,4,5-T Indefinite Implications of Low Level Exposure of Dioxins X X Indefinite Mechanisms of Toxicity of the Chlorinated* prdioxins X X Indefinite X Indefinite Research Toward Understandsing the Molecular Level Mechanisms of Toxicity of TCDD and Related Compounds Synthesis of Selected Chlorinated dibenzo*prdioxins and Related compounds as Analytical Standards Indefinite �Page 9 FEDERALLY SPONSORED LABORATORY STUDIES AM) LITERATURE SURVEYS RELATED TO AGENT CRANCE 1YPE AGENCr STUDY EFFCRT Animal OF S i U U Y Environmental Analytical STAIUS Literature Completed Ongoing Estimated Completion Date DEPARTMENT OF FEALTO ADO WMAN SERVICES cont'd Methods for the measurement of dioxins and furans in human adipose tissue Indefinite Matrix Effect and Sub Parts* perrbillion Quantitative Analysis of TCDD by Mass Spectrometry *• With Special Reference to Milk Indefinite Toxic Actions of Tetrar chloroazobenzene Dioxins X Indefinite XenobiotLc Induction of Pleiotropic Responses in Liver X Indefinite Molecular, Biochemical Actions of Chlorinated'sp* dioxins Indefinite Mechanism(s) for Toxicity of Chlorinated Dibenzoidioxins Indefinite �Page 10 FEDERALLY SPONSORED LABORATORY STUDIES AM) LITERATURE SURVEYS RELATED 10 AGENT GRANGE AGENCY STUDY EFFORT T Y1? E O F S T U D Y Animal Environmental Analytical Literature STATUS Completed Qngping Estimated Completion Date NIEH3 Teratogenicity of TCDD T Cleft palata Induction (mice) 1986 Disposition of TCDD Fetal Distribution in mice 1986 2,3,7,8~Tetrachlorodiibenzofur amDis posi t ion in Rats, Mice, Guinea Pigs disposir tion 1983 1,2,4,6,8,9 Hexachlorodi* benzofuranrDisposition disposition metabolism 1986 1986 DDXIN Structure-Toxicity Rela* tionships 1984 Theoretical Modeling of Dioxin Receptor 1984 X Molecular Modeling of Dioxin Binding Proteins Molecular Basis of Dioxin Toxicity X Theoreti* cal Biochemical Lipid Assimilation NRSA X X July 1986 X Membrane /LP Receptor 1986 Nov. 1986 �Page 11 FEDERALLY SPONSORED LABORATORY STUDIES AM) LITERATtRE SURVEYS REIATED TO AGENT GRANGE AGENCY STtDY EFFORT 1 Y F L Animal O * Environmental b l U U Y Analytical STATUS Literature Completed Ongoing Estimated Completion Date ENVIROIMENTAL PROTECTION AGMCY Evaluation of Large Scale Combustion Sources X X Evaluation of Municipal Waste Combustors X X Bacterial Decomposition of TCDD X X Investigation of Bioavaila* bility to Fresh Water Fish of TCDDs in Fly Ash X Analysis of Environmental Samples for PCDDs and PGDFs DEPARTMENT OF AGRICULTURE Survey of Phenoxy Herbi*cide Use by Agricultural Commodity Survey of Phenoxy Kerbir cide Literature Annaul Biblior graphics Published �Page 12 FEDERALLY SPONSORED LABORATORY ST1DIES AN) LITERATURE SURVEYS RELATED TO AGENT GRANGE AGENCY STUDY EFFORT TYPE Animal OF Environmental S T U D Y Analytical STATUS Literature Completed Ongoing Estimated Completion Date DEPARTMENT OF AGRICULTURE cont'd Photolysis of 2,4,5-vT X Biological and Economic Assessment of 2,4,5»T and Silvex X TCDD Residue Monitoring in Deer Report in Preparation DEPARTMENT OF DEFENSE Environmental Chemistry of Herbicide orange and TCDD Indefinite VETERANS ADMINISTRATION Review of Literature on Herbicides, Including Phenoxy Herbicides and Associated Dioxins Published 1981 Annual update Approved Urinary 6-i-Hydroxy Cortisol: Physiological and Pharmaco*logic Studies (Including Agent Orange) 1982 Effect of TCDD on Lipid Metabolism 1983 �Page 13 FEDERALLY SPONSORED LABORATORY STIDIES AM) LITERAHRE SIRVEYS RELATED TD AGENT GRANGE AGEUCr STIDY EFECRT 1 Y F E Animal ul? Environmental b l U D Y Analytical Literature SlAIUS Completed Ongoing Estimated Completion Date VETERANS AEMINISTRATIDN cont'd Publication in Press Mechanisms of Dioxin Induced Toxicity Using the Chloracne Model * Phase I Behavioral Toxicity of An Agent Orange Component 2,4*D X Effects of 2,3,7,8*Tetra* chlorodibenzodioxin on Hepato* biliary function in Animals 1984 X 1986 Mechanism of TODD Absorption and Toxicity on lipid and lipoprotein Metabolism 1986 Metabolism of the Her hi* cides Present in Agent Orange and Agent Wiite 1986 TOM) Exposed Rhesus Monkeys: Effects on Behavior and Stress Hormones 1986 �Page 14 FEDERALLY SPONSORED LABORATORY STUDIES AM) LITERATURE SUNOS RELATED TO AGENT GRANGE 1 Y P L A(£NCY STUDY EFFORT Animal O f Environmental b l U D Y Analytical blAlUS Literature Completed Ongoing Estimated Completion Date VETERANS ADMINISTRATION cont'd Neuronuscular Toxicity of Agent Orange X X 1986 Mechanisms of Dioxin Induced Toxicity Using the Chloracne Model * Phase II X X 1986 Effects of Low Dose TCDD on Mammalian Chromosomes and liver Cells X Mechanism of Porphyria Caused by TCDD and Related Chemicals X X 1986 Effects of Agent Orange on Sleep X X 1986 1986 �Page 15 FEDERALLY SPONSORED LABORATORY STUDIES AM) LITERA1URE SIRVEYS RELATED TO AGENT GRANGE T Y P E 6 F- s T O b Y AGENCY Animal STUDY EFFORT ENVIRObMENTAL AGENCY Environmental Analytical STATUS Literature Completed Ongoing Estimated Completion Date ffiOT£CTE)N X Assessment of exposure to TDCC from contaminated media X( Though t-nd.se) Assessment of methods teed for analysis of human adipose tissue X( Lab-wise) December 1985 X X Evaluation of TOO destruction technologies December 1985 Oct. 1984 Behavior of TCDD in blood X X December 1985 Clearance of TCDD from dose organisms X X December 1985 December 1985 Analytical methods develop* ment of monoclonal anti* bodies X Workshop report on bio* availability December 1985 Movement of TCDD in the environment X X December 1985 Evaluation of combustion sources X X December 1985 �Page 16 FEDERALLY SPONSORED LABORATORY STIDIES AN) LITERATURE SIRVEYS RELATED TO AGENT GRANGE I YP E AGENCY STIDY EFFORT Animal OF S T U D Y Environmental Analytical Literature STAlUb Completed Ongoing Estimated Completion Date Analysis of background levels of TCDD in die IB environment December 1985 Health assessment of PCDDs December 1985 Health assessment of PCDFs December 1985 �AGENT ORANGE/DIOXIN EXPENDITURES AGENCY EXPENDITURES BY STUDY TYPE $152,455,000 TOTAL EXPENDITURES ANIMAL (12.8%) ANALYT (1 .6%) ENVIR (6.2%) UT (1 . % 2) STUDY TYPE EXPENDITURES HUMAN ANIMAL ENVIRONMENT ANALYTICAL LITERATURE TOTAL $119,293,500 19,522,000 9,382,000 2,368,000 1,890,000 $152,455,000 HUMAN (78.2%) �AGENT ORANGE/DIOXIN EXPENDITURES $152,455,000 TOTAL COST USDA (O.4%) $594,000 DOD (22.O%)$33,605,000 EPA (9.5%) $ 1 4 , 4 6 7 , 0 0 0 VA (5.3.3%) $81,286,000 X HHS (14.8%)$22,503,000 �HHS A.O./DIOXIN EXPENDITURES $22,50.3,000 TOTAL EXPENDITURES ANALYT (2.5%) $556,000 HUMAN (41 .1%) $9,244,000 ANIMAL (56.5%) $12,703,000 �DOD A.O./DIOXIM EXPENDITURES $33,605,500 TOTAL EXPENDITURES ANIMAL (Q.9%) $288,000 \ HUMAN (99.1%) $33,317,500 �USDA A.O./DIOXIN EXPENDITURES $594,000 TOTAL EXPENDITURES LIT (1O.8%) $64,000 HUMAN (89.2%) $530,000 �EPA A.O./DIOXIN EXPENDITURE ~S $14,467,000 TOTAL EXPENDITURES $2,146,000 ANIMAL (14.8%) UT (7.3%) $1,052,000 ANALYT (12.5%) $1,812,000 HUMAN i;o.c«%) $75,000 ENVIR (64.9%) $9,382,000 �V.A. A.O./DIOXIN EXPENDITURES $81 ,286,000 TOTAL EXPENDITURES t-1%)ANIMftL $774,000 $4,385,000 ~"""-x V \ \ .0%) $76,127,000 �Agent Orange Use In Vietnam Agent Orange was the most widely used of the various herbicides. During the period 1964*1970, approximately 12 million gallons were sprayed in Vietnam. In addition, approximately five million gallons of Agent White, composed of the chemical Picloram and 2, 4-D, and approximately three million gallons of Agent Blue composed of cacodylic acid were sprayed. Neither Agent White nor Agent Blue contained the contaminant dioxin. The herbicides were used to defoliate jungle areas to expose enemy troop movements and staging areas and to eliminate ambush opportunities. . B a s e perimeters, river banks and enemy crop resources were also defoliated. The principal means of distribution was by O123 fixed wing a i r c r a f t (Operation Ranch H a n d ) . Helicopters, back~packs, truck-equipped equipment and Navy river boats were also used. In all, it is estimated that 101 of the land area of South Vietnam was sprayed at least once. Its use was discontinued in late 1970 because of allegations of a link between 2, 4, 5»T and birth defects of children born in South Vietnam. These allegations have never been substantiated. All remaining stocks of Agent Orange were incinerated at sea near Johnston Island (a remote island in the South P a c i f i c ) in 1977. �THE WHITE HOUSE WASHINGTON SCIENTIFIC ISSUES AND AGENT ORANGE EXPOSURE October 27, 1983 Introduction: Dr. G. A. Keyworth Science Advisor to the President Briefing: Dr. Alvin Young Scientific Advisor, Veterans Administration Discussion �AGENT ORANGE EXPOSURE �"DIOXIN" IS A FAMILY OP 75 COMPOUNDS DIBENZO-PARA-DIOXINS �DIOXIN OP CONCERN 2,3,7,8-TCDD �TOXICITY OF 2,3,7,8-TCDD Acute Tox i c i t y : Single Dose LDgp (>ig/kg ) Guinea Pig Rat • Monkey Rabbit Dog House Hamster Bullfrog Han 0. 6 40 70 115 150 200 3,500 Over 1,000 No deaths reported �IN LABORATORY ANIMALS, DIOXIN CAUSES BIRTH DEFECTS FETAL DEATH CANCER MUTATION? �SOURCES OF HUMAN EXPOSURE Industrial Accidents Occupational Exposure Contaminated Industrial Wastes Herbicide Applications Contaminated Pood Low Temperature Combustion �USE OP AGENT ORANGE i IN VIETNAM 962 - 1 9 7 3 'OPERATION RANCH HAND" �Da Nang Phu Cat SOUTH VIETNAM 1969 RANCH HAND BASES Sien Hoa • Saigon (Tan on Nhut) �ESTIMATED QUANTITES OF HERBICIDES AND TCDD SPRAYED IN VIETNAM, JANUARY 1962 - FEBRUARY 1971* Chemical 2,4-D 2,4,5-T TCDD Pounds 55,940,150 44,232,600 368 �ESTIMATED QUANTITES OP HERBICIDES AMD TCDD SPRAYED IN UNITED STATES, JANUARY 1962 - JANUARY 1971 Chemical 2,4-D 2,4,5-T TCDD Pounds 327,627,000 78,100,000 650 �VIETNAM VETERANS ARE WORRIED ABOUT Birth Defects and Miscarriages Cancers S o f t T i s s u e Sarcoma Other Early f)eath Skin Disorders Chloracne PCT Disease Due to Dioxin in Tissue �BOW DO SCIENTISTS ADDRESS THESE COK*SRNS? EPIDEMIOLOGY AND HEALTH SORVEILLANCE CONSENSUS �EPIDEMIOLOGY: STUDY OP FREQUENCY AND CAUSE OF DISEASE IN BUMAN POPULATIONS CASE-CONTROL STUDY Experiences compared between subjects selected for Disease and- Subjects without the disease. COHORT STUDY - Exposed and non-exposed populations examined for disease. �SCIENTIFIC CONSENSUS ACHIEVED WHEN « Statistically significant data * Withstand peer review, and Results duplicated by others �MEDICAL CONSENSUS NOW RELATES DIOXIN EXPOSURE TO * Chloracne * Porphyria Cutanea Tarda (PCT) * Temporary Health Effects �DIOXIN EXPOSURE - TEMPORARY EFFECTS Headache Fatigue Muscle and Joint Pain Tingling in extremities Sexual dysfunction Loss of appetite and weight Sleep disturbances Impaired memory and learning ability Abnormal liver function �FBOERAL GOVERNMENT ADORBSSBS VETERAN CONCERNS: WHITE BOOSE CAPITOL \ AGENT ORANGE WORKING GROUP �CONCERN - BIRTH DEFECTS AND M I S C A R R I A G E S COMPLETED: EPA A R K A N S A S STUDY-1979 NIOSH NEW YORK STATE STUDY 1979 NEW ZEALAND APPLICATOR STUDY-1982 AUSTRALIAN BIRTH DEFECTS STUDY-1983 CONCLUSION: MEN AND WOMEN ARE AT NO INCREASED RISK ON-GOING: CDC/DOD/VA BIRTH DEFECTS STUDY- 1984 AIR FORCE HEALTH STUDY- 1984 �CONCERN - MORTALITY: COMPLETED: CONCLUSION: NUMBER/AGE/CAUSB FOUR INDUSTRIAL HEALTH STUDIES-1980-1983 FINLAND MORTALITY STUDY OP HERBICIDE APPLICATORS-1982 AIR FORCE HEALTH STUDYBASELINE MORTALITY-1983 NO EVIDENCE OP INCREASED DEATH RATE ON-GOING: NEW YORK STATE MORTALITY STUDY - 1984 VA MORTALITY STUDY - 1984 �CONCERN - CONNECTIVE TISSUE CANCER (SOFT TISSUE SARCOMA, STS) COMPLETED: SWEDISH STS STUDIES - 1978-1983 NEW ZEALAND STS STUDY-1932 FINLAND CANCER STODY-1982 INDUSTRIAL STUDIBS-1980-1983 CONCLUSION: NO CONSENSUS ON-GOING: NEW YORK STATE STUDY - 1984 NCI STUDIES - 1984-85 VA/AFIP STUDY - 1985 NIOSH REGISTRY STUDY - 1985 CDC STUDY - 1986 �CONCERN - OTHER FORMS OP CANCER COMPLETED: FINLAND CANCER STODY-1982 SWEDISH RISK EVALUATION OF PESTICIDES-1982 NCI FLORIDA PESTICIDE APPLICATOR STODY-1983 INDUSTRIAL STUDIES-1980-1983 CONCLUSION: ON-GOING: NO CONSENSUS AIR FORCE HEALTH STODY-1984 NIOSH DIOXIN REGISTRY-1985 CDC AGENT ORANGE STODY-1987 �CONCERN - CURRENT EVIDENCE: CHLORACNE RARE 41 ON-GOING STUDIES: AIR FORCE HEALTH STUDY �CONCERN - OTHER HEALTH PROBLEMS ON-GOING STUDIES: AIR FORCE HEALTH STODY-1984 7A TWIN STUDY-1986 CDC STUDIBS-1987 OTHER EFFORTS: VA AGENT ORANGE REGISTRY VA PATIENT TREATMENT PILE �CONCERN - DIOXIN IN BODY TISSUE COMPLETED: VA FEASIBILITY STUDY-1982 CANADIAN STUDY-1983 * CONCLDSIOHS: SMALL AMOUNTS DETECTED NO CORRELATION WITH EXPOSURE OR HEALTH ON-GOING: VA/BPA DIOXIN STUDY �SUMMARY Short-term health effects do occur Long-term health effects may occur - Mo conclusive evidence to date Massive research program underway on long-term effects �SCIBNTIFIC CONSENSUS EXPECTED * Birth Defects 1984 * Mortality 1984 * Soft Tissue Sarcoma 1985 Other Health Problems 1986-87 �ON-GOING VA PROGRAMS WHILE RESEARCH IN PROGRESS Health Surveillance - Agent Orange Registry - Patient Treatment File Health Care - Public Law 97-72 �CONCERN - OTHER FORMS OP CANCER COMPLETED: FINLAND CANCER STODY-1982 SWEDISH RISK EVALUATION OP PESTICIDES-1982 NCI FLORIDA PESTICIDE APPLICATOR STODY-1983 INDUSTRIAL STODIBS-1980-1983 CONCLUSION: ON-GOING NO CONSENSUS AIR FORCE HEALTH STODY-1984 NIOSH DIOXIN REGISTRY-1985 CDC AGENT ORANGE STDDY-1987 �CONCERN - CHLORACNE CURRENT EVIDENCE: RARE ON-GOING STUDIES: AIR PORCS HEALTH STUDY �CONCERN - OTHER HEALTH PROBLEMS ON-GOING STUDIES: AIR FORCE HEALTH STODY-1984 VA TWIN STDDY-1986 CDC STCDIES-1987 OTHER EFFORTS: VA AGENT ORANGE REGISTRY VA PATIBNT TREATMENT PILE �CONCERN - OIOXIM IN BODY TISSUE COMPLETED: VA PBASIBILITY STUDY-1982 CANADIAN STUDY-1983 CONCLUSIONS: SMALL AMOUNTS DETECTED NO CORRELATION WITH EXPOSURE OR HEALTH ON-GOING: VA/EPA DIOXIN STUDY �SUMMARY Short-term health effects do occur * Long-term health effects may occur - No conclusive evidence to date ' Massive research program underway on long-term effects �SCIENTIFIC CONSENSUS EXPECTED Birth Defects 1984 « • Mortality 1984 * Soft Tissue Sarcoma 1985 Other Health Problems 1986-87 �ON-GOING VA PROGRAMS WHILE RESEARCH IN PROGRESS Health Surveillance - Agent Orange Registry - Patient Treatment Pile Health Care - Public Law 97-72 �Background of Agent Orange Working Group On December 11, 1979, Stuart Eizenstat, Assistant to President Carter, requested HHS to take the lead in convening an Interagency Work Group (IWG) to study possible long»term health effects of phenoxy herbicides and contaminants ( T a b A). The IWG was to oversee, coordinate and set priorities among Federal government research activities in this area. In designing a research agenda, the IWG was to take into consideration the possible health effects of exposure to Agent Orange by Vietnam veterans. President Reagan announced on July 17, 1981, that he was reaffirming the mandate of the Interagency Work Group and his intention to "make its work a major priority of my Administration". The Interagency Working Group was renamed the Agent Orange Working Group (AOWG) and raised in status to Cabinet Council level (Tab B ) . In his implementing memorandum of August 21, 1981, Secretary Schweiker stated that the President had been motivated because he shared the widespread public and Congressional concern over possible adverse health effects among Vietnam veterans exposed to Agent Orange and other substances (Tab C). In the same memorandum the Secretary reaffirmed the charter language of December 11, 1979, and added the responsibility for guiding the epidemiologic study of the health of Vietnam veterans authorized by P.L. 96*151 as amended by P.L. 97*72. In appointing her Under Secretary as chair of the AOWG in a Press Release dated June 6, 1983, Secretary Heckler added her personal long time interest and concern for Vietnam veterans. "I am reaffirming this administration's commitment to the prompt and scientifically responsible resolution of the health concerns of Vietnam veterans who were exposed to Agent Orange and other environmental factors during their service to their country in that conflict" she said. (Tab D) The charter of IWG, and now of AOWG, is a broad mandate which provides in explicit terms the authority to design and direct all research activities on the health effects of exposure to phenoxy herbicides and contaminants, with exposure to Agent Orange by Vietnam veterans as one part of the total research design (Tab E). The contaminants mentioned include that class of chemicals known as the dioxins produced during the manufacture of these herbicides The renaming of the IWG by President Reagan focused the Work Group's primary responsibility on Agent Orange, but without a change in the language of the charter, a lack of clarity regarding the AOWG's purpose and scope resulted. �MEMORANDUM FOR SECRETARY OF DEFENSE SECRETARY OF HEALTH/ EDUCATION, AMD WELFARE ADMINISTRATOR OF VETERANS AFFAIRS SUBJECT: Interagency Work Group to Study the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants In recent months the public and the Congress have become concerned about adverse health effects to veterans following their possible exposure to herbicides, particularly Agent Orange, while serving in Vietnam. Although there are suggestions of adverse' health effects of human exposure to such herbicides and contaminants, there is currently an inadequate scientific basis for concluding that health • problems experienced by Vietnam veterans were caused by previous exposure to herbicides. Moreover, there is inadequate information on the long-term health effects of phenoxy herbicides in general. Individually, each of your agencies has a strong interest ir. resolving this issue. Several studies have been initiated to answer questions about the possible health effects of exposure to herbicides and more generally to the class of substances called the dioxins. Collectively, the Federal government needs to have reliable data and criteria on which to base decisions and policies which affect the entire country. 'Although I am aware that there has already been extensive interagency cooperation on these issues, I believe there is a need for formal interagency coordination. Therefore, I request that you establish an interagency work group to coordinate agency efforts to determine if there ara long-term health effects following exposure to phenoxy herbicides and contaminants, with special immediate focus or. exposure of Vietnam veterans to Agent Orange. This interagency group should: 1. Oversee, coordinate, and set priorities among Federal government research activities designed �e exposure to pher.cxy he rbicides to icr.chealth, effects. a research agenda to assure that the '-il Government conducts comprehensive on the long-term health effects of compounds, in response to both scienti.ic needs. The type and duration of ..f-.usn to Agent Orange by Vietnam veterans -iuiic' we considered in the research agenda design so" that the Veterans Administration will _ be able to establish sound policies for determining comncnsation for veterans exposed to Agent •: Vietnam, should a relationship ..........- :;vraicide exposure and Icng-terra adverse i;cai.rn effects be established. The research ngcnaa snould build on current agency activities, including the Department of Defense's Ranch Hand study. The interagency work group should identify ^ the appropriate agencies to conduct the recommended research, either individually or through joint efforts. n 3. Provide technical support to individual agencies and independent researchers in the formulation, development, and implementation of research on the bicmedical effects of phenoxy herbicides and contaminants. 4. Assure that the protocols and methodology of ongoing and proposed Federally funded research studies v/ill produce valid, reliable, timely, and relevant data, and periodically review the status of such research. 5. Assure that all relevant research findings, whether publicly or privately financed, are promptly nude available to the public and the Congress, in a comprehensible and comprehensive fashion. The work group should establish a working relationship with the Veterans Administration's Advisory Committee on Health-Related Effects of Herbicides and should promptly provide the Committee all relevant information as it becomes available. I am asking Secretary Harris to take the lead in convening the interagency group and woulc' like to have an initial report on the progress of the group submitted to me by �vxr February 15. The of current agency progress reports, other agencies on initial report should indicate the status activities, a proposed schedule for public and any recommendations for inclusion of the work group. I have asked the Office of Science and Technology Policy to be an ex-officio participant on the work group. In addition, the Depsrtment of Agriculture, the Environmental Protection Agency, and the Occupational Safety and Health Administration will initially participate on the work- gro-u? in; an observer status. Stuart E. Eii^nstat Assistant to the President for Domestic Affairs and Policy cc: Secretary of Agriculture Administrator, Environmental Protection Agency Assistant Secretary of Labor for Occupational Safety and Health Director, Office of Scienca and Technology Policy �/• THE WHITE HOUSE WASHINGTON July 17, 1981 MEMORANDUM FOR: SECRETARY R1CSARO SCHWE1XZR CHAIRMAN PRO-TZM, CABINS? COUNCIL OH HUMAN RESOURCES FROM: ROBERT CARL2SON EXECUTIVE SECRETARY OF HUMAN RSSOURC2S CABIN2T COUNCIL SUBJECT: Ag«nt Orange Wor3cing Group * , The 5«er«tariat of the Human Resources Cabinet Council has established an Agent Orange Working Group. The lead agency will be BBS, and participating members drawn from: Department of Defense Department of Agriculture Department of Health and Human Services Department of Labor Environmental Protection Agency Veterans Administration Action Office of Management and Budget Council of Economic Advisers Office of Science and Technology Office of Policy Development :c: Martin Anderson Edwin Gray �THE WHJTE H O U S E WASHINGTON AliS?1 1981 MEMORANDUM FOR; SECRETARY OF DEFENSE . SECRETARY OF AGRICULTURE SECRETARY OF LABOR DIRECTOR, OFFICE OF MANAGEMENT AND BUDGET ASSISTANT TO THE PRESIDENT FOR POLICY DEVELOPMENT CHAIRMAN, COUNCIL OF ECONOMIC ADVISERS DIRECTOR OF ACTION ADMINISTRATOR, ENVIRONMENTAL PROTECTION AGENCY AD NISTRATOR OF VETERANS AFFAIRS OF/2C£ OF SCIENCE AND TECHNOLOGY tY_" yztwtju^ FROM SEtRETARY'RICHARD SCHWEIKER CHAIRMAN.PRO-TEM, CABINET COUNCIL ON HUMAN RESOURCES SUBJECT Agent Orange Working Group The Administration has reviewed the excellent work of the Interagency work Group to Study the Possible Long^Term Health Effects of Phenoxy Herbicides and Contaminants and believes that it has made significant progress toward fulfilling its important mandate. Sy bringing together knowledgeable scientists -from the various Federal departments and agencies the Work Group has identified ongoing research activities on phenoxy herbicides and contaminants and begun to develop anc organize the means to carry out additional needed scientific research. President Reagan shares the widespread public and congressional concern over possible adverse health effects among Vietnam veterans exposed to Agent Orange and other substances. The President stated, during his meeting with national veterans organization leaders at the white House on July 17, 1981, that the Administration is giving special consideration to those concerns of Vietnam veterans. At the White House meeting, the President announced that the administration had re-established an expanded working Grouc as the Agent Orange Working Group and raised its status to Cabinet Council level. The President is personally determinec to assure that the full resources of the Federal government are �-2- available to support the working Group's continuing efforts. The decision to re-establish and expand the membership of the working Group and to make it an integral part of the Cabinet Council on Human Resources reflects the President's commitment and accords the highest priority to its mission. As Chairman Pro-Tern of the Cabinet Council on Human Rtsources, I am, accordingly, reaffirming by this memorandum the Agent Orange working Group's mandate of December 11, 1979 and providing specific guidance as to how that mandate is to be carried out in accordance with the Cabinet Council's decisions. The Department of Health and Human Services shall continue to have lead responsibility for overall direction and management of the Agent Orange working Group. The Secretary of Defense and the Administrator of veterans Affairs shall continue to assure that their respective agencies participate fully in all working Group activities. The Departments of Agriculture and Labor and the Environmental Prm action Agency, each of which have until now been observers, sr.dil assume full membership and their respective agency heads shall assure that those agencies participate fully in all work Group activities. In addition, ACTION, the Office of Management and Budget, and the Council of Economic Advisers, as well as the wnite House Office of Science and Technology Policy and the Office of Policy Development, snail assume membership on the working Group and the heads of those agencies and offices shall assure that the resources of their respective agency or office are fully available to support it. Also, the congressional Office of Technology Assessment, which has been actively involved in all working Group activities as an observer, will be invited to continue to participate ir that capacity, and the General Accounting Office, which has been extremely helpful to the working Grouo in the past, will continue to be kept abreast of developments and invited to advise and assist as appropriate. The working Group has initiated research efforts designed to find answers to many of the questions surrounding Agent Orange that have been raised. These efforts include the birth defects study being conducted by HHS' Centers for Disease Control, the Ranch Hand Study being conoucted by the Air Fores, the epidemiological study being planned by the Veterans Administration pursuant to P.L. 96-151, and the compilation by HHS' National Institute of Occupational Safety and Health of a national registry of workers exposed to dioxins. Each of these research activities, as well as tne other important research �-3* activities being conducted under the overall guidance of the working Group, are to be continued without interruption or delay. The working Group has developed an impressive record of scientific objectivity, impartiality and integrity and it is imperative to the success of the Working Group effort that this record and the Group's credibility be maintained. In this regard, regular progress reports to the Cabinet Council, the Congress and the public will continue to be made by the Agent Orange working Group. To assure effective leadership of the working Group, I am hereby appointing James Stockdale, HHS Deputy Under Secretary for Intergovernmental Affairs, as Chair. Also, I am appointing Or. Vernon N. Houk of the Center for Environmental Health of the Centers for-Disease Control as Chair of the Working Grouo's Science Panel. In addition, I am appointing HHS Legal Counsel Leslie A. Platt, who has served as legal adviser to and staff director of the working Group since its inception, to continue in tnose capacities. I know and believe you will find that these individuals share my commitment to carrying out this important mission. • Please review your representation on the working Group to assure that your agency or office is adequately represented 5y appropriate technical experts, scientists and policy-level officials. In order to facilitate the Group's effectiveness, it is of course important that each agency's total membersni: be limited. The first meeting of the full working Group has been scheduled for Friday, August 28, 1981 and a meeting of the Science Panel will be scheduled for shortly thereafter. Accordingly, please 'et Mr. Bart Kull, Special Assistant tc :-e Deputy Under Secretary for Intergovernmental Affairs (245-6154), or Dr. Peter Beach, HHS Director of Veterans Affairs (245-2210), know as soon as possible the name(s) z* your designated representative(s) so that briefing materials may be forwarded to them. Attached for your information is a copy of the memorancu" of the Executive Secretary to the Cabinet Council on Human Resources establishing the Working Group. Attachment cc: Comptroller General of the Urited States Director, Congressional Office of Technology Assessment ' Mr. Robert Carleson Mr. Edwin Gray �Ki DEPARTMENT Of HEALTH AND HUMAN SERVICES FOR IMMEDIATE RELEASE RuSSf>11 N«k"(2«> Monday, June 6, 1983 Health and Human Services Secretary Margaret M. Heckler today named her department's under secretary, John A. Svahn, as chairman of the Agent Orange Working Group of the Cabinet Council on Human Resources. The working group coordinates and oversees federal research Into the posslblHt; of long term adverse health effects resulting from exposure to phenoxy add herbicides used during the Vietnam War. The herbicides, principally Agent Orange, were s used primarily to defoliate dense jungle cover to reveal enemy troop movements and staging areas. "By designating the second highest official of my department as chairman, I am reaffirming this administration's commitment to the prompt and scientifically responsible resolution of the health concerns of Vietnam veterans who were exposed to Agent Orange and other environmental factors during their service to their country In that conflict. Jack Svahn1s leadership of this vital working group will help us get the answers we need," Secretary Heckler said. In response to veterans' concerns about the possibility of illness as a result of their exposure, the working group was created 1n late 1979. It was reestablished and upgraded to Cabinet Council reporting level by President Reagan 1n July 1981. Under the aegis of the working group, various federal agencies, including HHS1 Public Health Service, the Veterans Administration and Department of Defense, are conducting 64 separate research studies relating to Agent Orange and other health effects of service in Vietnam, at a cost estimated in excess of $100 million. As chairman of the working group, Svahn will report to the president through Secretary Heckler in her capacity as chairperson pro-tern of the Cabinet Council on �-2- Svahn was appointed under secretary of the Department of Health and Human Services March 8. Prior to that appointment he served as commissioner of Social Security since May 6, 1981. Following service 1n the U.S. A1r Force 1n 1968, Svahn held administrative positions with the state of California, the federal government and the private sector. I II �CHARTER Cabinet Council Agent Orange Working Group December 11, 1979, as Reaffirmed on August 21, 1981 The Agent Orange Working Group shall: 1. Oversee, coordinate, and set priorities among Federal government research activities designed to relate exposure to phenoxy herbicides to long-term health effects. 2. Design a research agenda to assure that the Federal government conducts comprehensive research on the longterm health effects of the compounds, in response to both scientific and policy needs. The type and duration of exposure to Agent Orange by Vietnam veterans must be considered in the research agenda design so that the Veterans Administration will be able to establish sound policies for determining compensation for veterans exposed to Agent Orange in Vietnam, should a relationship between herbicide exposure and long-term adverse health effects be established. The research agenda should build on current agency activities, including the Department of Defense's Ranch Hand study. The Working Group should identify the appropriate agencies to conduct the recommended research, either individually or through joint efforts. 3. Provide technical support to individual agencies and independent researchers in the formulation, development, and implementation of research on the biomedical effects of phenoxy herbicides and contaminants. 4. Assure that the protocols and methodology of ongoing and proposed federally funded research studies will produce valid, reliable, timely, and relevant data, and periodically review the status of such research. 5. Assure that all relevant research findings, whether publicly or privately financed, are promptly made available to the public and the Congress, in a comprehensible and comprehensive fashion. The work group should establish a working relationship with the Veterans Administration's Advisory Committee on Health-Related Effects of Herbicides and should promply provide the Committee all relevant information as it becomes available. 6. Provide guidance to the epidemologic study of the health of Vietnam Veterans authorized by P.L. 96-151 as amended by P.L. 97-72. �Agent Orange Working Group Organization Following a review of the work of the Interagency Working Group, President Reagan in July 1981 re-established and expanded the Interagency Work Group, raised its status to Cabinet Council level and renamed it the Agent Orange Working Group (AOWG). The purpose was to reflect his commitment to the work of the group and to place high priority on its mission. The President asked the Secretary of HHS, as Chair Pro-Tern of the Cabinet Council on Human Resources, to oversee its work. The AOWG now reports to the Cabinet Domestic Council. The AOWG membership includes representatives from the Veterans Administration (VA), Departments of State, Defense and Labor, the Office of Management and Budget, the Environmental Protection Agency, the ACTION Agency, the Council of Economic Advisors, the White House Office of Science and Technology Policy and the Assistant to the President for Policy Development. The Congressional Office of Technology Policy participates as an observer. The AOWG organization is headed by a Chair appointed by the Secretary as a member of the Cabinet. The Chair, AOWG, in turn appoints: 1.2. 3. 4. 5. Chair, Science Panel Legal Counsel Executive Secretary Chair, Resources Panel Chair, Public and Congressional Affairs Panel The Science Panel, composed of expert medical and scientific personnel drawn from various government agencies concerned with issues of public health, advises the AOWG on the conduct of research related to Agent Orange. The Science Panel includes two subpanels: a Research Agenda Subpanel to recommend needed research and a Research Review Subpanel to review all planned research for adequacy of design and conformance with the AOWG mission. The Resources Panel is concerned with the proper allocation of available resources among planned and on-going research and the avoidance of duplication of effort. The Public and Congressional Affairs Panel defines policies to be used in information dissemination to insure that such dissemination is timely, accurate and complete. �-2- In addition to these structures, the AOWG is advised by the Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants. This Advisory Committee is composed of pre-eminent scientists from outside the Government. membership with the current designated The agency represenatives from each and the staff of the AOWG are listed at Tab A. �DEPARTMENT OF HEALTH & HUMAN SERVICES Office of the Secretary Washington, D.C. 20201 AGENT ORANGE WORKING GROUP MEMBERSHIP DEPARTMENT OF HEALTH AND HUMAN SERVICES Lead Representatives: Mr. Dixon Arnett Acting Chair Pro Tempore, AOWG Deputy Under Secretary for Intergovernmental Affairs Department of Health and Human Services 200 Independence Avenue, S.W. Room 606-E, HHH Building Washington, D.C. 20201 (202) 245-0409 Dr. James 0. Mason Vice-Chair, AOWG Acting Assistant Secretary for Health Department of Health and Human Services 200 Independence Avenue, S.W. Room 716-H, HHH Building Washington, D.C. 20201 (202) 245-7694 Dr. Carl Keller*, Chair Science Panel Epidemiologist National Institute of Environmental Health Sciences• Room 2B55, Building 31 National Institute of Health Bethesda, Maryland 20205 (301) 496-3511 Mr. Edwin Weiss (AOWG Legal Counsel) Office of the General Counsel 330 Independence Avenue, S.W. North Building, Room 4460 Washington, D.C. 20201 (202) 475-0155 Dr. Peter Beach AOWG Executive Secretary Director of Veterans Affairs Office of the Under Secretary Room 632-F, HHH Building 200 Independence Avenue, S.W. Washington, D.C. 20201 (202) 245-2210 or 245-6156 ^Denotes Science Panel Member Revised: September 1985 �-2- DEPARTMENT OF HEALTH AND HUMAN SERVICES cont'd (Members) Dixon Arnett Deputy Under Secretary for Intergovernmental Affairs Department of Health and Human Services 200 Independence Avenue, S.W. Room 606-E, HHH Building Washington, D.C. 20201 (202) 245-0409 Shirley Earth AOWG Public/Congressional Affairs Panel, Chair US/PHS 200 Independence Avenue, S.W. Room 716-G, HHH Washington, D.C. 20201 (202) 472-5663 Lee Mosedale Policy Coordinator OS/ES HHH Building, Room 635-G 200 Independence Avenue, S.W. Washington, D.C. 20201 (202) 245-7462 • Dr. Vernon Houk* Director Center for Environmental Health Centers for Disease Control 1600 Clifton Road, N.E. Atlanta, Georgia 30333 FTS 236-4111 Commercial (404) 452-4111 Dr. David Rail* Director, National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, N.C. 27709 FTS 629-3201 Commercial (919) 541-3201 Dr. James S. Dickson, III Senior Advisor for Environmental Affairs Office of the Assistant Secretary for Health Department of Health and Human Services 200 Independence Avenue, S.W. Room 701-H, HHH Building Washington, D.C. 20201 (202) 245-6811 �DEPARTMENT OF HEALTH AND HUMAN SERVICES cont'd Dr. Renata Kimbrough* Research Medical Officer Centers for Disease Control 1600 Clifton Road, N.E. Atlanta, Georgia 30333 FTS 236-4324 Commercial (404) 454-4324 Dr. Philip Landrigan, Director* Division of Surveillance, Hazard Evaluations and Field Studies 4673 Columbia Parkway Cincinnati, Ohio 45226 FTS 684-4428 Commercial (513) 684-4428 Miriam Davis, Ph.D.* Staff Assistant/PHS AOWG Science Panel 200 Independence Avenue, S.W. Room 716-G, HHH Washington, D.C. 20201 (202) 245-6301 Dr. Robert W. Miller* Chair, Advisory Committee Clinical Epidemiology Branch National Cancer Institute - NIH Room 5A21, Landow Building Bethesda, Maryland 20205 (301) 496-5785 Dr. Marilyn Fingerhut* Section Chief NIOSH - EPI I 4676 Columbia Parkway Mail Stop R-15 Cincinnati, Ohio 45226 (FTS) 684-4411 Commercial (513) 684-4411 WHITE HOUSE OFFICE OF POLICY DEVELOPMENT Lead Representative: Dr. William Roper* Special Assistant to the President for Health Policy Old Executive Office Building Room 235 Washington, D. C. 20500 (202) 456-6722 �-4WHITE HOUSE OFFICE OF SCIENCE AND TECHNOLOGY POLICY Lead Representative: Dr. George Keyworth* Science Adviser to the President & Director, Office of Science Technology Policy Old Executive Office Building Room 358 Washington, D.C. 20500 (202) 456-7116 Dr. Alvin Young* Senior Policy Anaylst Office of Science Technology Policy New Executive Office Building Room 5005 Washington, D.C. 20500 (202) 395-3125 VETERANS ADMINISTRATION Lead Representative: Mr. Everett Alvarez Deputy Administrator Veterans Administration 810 Vermont Avenue, N.W., Rm. 1000N Washington, D.C. 20420 (202) 389-5428 Dr. Barclay Shepard (102)* Director, Agent Orange Projects Office Veterans Administration 810 Vermont Avenue, N.W., Room 308 Washington, D*C. 20420 (202) 376-7528 Dr. Lawrence B. Hobson (102)* Deputy Director Agent Orange Projects Office Veterans Administration 810 Vermont Avenue, N.W., Rm. 116 Washington, D.C. 20420 (202) 389-5534 DEPARTMENT OF DEFENSE Lead Representative: Captain Peter A. Flynn, MC, USN* Director, Professional Services ODASD(Health Promotion), OASH (Health Affairs) The Pentagon, Room 3E337 Washington, D.C. 20301 (202) 697-8973 �-5- DEPARTMENT OF DEFENSE cont'd Richard S. Christian, C.R.M.* Director, Environmental Support Group Army Agent Orange Task Force 1730 K Street, N.W., Room 210 Washington, D.C. 20006 (202) 653-1832 Lt. Col. Robert Capell* Asst. for Bioenvironmental Engineering Office of Surgeon General USAF/SGES Boiling Air Force Base Washington, D.C. 20332 (202) 767-5078 DEPARTMENT OF AGRICULTURE Lead Representative: Dr. Philip Kearney* Chief, Pesticide Degradation Lab U.S. Department of Agriculture BARC-West Building 050 - Room 100 Beltsville, Maryland 20705 (301) 344-3533 ENVIRONMENTAL PROTECTION AGENCY Lead Representative: Dr. Jack Moore* Assistant Administrator for Pesticides & Toxic Substances U.S. Environmental Protection Agency 401 M Street, S.W., (TD788) Washington, D. C. 20460 (202) 382-2902 Dr. Donald Barnes* Senior Science Adviser to the Assistant Administrator for Pesticides and Toxic Substances U.S. Environmental Protection Agency 401 M Street, S.W., (TS788) Washington, D.C. 20460 (202) 382-2897 �-6DEPARTMENT OF LABOR Lead Representative Mr. Donald Shasteen Assistant Secretary for Veterans Employment and Training Department of Labor Francis Perkins Building, Rm. S-1315 200 Constitution Avenue, N.W. Washington, D.C. 20210 (202) 523-9116 Mr. Stephen Mallinger* Deputy Director for the Director of Technical Support U.S. Department of Labor OSHA 200 Constitution Avenue, N.W. Room N-3651, FPB Washington, D.C. 20210 (202) 523-7047 ACTION Lead Representative Vacant James Hearn Deputy Director The President's Vietnam Veterans Leadership Program ACTION 806 Connecticut Ave., N.W. Room 1006 Washington, D.C. 20525 (202) 634-9339 COUNCIL OF ECONOMIC ADVISERS Lead Representative: Vacant �-7- OFFICE OF MANAGEMENT AND BUDGET Lead Representative: Mr. John Cogan Associate Director for Human Resources, Veterans & Labor Office of Management and Budget Old Executive Office Building Room 246 Washington, D.C. 20503 (202) 395-3120 Mr. Bernard H. Martin Deputy Associate Director for Labor, Veterans & Education Division Office of Management and Budget New Executive Office Building Room 7025 Washington, D.C. 20503 (202) 395-3971 Susan Jacobs Chief of Veterans Affairs Branch Veterans Affairs Branch Office of Management and Budget New Executive Office Building 726 Jackson Place, N.W., Rm. 7007 Washington, D.C. 20503 (202) 395-4500 Ms. Annette Rooney Budget Examiner Veterans Affairs Branch Office of Management and Budget New Executive Office Building 726 Jackson Place, N.W., Rm. 7013 Washington, D.C. 20503 (202) 395-4500 CONGRESSIONAL OFFICE OF TECHNOLOGY ASSESSMENT (OBSERVER) Lead Representative: Dr. Michael Gough* Senior Analyst United States Congress Office of Technology Assessment Washington, D.C. 20510 (202) 226-2070 �-8CONGRESSIONAL OFFICE OF TECHNOLOGY ASSESSMENT (OBSERVER) (cont*d) Ms. Hellen Gelband* Analyst Office of Technology Assessment United States Congress Washington, D.C. 20510 (202) 226-2070 DEPARTMENT OF STATE Lead Representative: Mr. William J. Walsh, III Biomedical Research Officer Office of Environment and Health Department of State Room 7820 Washington, D.C. 20520 (202) 632-4824 Dr. Charles E. Brodine, M.D.* Assistant Medical Director for Environmental Health and Preventive Medicine Office of Medical Services, M/MED Department of State, Rm. 4253 Washington, D. C. 20520 (202) 632-5337 * Mr. Steve Johnson Vietnam Desk Officer Bureau of East Asia and Pacific Affairs Department of State, Room 5210 Washington, D.C. 20520 (202) 632-3132 �Agent Orange Working Group Public Affairs Panel Ms. Shirley Earth Chair USPHS/Public Affairs Room 716G Hubert H. Humphrey Bldg. 200 Independence Avenue, S. W. Washington, D.C. 20201 Mr. William J. Walsh, III Biomedical Research Officer Office of Environment and Health Department of State Room 7820 Washington, D.C. 20520 Lt. Colonel Edwina Palmer Department of Defense Public Affairs Room 1E794 The Pentagon Washington, D.C. 20301 Mr. Robert Putnam 106 Veterans Administration Public Affairs 810 Vermont Avenue, N.W. Washington, D.C. 20420 Ms..Inez Artico A-107 Public Affairs Environmental Protection Agency 401 M Street, S.W. Washington, D.C. 2046 Mr. Donald Berreth Centers for Disease Control Room 2067, Building 1 Atlanta, Georgia 30333 �Advisory Committee on Special Studies The Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants had its genesis in the directives of the White House for an independent review from scientists outside the Government of the Air Force Ranch Hand Study (Tab A). This study compared mortality and morbidity of the Air Force personnel involved in the spraying of Agent Orange in Vietnam with a group of Air Force personnel who were not exposed to the herbicide. Because of the value of this kind of independent review, the Advisory Committee on Special Studies was chartered to permit it, at the discretion of the Chair, Agent Orange Working Group (AOWG), to undertake a review of any study, proposed or on-going, which falls within the purview of the AOWG. The Advisory Committee on Special Studies is established under the provisions of the Advisory Committee Act and is governed by the regulations of 45 CFR Part 11. The Charter of the Committee is at Tab B, and its membership is listed at Tab C. �THE WHT- H'-V-SF: Scr,tc:rbcr 1G, 1980 ' -.' ' •.•'•'"•I ".; | V ., ,.."' ; IJ <*J k.i dO MEMORANDUM FOR THE SECRETARY OF DEFENSE THE SECRETARY OF HEALTH AND HUMAN SERVICES-x THE SECRETARY OF AGRICULTURE THE ADMINISTRATOR OF VETERANS AFFAIRS THE ADMINISTRATOR OF THE ENVIRONMENTAL PROTECTION AGENCY THE ASSISTANT SECRETARY OF THE OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION SUBJECT: Epidemiological Study of Ranch Hand Personnel V' Last December, I asked you to participate in <r- « interagency work group to coordinate federal agoncy efforts to determine if there are long-term health effects following exposure to phenoxy herbicides and contaminants, with special immediate 'focus on exposure of veterans to Agent_Orange in Vietnam. I am gratified by the progress that the.Work Group has made in a short period and by the respect that the Work Group has earned with the Congress and the public. The members of your agencies who have participated on the Work Group should be commended for their diligence and spirit of cooperation. "r.-'^uy , I air. i;\ f r ;•.- ino S^occ r ri.ry ;: ; . •.•..•;! rr,,it T '. v^ cc;,c-.::: :;. winh the Intcracwncy v.'ork Group's rcco;..-"--nd i-: "n L'nat the Air Force proceed to conduct the? Fp i r.r:v i ^ !<_'••:: e.i 1 Su'.u:y c :' 'vir.ch li.it'id Pet'sor.iio 1 . I strongly i^l;.".- •:;,::. -m •.•*;•>;:; t : • '. c<..'..'potieii t of tins c i fort must be \ t,;.':. •; •t'fv.'.cn t re ^ Lew v ind ••ionitoring over the n'jxt few yi.-.-irs ITy tTTTo nTT^TTiTTeiTcy '.-.'or'-. Group's Scientific T^acl. In addition, I look to the Work Group uc urovuie s u b s t a n t i a l resistance to the Veterans Adrnin i st rat i or., who <il«o w i l l conduct a major op: douiiologi cal ptudy of the rorr.ible lonetni/m health efforts in veterans of service i,-, V •' ^t nnm. T':•.•:• V.'ork Group's expertise and credibility w i l l nr^vir.e v a l u a r l - _ assistance to tiic v;». �dr:r.onstruted as well as the concinuino ;-o:!t.;i r\ r^nts for f;i?vcrr.r,-"::':."!l c^v.cios or. f'-.cnc::^ h^rbicicc r, rrrr.!: Pr.zc 2nd I wish now to reaffirm the mandate of the InLcragcncy Work Group. I hope that your agencies continue to give participation on the Work Group as much importance in the future as they have in the past. T/-~&fal Stuart E. Eizenstat Assistant to the President for Domestic Affairs and Policy �<• '•» • . -» » 1 THE WHITE Hbu'3 WASHINGTON September 16/ 1980 MEMORANDUM FOR THE SECRETARY OF DEFENSE The Air Force has sought guidance from the Interagency Work Group on the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants on whether it should proceed with the Epidemiological Study of Ranch Hand Personnel because the National Academy of Sciences review of the Air Force protocol had expressed concern about the credibility of the Air Force to conduct the study. Ranch Hand personnel, who applied Agent Orange between 1962 and 1971 in Vietnam, are the only population whose frequency and duration of exposure to Agent Orange are known with any accuracy. The Interagency Work Group agrees with the Air Force that the results of the Ranch Hand study should provide valuable information about the long-term health effects of exposure by veterans to Agent Orange in Vietnam. Over the past 20 months, the Air Force has made a conscientious effort to design a scientifically valid study responsive to the recommendations of five separate peer reviews, including that of the National Academy of Sciences. After a thorough review of the proposed final study protocol, which includes certain changes based on the separate peer reviews, and after consultation with the Air Force scientists responsible for the study, the Work Group recommended to me that the Air Force be instructed to carry out the Ranch Hand study. In light of the progress already made by the Air Force and the need to proceed expeditiously with this important study, Frank Press and I concur with the Work Group'-e recommendation. There remains deeply"felt concern among some Vietnam veterans and others about the objectivity of the Air Force to study the possible health effects of Agent Orange. While affirming the capability of the Air Force to assure the proper conduct of the study, the Interagency Work Group has suggested that this concern can be reasonably addressed by independent review and monitoring of the study. I believe that the Scientific Panel of the Interagency Work Group, which is already familiar �with the Ranch Hand protocol, is tne appropriate body to oversee the study and to provide technical assistance, as needed, to the Air Force scientists responsible for the study. For the--purpose of assuring the public that the -, study'results are reliable and valid, the Work Group plans to augment the Scientific Panel with reputable scientists fchp government, including those suaoftsted hy veterans organizations. The Interagency Work Group noted that the evaluation of Ranch Hand personnel may have to continue for a lengthy period of time in order to have a better chance of detecting latent or subtle health effects, particularly related to cancer. The Air Force, in consultation with the Scientific Panel, has already designed the protocol to reflect this recommendation. I an advised that the Ranch Hand study presents a number of difficult technical problems. While recognizing *:he need to obtain study results promptly, the Air Force's p^.mary responsibility must be to assure that the results will be reliable and valid. I urge the Air Force to utilize fully the expertise of the Scientific Panel of the Interagency Work Group to advise them on the difficult decisions that will surely arise during the course of the study. In closing, I would like to reaffirm the importance of the Ranch Hand study to Vietnam veterans and their families. The Interagency Work Group and the White House are prepared to offer any assistance that the Air Force may require in discharging its responsibility to conduct a high quality scientific investigation. Stuart E.£Eizenstat Assistant to the President for Domestic Affair> and Policy �CHARTER ( A s Amended M a y 1984) Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants Purpose By memorandum of December 11, 1979, the Assistant to the President for Domestic Affairs and Policy directed the establishment of an Interagency Work Group to Study the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants (Work Group) under the leadership of the Secretary of Health and Human Services. The Work Group was specifically directed to assure that the protocols and methodology of proposed federal research studies will provide reliable data, as well as to provide technical support to individual agencies in the implementation of research. On August 1, 1980, the Work Group recommended that the United States Air Force conduct its proposed Epidemiologic Studies of Ranch Hand Personnel (Rand Hand Study) and that the conduct of the study be overseen by an independent monitoring committee. By memorandum of September 16, 1980, the Assistant to the President for Domestic Affairs and Policy directed the Air Force to conduct the Ranch Hand Study. In addition, the memorandum directed the Scientific Panel of the Work Group, augmented by scientists from outside the government and including those suggested by veterans organizations, to oversee the study arid to provide technical assistance, as needed, to the Air Force. On July 17, 1981, the President re-established the Interagency Work Group as the Agent Orange Working Group (A.OWG) and elevated it to Cabinet Council status. On August 21, 1981, the Secretary, DHHS, Acting as Chairman Pro-Tern, Cabinet Counsel on Human Resources, reaffirmed the Work Group's mandate of December 11, 1979 and appointed the Deputy Undersecretary for Intergovernmental Affairs as Chair of the AOWG. Authority The Committee on Special Studies was established under the provisions of section 222 of the Public Health Service Act, as amended, 42 U.S.C. 217a. The Committee is governed by the provisions of 45 CFR Part 11 which sets forth standards for the creation and use of advisory committees. I / I I �- 2- Function The Advisory Committee on Special Studies Relating to the Possible Long-Term Health Effects of Phenoxy Herbicides and Contaminants shall advise the Secretary and the Chair, Cabinet Council Agent Orange Working Group (AOWG), concerning: 1. Its oversight of the conduct of the Ranch Hand Study by the Air Force; 2. Its oversight and evaluation of the Agent Orange/Vietnam Experience Study mandated by Section 307 of P.L. 96-151 as amended by P.L. 97-72; and 3. Other studies in which the Secretary or the Chair, AOWG, believes involvement by the Advisory Committee is desirable. The Advisory Committee may provide technical assistance to the study under its consideration. On the basis of its oversight and evaluation, the Advisory Committee may, inter alia, recommend to the Secretary and the Chair, AOWGT(a) approval, (b) deferral because of a need for further evaluation, (c) disapproval in whole or in part, or (d) imposition of additional conditions which in its judgemnt are necessary to assure or protect advancement of the study under consideration. Structure The Committee shall consist of the Secretary, or designee, as Chair, and eight members selected by the Secretary from authorities knowledgeable in fields related to the studies under its oversight and evaluation. The Executive Secretary shall be selected by the Chair. Management and support services shall be provided by the National Cancer Institute. Meetings Meetings shall usually be held quarterly at the call of the Chair, who shall also approve the agenda. A government official shall be present at all meetings. Meetings shall be open to the public except as determined otherwise by the Secretary; notice of all meetings shall be given to the public. �Meetings shall be conducted, and records of the proceedings kept, as required by applicable laws and Departmental regulations. Compensation Members who are not full-time federal employees shall be paid at the rate of $100 per day, plus per diem and travel expenses in accordance with Standard Governmental Travel Regulations. Annua1 Cos t Estimate Estimated annual cost for operating the Committee, including compensation and travel expenses for members but excluding staff support, is $19,736. Estimate of annual man years of staff support required is one-quarter, at an estimated annual cost of $8,380. Reports An annual report shall be submitted to the Secretary through the Chair/ AOWG, not later than November 1 of each year, which shall contain as a minimum a list of members and their business addresses, the Committee's functions, dates and places of meetings, and a summary of Committee activities and recommendations made during the fiscal year. A copy of the report shall be provided to the Department Committee Management Office. Termination Date The duration of the Advisory Committee on Special studies Relating to the Possible Long-Term Effects of Phenoxy Herbicides and Contaminants is five years. Unless renewed by appropriate action prior to its expiration, the Committee will terminate on January 19, 1985. �PROFESSIONAL AREA BREAKDOWN - ADVISORY COMMITTEE ON SPECIAL STUDIES RELATING TO THE POSSIBLE LONG-TERM HEALTH EFFECTS OF PHENOXY HERBICIDES AND CONTAMINANTS Authorized Positions: Name Term Ending Corns tock Friedman Duration of Committee Duration of Committee Kreiss Duration of Committee Kurland Monson Nelson Ramey Duration Duration Duration Duration of Committee of Committee of Committee of Committee Expertise Epidemiology Pediatrics, human genetics Occupational Health, epidemiology Epidemiology, neurology Epidemiology Toxicology Statistics, psychology 8 Prof ./Lay/Res. Geog. Dist. X X MA TX X CO X X X X X MN MD NY NC PROPOSED CANDIDATE FOR VACANCY Pardes Duration of Committee Psychiatry Minority/Female NY X �CONGRESSIQNALLY AUTHORIZED EPIDEMIOLOGICAL STUDY In January 1979, the Congress enacted P.L. 96-151 which directed the Veterans Administration (VA) to investigate health effects of Agent Orange. The authorization was expanded in November 1981 by P.L. 97-72 to include "other factors." In January 1983, responsibility for design and execution of the study was formally transferred from VA to the Centers for Disease Control (CDC), with resources, both FTE's and funding, to be provided by VA. The CDC protocol for conducting the study was completed and distributed for scientific review in May 1983. Principal review was conducted by the Office of Technology Assessment. Reviews were also conducted by the Agent Orange Working Group Science Panel, by the Advisory Committee on Special Studies Relating to the Possible Long Term Health Effects of Phenoxy Herbicides and Contaminants (which oversees the Air Force Ranch Hand Study), and by the CDC Ad Hoc Review Panel. National veterans' organizations were invited to comment. All reviews were completed by September 1983. The CDC protocol contains three study components: (1) Vietnam Experience; (2) Agent Orange; and (3) Selected Cancers Study. 1. ' The Vietnam Experience Study is to determine whether veterans who served in Vietnam are at greater risk for poor health than are similar veterans who did not serve in Vietnam. The study will identify, from personnel records, 6,000 one-term Army veterans who have served in Vietnam and 6,000 similar veterans who have never been in Vietnam. All of these will be followed for mortality or given a telephone interview covering general health information and demographic data. 2,000 from each group will be given comprehensive physical and psychological examination and health outcomes for the two groups will be compared. The questionnaire for this study has been reviewed by the Science Panel and cleared by OMB. A pilot test to determine locatability and participation rates of prospective subjects has been completed and reviewed by the Science Panel. Participation rates were better than anticipated and the study is preceding to the main data collection phase. Concerns were raised by the Science Panel that self-reported health data, including information on reproduction outcomes, should be verified from medical and/or vital records or not collected at all. Some �-2- plans for utilization of these data are currently being developed at CDC and will be discussed at a Science Panel meeting in the near future. 2. The Agent Orange Study is to determine whether Vietnam veterans who were highly likely to have been exposed to Agent Orange while in Vietnam are at greater risk for poor health than are Vietnam veterans with similar experiences while in Vietnam but very unlikely to have been exposed to Agent Orange while there. The study will identify, from Battalion Daily Reports, 6,000 one-term Army Vietnam veterans who were likely to have been exposed to Agent Orange on several occasions, 6,000 similar Vietnam veterans who were not likely to have been exposed to Agent Orange, and 6,000 Vietnam veterans known to have served in areas where Agent Orange was never used. All of these will be followed for mortality or given a telephone interview and 2,000 from each group will be examined as in the Vietnam Experience Study. The questionnaire for this study is similar to the one being used in the Vietnam Experience Study. The pilot has not been completed but should yield similar results, to the one which has been used for the Vietnam Experience Study. Since the identification of Agent Orange exposed and unexposed subjects who are similar in other ways is crucial to the successful completion of the Agent Orange Study, the selection of the three study cohorts will be reviewed by the Science Panel when this stage has been completed and before the main study begins. 3. The Selected Cancers Study is to determine whether Vietnam veterans are at greater risk for certain cancers than the rest of the population. The study will select post 1985 diagnoses of soft tissue sarcoma, Non-Hodgkins Lymphoma and other cancers from newly identified entries into the Surveillance, Epidemiology, and End Results (SEER) Registries sponsored by the National Cancer Institute. These registries cover approximately 10-12 percent of the U.S. population including both rural and urban residents. Cancer cases from the appropriate age group will be interviewed via telephone and their Vietnam experience compared to that of age matched controls selected from the same communities by random digit dialing. �-3- The questionnaire for this study has been reviewed and cleared by the OMB. Data collection begin in 1985 and the names of identified Vietnam veterans are submitted to the Army and Joint Services Environmental Support Group for records review and assignment of an "Exposure Opportunity Index". This study should provide a good estimate of whether service in Vietnam and/or at least minimal exposure to Agent Orange is associated with an increased risk for Soft Tissue Sarcomas, Non-Hodgkins Lymphoma and certain other cancers 15 to 20 years later. �CDC - Birth Defects Study The CDC Birth Defects Study was a Case-Control Study designed to determine if the fathers of babies with major birth defects were more likely to have served in Vietnam than fathers of healthy babies. The study was conducted among all identified severely affected cases from a population based Birth Defect Registry in the Atlanta, Georgia, metropolitan area and included almost 5000 major defects and 3000 normal babies born in the same hospitals at nearly the same time. Results of this study indicated that the risk for having a major birth defected child, diagnosed up to the first year, was no greater for Vietnam veterans than for other veterans, or for other men in general. In addition, there was no statistically significant increase in the relative risk for a Vietnam veteran fathering a baby with any individual type or group of defects compared to other men. In addition to measuring the risks associated with the Vietnam experience per se, the investigators at CDC worked with the Department of Defense Army Agent Orange Task Force in assigning some measure of the likelihood for an opportunity for exposure to Agent Orange for as many Vietnam veterans as had available information. Two such indices (EOI) were created which were similar, but not identical. The analyses reported by CDC using these indices .indicated an increased risk for fathering babies with three different defects with increasing opportunities for exposure on at least one of the indices. The three defects were spina bifida, cleft lip with or without cleft palate, and a group of neonatal neoplasms. Whether these findings are the result of chance occurrence when multiple comparisons are made, which is highly probable, cannot be determined with certainty. It is also quite possible that the indices themselves were sufficiently inaccurate as to render them uninterpretable, particularly since they were in the developmental stage at the time. It is not possible to make a definitive evaluation of these findings at this time. At the suggestion of Congress, and as a matter of appropriate public interest, the Science Panel, through its Research Agenda Subpanel, is preparing a statement on the state-of-the-art of Reproductive Outcome research on the offspring of Vietnam veterans fathers. The purpose of this report will be to develop a research agenda of further research which needs to be done on this issue. �Soft Tissue Sarcoma - International Studies The Science Panel reviewed international studies of the possible association between exposure to phenoxy acid herbicides and their contaminants and soft-tissue sarcomas. It was determined that these studies were inconclusive, that it would not be useful to engage in further in depth analysis of the already published data and that there are several studies currently underway that should enable a more definitive assessment of the possible association between soft tissue sarcoma and other cancers and exposure to phenoxy herbicides and contaminants to be made in the next several years. �NATIONAL CANCER INSTITUTE - CASE-CONTROL STUDY OF SOFT TISSUE SARCOMAS AND LYMPHQNAS AND THEIR RELATIONSHIP TO HERBICIDE APPLICATORS IN KANSAS The purpose of the Case-Control Study of these two cancers is to determine, by interview, whether cases of Soft Tissue Sarcoma and/or Lymphoma are more likely to have been occupationally exposed to phenoxy acid herbicides and contaminants than a matched comparison group. Cases were obtained from a population based tumor registry covering the whole state of Kansas and controls were matched for age, sex, race and residential area of the state. Kansas was chosen as a site for this study because, in addition to the existence of a tumor registry, the agricultural practices in Kansas wheat growing areas have included considerable application of 2,4,5-T without other concomittant pesticide use. The Science Panel reviewed the original protocol for this study which is nearing completion under contract to the National Cancer Institute. The Science Panel is particularly interested in the outcome of this study since it should be useful in evaluating the possible associations between certain cancers and herbicide exposures which have been suggested from several studies conducted in Sweden. National Cancer Institute - Study of Soft Tissue Sarcomas and Non-Hodgkins Lymp"homa in Thirteen counties in Washington State The Batelle Corporation, under grant from the NCI, is conducting a study of Soft Tissue Sarcoma and Non-Hodgkins Lymphoma in the 13 county area around Seattle, Washington which is covered by a population based Tumor Registry. The study will interview in depth for occupational exposure, residential history and home use of herbicides, especially 2,4,5-T. It is intended to verify such use from employment records, reported to be available in this region where much 2,4,5-T has been used. A comparison of the amount and rate of exposure of cancer cases will be made to a comparison group, the nature of which is unknown (to us) at present. The Science Panel reviewed a very early version of this proposal in 1981, but was not involved in the formal review process. The Science Panel is interested in the outcome of this study since it should help in further evaluating the relationship between certain cancers and exposure to dioxin contaiminated herbicides. �AIR FORCE RANCH HAND STUDY The purpose of the Ranch Hand Study is to determine whether the 1247 Air Force personnel who were involved in the spraying of Agent Orange (and other herbicides) in Vietnam were more likely to suffer ill health than a comparable group of Air Force personnel who were not involved in herbicide spraying activities. The aerial spraying of herbicide in Vietnam was code named Operation Ranch Hand and thus all of the Air Force personnel involved in the loading, operating and maintaining of the C123 Aircraft used in this operation were termed Ranch Handers. The comparison group consists of Air Force personnel who operated and maintained C130 aircraft in Southeast Asia and who were not involved in herbicide activities. The comparisons are matched to the Ranch Handers by age, race and military rank and specialty. The study will include comparing mortality from various causes between the Ranch Handers and the comparisons (since their service in Southeast Asia) with annual updates every year. It will also include comparing morbidity between the two groups based on an initial telephone interview and an extensive physical, laboratory and psychological examination every 3 to 5 years. The study is intended to continue for 20 years from 1981. The Science Panel originally reviewed the protocol for the Ranch Hand Study in 1981. The study is of particular interest since the Air Force estimated at that time that many of the Ranch Hand personnel were exposed to Agent Orange at a rate 1000 times greater than almost any of the rest of the Armed Forces in Vietnam. The first Baseline Mortality Results from this study, published in 1983, indicated virtually no difference in mortality between the Ranch Handers and their comparisons through 1982. The Science Panel reviewed this report in the light of a critique which had been prepared by the Vietnam Veterans of America and suggested that a lay-language version of the report would be easier to understand than the rather detailed version which was released. The second interim report is scheduled for release in the very near future and is currently under review by the Advisory Committee for Special Studies. Data collected during the interview and the first examination were released as the Baseline Morbidity Results in early 1984. The most interesting findings from this report included: 1. an increase in non-melanoma skin cancer among Ranch Handers. This finding will be further studied at the second examination to determine if exposure to sunlight has played a significant role since exposure to solar radiation is the acknowledged primary cause of skin cancer in the U.S.; �there was a significant increase in abnormal pulses of the extremities among the Ranch Handers. This will be further explored during the second examination since it is poorly understood and currently has no direct health related consequences; and an increased number of minor birth defects (mostly birth marks) neonatal deaths and physical handicaps to children were reported by Ranch Hand parents than by comparisons. Each of these is currently being verified through the compilation of appropriate medical and vital records for all study subjects as requested by the Agent Orange Working Group. A progress report on this should be available imminently. �PROPOSED STUDIES OF INTEREST TO THE SCIENCE PANEL Female Veterans Study The Science Panel reviewed a proposal to study female Vietnam veterans which had been prepared by CDC. The proposed study would interview all, and examine 2000, of the approximately 7000 female veterans who served in Vietnam, who can be located, and who agree to participate. The Science Panel feels that, even though the study appears logistically feasible, it may not be the most efficient nor appropriate design to test possible adverse health effects among female Vietnam veterans. The Panel recommends that specific hypotheses relating Vietnam exposures and adverse health effects among female veterans be formulated, and then a suitable research design developed and evaluated. Veterans Administration - Twin Study A concept proposal for a study of identical twins - one of whom served in Vietnam and one of whom did not - was reviewed and approved by the Science Panel in 1982. The purpose of the study would be to compare physical and psychological health of the two members of an extremely closely matched pair of subjects who differed in their exposure to the Vietnam Experience including possible exposure to Agent .Orange. The final protocols for this study has subsequently been fully developed and we understand is currently under review. �THE STATE OF AGENT ORANGE RELATED RESEARCH IN THE FEDERAL GOVERNMENT The FY 1985 Report of the Science Panel of the Cabinet Council Agent Orange Working Group September 1985 �The State of Agent Orange Related Research in the Federal Government The PY 1985 Report of the Science Panel of the Cabinet Council Agent Orange Working Group OUTLINE EXECUTIVE SUMMARY I. Introduction II. Brief History of the Agent Orange Working Group (AOWG) III. Rationale for the Research Efforts Commencing in 1980 A. What was known 1. Effects in animals 2. Effects in humans B. What was not known 1. Effects in animals 2. Effects in humans 3. Information management IV. Federal Research Related to Agent Orange: 1981-1987 A. Effects in animals B. Effects in humans C. Other 1. Information management 2. Environmental fate and transport 3. Monitoring 4. Risk assessment V. Evaluation VI. Future Directions APPENDIX A — Membership of AOWG APPENDIX B -- Project-by-project listing of agency AO-related research efforts APPENDIX C — Agency summary statements of AO-related research efforts �HHS A.O./DIOXIN EXPENDITURES $22,5O.3,OOO TOTAL EXPENDITURES ANALYT (2.5%) §556,000 HUMAN (41 .1%) $9,244,000 ANIMAL (56.5%) $12,703,000 \ \ �DOD A.O./DIOXIM EXPENDITURES $33,605,500 TOTAL EXPBJDITUKES ANIMAL (O.9%) $288,000 \ \. HUMAN (99.1%) $33,317,500 �USDA A.O./DIOXIN EXPENDITURES $594,OOO TOTAL EXPENDITURES LIT (10.8%) $64,000 x. \ \ \ \ HUMAN (89.2%) $530,000 �EPA A.O./DIOXIN EXPENDITURES $14,467,000 TOTAL EXPENDITURES $2,146,000 ANIMAL (14.8%) LIT (7.3%) / $1,052,000 / ANALYT (12.5%) $1,812,000 HUMAN (O.C.%) $75,000 \ \ I / ENVIR (64,9%) '' $9,382,000 �A.O./DIOXIN EXPENDITURES $81 ,286,000 TOTAL EXPENDITURES $774,000 (O.i $4 , 385 , 000 1 \ <, ! \ \ (£H.O%) $76,127,000 �APPENDIX C AGENCY SUMMARY STATEMENT OF AO-RELATED RESEARCH EFFORTS �ENVIRONMENTAL PROTECTION AGENCY Research Program Associated with Chlorinated Dibenzo-p-dioxins (CDDs) and Dibenzofurans (CDFs) The US Environmental Protection Agency (EPA) has been concerned with CDDs/CDFs, particularly 2,3,7,8-TCDD, since the early 1970s. Much of the early work was related to 2,3,7,8-TCDD as a contaminant in the herbicde 2,4,5-T and included analytical methods development and its application to monitoring data. While the Agency's research work with humans has been limited, it has been important. In the late 1970s, a controversial epidemiological study triggered immediate regulatory action by the Agency. During the same period, the Agency conducted an investigation of 2,3,7,8-TCDD in the human milk of mothers living in areas in which 2,4,5-T had been used. No confirmed positive residues were detected in any of 100 samples. The Agency has detected trace amounts of 2,3,7,8-TCDD in some human adipose tissue samples. Ongoing collaborative efforts with the Veterans Administration is aimed at analyzing samples of human adipose tissue collected during the 1970s to determine whether or not Vietnam service personnel have greater residues of 2,3,7,8-TCDD than do a comparable group of individuals who did not go to Vietnam. In addition, EPA has conducted assessments of the potential human risks associated with exposure to 2,3,7,8-TCDD and some of the other CDDs/CDFs. These "ballpark" risk estimates have been useful in .reaching regulatory decisions. During the 1980s, the EPA research program for CDDs/CDFs has focused on environmental and risk management concerns. Specifically, Congress directed the Agency of conduct a National Dioxin Study, the aim of which is the investigation of potential "hot spots" across the country and the determination of background levels, if any, of 2,3,7,8-TCDD in the environment. This current effort builds on more limited, but more focused, Agency efforts searching for 2,3,7,8-TCDD in envivonmental samples. In an attempt to conduct such investigations more quickly and inexpensively, the Agency has sponsored research to develop new methods of analysis of CDDs/CDFs. In order to better understand the significance of reports of CDDs/CDFs in the environment, EPA is conducting studies in the environmental transport and fate of these compounds, with a particular emphasis on the bioavailability and possible movement into the human food chain. Large-scale combustion is under special investigation as a possible source of CDDs/CDFs in the environment. A major thrust of recent EPA efforts has been in the direction •of controlling, managing, and/or destroying CDDs/CDFs once they are found in the environment. Methods have been found which successfully destroy 2,3,7,8-TCDD in contaminated soil and liquids. Procedures are being developed to minimize the emission of CDDs/CDFs from combustion sources. �VA/AFIP Soft Tissue Sarcoma Study The possibility that exposure to phenoxy herbicides may induce rare forms of cancer in humans such as soft tissue sarcoma (STS) has been suggested from recent studies in Sweden. Subsequently, there is much concern in the United States that many veterans who served in Vietnam might have had a significant exposure to the phenoxy herbicides including Agent Orange and, therefore, might be at increased risk of developing STS. In view of the concern raised by many veterans and conflicting findings in the scientific literature, the VA, in collaboration with the Armed Forces Institute of Pathology (AFIP), is conducting a case control study in which 250 individuals with STS are compared with 750 individuals without STS with respect to Vietnam service, probable Agent Orange exposure and other host and environmental risk factors. The study is conducted in two phases. Phase I of the study will investigate whether service in Vietnam during 1965-1971 increased the risk of developing STS. Military service information, in particular Vietnam service status, for each case and control patients will be obtained from a review of the patient's military personnel records archived at the National Personnel Records Center in St. louis, Missouri!. Phase II of the study will investigate other host and environmental risk factors for the development of STS based on information obtained from telephone interviews with the subjects or their next-of-kin. Information on risk factors such as occupational and non-occupational exposure to pnenoxy herbicides, ionizing radiation asbestos, arsenic, vinyl chloride, and genetic synodromes will be obtained from the interviews and analyzed individually and jointly with respect to the risk of developing STS. As of July, 1985, 58% of the study subjects (616/1,066) have been located and have completed the telephone interview. Data collection will be completed by March, 1986 and the final report is expected in late 1986. �VA Mortality Study The Vietnam Veterans Mortality Study is designed to assess mortality patterns of U.S. servicemen in the Army or Marines who served during a portion of the Vietnam era. A sample of 75,000 veterans deaths has been selected from the ^ BIRLS files. For each of the deaths, military service and cause of death information are being collected and coded. The two types of data will be merged and analyzed to compare the mortality experience of veterans who served in Vietnam with veterans of the same era who did not serve in Vietnam. Various analytical approaches are planned including classical proportionate mortality ratio (PMR) analyses as well as categorical data analyses. As of August 1985 the military records search and abstracting have been completed for 98% of total cohort of 75,000. Ninety nine percent of the expected 72,000 death records have been received. However, about 15% of the records received did not include the cause of death information. Extensive tracing efforts have been made using both internal records and records maintained by other government agencies for all veterans whose VA claims folders lacked the cause of death information. Completeness, accuracy and consistency of data on numerous variables (e.g., age, race, year, of death, cause of death, branch of service, rank, MOSC, years of active duty, separation year, length of service in Vietnam, industry, occupation) are being checked in preparation for analysis. The final report is expected in late 1985. �Alternate Methods for Assigning Agent Orange Exposure Status to Vietnam Veterans Exposure Opportunity Index (EOlT Some time ago the Joint Services Environmental Support Group (then the Army Agent Orange last Force (AAOTF) began to develop methods to estimate potential exposure to Agent Orange among Vietnam veterans. The method to be used in the proposed Agent Orange Morbidity and Mortality Studies currently underway by CDC involves detailed day-by-day tracking of both military units and individuals while in Vietnam. Amassing the information necessary to do this requires considerable effort and yields simultaneous information on all of the members of a given military unit. The method is thus suitable for identifying cohorts, but is extremely inefficient for determining potential exposures of individuals selected by other means. Furthermore, the necessary records apparently do not exist for many units in Vietnam, particularly non^Army units, and is the major reason why the CDC Epidemiological studies are confined to veterans of the Army. In order to obtain some information on the possible exposure to Agent Orange of veterans identified through other sources, an alternative method was proposed by the AAOTF. The Science Panel was briefed on, and reviewed in depth the alternative procedures^ for assigning Exposure Opportunity Indices (EOI) to Vietnam veterans. These procedures are based on the place, time and job specialty of veterans while in Vietnam as indicated in personnel records, military unit quarterly reports and herbicide application records from Vietnam. The method was proposed by the Department of Defense, and was developed by the Army and Joint Services Environmental Support Group in conjunction with the investigators of the CDC Birth Defects Study. Even though the alternative method is somewhat subjective and confounds combat status with exposure to herbicide, all of the members of the Science Panel agree that the method as developed, can provide an individual estimate of the relative likelihood for at least some exposure to Agent Orange while in Vietnam. Attempts to establish whether such exposures are capable of compromising health status is the business of ongoing health and mortality studies. �AGENT ORANGE LITIGATION In 1979, a class action was commenced in the United States District Court, Eastern District of New York, charging the United States and a major portion of the chemical industry with deaths and injuries to tens of thousands of Vietnam veterans who came in contact with herbicides used in the war in Southeast Asia. The suit also claimed that as a result of the veterans' exposure, their children suffer severe birth defects. After five years of numerous motions and extensive discovery, a settlement amount of $180,000,000 was negotiated between the plaintiff-veterans and the defendants-manufacturers and approved by Chief Judge Jack B. Weinstein on June 11, 1984. Following this settlement, a $10 billion class action was filed against the United States on behalf of the servicemen, their wives and children. The class action alleged, among other things, failure to warn, and pre-induction, in-service, and post-discharge negligence. At the same time, the defendants expressed their intention to press third-party contribution and indemnity claims against the United States, to recover all costs associated with their defense of the litiga* tion, including the amount of the settlement. The United States moved to dismiss the p l a i n t i f f s ' class action and, on December 10, 1984 Judge Weinstein denied class certification and dismissed all claims brought by the servicemen. The Court also found that there is no credible medical or scientific evidence supporting claims of male-mediated birth defects or miscarriages, but reserved final judgment on these claims for ninety-days. The United States will also seek dismissal of all thirds-party claims pending against it. Judge Weinstein has established a 28 member advisory board to advise the Court on how the settlement trust fund proceeds might be best utilized. The Justice Department has refused to allow federal personnel to participate in any way in the settlement process. Judge Weinstein has reserved final approval of the settlement pending review of the settlement distribution plan and resolution of all counsel fee disputes. �.Veterans Administration Advisory Committee On Environmental Hazards The Veterans Administration Advisory Committee on Environmental Hazards and its Scientific Council were created by the Veterans' Dioxin and Radiation Exposure Compensation Standards Act, P.L. 98*542, enacted on October 24, 1984. The functions of this Committee and its Council are not perceived to encroach on, or duplicate the efforts of the Agent Orange Working Group (AOWG). The Veterans Administration Advisory Committee is distinguished from the Agent Orange Working Group in that the Agent Orange Working Group is solely concerned with risk assessment and the Veterans Administration Advisory Committee and its Scientific Council are concerned with risk management. P.L. 98*542 .requires, inter alia, that the VA Administrator prescribe regulations on adjudicating claims based on dioxin and radiation exposure after considering the recommendations of an advisory committee and its scientific council. The Advisory Committee on Environmental Hazards created by the Act icons is ts of fifteen/, members appointed by the VA Administrator. Eleven of these, of whom none may be from the Armed Forces, the VA, or Defense and not more than three may be federal employees, are appointed in consultation with the Director, NIH. These members must include three authorities on dioxin, three on ionizing radiation, and five on epidemiology or a related field. These eleven members also constitute the Scientific Council of the Committee. The Council is divided into two eight member panels which will, respectively, evaluate studies on dioxin and radiation exposure. The Scientific Council reports to the Committee and to the Administrator directly. The balance of the Committee is made up of four individuals from the general public with special concerns regarding exposure to dioxin or radiation. The Chief Medical Officer and Chief Benefits Director of the VA are ex officio members. �SENATE VETERAN AFFAIRS COMMITTEE 99TH Republicans CONGRESS Democrats Sen. Frank H. Murkowski, (R-AK) Chairman Sen. Sen. Sen. Sen. Sen. Sen. Alan K. Simpson, (R-WY) Rudy Boschwitz, (R-MN) Robert T. Stafford (R-VT) Arlen Specter (R-PA) Jeremiah Denton (R-AL) Strom Thurmond (R-SC) Sen. Dennis DeConcini (D-AZ) Sen. Alan Cranston (D-CA) Sen. Jay Rockefeller (D-WV) Sen. George J. Mitchell (D-ME) Sen. Spark M. Matsunaga (D-HI) �COMMITTEE MEMBERS AND STAFF VETERANS' AFFAIRS COMMITTEE ON VETERANS AFFAIRS SR-414 224-9126 Frank H. Murfcowski, Alaska, Chairman. Alan Cranston, Calif. Spark M. Matsunaga, Hawaii Dennis DeConcini, Ariz. George J. Mitchell, Maine John O. Rockefeller, IV, W. Va. Alan K. Simpson, Wyo. Strom Thurmond, S.C. Robert T. Stafford, Vt. Aden Specter, Pa. Jeremiah Oenton, Ala. Rudy Boschwitz, Minn. STAFF MCMWMS Alpert Cynthia PROF ST M SR-420A Alvarado, Tina RECP SR-414 Billica. Nancy MIN RES ASST SH-202 Boertlein, Judy ST ASST SR-412 Brew, William MIN COUN sn-202 Eckhardt, Kay ST ASST SR-420 Hocks, Becky CHF CLK/LEQISLATIVE CLK SR-«i2 Hughes, Charlotte MIN CASEWKR SH-202 Maraz, Stacy ST ASST SR-420 McTighe, Cathy COUN SR-420A Moore, Jim PRESS ASST SR>420A 46210 49130 40576 46213 40767 49132 46236 44112 40206 46266 44921 Moore, Lisa RES ASST SR-420A Phinney, Al COUN SR-420 Polzer, Babette MIN PROF ST SH-202 Post, Ingrid MIN CHF cut SH-202 Principi, Anthony J CHF COUN/ST OIR SR~*IO Schratwieser, Hugh PROF ST M SR-420 46230 47636 4677S 46204 49126 46263 Scott, Ed MIN QEN COUN SH-202 46262 Steinberg, Jon MIN CHF COUN/ST OIR SH-202 46202 Susman, Julie OPTY ST OIR/LEQ OIR/OPTY CHF COUN SR-414 Yoder, Chris PROF ST M SR*420 (No Subcommittees) 46293 46212 �CHAIRMAN COMMITTEE ON VETERANS' AFFAIRS SIN. "RANK H. MURKOWSKI (R AK) Committaa on Enargy & Natural Raaooreaa Subeommmaa on Enargy & Minaral Raaourcas Subeommmaa on Enargy Ragulation, Chairman Subeommmaa on Watar & Powar Commfttaa on Foraign Ratetiona Subeommmaa,on Eaat Asian & Paeifie Affair*. Chairman Sutcommmaa on International Economtc Policy Subeommmaa on Waatam Hamiapnara Affatrt S«n. Frank H. Murkow*ki Commrttaa on Vatarana' Affaira Salact Commrttaa on Indian Affaira of Fairbanks Republican—Jan. 3, 1981 �ASSISTANT MAJORITY LEADER Sea. Alan K. Slmpwa of Cody Republican—Jtn. I, 1979 SIN. ALAN K. SIMMON (ft WV) Committal on invfronmem > PufcOc Worto Subcommittee on Environmental Pollution Subeommmaa on Nudaar Regulation. Chamnan Subcommmaa on Toxic Subatancaa & Environmantal Oversight CommHta* on Th« Judietafy Subcommmaa on Courts Subcommittee on immigration & Refugee PoHcy. Chairman Subcommittee on Seoaration of Powers Committee on Veteran*' Affairs. Chairman �HOUSE VETERANS AFFAIRS COMMITTEE 99TH CONGRESS Republicans Democrats G.V. (Sonny) Montgomery, Miss. Chairman Don Edwards, (D-Calif) Bob Edgar, (D-Pa) Sam B. Hall, Jr., (D-Tex) Douglas Applegate, (D-Ohio) Richard C. Shelby, (D-Ala) Dan Mica, (D-Fla) Thomas A. Daschle, (D-S.Dak) Wayne Dowdy, ((D-Miss) Lane Evans, (D-I11) Marcy Kaptur, (D-Ohio) Alan B. Moliohan, (D-W.Va.) Timothy J. Penny, (D-Minn) Harley 0* Staggers, Jr. (D-W.Va) J. Roy Rowland, (D-Ga) John Bryant, (D-Tex) James J. Florio, (D-N.J.) Kenneth J. Gray, (D-lll) Paul E. Kanjorski, (D-Pa) Tommy F. Robinson, (D-Ark) John Paul Hammerschmidt, (R-Ark) Chalmers P. Wylie, (R-Ohio) Elwood Hillis, (R-Ind) Gerald B.H. Solomon, (R-N.Y.) Bob McEwen, (R-Ohio) Christopher H. Smith, (R-N.J.) Dan Burton, (R-Ind) Don Sundquist, (R-Tenn) uon ounuquisc, (,&.Michael Bilirakis, (R-Fla) Bilirakis, Nancy Lee Johnson, Vi. w~ Guy V. Molinari, (R-N.Y. Thomas J. Ridge, (R-Pa) Bill Hendon, (R-N.C.) John G» Rowland, (R-Conn �COMMITTEE MEMBERS AND STAFF VETERAMS AFFA(RS COMMITTEE ON VETERANS' AFFAIRS 335 CANNON HOB 225-3527 G. V. (Sonny) Montgomery, Miss.. Chairman Don Edwards, Calif. Bob Edgar, Pa. Sam B. Hall. Jr.. Tex. Douglas Applegate, Ohio Richard C. Shelby, Ala. Dan Mica. Fla. Thomas A. Daschle. S. Oak. John Paul Hammerschmiat. Ark. Chalmers P. Wylie. Ohio Elwood Hillis. Ind. Gerald B. H. Solomon, N.Y. Bob McEwen, Ohio Christopher H, Smith, N.J. Dan Burton, Ind. Don Sundquist, Tenn. Michael BUirakis, Fla. Nancy Lee Johnson, Conn. GuyV. Molinari, N.Y. Thomas J. Ridge, Pa. Bill Hendon, N.C. John G. Rowland, Conn. Wayne Dowdy, Miss. Lane Evans. III. Marcy Kaptur, Ohio Alan B. Mollohan, W. Va. Timothy J. Penny. Minn. Hartey O. Staggers, Jr., W. Va. J. Roy Rowland, Ga. John Bryant. Tex. James J. Florio, N.J. Kenneth J. Gray. III. Paul E. Kaniorski, Pa. Tommy F. Robinson, Ark. MAJORITY STAFF Burtey. Suzy FILE CLK 335 Burnett, Aden* AOMIN ASST 335 Cochran, JHl PROF STF MEM EDUC. TRAIN, EMPLOY 335 Daw*. Barbara STF ASST HOSP, HEALTHCARE 33a Evans, Semmes STF ASST 337 Fleming. Mack CHF COUN & STF OIR 33S Frone. Stanley STF ASST 335 53527 59165 53527 59154 59164 53527 53527 Grant, Bob PRTG CLK 33S i Holley, Jim PROF STF MEM PUB AFRS 337 Kitker, Beth STF ASST EDUC. TRAIN, EMPLOY 335 MeOermott. Mary FIN CLK 335 53535 53664 59112 59557 Moon. Arnold COUN COMPCNS. PENS. INS 337 Parker. Pam STF ASST OVERSIGHT a INVEST 33S Raymond. Vic PROF STF MEM 338 Richardson. Jean STF ASST COMPCNS. PENS, INS 337.. Royce, Gloria PROF STF MEM HOUS & MEMORIAL AFRS 337 53569 59044 59154 53569 Ryan, Patrick COUN 335 Shultz, Richard COUN OVERSIGHT & INVEST 335 Sniffen, Candis Lee LEGIS ASST 335 Tippett, Patricia RECEPT 335 59154 53541 S3S27 53527 53664 McOonell. Jack PROF STF MEM HOSP, HEALTH CARE 338 :... 59154 MINORITY STAFF Brandes. Sharon A PROF STF MEM 333A Oonohue, Patricia AOMIN ASST 333 Forrest. Sue STF ASST 333A 59756 53551 59756 Smith, Kingston OPTY COUN 4 STF OIR 333A Wilson, Rutus COUN & STF OIR 333 S97S6 53551 SUBCOMMITTEE STAFF CaWweii, Anne PROF STF MEM, HOUS & MEMORIAL AFRS 2443 52665 Dunshm, Michael PROF STF MEM, EDUC, TRAIN. EMPLOY 2465 52901 Fuller. Richard PROF STF MEM, HOSP. HEALTH CARS 3362 52011 Gallion, Edward MIN PROF STF MEM. COMPENS. PENS. INS 2342 55614 Sechrist. Timothy PROF STF MEM. COMPENS. PENS, INS 2464 56265 251 �VETERANS AFFAIRS U.S. HOUSE OF REPRESENTATIVES SUBCOMMITTEE ON OVERSIGHT AND INVESTIGATIONS 335 CANNON HOB 225-3541 G. V. (Sonny) Montgomery, Miss., Chairman Elwood Hillis, Ind. Dan Burton, Ind. Don Sundquist, Tenn. Nancy Lee Johnson. Conn. Thomas J. Ridge, Pa. Don Edwards, Calif. Kenneth J. Gray, III. Sam B, Hall, Jr., Tex. Timothy J. Penny, Minn. J. Roy Rowland, Ga. Tommy F. Robinson, Ark. MAJORITY STAFF. 53541 MINORITY STAFF.. 59756 SUBCOMMITTEE ON HOSPITALS AND HEALTH CARE 338 CANNON HOB 225-9154 Bob Edgar, Pa., Chairman Dan Mica, Fla. Wayne Dowdy, Miss. Lane Evans, III. Marcy Kaptur, Ohio Alan B. Mollohan, W. Va. Timothy J. Penny, Minn. Harley O. Staggers, Jr., W. Va. J. Roy Rowland, Ga. John Bryant, Tex. James J. Florio, N.J. !vPaul E. Kanjorski, Pa. Tommy F. Robinson, Ark. Richard C. Shelby, Ala. Thomas A. Daschle, S. Dak. John Paul Hammerschmidt, Ark. Elwood Hillis, Ind. Gerald B. H. Solomon. N.Y. Bob McEwen, Ohio Christopher H. Smith, N.J. Michael Bilirakis, Fla. Nancy Lee Johnson, Conn. Guy V. Molinari, N.Y. Thomas J. Ridge, Pa. Bill Hendon, N.C, John G. Rowland, Conn. MAJORITY STAFF. 59154 MINORITY STAFF.. 59756 SUBCOMMITTEE ON COMPENSATION, PENSION, AND INSURANCE 337 CANNON HOB 225-3569 Douglas Applegate, Ohio, Chairman Sam B. Hall, Jr., Tex. G. V. (Sonny) Montgomery, Miss. Dan Mica. Fla. Wayne Dowdy, Miss. Lane Evans, III. Tommy F. Robinson, Ark. Gerald B. H. Solomon. N.Y. Chalmers P. Wylie. Ohio John Paul Hammerschmidt, Ark. Dan Burton, Ind. Guy V. Molinari, N.Y. MAJORITY STAFF.... 53569 MINORITY STAFF.... 59756 252 �COMMITTEE MEMBERS AND STAFF VETERANS AFFAIRS SUBCOMMITTEE ON EDUCATION, TRAINING AND EMPLOYMENT 335 CANNON HOB 225-9166 Thomas A. Daschle, S. Oak., Chairman Lane Evans, III. Marcy Kaptur, Ohio John Bryant, Tex. James J. Florio, N.J. Kenneth J. Gray, III. Bob McEwen. Ohio Chalmers P. Wylie, Ohio Gerald 8. H. Solomon, N.Y. BUI Hendon. N.C. MAJORITY STAFF 59166 MINORITY STAFF 59756 SUBCOMMITTEE ON HOUSING AND MEMORIAL AFFAIRS 337 CANNON HOB 225-9164 Richard C. Shelby, Ala., Chairman Bob Edgar, Pa. Douglas Applegate, Ohio Alan B. Mollohan, W. Va. John Bryant, Tex. James J. Florio, N.Y. Christopher H. Smith, N.J. Don Sundquist, Tenn. Michael Bilirakis, Fla. John G. Rowland, Conn. MAJORITY STAFF 59164 MINORITY STAFF 59756 �(AH S9iun|OA) - L - ON SUJXOIQ peiepossv pue seppjqjGH Axoueqj uo ejniejejn om»uep.s ^o s.isdouAs sueeie �VA CONTRACT NO: V101(93)P-953 C( SYNOPSIS OF SCIENTIFIC LITERATURE ON PHENOXY HERBICIDES AND ASSOCIATED DIOXINS Prepared for Contracting Officer's Technical Representative: Barclay M. Shepard, M.D. Director, Agent Orange Projects Office Department of Medicine and Surgery Veterans Administration 810 Vermont Avenue, N.W. Washington, D.C. 20420 c o Submitted by: Clement Associates, Inc. 1515 Wilson Boulevard Arlington, Virginia 22209 �PREFACE In October 1981, the Veterans Administration published the first two volumes of a comprehensive report entitled Review of Literature on Herbicides, Including Phenoxy Herbicides and Associated Dioxins. A continuation of this important effort resulted in the preparation and publication in April 1984 of volumes III and IV. At this point it was thought that a summary in layman's terms, with emphasis on health effects would be helpful to the general public's understanding of the complex and often controversial issue of Agent Orange. Consequently this summary has been prepared to fill that need. It should be noted that this synopsis includes only that body of scientific literature published through December 1983, and therefore does not include the results of more recent research such as the study of birth defects conducted by the Centers for Disease Control and published in August 1984. Also not included is the mortality study of Australian Vietnam-era veterans published in September 1984. The results of these and other more recent repons will be summarized in a similar synopsis currently being developed by the VA for publication in the near future. It is hoped that these laylanguage summaries will serve as useful supplements for assisting non-technically oriented readers in understanding both the significance and impact of such literature and thereby assist in the ultimate resolution of the many and varied issues related to the phenoxy herbicides and associated dioxins. Agent Orange Projects Office Veterans Administration Washington, D.C. 1985 �CONTENTS Page Preface 1. Introduction 1 2. What is Agent Orange? 1 3. Who was exposed? 2 4. What do we know about the health effects? 2 5. How do we determine the health effects? 3 6. Summary of the studies on health effects: Cancer ; Reproductive effects 6 8 Enzyme effects 10 Effects of the immune system 12 Chloracne 13 Neurobehavioral effects 15 Other toxic effects 16 7. Summary and conclusions 17 �1. Introduction For the past several years the Veterans Administration, in response to the concerns of veterans who served in the war in Vietnam, has been conducting or sponsoring research on the health effects of Agent Orange, the principal herbicide used by U.S. military forces in that country and to which some American military personnel were exposed. In April 1984, under contract to the Veterans Administration, Clement Associates, Inc., a research firm in Arlington, Virginia, completed a two-volume survey of the extant scientific literature on the health effects of Agent Orange. The material that follows is a lay summary of that survey and is published because the Veterans Administration believes that it will be of interest to Vietnam veterans and others who have been following the Agent Orange issue. 2. What is Agent Orange? "Agent Orange" is a name that has come to be used to describe a particular type of chemical herbicide that was used in military operations in Vietnam from 1965 to 1971. The name came from the orange stripe that identified the 55-gallon drums in which the herbicide was shipped and stored. Agent Orange was not a single chemical compound but rather a mixture of chemicals containing equal amounts of the two active ingredients, 2,4-D and 2,4,5-T. These weed-killing chemicals enjoyed extensive commercial and private use in the United States and in many countries around the world from the 1940s well into the 19705.^ 2,4-D is still used extensively in this country and abroad. Like many industrial chemical mixtures, the Agent Orange that was manufactured during the Vietnam era contained small quantities of impurities. These impurities included chemicals used in the production of 2,4-D and 2,4,5-T as well as by-products which developed during the manufacturing process. Some of the impurities were a family of closely related compounds known as polychlorinated dibenzodioxins which, as a group, have often been called "dioxins." One of these dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD, has been extensively tested in experimental animals and is believed to be the most toxic member of the dioxin family. TCDD is one of the contaminating dioxins in 2,4,5-T. In the remainder of this report the term dioxin will be used to refer to any of a number of different polychlorinated dibenzodioxins, usually unidentified. The term TCDD will be used to designate the specific chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Agent Orange was produced by several manufacturers in a number of chemical plants throughout the United States under contract to the Department of Defense, which specified the composition of the herbicide. Therefore the nature and amount of the active ingredients were the same regardless of the manufacturer. Although Defense Department specifications set an upper limit on the total amount of impurities that could be present in a batch of Agent Orange, it is certain that both the exact amount and the nature of these impurities varied from batch to batch, from year to year, and from manufacturer to manufacturer. Furthermore, since very little attention was paid to the importance of the impurities in Agent Orange until 1 �late in the Vietnam experience, there is relatively little information available on the amount of the impurities contained in the herbicide shipped to Vietnam. Agent Orange was somewhat different from commercial formulations of this class of herbicides made and marketed in the United States and in other countries around the world. In addition, we don't really know precisely all the types and amounts of the impurities that were present in Agent Orange, and furthermore we don't have any accurate way to find out. Because there is considerable evidence that the health effects of these herbicide mixtures depend heavily on the amounts and types of impurities such as dioxins which were present in the mixture, we can accept, only with reservations, information on health effects obtained from studies of people exposed to other herbicide preparations containing 2,4-D, 2,4,5-T, or both. If we hope to understand the health effects of Agent Orange with a high degree of certainty, it is essential to identify and study people who were exposed to Agent Orange. 3. Who was exposed? The only individuals who are known to have been exposed to Agent Orange are those who were exposed during its manufacture and distribution or as a result of its use in Vietnam. Because Agent Orange was considered relatively safe at the time of its use, however, there were no systematic studies to determine how much Agent Orange might enter a person's system as a result of exposure in a manufacturing plant, during spraying operations or other applications, or from entering an area that had already been sprayed. Another way of determining exposure is to depend on people's memory of when and how often they might have been exposed. Unfortunately, several different types of chemicals were manufactured in most of the plants that manufactured Agent Orange. In addition, several other herbicide mixtures as well as insecticides and other chemicals were used in Vietnam. It would be very difficult for most individuals to know when they were exposed to Agent Orange specifically and how much exposure they received. The Air Force did keep records of most of the aerial herbicide spraying missions. By combining this information with data from records of the location of military units, the probability of exposure from aircraft spraying can be estimated. Those people who were actually involved in the handling and application of Agent Orange were undoubtedly among the most heavily exposed, but it is not possible to determine accurately the amount to which they were exposed. 4. What do we know about the health effects? As one might guess from the information above, we don't have precise and direct information on the human health effects of Agent Orange itself. Scientists cannot identify people who were definitely exposed to known quantities of Agent Orange in order to compare such a group to people who were not exposed to Agent Orange or similar herbicides. Furthermore, Agent Orange as such was not tested in experimental animals at the time of its manufacture and use. 5. How do we determine the health effects? Since we cannot study the human health effects of Agent Orange directly, we must use other techniques to learn what health effects might result from exposure to this material. Several methods are available and all of them have been used during the last 10 or 15 years. Each has limitations that make it difficult for scientists to reach definitive conclusions about the adverse human health effects of Agent Orange. Nevertheless, if scientists and health professionals review the entire body of information that has become available from all these approaches, certain patterns emerge. It is now possible to begin reaching tentative conclusions about the health effects of Agent Orange. However, these conclusions are still somewhat uncertain. The results of studies which are currently in progress or planned will go a long way toward removing this uncertainty, but, for the general reasons described above and for specific reasons described below, it is quite likely that we may never be completely sure of what the health effects of Agent Orange are. This same uncertainty exists for many environmental health issues and is a result of the normal limitations of science. One of the most promising approaches to studying the health effects of Agent Orange is to evaluate the health of people who may have been exposed to it as a result of the Vietnam experience and to compare their health with that of people who were not exposed to these herbicides. A few such studies have been conducted and several more are in progress. Some of the limitations of these studies have already been mentioned. We don't have reliable records of everyone who was exposed, so assumptions are made such as "any veteran who served in Vietnam was exposed to Agent Orange" (Australian Veterans Health Study) or "any individual who was assigned to Operation Ranch Hand was heavily exposed to Agent Orange" (U.S. Air Force Epidemiology Study). These assumptions may lead to the inclusion in the "exposed" group of people who had very little exposure. If enough of these people are mis-classified as to exposure, scientists will not be able to detect any real health effects that might be present in those who were actually heavily exposed. In other words, the greater the mis-classification rate, the less reliable are conclusions regarding health effects of exposure. Another serious limitation is that it is very difficult to select a group of "unexposed" people who can be closely matched with the people in the "exposed" group. Ideally, the two groups should be the same except for their potential exposure to Agent Orange. This means that individuals in both groups should not only be the same in age, weight, and sex, but they should also have similar smoking habits, diets, jobs, life styles, and places of residence. Another problem inherent in these studies relates to the widespread use in the United States of commercial herbicides that are similar to Agent Orange. In addition, dioxins are known to be present in other industrial chemicals in the environment. It is therefore very possible that some individuals in the "unexposed" group have actually been exposed to the ingredients of Agent Orange at other times and in other places. �small town of Seveso immediately downwind of the plant. In succeeding weeks many persons living in Seveso showed signs of dioxin exposure, the most prominent being chloracne, a form of acne which includes the appearance of blackheads around the eyes and ears and in some cases covers much of the body. Another problem with studies of people who were exposed to Agent Orange is that a relatively short period of time has elapsed since exposure took place. The phenoxy herbicides contained in Agent Orange were first used in Vietnam in 1962. Heavy use and potentially heavy exposure to Agent Orange did not begin until three years later, so the time that has elapsed since most veterans were exposed has been about 15 to 20 years. Certain adverse health effects such as cancer, heart disease, and 'respiratory problems that result from exposure to chemicals may take many years to develop. Increased cancer rates due to smoking or exposure to toxic chemicals have been shown to reach a peak 20 to 30 years after exposure. Thus, a lack of evidence of increased rates of cancer and heart disease in populations exposed to Agent Orange might suggest that exposure to Agent Orange does not increase the risk of developing these diseases. On the other hand, it might be that they haven't had time to appear in sufficient numbers to be detected. No direct measurements were made of the chemicals in the accidental gas cloud itself but it has been possible to estimate the dioxin exposure of people in different areas by three independent methods. The first was a calculation of the distribution of the dioxin based on the nature of the chemical reaction, the quantity of ingredients, and the wind direction and speed at the time of the accident. The second method recorded biomedical changes, such as the death of birds and other wild and domestic animals and the appearance of chloracne in people. These changes were then correlated with the geographic location of each person or animal affected. The third method, performed somewhat later, was the actual analysis of the soil for dioxin. This gave results which were judged to be in agreement with those of the other two methods. In addition, reports by the exposed individuals provided supplementary and confirmatory information. The studies of populations who were probably exposed to Agent Orange as a result of the Vietnam experience have not yet provided clearcut answers to questions about its health effects. This is the result of some of the limitations described above. Furthermore, future studies of this type will not be capable of answering all these questions. It is therefore necessary to ask, "Where else can we look for these answers?" One potentially valuable source of information is the study of human populations with exposure to commercial herbicidal mixtures that were similar, but not identical, to Agent Orange. A number of such studies are available. Most are of workmen who sprayed herbicides on the job, but some are of populations who lived in areas where herbicides containing 2,4-D and 2,4,5-T were used. Most of these studies are subject to the same limitations as those of the people exposed to Agent Orange. In all of these studies, the determination that a person is or is not exposed is based largely on that person's memory of past events or, in many cases, simply on where the person lived or worked. Also, people may be included in the exposed group who worked at a job or lived in an exposed area for only a few weeks. On the other hand, people may be included in the unexposed group if they are currently working in jobs or living in areas where they are not exposed to herbicides but who may have been exposed to herbicides in some previous job or place of residence, perhaps even without knowing it. Either type of error decreases the ability of scientists to detect possible effects of exposure to the chemical. Other potential sources of information about the health effects of Agent Orange are studies of humans who were exposed to some of the components of Agent Orange. There are a number of groups of people throughout the world who were exposed to dioxins as a result of industrial accidents or unintentional release of dioxin into the environment. Several of these groups "have been followed for a number of years and much information has been gathered. It is difficult, however, to judge how relevant these findings are to people exposed to Agent Orange. The specific dioxins to which these people were exposed were not always completely or accurately identified, and they may be somewhat different from those found in Agent Orange. One of the most widely publicized incidents in which humans were exposed to dioxins was the explosion of a chemical reactor at the ICMESA plant near Milan, Italy, in July 1976. A cloud of chemicals containing relatively large quantities of dioxins blanketed a portion of the • In the areas with the most intense exposure, animals and birds died; humans did not. People experienced a variety of symptoms shortly after the explosion including weakness, headache, loss of appetite and weight, insomnia, impotence, nausea and abdominal pain. There was also a burning sensation and an eruption of the skin, but the role of dioxin, as opposed to other more caustic chemicals suspected of being present in the cloud, is unclear. The symptoms cleared up within a brief period but one characteristic skin change, chloracne, persisted. Chloracne was present, especially in children under the age of 14. In the most heavily contaminated areas about 20 per cent of the children developed the skin disorder. The changes gradually cleared over the ensuing months. 1 Early after the exposure there were laboratory results suggesting changes in liver function, but the test results did not differ a great deal from those obtained in an unexposed, control population. Within a year after the exposure careful examinations showed some problems with the nerves controlling muscle function. These changes apparently disappeared within the following two or three years. It is not clear that the exposure to dioxin had any effect on the pregnancy rate, the miscarriage rate or the birth rate since there are no good statistics from nearby communities with which to compare the exposed populations. There is no convincing evidence that the dioxin caused birth defects, interfered with growth, disturbed resistance to disease or increased the death rate. Some details of these results may be questioned because of the difficulties encountered in collecting the data. It is reasonable, however, to say that the Seveso accident did not result in a very serious or life-threatening effect on the health of exposed persons, at least in the near-term. It is too soon to draw final conclusions regarding possible delayed effects. A final potential source of information about the adverse health effects of Agent Orange includes studies using experimental animals. Care must be taken in interpreting the results of animal studies because animals may respond quite differently from humans in the way they absorb chemicals, in the distribution of these chemicals in the body, in the way the chemicals �are broken down or stored in the body, and in the way they are eliminated. Differences in body size, diet, lifespan, and the way individual organs function may also cause animals to respond differently from humans. For these reasons responsible scientists are reluctant to base predictions of human health effects on animal studies unless the chemical has been tested in several species of experimental animals and there is a good basis for believing that the test animals are similar to humans in the way they respond to the chemical. cancer) among his patients. All three of these patients had served in Vietnam but no other information was given about them. Comparisons between groups exposed to the herbicides or to dioxins and unexposed groups have shown no overall increase in cancers. Attention has centered on certain types of cancers. There have been 11 reports of studies of cancer in men who were employed in jobs that involved the spraying of herbicides similar to Agent Orange. Eight of these studies were limited to men who sprayed herbicides containing 2,4-D or 2,4,5-T. The other three studies were of workers exposed to agricultural chemicals in general, including herbicides. These three studies are not discussed here because of the uncertainty regarding exposure. The eight remaining reports are also based on groups of workers whose exposure was of doubtful duration and intensity. Two of the eight studies of 2,4-D or 2,4,5-T indicated that there was an association between exposure and the incidence of soft-tissue sarcoma. A third study showed an association between exposure and lymphoma, and one study showed an association between exposure and stomach cancer. Another of these eight reports described five cases of lymphoma with cutaneous (skin) lesions seen in an English hospital. Four of the five patients worked with 2,4-D or 2,4,5-T. A case-control study reported an association between herbicide exposure and cancer of the nose and throat. The remaining three reports showed no association between exposure and any form of cancer, although one suggested a slight association with softtissue sarcoma. For reasons noted earlier, Agent Orange when it was first used was not tested in experimental animals and, because the amount and identity of the impurities in Agent Orange varied,, it cannot be exactly reproduced for studies in experimental animals now or in the future. It is therefore necessary to rely on the results of experimental studies of herbicide mixtures similar to Agent Orange as well as studies of individual components of Agent Orange such as 2,4-D, 2,4,S-T and TCDD to serve as a basis for predicting the human health effects of Agent Orange. The remainder of this report on the health effects of Agent Orange summarizes the information available as of early 1984 from all the types of studies described above. The section that follows provides a discussion of each of the suspected or potential health effects and in each case the available evidence is evaluated as a whole. For more detailed information regarding specific studies the reader is urged to refer -to the Review of Literature on Herbicides, Including Phenoxy Herbicides and Associated Dioxins, Volumes I, II, III and IV, published by the Veterans Administration. 6. Summary of the studies on health effects Cancer To date only one systematic study of cancer in military personnel exposed to Agent Orange in Vietnam has been published. In this study of Air Force personnel who were engaged in Operation Ranch Hand (the herbicide spraying operation in Vietnam), there was no increased occurrence of serious or life-threatening forms of cancer, but a greater incidence of a type of skin cancer was found in the exposed group compared to a control group of military personnel who were not exposed to Agent Orange. This type of skin cancer is a very common, localized form that is known to be associated with exposure to sunlight. Further studies need to be done to determine whether Ranch Hand personnel were more likely to have been exposed to sunlight than were the members of the comparison group. There was also a slightly increased incidence of cancer of the mouth and throat in the Ranch Hand group, but this excess is so small that it may be due to chance. Two other reports are available on cancer in Vietnam veterans but in neither report was there any confirmation of exposure nor were matched control groups used. In one survey, based on Vietnam veterans who registered with the VA's Agent Orange Registry, a somewhat higher proportion of mouth and throat cancer and of lymphoma (cancer of the lymphatic system) was found compared to the same proportion of cancers among U.S. males aged 25 to 39. In the other report, a physician in Atlanta reported three cases of soft-tissue sarcoma (a rare : Of seven studies on populations exposed to dioxins either in the workplace or in -the environment, two showed an increased incidence of cancers. A study of workers exposed to dioxin as a result of a reactor explosion in a 2,4,5-T manufacturing plant in Germany in 1953 showed an excess of stomach cancer. Another study of the residents of Midland County, Michigan, where Dow Chemical Company has a large plant, revealed an increased incidence of soft-tissue sarcoma in women between 1960 and 1980. This finding is unlikely to be related to dioxin exposure, however, because the excess cancer was seen only in women and several of the people with soft-tissue sarcoma had lived in Midland County only a short time before the diagnosis of cancer and had little or no connection with the company. Three separate reports describe two cases of lymphoma and three cases of soft-tissue sarcoma in workers who may have been exposed to dioxin. These are isolated case reports, and they contained little evidence of dioxin exposure. Two studies of workers occupationally exposed to dioxin revealed no excess incidence of any form of cancer. None of the studies of cancer in humans exposed to Agent Orange, related herbicides, or dioxins provides an answer to the question of whether Agent Orange might cause cancer in humans. When all the reports are taken together, however, certain patterns appear that provide suggestive evidence that exposure to dioxin-contaminated herbicides may be associated with an increased incidence of cancer. Thus, seven reports suggest a relationship between such exposure and soft-tissue sarcoma. Four reports point to a possible connection with lymphoma. Two studies show an association with stomach cancer and three reports suggest a possible association with cancer of the mouth, nose, or throat. �The results of animal studies lend support to the hypothesis that dioxins and dioxincontaminated herbicides may cause cancer in humans. Six studies of the potential for TCDD to cause cancer in animals were positive when relatively large doses were given. TCDD painted on the skin of mice caused cancers related to soft-tissue sarcomas. Four studies in which rats were given TCDD by mouth showed that the rats developed cancer of the liver, mouth and nose, tongue, adrenals, and thyroid. In two studies in which TCDD was given to mice by mouth, liver and thyroid cancers resulted. Several studies suggest that when TCDD is given to mice with other cancer-causing chemicals, it increases the response to those cancercausing chemicals. As yet there have been no published studies which show that Agent Orange or simitar commercial herbicides have a demonstrated potential for causing cancer in laboratory animals. A few studies designed to measure the effect of 2,4-D and 2,4,5-T on rats and mice have been negative for cancer, but these studies were not adequate to detect a small increase in cancer in the treated animals. The current evidence, though far from conclusive, justifies continued surveillance of people who have been exposed to dioxin and dioxin-contaminated herbicides in order to confirm or deny an increased incidence of cancer which can be attributed to that exposure. Two studies have been reported of men who were exposed to herbicides similar to Agent Orange. A study of wives and children of herbicide sprayers in New Zealand showed no increases in birth defects, stillbirths, or miscarriages when compared to the population of New Zealand as a whole. There was a very small increase in the incidence of heart defects, but this may have been due to chance. Another study of children born to the wives of men who sprayed herbicides for the Long Island Railroad showed no increase in major birth defects but two relatively minor birth defects—minimally deformed feet and tear duct obstruction—were seen in excess. Several studies have been conducted to ascertain whether there are increased incidences of spontaneous abortions, stillbirths, or birth defects in areas where herbicides similar to Agent Orange have been heavily used. In these situations there is the potential for exposure of both parents as opposed to exposure of only the father as in the four studies discussed above. One of these general population studies gained a great deal of publicity in the late 1970s when it was asserted that women living in the vicinity of Alsea, Oregon, experienced a higher rate of miscarriage than did women living in other parts of Oregon where herbicides were not commonly used. Careful review of this study by expert scientists has resulted in a consensus that the results were misinterpreted and that the study did not show the claimed effect. Reproductive effects The various possible causes of reproductive abnormalities are difficult to determine because there are fairly high rates of birth defects, stillbirths, miscarriages, and sterility in all populations. For example, between three and six percent of all children are born with some kind of defect. The percentage varies depending upon how serious a disturbance has to be before it is recorded as a defect. In addition, some defects are not noted at birth, but show up later in childhood or beyond. Two systematic studies of reproductive performance and outcome among men who may have been exposed to Agent Orange in Vietnam have been published. In the first of these the Australian government sponsored a study to see whether birth defects were related to the father's service in Vietnam. No association was found, although there was a slightly increased risk of heart defects and Down syndrome among the children of Vietnam veterans. In the study of Operation Ranch Hand personnel discussed in the cancer section above, a small increased incidence of miscarriages following Vietnam service was found among the wives of the Ranch Hand group when compared to wives of the control group. The same difference, however, was observed for pregnancies occurring prior to Vietnam service. There were also slight increases in deaths of newborn babies and minor birth defects. There may have been slight increases in learning disabilities and physical handicaps among children of Ranch Hand personnel. The significance of these findings is not clear because most of the increases are very small, and many of these differences disappear if the data are analyzed differently. In addition, these differences were based on self-reporting and at the time of the initial report had not been confirmed by a review of medical records. More recently, a study of people living in an area of New Zealand where herbicides containing 2,4,5-T were often used revealed an increase in the occurrence of clubfoot in children in the area. Other small and perhaps insignificant increases were found in heart defects and malformations of the penis. A study conducted in Hungary looked at the rate of five major birth defects in that country's general population over a five-year period in which the use of 2,4,5-T increased greatly. No changes in the rates of these birth defects were found. Four studies have been conducted of men exposed to dioxin as a result of working in plants where 2,4,5-T was manufactured. None of these studies' showed a clearcut effect on reproductive outcomes. Two of them did show a slight increase in spontaneous abortions in the wives of the workers. Two studies of the population exposed to dioxin as a result of the ICMESA accident at Seveso suggest that there may have been an increase in birth defects (particularly of the heart) and an increased incidence of spontaneous abortions in the year following the accident, but their validity is questionable because the reporting of birth defects and abortions was generally unreliable. The studies of the reproductive effects of 2,4-D, 2,4,5-T, and TCDD in experimental animals are of limited usefulness in helping to predict the reproductive effects of Agent Orange in male Vietnam veterans. In almost all of the animal studies, the herbicide or dioxin was given to pregnant females rather than to male animals. In the one study in which the mixture found in Agent Orange was fed to male mice, it had no effect on reproductive performance or on the offspring. In two studies, relatively uncontaminated 2,4,5-T and TCDD were fed to both male and female rats and reproductive performance and outcome were recorded for three successive generations. These studies showed that both 2,4,5-T and TCDD decreased the number of live births and the weight of newborn animals, as well as causing an increase in birth defects of the kidneys. Numerous studies in which TCDD was given to pregnant females in relatively large �doses indicate that it can cause defects in the developing fetus. TCDD causes birth defects in pregnant rats, mice, rabbits, and monkeys when given by mouth or injection. It also causes an increase in the number of spontaneous abortions and a decrease in birth weight of newborn animals. In summary, no study of reproduction in humans exposed to Agent Orange conclusively shows an adverse effect which has been caused by the herbicide. Scientists believe, however, that people with known exposure to TCDD-contaminated chemicals should be observed for possible adverse reproductive effects. Enzyme effects One of the best studied effects of dioxins in experimental animals is the ability of these compounds, especially TCDD, to alter the activity of certain enzymes. Enzymes are proteins that serve as catalysts in the formation or breakdown of various chemicals in the body. In some cases many enzymes are involved in the alteration of just one chemical, whereas other enzymes are capable of acting upon an entire class of chemicals. It is very difficult to study the effects of chemicals on enzyme activities in humans. Most enzymes are located in tissues where metabolic activity is greatest, such as the liver, lungs, intestines, brain, and reproductive organs, and these tissues are the least accessible to study. Furthermore, there are large differences among people in their baseline metabolic activity. About the only approach available is to look at the levels of chemicals produced by enzyme reactions that appear in the blood or urine and determine whether they are different in people exposed to a specific compound when compared to people who are nor exposed to that compound. Only a few studies of enzyme activities have been conducted in animals which have been fed or otherwise dosed with 2,4-D and 2,4,5-T. These studies suggest that these compounds do not cause major alterations in enzyme activities, and some of the small effects seen may be the result of contamination of these chemicals with small amounts of dioxin. A number of studies of TCDD, on the other hand, have shown that it alters the activity of some enzymes in experimental animals. The best studied effect as an increase in the activity of an enzyme known as aryl hydrocarbon hydroxylase (AHH). AHH is important because it makes certain chemicals more soluble in water and, thus, more likely to be excreted in the urine. Very small amounts of TCDD cause large increases in the activity of this enzyme in rabbits, mice, rats, guinea pigs, hamsters, birds, fish, and monkeys. In several studies in which living cells were taken from humans and allowed to grow in a culture medium, the addition of TCDD to the culture caused an increase in AHH activity in the cells. It is interesting that in two studies of human populations exposed to dioxin as a result of industrial accidents (one at Seveso and the other at a 2,4,5-T manufacturing plant in England), scientists found elevated levels of d-glutaric acid in the urine of exposed people. This chemical 10 is believed to be formed by enzymes that are very closely associated with AHH. This finding adds support to the theory that TCDD may stimulate AHH activity in humans. What are the health implications of stimulation of AHH activity? This is a difficult question to answer because the role of AHH is not yet fully understood. Evidence from animal experiments and some human evidence indicate that some of the aryl hydrocarbons that are altered by AHH are cancer-causing. Some experiments in which TCDD was given to animals several days before they were exposed to cancer-causing aryl hydrocarbons showed that it protected the animals against cancer. Thus, TCDD caused an overall health benefit. Unfortunately, the picture is much more complicated than that because, if TCDD is given to animals at the same time as the aryl hydrocarbon rather than a few days earlier, the TCDD binds to the site of the AHH enzyme that is responsible for changing the aryl hydrocarbon and prevents the AHH enzyme from doing its job. Thus, administration of TCDD with aryl hydrocarbon causes more cancer than does the aryl hydrocarbon itself. An additional complication is that there is evidence that AHH catalyzes other tranformations and that some of them may convert inactive chemicals into toxic ones. In the absence of complete information, the fact that TCDD stimulates AHH activity must be viewed as a potentially adverse effect. Animal studies have also shown that TCDD alters some enzymes that are involved in the manufacture of heme, the portion of the hemoglobin molecule that binds oxygen in red blood cells. Animal studies indicate that TCDD decreases the activity of an enzyme known as uroporphyrinogen decarboxylase in the liver. This results in a decrease in the amount of heme synthesis and a build-up of the chemicals known as porphyrins from which heme is formed. As the porphyrin level builds up, more porphyrins are excreted in the urine. A number of animal experiments have shown that the pattern and amount of porphyrins excreted in the urine changes after treatment with TCDD. Two studies of workmen exposed to dioxin have shown increased urinary excretion of porphyrins. The Air Force study of personnel involved in Operation Ranch Hand has also shown that there are more men with abnormally high porphyrin levels in the exposed group than in the comparison group, although this finding correlates more strongly with alcohol use than it does with potential exposure to Agent Orange. Interference with porphyrin metabolism may result in a condition known as porphyria cutanea tarda (PCT) in which the skin blisters and later becomes dry and brittle, particularly on exposure to sunlight. Workers who were exposed to dioxins as a result of two industrial situations developed this condition but in both instances the men were also exposed to another chemical known to cause PCT. The available medical evidence indicates that there are no lasting adverse human health effects that result from alterations in porphyrin metabolism due to exposure to TCDD. The body adjusts by producing sufficient heme to meet the oxygen-carrying needs of the body. PCT is a relatively rare manifestation of changed heme metabolism and may be caused by 11 �other external factors, such as alcohol consumption. There is also a known genetic factor which influences the development of PCT. PCT resulting from exposure to such chemicals as dioxins and similar compounds is reversible and disappears after exposure. Another enzyme activity for which there is indirect evidence of interference by dioxins is related to the conversion and storage of fats. Studies of workmen exposed to dioxins showed increased blood levels of fat molecules known as triglycerides. Although elevated levels of some triglycerides are known to be associated with heart disease, to date there is no conclusive evidence of an association between heart disease and dioxin exposure. Although it appears that dioxins have the ability to alter the functions of a number of enzymes, at present none of these alterations has been shown to be associated with any serious or irreversible adverse health effects in humans. However, any influence that substantially alters the way the body handles internal and external chemicals must be viewed with concern. It should be remembered that as in the case of most of the effects of these chemicals, the active herbicide ingredients 2,4-D and 2,4,5-T by themselves are not known to affect the enzyme system in humans. Effects on the immune system Unlike such well-studied and relatively well-understood systems of the body as the cardiovascular and digestive systems, there is still much of the "immune system" which is not well understood. It is currently the subject of intensive research to better understand its chemistry, mechanisms, and functions. The immune system is involved in a large and complex array of processes that defend the body against foreign chemicals, disease-causing bacteria, viruses, foreign cells from outside the body, and abnormal cells from within the body. Virtually all of the body's organs and tissues participate in these processes to a greater or lesser extent. Because of the lack of basic knowledge in some areas, it is difficult to assess the impact of chemicals on the immune system. One problem is that the system functions in many different ways. A chemical to which the body is exposed may activate only one or two of dozens of known defense mechanisms. Therefore, it may be necessary to run a large number of different tests to detect these changes. Since many of these tests are very complex and some require the examination of body tissues, it is especially difficult to study altered immune function in humans. Two additional factors make it difficult to detect such changes in humans. First, there are tremendous differences among people in the manner in which their immune systems operate. For example, there is a wide variation in the way different people manifest an allergic reaction, which is one of the ways the immune system functions. Second, many activities of the immune system have no obvious or external manifestations. It is usually not possible to assess a person's immune function by a simple physical examination. These changes in immune function may only be reflected by subtle variations in indirect indicators, such as increased susceptibility to infections or increased sensitivity to materials that cause allergic reactions. One result of these problems is that the effect(s) of chemicals on the immune system of humans may 12 be very subtle and difficult to detect. Highly specialized and complex tests are often needed to detect these changes. There is no evidence that 2,4-D or 2,4,5-T by themselves alter the immune function of animals. There have been no studies of humans exposed to Agent Orange or similar herbicides that show an adverse effect on the immune system, and there have been no reports of increased allergies or of increased susceptibility to infection, either of which might indicate altered immunity. On the other hand, there have been no studies reported that were designed specifically . to look for such an effect in humans soon after exposure. There is considerable evidence, on the other hand, that TCDD interferes with the functioning of the immune system in experimental animals. When TCDD is given to animals, a common effect is a decrease in the size of the thymus, an organ that is involved in the immune system. This effect occurs at doses lower than those that cause changes in other organs. At even lower doses, TCDD interferes with the ability of the animal to produce certain types of white blood cells in response to the presence of foreign materials in the blood stream. In some studies, this effect is paralleled by decreased resistance to bacterial and viral infections. It appears that TCDD has the ability to suppress the immune system in unborn animals when the TCDD is given to pregnant females. Sensitivity decreases in newborns but significant effects can still be seen in adult animals treated with TCDD. In fact, immune suppression is the most sensitive indicator of TCDD exposure in mice, occurring at doses below those that cause changes in enzyme activity. Furthermore, although immune function improves after exposure ends, it remains relatively depressed for a very long time in experimental animals. Most studies of humans who have been exposed to dioxins have not included tests of immune function. There has been a study of children who lived in the heavily contaminated area of Seveso, Italy. The results of this study showed that these children had higher levels of certain immunologically active blood components than did children from uncontaminated areas. The body also produced more white blood cells in response to certain foreign materials. These results suggest that exposure to dioxins stimulated immune function in these children rather than depressing it, as seen in the animal experiments. This finding is not inconsistent, however, with experimental findings that some chemicals which depress immune function at high doses may actually stimulate immune functions at low doses. Another study of workers exposed to dioxin as the result of an industrial accident has been reported to have shown decreased immune function in the exposed workers 10 years after the accident, but this study has not been published and cannot be independently reviewed. These results, taken together, fall far short of providing convincing evidence that dioxin exposure can cause altered immune function in humans. Nevertheless, the evidence of such effects in experimental animals provides some basis for concern that exposure to dioxin may adversely affect immune function in humans. Chloracne Chloracne is a skin condition that is known to result from exposure to a group of structurally similar compounds in which chlorine atoms are bound to an aromatic hydrocarbon. One of 13 �exposed than workers who did develop chloracne. Thus, whereas chloracne may be a sensitive indicator of exposure to dioxins in some people, it may not be in others. Therefore, the absence of chloracne is not necessarily a reliable basis for concluding that a person has not been exposed to a chemical which is known to cause chloracne. these compounds is TCDD. As its name suggests, chloracne, is similar in appearance to the common forms of acne that affect teenagers and usually appears within a few weeks after exposure to the chemical that causes it. Neurobehavioral effects The first sign of chloracne may be excessive oiliness of the skin. This is accompanied or followed by the appearance of numerous blackheads. In mild cases the blackheads may be confined to the area around the eyes extending along the temples to the ears. In more severe cases blackheads may appear in many places on the body. The blackheads are usually accompanied by fluid-filled cysts and by an increased or darker growth of body hair. The skin may become thicker and flake or peel. In severe cases, the acne may result in opens sores and permanent scars. The condition fades slowly after exposure. Minor cases may disappear altogether, but more severe cases may persist for years after the exposure. It has been known for some time that exposure to relatively large amounts of 2,4-D, such as might occur when it is being mixed or sprayed, can cause adverse effects on the nervous system. Workmen who splashed 2,4-D on their skin or who stood for a long time in 2,4-D spray mist developed a variety of symptoms including tingling or decreased feeling in the hands and feet and tightening of muscles in the arms and legs. Examination of these workmen showed the loss of the knee-jerk reflex and an increase in the time for nerve impulses to travel from the hands or feet to the spinal cord and back. Studies in experimental animals give results similar to those seen in humans. These studies suggest that 2,4-D interferes with the transmission of nerve impulses to muscles. If the exposure is minimal the nervous system recovers. However, sustained exposure of experimental animals to relatively large quantities of 2,4-D may cause long-lasting changes in the brain and spinal cord itself. It is well known that chloracne can result from exposure to dioxins. In seven reported situa' tions where workers were exposed to dioxins as a result of industrial accidents or poor housekeeping practices, many of the workers and, in a few cases, members of their families developed chloracne. Chloracne was also diagnosed in 187 people, mostly children, Jiving in the section of Seveso that was most heavily contaminated with TCDD as a result of the ICMESA accident in 1976. Two laboratory workers who were exposed during the synthesis of TCDD developed serious cases of chloracne. There are no authoritative reports in the literature that document an association between exposure to Agent Orange or similar herbicides and chloracne. The Air Force study of Ranch Hand personnel showed no excess of acne in those individuals when compared to unexposed controls and no cases of chloracne were found. Most of the epidemiologic studies of occupational groups involved in the spraying of Herbicides like Agent Orange do not report the presence of chloracne among the workers who were studied. A research effort looking for cancer among herbicide sprayers in Finland turned up a few cases of possible chloracne, one of which was diagnosed by a dermatologist. It would appear, therefore, that chloracne is not a sensitive indicator of exposure to herbicides like Agent Orange. Animal studies are of little use in measuring the potential of Agent Orange for causing chloracne in humans. The ingredients 2,4-D and 2,4,5-T have not been extensively tested, but it appears that they do not cause chloracne or similar skin conditions in experimental animals. Different kinds of animals react differently to TCDD, but it causes skin conditions very similar to chloracne when applied to the ears of rabbits and to the skin of certain kinds of mice. Scientists disagree, however, as to whether these skin effects are identical to human chloracne. Some types of experimental animals fail to show any acne-like condition when treated with TCDD. It seems that only monkeys exposed to TCDD develop a skin condition that appears identical to human chloracne. One conclusion that is gaining support on the basis of both animal and human studies is that susceptibility to chloracne may be genetically controlled. Two individuals equally exposed to TCDD may respond differently because of variations in inherited susceptibility. This would explain why some of the workers exposed to dioxins in each of the seven industrial incidents did not develop chloracne, even though there is no reason to believe that they were less 14 A few studies of humans and experimental animals exposed to 2,4,5-T have failed to show any nervous system effects such as those caused by 2,4-D. There is some evidence, however, that humans exposed to dioxins as a result of industrial exposures or accidents may suffer impaired nervous system function. A wide range of signs and symptoms have been reported in these people including pain in the arms and legs, numbness in the hands and feet, muscular weakness particularly in the legs, headache, loss of memory and concentration, sleep disturbances, nervousness, and emotional and behavioral abnormalities. The speed of nerve impulses was slowed in two groups of workers who were probably exposed to dioxins. J There have been very few studies of the effects of TCDD or other dioxins on the nervous system in animals. It is not clear why this knowledge gap exists, but one possible explanation is that the doses of TCDD needed to cause detectable signs of nervous system damage in experimental animals are higher than those that cause other serious toxic effects. Scientists have therefore tended to concentrate on the other effects. Whether nervous system and psychologic effects have occurred in individuals exposed to Agent Orange as a result of the Vietnam experience is unclear and controversial. It has been suggested that Vietnam veterans experience a high rate of psychologic problems, with certain symptoms appearing quite frequently. These symptoms include nervousness, disturbed sleep, irritability and short temper, depression, and suicidal thoughts. Many psychiatrists consider that some of these comprise a distinct collection of symptoms or a syndrome known as posttraumatic stress disorder and that this syndrome is unrelated to any chemical exposure. Evidence in support of this conclusion is that individuals such as prisoners of war and hostages who have undergone sustained stress display similar symptoms. Unfortunately, there are almost no systematic studies of nervous system function or psychological problems among individuals exposed to Agent Orange. The recent Air Force 15 �study of Ranch Hand personnel showed no difference between the exposed group and unexposed controls in several measurements of nervous system function including the speed of nerve impulse transmissions. On the other hand, when Ranch Hand personnel were evaluated by analyzing answers to questions on some of the tests designed to detect emotional disorders or personality disturbances, psychiatrists concluded that they were different from the comparison group and showed tendencies toward traits defined as "hypochondria, depression, hysteria, and schizophrenia." Ranch Hand personnel were also said to feel more isolated and to have a higher degree of nervousness and anxiety, to be more easily startled, and to experience more psychosomatic illness than did the comparison group. These differences were minor and are difficult to interpret. The methods used in this study would not show whether the differences between groups were due to post-traumatic stress, Agent Orange exposure, or both. Animal studies have suggested another aspect of the toxicity of TCDD which may have implications for human health. It has become increasingly clear that some animals are relatively resistant to some of the toxic effects of TCDD compared to others. Recent research has shown that this difference in susceptibility is genetically influenced and that mice with just one parent in common can show large differences in susceptibility to the toxic effects of TCDD. The effects for which susceptibility appears to be genetically controlled include the appearance of birth defects in the offspring of female mice exposed to TCDD, the increased activity of several enzymes including AHH and uroporphyrinogen decarboxylase, depression of immune function, chloracne, and the lethal effects of TCDD. This suggests the possibility that humans as a group who are known to be genetically very diverse, may have a wide variation in susceptibility. 7. Summary and Conclusions The fact that self-perception of psychologic problems is an important component of such an analysis was shown in a study of 100 veterans who were asked about their exposure to Agent Orange and their current mental and emotional well-being. Their potential exposure to Agent Orange was independently assessed by comparing their service records with records of the time and location of herbicide spraying missions in Vietnam. The frequency and seriousness of psychologic and emotional problems correlated very closely with how much herbicide the veterans believed they were exposed to, whereas the correlation was much weaker when the comparison was based on how much herbicide exposure the records showed. What can we say about the health effects of Agent Orange? From the evidence now available we can arrive at almost no definitive conclusions. The limited evidence available suggests that 2,4-D and 2,4,5-T by themselves are not highly toxic to humans. 2,4-D appears to be capable of causing nervous system toxicity but only in situations where there is very highlevel exposure. 2,4,5-T may contribute to birth defects when pregnant females are exposed. There is no evidence that purified 2,4-D or 2,4,5-T cause cancer, change the activity of enzymes, affect the immune system, or cause chloracne or porphyrja cutanea tarda in humans. The issue of the effects of Agent Orange on nervous system and psychologic performance is probably the most difficult health issue to resolve. There is a great deal of human and animal evidence that both 2,4-D and TCDD can adversely affect the nervous system. All of this evidence suggests that these effects are the result of short-term high level exposure rather than sustained exposure to lesser amounts. Other toxic effects Studies of people exposed to Agent Orange or similar herbicide mixtures have failed to reveal any significant toxic effects other than those discussed above. Other effects have been attributed to TCDD, however. As was mentioned briefly in the section on enzyme effects, there is suggestive evidence of a higher incidence of heart attacks among workmen exposed to dioxins in industrial accidents. This evidence is far from conclusive, but it is sufficient justification for continuing to observe the health of people exposed to dioxin, especially since it may take many years after exposure for adverse effects on the heart to show up. The most dramatic sign of fatal dioxin poisoning in experimental animals is an apparent loss of appetite which leads to general body wasting. The animals eventually die of a condition very similar to starvation. This effect is observed following a large single dose of TCDD. No similar effect has been described in humans, so it may be of little relevance to human health. The mechanism by which TCDD causes this apparent loss of appetite is unknown and is the object of much current research. Some results suggest that TCDD may interfere with an appetite regulating system in the brain or thyroid. 16 ' There is very little direct evidence that Agent Orange causes adverse health effects in humans, but this may be the result of our limited ability or inability to identify different groups of people or large numbers of people with well-defined exposure and exposure to a known amount of the substances of concern. If adverse human health effects are found as a" result of present or future research efforts, it is highly likely that these will be the result of the effects of toxic impurities such as dioxins, especially TCDD. The limited evidence of TCDD toxicity in humans comes from studies of humans exposed to dioxins, and indirectly from studies of dioxin toxicity in experimental animals. These studies provide some support for the possibility, but do not prove, that exposure to dioxin-contaminated herbicides may cause adverse health effects in humans. These adverse effects may include chloracne, cancer at several different sites, spontaneous abortion and birth defects in the offspring of exposed females, altered enzyme activity, altered porphynn metabolism, and altered immune function. Effects for which the available evidence is very inconclusive but which should be the subject of further study are neurobehavioral effects, including psychologic effects and heart disease. Chloracne does not seem to be of significant importance since it has not been commonly observed even among individuals heavily exposed to herbicides. Therefore chloracne does not appear to be a sensitive indicator of exposure to dioxin-contaminated herbicides. What will future studies tell us about the health effects of exposure to Agent Orange? Studies that are planned or in progress have the potential to reduce much of the uncertainty about the health effects of exposure to Agent Orange. However, because of very serious problems in determining the exact amount and nature of exposure and in choosing appropriate 17 �exposed and unexposed groups to examine, these studies will never be able to demonstrate conclusively the absence of a toxic effect. The areas in which future studies may be able to : provide the most information are the delayed effects such as cancer. 'Studies in experimental animals can still be helpful in suggesting possible adverse health effects of Agent Orange. Particularly helpful would be studies of the purified components of Agent Orange separately and in known combinations. Other important areas of investigation include effects on immune function and the genetic control of susceptibility to the toxic effects of dioxin. In the meantime, exposed individuals can get some degree of reassurance from the fact that despite their inadequacies, the studies which have been completed to date have revealed no widespread or major adverse health effects among the people who were exposed. There is no evidence that the psychologic disturbances seen in Vietnam veterans are the result of exposure to Agent Orange. For many-of the potential health effects, there is little probability that they will first appear years after exposure. These include reproductive and enzyme effects, chloracne, and neurobehavioral problems. It is possible that cancer may first appear years after exposure. Persons exposed to Agent Orange should take no exceptional precautions beyond those that are prudent for everyone, i.e., consume a balanced diet, exercise regularly, have regular medical checkups, be alert for tell-tale signs of cancer, abstain from smoking, and use alcohol moderately, if at ail. 18 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5740 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Compilation of Information on the Federal Government and Agent Orange ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/d153b2c16ef0727d91ea68e9098e0c39.pdf 3e3215c3c49fbb59e9002624ab286f68 PDF Text Text Item D Number °5739 G Hot Scanned Author Corporate Author ROPOrt/ArtlOlfl Tlth Response to the AOWG Science Panel Review of the NIOSH Draft Protocol for a Mortality Study of Workers Exposed to Dioxin Journal/Book Title Yoar 000 ° Month/Day Color TJ Number of toiaQes o Descrtoton Notes Tuesday, March 26, 2002 Page 5739 of 5743 �RESPONSE TO THE AOWG SCIENCE PANEL REVIEW OF THE NIOSH DRAFT PROTOCOL FOR A MORTALITY STUDY OF WORKERS EXPOSED TO DIOXIN We are grateful to the members of the Science Panel for their careful review of our protocol and for their constructive and supportive comments. We respond here to the comments received. A. Points Raised in the Summary Statement of the Science Panel. 1. The reviewers endorse the value and utilization of our exposure index, •recommending that it be carefully constructed, that it quantify exposure if possible, and that it be used to create categories which will allow us to evaluate a dose-response relationship. We agree with the Panel's assessment of the value of the exposure index. We are working hard to make it quantifiable and to ensure its accuracy,. It is our intention to use it to assess a dose-response relationship. We are scheduled to finalize the structure and use of the exposure matrix with our NIOSU Special Peer Review Panel by March, 1985. 2. The reviewers recommend that we should not separately analyze the chloracne workers as a single highly exposed group. They believe this may be misleading since compounds other than dioxin are chloracnegens and because individuals vary in their susceptibility to chloracne. Additionally, the Panel recommends that we reserve the comparison of �chloracne among different subgroups of workers as confirmation for an exposure matrix which is based on other data. We have not yet finalized a method for utilization of the person known to have chloracne. We are scheduled to develop this section of the protocol and present it to our NIOSH peer review panel by March, 1985. We plan to analyze the chloracne subcohort as a group with highly probable exposure. We have collected information at each company about the presence of other potential chloracnegens. Since the known chloracnegens are very few, we believe we can exclude from the chloracne group those persons with potential confounding exposures. Following the suggestion of the Science Panel and also of several NIOSH peer reviewers, we will use the chloracne group as confirmation for the exposure index rather than as a component in its construction. 3. The reviewers supported our concern that soft tissue sarcomas cannot be identified accurately from death certificates, and noted the absen/e of population rates based on pathologically reviewed specimens. The Panel suggested that the creation of a reference population is a formidable undertaking and recommended that a feasible approach at this time may be to use a minimally exposed subgroup of the Registry as an internal standard. The Panel points out that even this approach will require a considerable review of pathological specimens and clinical records, and will have low power for rare tumors unless there is a very steep dose-response gradient. �We appreciate the recommendation. We believe that there will be too few deaths in this study to use the low exposure group to generate comparison rates for soft tissue sarcoma. We have not yet completed our efforts to ascertain whether we can identify any useful ' population-based data or whether we can conduct a useful pathology review to generate stable comparison rates. Our current priority is to complete the analysis of the study as it was designed, using the NIOSH Life Table Analysis System, which is based on death certificate data. We will then complete a more appropriate and thorough analysis of the soft tissue sarcoma outcome. A protocol for this effort will be prepared for review by the NIOSH B. Special Peer Review Panel. Individual Reviewer Comments. The Science Panel members brought their written comments to the meeting of May 29, and most of their questions and suggestions were addressed during ' oiirCjengthy, discussion at that time. One remaining question is considered here. What is the schedule for completion of open-ended items in the protocol and for meeting with the NIOSH Special Peer Review Panel? We are currently working on the two major items not yet detailed in the protocol: development of the exposure matrix and determination of a methodology for use of the "chloracne subcohort". Our NIOSH peer reviewers are working with us on an "as needed" basis. We will revise the �1982 draft protocol using the comments we have received from our NIOSH reviewers and the Science Panel, and we will hold a meeting in March, 1985 with our NIOSH Special Peer Review Panel to finalize the protocol. At this meeting the Panel also will review our analytic methods, because the group has been charged also with a continuing review of our data collection, analysis of data, and generation of draft and final reports. The reviews will be accomplished in scheduled meetings and on an "as )' needed" basis. �Executive Summary: Response to the AOWG Science Panel Review of Protocols for NIOSH Dioxin Morbidity and Reproductive Studies 1. CHOICE OF PLANTS FOR STUDY Plants in Missouri and New Jersey plants were chosen for study for several reasons, including requests from the States for assistance in evaluating those workers. The New Jersey cohort can readily be justified on scientific grounds because of the high proportion of workers with documented chloracne (about 20%) and therefore evidence of exposure. Because a pilot study will be required, we suggest that a reasonable approach will be to use the Missouri plant as a pilot effort, with the New Jersey cohort serving as the major study plant. 2. REFERENT GROUP Neighborhood referents will be chosen only for exposed workers still living in-state (or in the surrounding geographic area), although all exposed workers will be invited to participate in the study. In-state workers appear to be similar to those who moved out of state with respect to date of birth, date of hire, and duration of employment. Logistical obstacles to obtaining an industrial referent group outside the Registry remain daunting. 3. POWER The power of the morbidity study using in-state/contiguous geographic area workers from New Jersey appears to be adequate to detect statistically significant excesses of several major outcomes of interest detected in the recent studies of the Nitro, W.Va. cohort, including ulcer disease, abnormal pulmonary function, neuropathy on physical exam, and decreased libido (providing background prevalences and prevalence rate ratios are roughly similar to those in the Nitro, W.Va. workers). It will not be adequate to detect subgroup excesses of outcomes such as coronary heart disease or impotence. Power calculations show that two additional larger plants would have to be studied in order to detect excesses of these outcomes. 4. STAFF AND FUNDING Even if funding is forthcoming to study the Missouri and New Jersey .workers, NIOSH does not currently have adequate staff positions to carry out the work. Any directive to proceed with this or an expanded study should be made with the recognition that a larger staff will be necessary if we are to proceed. 5. REPRODUCTIVE STUDY The study of New Jersey workers will probably be adequate to permit �detection of a 2.5rfold increase in spontaneous abortions. However, the study size is totally inadequate to study either all major birth defects or neural tube defects. The question of whether the Registry population is an appropriate group for a birth defects study is a separate matter from that presented here. If a reproductive study of the entire Registry is desired, its feasibility and power to detect the desired outcomes should be evaluated at a later time. Design, efficiency, and cost considerations suggest that such a Registry-wide study be done as a separate and independent piece of research. �RESPONSE TO THE AOWG SCIENCE PANEL REVIEW OF THE NIOSH PROTOCOL FOR A STUDY OF PERSISTENT HEALTH EFFECTS IN CHEMICAL-HERBICIDE WORKERS AND IN COMMUNITY RESIDENTS OF UNKOWN EXPOSURE STATUS AND PROTOCOL FOR A STUDY OF ADVERSE REPRODUCTIVE OUTCOMES IN THE SAME STUDY POPULATION This response to the AOWG Science Panel's review of our protocols for the Medical/Morbidity and Reproductive studies first addresses the major points raised in the Science Panel summary "Discussion" and then selected points raised by the individual reviewers. Points raised in the "Discussion"; 1) Choice of plants for study We recognize the concern of the Science Panel over whether Missouri and New Jersey are the most suitable plants for study, and we wish to reiterate again the history of events that lead to their choice. In the spring of 1983, public concern over environmental dioxin contamination became urgent first in Missouri and then in New Jersey, and the state health departments approached NIOSH for assistance in evaluating workers who had been exposed to dioxin-contamininated processes. Because NIOSH had for several years envisioned a morbidity study of one, several, or many plants in the NIOSH Dioxin Registry, the request for assistance from two of the states in which two plants from the Registry were located provided an opportunity both to do research and to provide a public health service. �-2- As we discussed in the meeting with the Science Panel, the choice of the New Jersey plant can readily be justified on purely scientific grounds: of approximately 480 workers employed at the plant during its 20 years of operation, there were more than 100 cases of chloracne or suspected chloracne (industrial dermatitis). We can be certain that exposures to 2,3,7,8-TCDD existed, since there were no other known chloracnegens at this plant. Hexachlorobenzene, a confounder for both the porphyrinogenic and neurotoxic effects of dioxin, and in production and use in this plant and in the Missouri plant, has never been associated with chloracne. The Missouri plant had fewer workers (84), no documented chloracne, and briefer potential exposure periods. As noted in the Panel's review and in the history recounted above, however, "strong local interest" was "instrumental" in its selection. In view of this, we believe that the following approach to the study of these two plants is reasonable. Because a study even of the magnitude of that proposed will require a pilot study, and because it is customary to exclude "pilot study" subjects from the main analysis, we propose that we study both plants, but that the pilot study be conducted in Missouri rather than in New Jersey. In this way, the Missouri workers will be fully studied and their data can be separately analyzed. On the basis of this pilot effort, we can assess participation rates, locating and sampling methods for the referent group, and a number of methodological and logistical matters such as questionnaire acceptability, scheduling of participants, quality control of examination protocols, etc. Although this will not be an ideal pilot, it will provide valuable experience and still allow a full study of the Missouri plant �-3- within the context of this project. The main study (or its first phase) can then be conducted in New Jersey on that larger group of workers, and no data from New Jersey will be lost because it was dedicated to the pilot study. 2) Choice of the referent group a. Neighborhood referents (and studying only exposed workers still resident in the state or surrounding area In addition to concern over the choice of these two plants, there is the added knotty problem of the appropriate referent group. As noted by the reviewers, we propose to use neighborhood referents matched on age, race, sex, and duration-of-residence-in-current-community, a proposal found acceptable by two of our epidemiological reviewers, Dr. Brian MacMahon and Dr. Clark'"'Heath. / ^Cr However, because about a third of the New Jersey workers now reside out TT state, the Science Panel reviewers expressed concern that it may not be feasible to obtain neighborhood referents for the workers no longer in the area and to persuade them to travel to a distant examination site. Participation rates may suffer accordingly. Therefore, we propose to adopt the Panel's recommendation and Dr. MacMahon1s independent proposal that we focus our study on those exposed workers still residing in the States of Missouri and New Jersey (and surrounding areas within a reasonable travel �-4- distance, e.g. 100 miles). We would obtain neighborhood referents only for this in-state' group. We can also study those out-of-state exposed persons willing to participate, but we will not attempt to obtain out-of-state "neighborhood" referents for that group. Thus for each plant, we would have three groups in the studyi in-state exposed, their neighborhood referents, and out-of-state exposed. This would permit comparisons among the three groups. Even though the neighborhood referents will be matched to the exposed, the matching can be broken if necessary, since the abandonment of matching in a cohort study will decrease efficiency but will not compromise validity. A related matter which should be examined before deciding whether it is a reasonable approach to study the in-state exposed groups is a consideration of the similarities and differences between the groups that remained in-state and those moving out-of-state. We examined frequency distributions for in- and out-of-state exposed persons with respect to decade of birth, decade of hire, and duration of employment. Because we examined only those entries with correctly coded social security numbers, date of birth, etc., the total number of living, located workers is 431 (instead of 447), 355 of whom were from the New Jersey plant. According to this run, there were 254 (72%) of surviving New Jersey workers still residing in New Jersey, New York, or Pennsylvania (with 101 living elsewhere), and 59 (78%) of surviving Missouri workers residing in Missouri, with 17 residing elsewhere. The accompanying histograms show this comparison for the New Jersey plant. As can be seen from the histograms (Figures 1-3), the workers who moved out of �the geographic area were a bit younger and started their employment a bit later. Although a larger proportion of the out-of-state group (19%) than of those remaining in-state (13%) worked more than ten years, the absolute number of persons working more than ten years was greater in the group remaining in the New Jersey area (32 in-state vs 19 out-of state). Overall, the groups appear fairly similar, at least according to these parameters. b. Industrial referents We are reluctant to embark on trying to obtain a separate industrial cohort (a plant which is not_part of the Registry) as a comparison group, for the reasons outlined in the protocol. To summarize those reasons: a suitably large plant without obvious confounding exposures and which operated during the same time period as the New Jersey plant (1951-69) would have to be identified in the Newark or northern New Jersey area (and perhaps for the Missouri workers as well, which should prove more difficult). We would then have to gain access to the plant and its personnel records solely for the purpose of obtaining a "control" group, something which has never been done for a large NIOSH study. Follow-up procedures to determine vital status and address, through social security, IRS, and special search agencies, would be the same as for the exposed plant and will take up to a year to accomplish. (With this method, it may not- be possible to identify short-term workers who left the company.) Once identified, workers still living in the area would have to be evaluated to see that the age, race, and sex distribution of the workforce is comparable to that of the exposed cohort of workers still living �-6- in the New Jersey area. have to be sought. If not comparable, a different comparison group would If deemed comparable, the workers would then be approached to request their participation in the study. The cooperation of both the company management and the union would be required. Depending on the nature of the company and its management, and on the possibilities for future litigation by workers if ill health effects are discovered in the "control" group, resistance to allowing NIOSH access to its personnel records may be considerable. In addition, unexpected confounding exposures in the selected referent plant may bias the results or even make comparisons impossible because of irreducible confounding. If, despite these obvious logistical difficulties, the Science Panel feels strongly that the validity of our study will be too severely compromised without the use of an industrial cohort as a referent group, we should reconsider the .issue with our Peer Reviewers. Such an addition to the present study will add considerably to the time and expense required before we can begin. The Science Panel suggested that we consider inclusion of. an additional exposed plant from the Dioxin Registry which may have had workers in sufficient numbers to provide an "internal" referent group. While this is an appealing suggestion for methodological reasons, the study of a second or third plant in this phase of the study may not be necessary for reasons of statistical power, according to the results of our power calculations shown in the next section. �-7- (3) Power calculations have been made for important outcomes based on the reduced size of the study if referents are obtained only for the in-state exposed persons in New Jersey (with added calculations to show the power obtained by adding more plants from the Registry as needed). The outcomes which we plan to study are numerous. They include the following categories: a. HISTORICAL HEALTH INFORMATION: Medical questionnaires will be used to ascertain the following health outcomes: Prior physician diagnoses of pneumonia, liver diseases (jaundice, hepatitis, cirrhosis, enlarged liver), coronary heart disease (heart attack or angina), nervous breakdown, neuropathy, ulcer disease, chloracne, adverse reproductive outcomes (miscarriage, abortion, stillbirth, birth defect, infertility) or cancer. As the major illnesses about which there has been the greatest concern, these outcomes will be confirmed by obtaining medical records. Patient report of a physician diagnosing or treating him/her for elevated lipids, hypertension, pulmonary diseases, genitourinary diseases, allergies, blood diseases, other nervous system disease, arthritides, skin diseases (e.g. eczema, psoriasis), thyroid problem, diabetes, etc. As outcomes which have been reported but for which the evidence is either less compelling, or the outcome alone does not necessarily represent �-8- morbidity, or it represents a confounder, patient reported information will be regarded as adequate for our purposes. No medical records will be obtained. Current or past symptoms (include symptoms referrable to porphyria, hirsutism, neuropathy, depression, changes in vision, hearing, and taste, emotional lability, sleep disturbances, and chronic bronchitis). No medical records will be obtained. b. PHYSICAL EXAMINATION (general, dermatologic, and neurologic—the latter including both physician administered and quantitative sensory testing) c. NEUROBEHAVIOURAL/PSYCHOLOGICAL BATTERY d. NEUROPHYSIOLOGIC TESTING (nerve conduction testing) e. PULMONARY FUNCTION TESTS f. BIOLOGICAL SAMPLES (blood and urine) Hepatic function/lipids GGT, SGPT, alkaline phosphatase cholesterol, triglycerides, HDLn:holesterol Hematopoetic: CBC with differential and platelets �-9- Metabolic/endocrine Thyroid screen Fasting blood sugar, 2 hour post prandial blood sugar Testosterone and gonadotropins Urinalysis with microscopic Urinary porphyrins D-glucaric acid in urine To attempt to do power calculations for each of these seems unnecessary, since background prevalences of many possible abnormalities are either unknown, or the isolation of a single biological test (eg, GGT) for power calculations would seem too obsessively narrow a focus. Therefore, we performed power calculations for several important medical and reproductive outcomes which clearly imply major morbidity and for which the background prevalence is known or at which we can guess based on work in other dioxin-exposed cohorts. These include in Table I (1) ulcer disease (physician diagnosis of ulcer disease during or since employment at the exposed plant); (2) abnormal pulmonary function tests in exposed persons who are current smokers, implying some interaction between exposure and smoking to produce chronic obstructive pulmonary disease (FEV^FVC less than 80% predicted); (3) heart disease (physician diagnosis of angina or history of myocardial infarction); (4) �-10- neuropathy (sensory neuropathy on physical exam); and (4) impotence and decreased libido. Table II includes power calculations for spontaneous abortion, major birth defects, and for neural tube defects. The outcomes in Tables I and II are those other than chloracne that were positive in some subgroup of the Nitro, West Virginia cohort (ulcer disease, abnormal PFT's, and CHD), that have been implicated in other studies of occupationally exposed groups (ulcer disease, CUD, neuropathy), or that are of major concern in relation to dioxin without clear evidence in an occupationally exposed cohort (spontaneous abortion, reproductive abnormalities). Power calculations are done including the Hew Jersey cohort alone (Plant A), and then with the addition of two more plants sequentially. Plants chosen for possible addition are those in the Registry which have not been studied or have not been well studied, and which have the largest appropriate warke-r^populations. CONDITIONS AND ASSUMPTIONS GOVERNING THE POWER CALCULATIONS IN TABLE I The Suskind study of the Nitro, West Va. cohort (JAMA, 251(18):2372-2380, 1984) showed a statistically significant, three-fold increase in ulcer disease in the exposed group overall, with a background prevalence in 'their unexposed group of nearly 6%. That study found a statistically significant excess of abnormal pulmonary function in current smokers who had been exposed (26% in exposed current smokers, 6.7% in unexposed current smokers). The Suskind study also showed a sixrfold excess of angina in the exposed group less than �-11fifty years of age (with a prevalence in the unexposed of 1%, and an excess (2% in the exposed, 0% in the unexposed) of "coronary artery disease", which was not defined further. Impotence and decreased libido occurred as a four-fold excess in the under-50 age group, with backgound prevalences in the unexposed group of 2% and 5%, respectively. Moses1 study of the Nitro workers I (AJIM, 5(3):161-182, 1984) showed a 3-4 fold excess of myocardial infarction and angina in the under 60 year old age group of those with chloracne, compared with those without chloracne (background prevalence=4%). Moses also found an 18% prevalence of sensory neuropathy on physical exam (decreased sensation to pinprick in the lower extremities) in those with chloracne, and a 0% prevalence in those without chloracne. The power calculations shown in Table I are based on the background prevalences in the studies described above, and also utilize the following assumptions; 50% of the cohort will be alive, locatable, and still remaining in the surrounding geographic area (as,was the case in New Jersey). Eighty percent of that group will participate. Thirty percent of the group will be under fifty years old, and 55% will be under 60 (as in New Jersey). Twenty percent of the cohort will have had chloracne (based on our knowledge of New Jersey, although the prevalence was higher in the Nitro cohort), and 35% will be current smokers (as in the Nitro cohort). The Missouri plant is not included in Table I, since it will serve as the pilot. Plant A is the New Jersey plant, and Plants B and C are the two plants from the Registry which would seem the best candidates for a medical study. �-12- The overall plant populations are given in parentheses next to each alphabetical designation. The potential study group size from each ,plant for each outcome is given in parentheses (n^ ) beneath the power achieved by using the additional population from that plant. The alpha level chosen is .05 (one-tail test), and the Rothman-Boice Hewlett Packard program for study size, and power calculations was employed. �-13- TABLE I ESTIMATED POWER FOR SELECTED MEDICAL OUTCOMES POWER Plant Plant Plant A (490)+ B (325)+ C(2194) OUTCOME (Based on Suskind study—exposed vs. unexposed) Ulcer PRR*=3 99% (n=190) Abnl PFT's PRR=3+ 96% (n=65) Libido PRR-4 *PRR=prevalence rate ratio 40% 60% 99% (n=60) Impotence PRR=4 (n=40) (n=260) 83% �-14- Table I (continued) s OUTCOME (Based on Suskind study) Angina PRR-6 40% (under 50 yrs) (n=60) Coronary PRR=20 artery disease 7% (n«60) 63% 99% (n=40) (n=260) 21% (n=40) 98% (n=260) (under 50 yrs) (Based on Moses study—chloracne vs. no chloracne as exposure indicator) Neuro. PRR=18+ 100% (Even if the prevalence in the exposed or chloracne group is only half that seen by Moses, i.e. 9% instead of 18%, the power would still be 86% using the New Jersey plant alone, although this assumes the same distribution of confounders in the exposed and referent populations.) Myocardial infarct. PRR=3+ (under 60 yrs) Angina PRR-3+ (under 60 yrs) 23% (n=20) 37% (n=l4) 87% (n=96) 30% 50% 96.5% (n=20) (n=14) (n=96) �-15- CONDITIONS AND ASSUMPTIONS GOVERNING THE POWER CALCULATIONS IN TABLE II The power calculations shown in Table II are based on the same basic assumptions used in Table I which were that 50% of the cohort will be alive, locatable and living in the surrounding geographic area and 80% will participate. In addition, we assumed that 20% of the cohort worked a minimum of 5 years, was less than 50 years old at the time of hire, and each had an average of 1.5 children. Very few studies have been conducted which examine paternal exposure as a risk factor for adverse reproductive outcomes. The few studies that have been done, which include anesthetic gases and vinyl chloride, have shown risks of tworfold or below for spontaneous abortion and of less than 1.5 fold for congenital malformations. The background prevalence of spontaneous abortion is approximately 15% of all pregnancies. In calculating power, we assumed a potential risk between 2.0 and 3.0 for spontaneous abortion. The background prevalence of all major congenital malformations is approximately 2.5% of all live births. The prevalence of neural tube defects is, on average, about 0.5%. The CDC study of Vietnam veterans (JAMA 252:903-912, 1984) showed a statistically significant trend for the risk of spina bifida with increasing exposure, with a risk of 2.7 in the high exposure category. Our power calculations are based upon detection of a three-fold risk in the exposed group. �-16- If exposure increases the risk of only a few malformations, we would expect the overall risk for total major malformations to be lower than individual defects. We therefore selected a two-fold risk as reasonable. Table II ESTIMATED POWER FOR REPRODUCTIVE OUTCOMES PLANT OUTCOME Spontaneous Abortion A(51*) RR=2 RR-3 B(86) C(323) 43% 62% 82% 96% (n=60)** (n=101) 99% (n=380) All Major Birth Defect RR=2 14% 19% 48% Neural Tube RR-3 9% 13% 33% * - estimated number of/live births ** — estimated number of pregnancies z alpha " 1.645 (one pailed) �-17- COMMENTS: * j* As can be seen in the preceding tables, ulcer disease, abnormal pulmonary function in smokers, sensory neuropathy on physical examination, diminished libido and spontaneous abortion may all be detectable in the New Jersey plant workers alone. Thus, in the study as .presently designed, we have a reasonably good chance of finding a number of important outcomes, assuming some similarities to the Nitro i cohort. However, since there are inconsistencies even within the two studies of the West Virginia workers, we may expect that our findings will be somewhat different (for example, Suskind reported no abnormal neurological findings on physical exam in his group, while Moses reported a high prevalence of sensory neuropathy among chloracne victims). Should the prevalences of these various outcomes when verified by physician records and our examinations be less than those in the Nitro workers, our power will decrease as well, and a larger study may be required. However, we should expect to see some indication of excess, even if statistically significant excesses are not found. If this is the case, additional plants may then be studied. The detection of impotence and coronary heart disease events will require the addition of at least two more plants from the Registry. A benefit of adding other plants from the Registry at a later time would include not only increased power but "internal" referent groups from some of the larger plants in the Registry (such as Plants B and C). �-18- The reproductive component, which is a small part of the medical study, may have adequate power to detect an excess of spontaneous abortions. It is totally inadequate for the study of birth defects, in particular neural tube defects. This study was not designed to investigate primarily reproductive outcomes. We have not, therefore, presented power calculations for reproductive outcomes for the total Registry population. The question of whether the Registry is an appropriate cohort for investigation of birth defects is a separate matter from that presented here. If a reproductive study of the entire registry is feasible, efficiency and cost considerations dictate that it be done as an independent study utilizing telephone interviews for data collection. PROPOSAL: As noted earlier in this memo, we believe that a practical approach would be to study the Missouri and New Jersey plants, with the modifications in approach proposed above (i.e., utilize the Missouri plant as a pilot; study exposed workers from both plants who are still residents of their respective states or surrounding areas, using neighborhood referents, and invite out-of-state exposed workers to participate but without referents). Because our study will obtain medical records to verify important physician diagnoses and will use an age, sex, etc.-comparable referent group, we may anticipate / somewhat more reliable results than have been obtained by other earlier occupational studies. �-19- In view of our power calculations, it would seem unnecessary to plan at the present time to study additional plants, since we may be able to detect several important medical outcomes, with the exception of coronary heart disease events and birth defects. As noted, other plants from the Registry can be added later, using the same protocol, since different study sites will be required in any event. It must also be stated that, if funds are authorized to carry out the study as planned thus far, NIOSH personnel resources would need . substantial augmentation to carry out the study without making deep inroads into other research areas. Positions for additional professional staff are needed before the project even as it is currently conceived can proceed. If the Science Panel feels that the study of additional plants is desirable, since it will clearly afford greater power for some rarer medical events and for reproductive outcomes, this recommendation should be made in recognition of NIOSH1 s need for additional financial and staff resources to carry out both the currently planned and extended studies. Additional Comments from Science Panel Members Since the Science Panel members brought written comments to the meeting of May 29, 1984, many of their concerns were discussed during that meeting. Other major comments were discussed in the preceding pages. We respond here to several comments from reviewers which may have been partially or fully discussed but which reviewers may wish to have in written response form from us. �-20- 4) Verification of reproductive outcomes All adverse reproductive events will be verified through medical records review, in addition to verification of major medical conditions. 5) Interviews with ex-wives Former wives of exposed and unexposed subjects will be contacted and interviewed about their reproductive history, as suggested by the Science Panel. 6) Reproductive histories Study participants will be asked about their complete reproductive histories. 7) Obtaining sensitive information Data on induced abortions, contraception, infertility, and impotence will be obtained. Since the wives will be interviewed about their entire reproductive histories, data concerning children born out of wedlock will be included in the data collection. We believe that these responses address the major concerns of the Science Panel members. ��-Z'<9V4 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5739 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Response to the AOWG Science Panel Review of the NIOSH Draft Protocol for a Mortality Study of Workers Exposed to Dioxin ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/7f72f1190dbe21f781b4ae8af49b533d.pdf 510db65ce3103d7f4ec029eac54d00a5 PDF Text Text Item D Number °5738 D ^t Scanned Author Corporate Author Report/Article TltlB Science Panel Review of Epidemiological Studies Proposed by the National Institute for Occupational Safety and Health Based on a Registry of Workers Known to Have Been Exposed to Polychlorinated Dibenzo Dioxins, Draft Journal/Book Title Year 000 ° Month/Day Color Number of Images D ° Descrlpton Notes Tuesday, March 26, 2002 Page 5738 of 5743 �Science Panel Review of Epidemiologlcal Studies Proposed by the National Institute for Occupational Safety and Health Based on a Registry of Workers Known to Have Been Exposed to Polychlorinated Dibenzo Dioxins The Science Panel of the Agent Orange Working Group met on May 29, 1984 from 10:00 a.m. to 1:00 p.m. in Washington, D.C., to discuss two protocols prepared by the National Institute for Occupational Safety and Health (NIOSH). The members present at this meeting were as indicated on the attached list of two^sf £fee-NIGSHsinves$i gators who had been Qfsthe pr^toc^ls wWch were reviewed. Several Science Panel members had prepared written comments which are included at Tab B of this review. A brief summary of the review with recommendations to the Agency for Toxic Substances and Disease Registries was prepared immediately following the meeting and is included at Tab C. The proposed studies include a Mortality Study, a Morbidity Study and a Reproductive Outcome Study associated with the Morbidity Study. The brief description and comments on each of these studies which follows is based on individual reviewers' written comments and discussions among reviewers during and following the May 29, 1984, meeting. The presence of two of the NIOSH investigators (Drs. Fingerhut and Moody) at the meeting was very helpful in clarifying a number of issues and providing additional information on the current status of these studies. Review of Draft Protocol for a Mortality Study of Workers Exposed to Dioxin �Description Investigators at the National Institute for Occupational Safety and Health (NIOSH) have identified 15 manufacturing facilities in the United States which have produced products likely to be contaminated with polychlorinated dibenzo dioxins (PCDD) during the last 40 years. Manufacturing practices and personnel records exist for 13 of these which involve approximatley 6000 workers with some likelihood of having been exposed to these chemicals. Most of these workers have been identified and demographic information, work histories, and medical information obtainable at the manufacturing facilities are being assembled. Several classes of workers will be included in a Dioxin Registry Cohort to be followed for mortality experience and cause of death. These include production workers and formulators in departments which made or formulated pentachlorophenol (PCP) and trichlorophenol (TCP) and its derivatives, maintenance and salaried workers known to have been assigned to these departments, all workers in plants whose total or predominant output was phenoxy acids or chlorophenol and workers present during explosive release of a TCP reactor or who were involved in the cleanup process. Vital status will be determined by standard methods and overall cause-specific mortality ratios will be computed using life table methods and United States mortality rates as the standard for comparison. Eighty-nine causes of death will be examined, including those of obvious interest at this time. Analyses will include race and sex specific comparisons as well as the effects of latency and duration of exposure. In addition to an analysis of the entire Registry cohort, some attempt will be made to do separate analyses on subgroups experiencing different dioxin �JJK0F7 exposures. These may include workers from different plants, those producing different products or involved in TCP accidents and other estimates of varying exposure including the presence of chloracne. Some attempt will be made to control for potential confounding chemicals such as 2,4-D, MCPA and chlorinated benzenes in so far as company records of work histories will enable this to be done. Discussion The investigators have already done an excellent job of identifying workers who may have been exposed to PCDD. Following these to determine vital status and ,-ce^ and should be= encouraged on a -l^^^-nQ^*^«a^ toweve^whate ^ttoee^poptrtatiefl" data wi 11 be most useful for comparison at this time. Cause-of-Death-Specific Mortality rates based on death certificate diagnoses are available for the general population of the United States and will be compared with those of registrants. If death rates are lower among registrants than expected from the general population, this will be interpreted as the "Healthy Worker Effect." If death rates are higher among registrants, it will be tempting to interpret this as "due to" exposure to PCDDs. Unfortunately, these two opposing effects can cancel each other, particularly with the limited number of registrants available for follow up. One of the ways in which this problem might be handled is to develop the possibility for determining if there exists a dose-response relationship. The investigators have obtained information on duration and type of job assignment for many of the registrants and are currently refining their estimate of duration and level of exposure based on these data. Science Panel reviewers �strongly urge support for this activity with an attempt to quantify exposures where possible. Results of this study would be most useful 1f particular types of exposure, such as persons present during or following an explosive release of a TCP reactor, production workers, formulators, pesticide applicators and other persons in contact with PCDDs could be arrayed 1n order of exposure for other studies as well. The NIOSH Investigators have indicated that they may separately analyze the several hundered workers who have suffered from chloracne as a particularly highly exposed group. The Science Panel feels that this could be misleading since a number of other chemical compounds are also chloracnigens and individuals vary 1n their susceptibility to chloracne. The Panel suggests that the investigators reserve comparing the relative rate and severity of chloracne among different groups as confirmation for an exposure index based on other data. Finally, there is concern that some rare cancers, particularly soft tissue sarcoma, cannot be accurately identified from death certificates. The NIOSH investigators' own experience has already indicated as much among some of the same subjects which will be included in the mortality analysis. Unfortunately, the special review of pathologic specimens and clinical materials which is needed to make a more accurate assessment of cell types is not available for the general population. Since the creation of a reference population is a formidable undertaking, using a minimally exposed subgroup of the Registry as an internal standard appears to be the most feasible approach at this time. Even this will require considerable review of pathological specimens and clinical records and will have low power for rare tumors unless there is a very steep dose-response gradient. Also, this further emphasizes the need for a carefully constructed exposure index. �Review of a Protocol for a Study of Persistent Health Effects in Chemical-Herbicide Workers and in Community Residents of Unknown Exposure Status and Review of Draft Protocol of Adverse Reproductive Outcomes Among Chemical Workers and Community Residents Participating in a Morbidity Study ou Description Within the Dioxin Registry briefly described in the "Review of Draft Protocol for a Mortality Study of Workers Exposed to Dioxin" are two subgroups which have been considered suitable for studying long-term morbidity: a New Jersey plant producing phenoxy herbicides between 1951 and 1969 with about 500 workers, approximately 100 of whom had chloracne, and a Missouri plant with about 80 workers -producting 2j4v5^4B«k:he*^kl®e@pb«Re;letweeft 1968.and-J^Sb ;As: many as pos s*tif* ? sible "of the :447~sut^iv w^affd:^ w111 be questioned and examined along with a set of neighborhood controls of about equal size. It is the aim of the study to "provide useful information about the persistence of biologically significant medical effects and reproductive outcomes" which may be related to exposures to dioxin among workers. The comparison group will be matched for age, sex and race as well as length of residence in the community (+ 5 years). It is also proposed to offer a financial incentive of $100 to all participants and to abandon the study if less than 75% of locatable subjects and their controls agree to participate. Some additional information on potential confounding exposures to other chemicals will be obtained from company records and employee histories and dealt with during analysis. It is anticipated that the study will be pretested and piloted among 50 New Jersey workers and their controls. The Reproductive Outcome Protocol states that "the objective of this study is to determine if occupational exposure to dioxin ... is associated with decreased fertility, spontaneous abortions, stillbirths or congential malformations in the offspring of male workers." The study will be part of the �morbidity study previously described and will entail a retrospective cohort design based on interviews of male workers and their wives. It is also planned to collect birth, fetal death and infant death certificates for verification of reported reproductive outcomes. Discussion One of the first questions which arises in reviewing these protcols is why the New Jersey and Missouri plants were selected as sources for the study population. The investigators stated that the New Jersey plant was fairly large and apparently quite contaminated as indicated by the fact that 20% of the workers are reported to have had chloracne. Strong local interest in studying this problem in both New Jersey and Missouri, however, seem to have been at least as instrumental in the selection, and may enhance participation if this interest can be exploited. The protocol includes a discussion of several possible choices for selecting comparison subjects and concludes that neighborhood controls matched on age, sex, race and length of residence, are most appropriate. Members of the Science Panel feel that this may introduce selection bias in that motivation for participation will be different, particularly among subjects currently living at some distance from the examination sites. The Science Panel suggests study subjects (and their controls) include only persons currently residing in New Jersey and Missouri, or in close neighboring areas. The investigators have indicated that approximately half of the New Jersey subjects no longer live in New Jersey and currently reside in some 38 different states. If additional subjects are needed to increase the statistical power of the study, another plant should be selected for inclusion. This would enhance the study if a plant is selected which can contribute unexposed in-plant comparison subjects as well as neighborhood controls. �Although not included in the protocol, the investigators intend to verify reproductive events through medical record review. This will be particularly important for those items not reliably reported on vital records, such as birth defects, spontaneous abortions and early miscarriages. Another procedure which the Science Panel strongly recommends is that former wives be interviewed for reproductive outcomes. In order to maximize the number of reproductive events for analysis and cover the younger ages, pregnancies engendered during the entire reproductive period should be included. This is particularly important considering the large proportion of short-term workers and the length of time (well over 10 years)_sinceanyiofrthem were employfd at these plants. As is indicated in the protoeoh if» order to make "a meaningful interpretation of results from the detailed health examinations and tests on these subjects, it will be essential that an accurate assessment of exposure is available. Records of job assignments from the New Jersey plant appear to be useful for this purpose, but the comparisons will have no such records and must rely on occupational historical data. Of concern are possible differences in exposure to chemicals other than dioxin among both groups. This is a good reason for including an additional plant with both exposed and unexposed chemical workers in the study. Job assignment records might then be used to construct an index of exposure to a number of chemicals in addition to those likely to be contaminated with dioxins. Other suggestions, not included in this discussion, can be found among individual reviewers' comments. �o -I 3> ^ -^ ^K ^ V ^~V~ 7 jv * N, ^.^4^ * 7\^ P £/ ^^t 6^ « 0 C> g ^> -« ^sa o ^s» 1 i �TAB Individual Reviewers' Comments on "Draft Protocol for a Mortality Study •of Workers Exposed to Dioxin" Reviewer #1 I have reviewed the two epidemiological research protocols for studies of occupational exposure to dioxin. Both are meritorious and needed. The mortality study, which is already in progresss, unquestionably warrants additional funds for completion. I concur with the previous reviewers of this study. Reviewer #2 The investigators have already assembled a cohort of workers possibly exposed to a chemical(s) which has no commercial value and for which no records exist. There seems to be every reason to compare mortality experience of this group with an appropriate comparison group given the known high toxic1ty of the chemical under consideration and the length of follow up which can be achieved— now and in the future. Several matters of concern may improve the usefulness and Interpretation of mortality and other studies based on the D1ox1n Registry included in the Protocol for a Mortality Study. Primary among these is a method for assigning exposure status to members of the cohort. While it is clear that the investigators are attempting to do this, there 1s little in the protocol to indicate how or even whether this can be done. It may not be possible to make such an estimate for every member of the Registry, but for those which can be so assigned, this should become part of their record(or at least some estimate of relative exposure). As suggested by other reviewers, this should probably not be based on the presence of chloracne, but rather "tested" by the rate or severity of chloracne. Another item is the choice of the U.S. population mortality rates for comparison. This will certainly confound the healthy worker effect which was found, for example, 1n the Project Ranch Hand II Mortality Results. Unless more appropriate comparison mortality rates are used, it becomes even more Important to use Internal comparisons—and thus estimate at least relative exposure among different groups 1n the cohort. The Investigators should be complimented for the difficult job already accomplished. Further suggestions for Improving these studies are expected to be continuing activities and will depend on the collection of Information already underway. �Reviewer #3 1. The draft protocol for the above study, the "Description of the Dioxin Registry Sites," the accompanyinq memoranda and the reviewers' comments were examined by , The draft protocol was prepared in late 1982 and undoubtedly has been modified since then. Our comments, therefore, may be outdated and our suggestions may well have been taken before they were made. 2. The study proposes to compare the number of deaths in the exposed workers to the expected number of deaths generated from U.S. mortality rates for 89 causes of death including soft tissue sarcoma. This is, of course, the usual modified life table method for analysis of data on mortality. Although it is not described in the draft protocol, the author recognized elsewhere the pitfall of using death certificate information for a mortality study, especially soft tissue sarcoma. It is well known that a substantial portion of the soft tissue sarcoma deaths coded on the death certificates were not confirmed by hospital records (Percy et al, 1981). In light of this problem of misclassification of disease and lack of readily accessible mortality data from industrial population (e.g., age, sex, race, calendar year, and cause — specific mortality data), it is desirable to have an additional comparison group developed from an industrial population. There may be practical reasons (legal, logistic, budgetary) for not pursuing this. But if the author plans to review the hospital records or pathology of cancer deaths, it is necessary to apply the same criteria to the comparison group in order to improve the comparability. 3. No mention is made of going beyond the death certificate to determine the cause of death. It certainly would be advisable to confirm the reported causes at least by review of the medical records. Russell emphasizes the need for confirmation of the diagnosis of soft tissue sarcoma by recognized experts. This would avoid false positives. We suggest that an expert pathologist review tissues and/or slides from any malignancy that is not clearly a carcinoma. This would reduce the chances of false negatives and would provide confirmation for the diagnosis of malignant lymphoma as well. Pathology reviews would also provide classification by tissue type with little extra effort. 4. It may be important to consider separately individuals exposed during, or as a consequence of, an explosion (p. 18, "third definition"). Both the intensity and the duration of exposure from these episodes would be very different from the chronic exposure to lower amounts of chemicals during manufacturing. �5. The necessity for determining the duration and level of exposure to 2,3,7,8-TCDD is emphasized in the protocol and in the reviewers' comments. The inaccuracies in attempting to do this are also recognized. Even the use of chloracne as an indicator of exposure (page 26) is questionable since other chlorinated organic chemicals also produce the skin changes (page 15) and the condition is often confused with acne vulgaris. One source of information about exposure may be used but is not specifically mentioned. Chemical engineers and production chemists are usually aware of details of the processes used, of the adequacy of controls and safety measuresr and of the likelihood of exposure during operations. 6. As indicated by the author (p. 28) the power to detect outcomes of certain rare causes of death is inadequate. Unless the true risk of dying from soft tissue sarcoma, liver cancer, or stomach cancer is greater than four fold, the study may not be able to detect £he excess. 7. Despite the unavoidable difficulties and limitations, the Dioxin Registry Mortality Study should yield valuable information on the effects of chemical exposure. �Reviewer //4 Considering the massive amount of data already accumulated and the urgent need to shed light on the soft tissue sarcoma relationship with dioxins, this member would recommend continued funding of the program to completion. The following comments are provided with respect to the Draft Protocol and reviewer comments: 1. On page 18, lines 8-10, of the draft Protocol it states that if no record of assignment exists, but the primary production of the company was phenoxy acids or chlorophenol, all males will be considered as exposed. This may be a flawedassumption leading to a dilution of truely exposed persons especially when the worker was employed for a short period at that production facility. Similarly on lines 19-22 of the same page, it is stated that for two sites, incomplete records exist which only list a job title held at one point in time. In this case, the individual will be assumed to have held that job throughout the term of his employment with the company. In this assumption it would seem that an unusally long exposure time might result when such was in fact not the case. It would seem better to limit subjects to those in which we had valid employment records covering their entire > period of employment. 2. On page 19, second paragraph states that an effort will be made to develop a model predicting probable levels of exposure for each type of worker. Factors in this model are then listed. This seems to be a very worthwile effort when one considers the great possible significance of this NIOSH study. 3. Page 20 of the Protocol contains a discussion of potential confounding exposures which may exist. It would improve the discussion by including the types of canc€r*^roduced4juarri^ found 1n_Z»4=IL - The same coTSnent^appWes^to ^i440*rtd:^PAiawl itheir effeet-an risk of cancer- tn tamaasvtzMeiagrfie Jdltuthewhich states that potentially confounding exposures will be difficult to assess. Therefore, every effort should be made to obtain detailed employee work histories, Dr. Enterline in his comments of Dec. 14, 1982 shares in a manner our concerns in his comments numbered 1 and 5. His point of "never categories of exposure" covered in comment 6 also has merit because of the unusually low mortality rate of chemical workers. 4. The comments provided by Dr. Thomas J. Smith in numbered paragraph 2 states our concern very succintly with respect to any dose-response relationship for TCDD and cancer risk. Finding these highly TCDD exposed workers may be a difficult task. 5. In numbered comment 4, Dr. Smith clearly expresses a concern which we have shared regarding other isomers of dioxin being aggressive human carcinogens and that one or more of the other substances such as the herbicides might be synergists or antagonists of TCDD's action. We do not want to lump improper categories of exposure and end up with suspect results. �Reviewer #5 I understand that this study has been referred to, if not critically examinined-, by the AOWB -for a number of years. We all have the feeling that this study will be useful, but a review the documents provided to the Science Panel does raise some questions: 1. The extent of previous review is not clear. The documentation refers to a panel of 6 outside reviewers which was convened on Dec. 16, 1982, to receive and discuss comments and issues associated with a Dec. 1, 1982 draft. A March 23, 1983 memo summarises this meeting, which is referred to as the "first" meeting. The memo also notes the unanimous agreement to meet again after the protocol had been modified. There is no indication as to whether or not these planned events actually occurred. The concern is how and whether the comments of these reviewers have been addressed. The reaction to a number of the comments could be critical to the final results. Is there a more current protocol than one we received? 2. Has any progress been made in handling the multiple comparison question? The study sets forth four diseases as hypothetical ly linked to "dioxin" exposure, and yet the protocol indicates that comparisons will be made on 89 causes of death. In animal studies researchers often use the Bonferroni correction factor when considering multiple comparisons. Would this not be appropriate in this case also? 3. Given that^the^FOwer o-T^the fi^udy h y p ot hese«-=^a^^^nint^titl^~v^r^^ cdhtTnLJiarEiljn of the study? 4. The protocol mentioned a July, 1985 review by the Special Peer Review Panel, which is presumably the panel of six who reviewed the Dec. 1979 protocol. What role is there in the review loop for the Science Panel and/or the oversight committee for the Ranch Hand Study? Given the import and impact that this study is likely to have, I would suggest that the AOWG be closely involved. �Individual Reviewers' Comments on "Protocol for a Study of Persistent Health Effects, etc." and Draft Protocol for "Adverse Reproductive Outcome's, etc," Reviewer //I Ohe morbidity and reproductive outcome study is an ambitious and important project. Ohe purpose is to perform a careful evaluation of workers who were occupationally exposed to dioxin. Hie reviews and the authors' response to the reviews have addressed all of my concerns which centered on type of control population, exposure indices, and confounding exposures. The authors do an excellent job of responding to the reviewers' comments. I have little to add beyond what has already been written. First, I wish to know what is the status of the planned neurological testing. I believe that this aspect of the study is critical, particularly in light of the frequently reported neurological and behavioral changes in the Vietnam Veteran population. It is my suggestion that neurologists, rather than "neurologist-surrogates", be actively involved in the examination of the study population. Second, I would like to know what the authors mean when (in their response to reviewers) they write that, in the event that the study is abandoned because of poor participation rates, "an alternative 'public health survey1 of workers who wish to be examined may have to be conducted, for public health and public credibility reasons." Reviewer #2 The d 1 se uSttoiT "> of fcac kgr ©u nd 1 nf ormat'i oni: on -pos s1tole fte a1 1 N -'effect £ and - tM ; -=^-~ ratlonalejf or ;_«xami nation f>r0c€dures" are adequate, -although a detailed -el-: .l~! discussion ^crf 1iow"and"wHeTe~the examination w i l l b e conducted 1s lacking. This may have some relevance to participation rates. The sample which appears likely to be available for study appears rather small. An important consideration is whether detectable biological and health differences between dioxin exposed workers and controls are likely to occur. It was of great concern during review of the Air Force Project Ranch Hand II Study whether twelve hundred Ranch Handers were sufficient to detect meaningful health differences. Perhaps some consideration should be given to the expected outcome of various test results and the possibility of expanding the cohort size by adding additional groups. One of the variables which should be considered for matching has to do with employment history. Something like a healthy worker (or unhealthy non-worker) effect may be introduced if the comparison group has a sufficiently different employment experience. This would be in addition to possible chemical exposure effects which might be included among the controls. The investigators' discussion of the problems associated with the choice of various possible alternative control groups is welcomed but should be supplemented with the likely effect of the various alternatives including the use of neighborhood controls. �c of these events makes It unl ke v thl?Tj!J °?$5 J lack,of med1ca1 confirmation that information which ca e d e r i v e f om v til SXJJ9" ?111 5e 1s bta1ned' "° ° that wives need be interviewed at all. ThistudS nrlllh?*"' 1J Un11ke1y incorporated Into theMorbidity Study withonl5 a^l ^ L ? b??* be i S *ore ngorous ascertainment ofVoL'livVe^ Reviewer #3 1. In these comments, we consider the "Protocol for a Study of Persistent Health Effects in Chemical-herbicide Workers and in Community Residents of Unknown Exposure Status," dated April 1984 (referred to as "health effects protocol") and the draft protocol for "Adverse Reproductive Outcomes Among Chemical Herbicide Workers and Community Residents Participating in a Morbidity Study," dated March 1984 (referred to as "reproduction protocol"). The material submitted included the comments of prior reviews and the investigators' responses. It did not include the questionnaires, ) physical Examination details, thfr clinical; chemistrydeterminations, nor the ancillary tests to be performed. There-may also-have been revisions of the protocols to include some suggestions made here. 2. It is difficult, if not impossible, to form an accurate, comprehensive opinion •concerning protocols for , clinical-epidemiological studies when so much operational material is not available. I comment on the protocols with this reservation. 3. The health effects and reproduction studies share certain difficulties, including the likelihood that estimates of exposure to TCDD will be inaccurate and that the subjects will have been exposed to varying and often unknown amounts of other biologically active chemicals. The small sample size will also limit the significance of many negative findings. These difficulties beset all studies of phenoxy herbicides and dioxins that attempt to examine exposed individuals in detail. 4. The quality of the control group is debated by prior reviewers but the use of neighborhood cohorts remains questionable. A group of chemical workers not exposed to dioxin offers enough advantages to make it worthwhile to consider it as an alternate or an additional control cohort. 5. In the health effects study, major considerations center around particulars of the questionnaire, the manner of performing and recording the physical and psychological examinations, and the other tests. It is extremely important to confine the laboratory testing to meaningful determinations that are readily standardized, non-experimental, and detect significant abnormalities. The latter do not include wall-known physiological variants, possible causal mechanisms for adverse effects that are not yet established, or changes known to be produced by common activities such as smoking, drug abuse, or dehydration. The testing will produce an enormous amount of data and the attempts to sort out confounders such as drug effects or dehydration can confound the statisticians. �3. Page 17 of the Protocol relates that production or pnenoxynero.t.u^ at the Missouri plant only took place for seven months (May-November) in1968. This would seem to be a short term exposure period with many years following 1n which the workers could have had other work exposures and other effects such as from alcohol and drugs could assume Importance. Therefore bias may be Introduced from this small short duration sample of exposed workers. 4. It seems possible that the male member of the family could bring home on his body or clothing TCDD and/or dloxln contamination and thus cou <« expose his wife Indirectly. Hence why restrict conceptions to those after 11 weeks of employment His wife could be pregnant when the husband went to work and we could have Indirect gestatlonal exposure of the wife. 5 It would seem that as Dr. Richard Hornung points out in his conments that a time-weighted exposure index would be very important 1f we expect to achieve valid results. 6. Reference the last paragraph of page 24 of the Protocol. Given that the est mates of sample size are crude with respect to concep^ons which took place, why have the Investigators not already considered the Inclusion^ other Seal plant sites in the NIOSH registry to make very sure that enough conteptioniT from ?*pn**d workers woul* b& ensured to give resul ts wvth the needed power? Reviewer #5 1. Comments common to both protocols a. The documentation supplied clearly lays out the comments of the reivewers and the investigators' reactions. Some questions may remain, but at least the issues are plainly presented. It is still not clear, however, whether chlorance be used as an indication of exposure to 2,3,7,8-TCDD or not? The response to comments suggests that the standardized fertility rates will not be used. The current protocol suggests that they will. This appears to be inconsistent. The response to comments implies that the reproductive effects of dioxin will be repairable, but suggests that the enzyme induction may not be. Is there a basis for this apparent inconsistency? b. Is the total amount ( $ 2 . 0 3 6 , 0 0 0 ) being sought from Superfund? Does such a study fall under the Superfund rubric, since the populations under study are not associated with waste site exposures? c. Given the acknowledged complexities/difficulties involved: Limited populations Problems of recall bias The expense of the study Problems with confounders at both plants The length of time since exposure — a likely advantage only in the cas'e of cancer, which, itself, should manifest itself in the Dioxin Registry Mortality study. The question of comparability of referents The multiple comparisonsissue The ambiguities likely to be associated with any results The lack of comparable populations for confirmatory studies Problems in determining existence and extent of exposure Reservations articulated by some of the reviewers Etc. it is questionsable whether the results of such a study can iustifv the excense. oarticularlv in liaht of other (related. �2. Comments on the Morbidity Study , a. Studies on nerve conduction velocity and measurements related to the immune system will be conducted. In the former case, apparently there are sufficient data that some investigators feel comfortable in saying that a test population is, or is not, within "normal" ranges. Can the same be said about the immunological measurements? What is one to make of any differences observed? For example, the famed Ward study and the work by Prince have been examined (to the limited extent possible), and there seems to be little one can infer from such results. Will the situation be any different in this study? It would seem that some fundamental research needs to done in this area before gathering additional data on a highly controversial subject that would both beg for, and defy, clear interpretation. b. Could the question of the PCB fingerprint be treated by a phased approach? That is, the GC/MS analysis would be done only if the enzyme patterns differed remarkably between the two groups. c. Reference is made to determining referent exposure status on the basis of questionaire data. Without seeing the questionaire it is difficult to determine whether this is likely to successful. Is the implication that the exposure status of the exposed group should also be determined from questinaire data "for reasons of comparability"? Taken literally, the approach does not seem reasonable for the exposed group, where employment records provide a more objective testimony. 3. Comments on the Reproductive Study a. It is unclear whether there are particular hypotheses being tested or not. Some of the commenters and the response to those comments suggest that the study is really a hypothesis generating study, rather than a hypothesis testing study. In such a case, the population size, power, etc. considertions are of less importance. And yet, the protocol seems to return to the idea of testing various hypotheses. Which is it? b. The high turnover rate, especially at Plant 01 (more .than 70% of those in their "primary reproductive years" employed for less than 3 months), raises questions about attributing any observed effects to this particular chemical exposure; particularly for pregnancies which occur years later—perhpas after one or more successful pregnancies. c. The wives' telephone interviews will be conducted with the current wife. From a biological plausability point of view it would be the wife at the time of exposure that would have the greatest knowledge of the pregnancies of greatest interest. The protocol explicitly rules out such interviews. What are the implications for the study? What happens in the case of widowers? What would be the implications for the study if one of the groups had longer term marriages than the other; i.e., more "relevant wife" interviews than the other? Is sufficient information be gathered on the wives to detect possible problems there; e.g., congenital, familial, hereditary, etc. problems? d. The protocol treats "habitual aborters" (defined as 3 or more consecutive fetal losses) differently. Is this a generally agreed upon definition? Why not two consecutive losses? Why not three losses total? This definition might, in fact, be throwing out the most signficant evidence of a longer term effect. �6. No details are given about the data collection or the handling, processing and protecting of the information from disclosure. Quality control measures in these areas will be important because of the great numbers of data. The quality control will be especially important if the examinations are to be conducted by two sets of examiners, i.e., in New Jersey and Missouri. 7. The Ranch Hand investigators found that it was highly desirable to have a physician review directly with the subject or control the results of the health examination. This could be done by telephone if the persons are unable to return for their results when laboratory data are available. 8. The reproduction protocol introduces a number of methodological questions. It is possible to elicit very "sensitive" reproductive information during questioning by a physician. There would seem to be adequate reasons for including data about pregnancies caused by a man outside wedlock, about induced abortions whether legal or not, about sterilizing infections such as gonorrheal salpingitis, and about children born outside*of wedlock. Details about impotence and the use of contraceptive techniques have been easy to obtain during medical questioning. In as much as these issues all bear on the question of fertility and reproductive failure they should be included. The confidentiality of the information must be assured, of course. 9. Consideration should be given to obtaining information from former wives and consorts. 10. Apparently no attempt will be made to confirm birth defects, late abortions or stillbirths by reference to hospital and pediatricians' records. Such confirmatory information has proved valuable if somewhat troublesome to obtain. 11. There have been few opportunities to study women who have been exposed to TCDD. The Registry contains at least 60 and it would seem advisable to examine all of them, especially with reference to possible reproductive effects. Indeed, this would be more valuable than the proposed study of the male workers since it was the women in Vietnam who claimed the most pronounced effects after exposure to Agent Orange. Further, there is no good evidence that male animals or men are reproductively abnormal as a specific effect of TCDD. The reproductive disturbance from TCDD in the laboratory has resulted from exposure of female animals. �Reviewer #4 * The following comments are provided with respect to the Protocol for a Study of Persistent Health Effects in Chemical-Herbicide Workers and in Community Residents of Unknown Exposure Status: 1. On page 30 of the Protocol it states that the sample of exposed workers should be about 300 (this number includes 90% follow-up, an estimated 123 dead, and 75% of the remainder). Based on this assumption and the cost proposal total of $2,036,00 (includes inhouse and contract costs) we would have an exposed Individual cost of $6,787.00 per person. This seems to be a very expensive study when so many potential unknowns enter into the real exposure of the worker to TCDD. Our concerns will be discussed in the following comments. 2. On page 28 of the Protocol there is a discussion of the fact that hexachlorobenze was manufactured until 1969 at the New Jersey plant and it is both a porphyrogen and a neurotoxin. Similarly ethylene oxide has been used at the Missouri plant for a number of years since 1971 and may potentially affect workers exployed at the plant after 1971. Ethylene oxide is known to have adverse reproductive effects and is a neurotoxin. Thus three of the effects to be surveyed in the dioxin exposed workers may also be affected by these two other chemicals. Why then have we not selected other plants and other worker groups as a basis for exposed workers? We seem to be asking for confounding effects with this cohort selection. Further, on page 21 of the Protocol, it states that there is no documentation of chloracne in the Missouri plant population and (on page 23) the statement is made that there is no other group of chemical workers in the local area with which a comparison can be made. 3. The Protocol discusses the estimation of exposure status on page 46. We fully agree with the first sentence which reads: "Estimation of exposure status will be difficult, since measurements of actual TCDD levels are rare or non-existent." Further on it states that chloracne can serve as an index of a given group's exposure level. We disagree as several other chemical compounds can cause chloracne and hence TCDD may not have been the cause of the condition. It would seem that true exposure variations including concentration and duration of exposure may be Impossible to obtain because of the lack of or poor quality of the employment records as has been discussed in other parts of the Protocol. The resutts of theiStttdy-may thus-fee subject to = §eriou& ^hahUenge es pec i a11y— if the 4. On page 49 of the Protocol, 1st paragraph it states that the Investigators have decided to present the study not as one of dixoin exposure, but of workers exposed to chemicals and herbicides, using Agent Orange as an example, and of community residents. Why does Agent Orange have to be mentioned at all? The study will not measure the effects of Agent Orange as the workers were certainly not exposed to Agent Orange in its final formulation and dissemination manner. Will some of the subjects even know what Agent Orange is? Why not relate the study to chlorine containing pesticides and let it go at that?. 5. No mention was found in the Protocol of any consideration of whether the exposed subjects or control subjects would be checked out for military service including servie in Vietnam. It would seem possible that some of these people may have been in military service and could have been exposed to Herbicide Orange while in the service. Similarly many of the control population could have used TCDD containing commercial weed killers on their farms or in their gardens. This might especially be the case in the controls around the Missouri plant which is in a farming area. �6. Page 51 of the Protocol provides a very truthful statement which Is the basis of our concern for the expediture of so much money on so few possibly dioxln exposed persons. It reads as follows: "Finally, m1sclassif1cat1on of exposure Is a potential source of bias, which if not differentially distributed between exposed and unexposed groups will Invariably bias results toward the null. If obtained job exposure records on referents Is deemed unfeasible, which it almost certainly will be. then exposure status can only be based on questionnaire data when the exposed and referent groups are compared, again for reasons of comparability," (Underlining added by us). The legal and political implications of the results of this study may be of great significance with respect to the effects of dioxin and more particularly TCDD exposure. Hence completion of a study based on questionable and even unreliable exposure data concerning TCDD concentration and duration may be a disservice to the Nation and Its concerned population. We note that Dr. Brian MacMahon of the Harvard School of Public Health shares our view that these studies may be very difficult to carry out and it 1s very much a question in his mind whether the results will be credible (Comments of Nov 7,1983,para 1.). Dr. William 0. Russell of North Ridge General Hospital in his comments of Dec. 14, 1983 points out that "An exposure Index of time, job performed, and some knowledge of plant location contaminations are but approximations, and imaging of Individual variations that could, on the one hand result in little or not true dioxin exposure for one Individual, yet, on the other hand, be more than several times that expected for another. In the equating of results, separate evaluation would be Indicated for only the chloracne Individuals since this change would be reliable most probably to the longest time exposure." This statement seems to further substantiate our concern for exposure variability and then finally falls back on chloracne as an idicator of choice. However, chloracne 1s not produced exclusively by TCDD. 7, Reference the last paragraph of Page 36 of the Protocol. The Digit Symbol Test subscale of the WAIS measures only a few cerebral functions. The Halstead-Reitan or Lurla-Nebraska are better measures of a variety of CNS dysfunctions. The following comments are provided with respect to the Protocol entitled "Adverse Reproductive Outcomes Among Chemical Herbicide Workers and Community Residents Participating in a Morbidity Study": 1. Page 19, Paragraph 2, states that reproductive history interviews of ex-wives will not be conducted as they would be difficult to obtain. So the interviews may be difficult to obtain, these former wives may be the very spouses that had children from the workers at their highest point of exposure and most recent exposure. Not at least trying to conduct Interviews of former wives would make the whole study suspect as very Important exposure effects would never be found. The Protocol then points out at the bottom of page 20 that the validity of the father's interview data on previous marriages can only be evaluated if ex-wives are Interviewed. So why do we not make a full and devoted effort to interview ex-wifes If we are going to have a credible study? 2. We share Dr. Renate Kimbrough's same concerns as expressed 1n numbered paragraph 2 of her review comments. We also feel that exposure is not defined very well and 1t is very possible that the dose received by different persons may very greatly and the time elapsed variations since exposure. �DEPARTMENT OF HEALTH & HUMAN SERVICES • Memorandum Date June 1, 1984 From carl A. Keller, Chair Pro Tern Science Panel of the Agent Orange Working Group (Cabinet Council) Subject Review of NIOSH Studies Based on the Dioxin Registry TO Vernon N. Houk, Assistant Administrator Agency for Toxic Substances and Disease Registries Pursuant to your request_oO!ay- 9 and .with: instructions from -the Chair of r^:^e ^=Et on May 2§, 1984, to a^PT5%?r^tew> p/roMto^^ of- Workers Exposed ~ to^Moxto wlm:^^ Institute for Occupational Safety and Health (NIOSH). These studies are based on an already identified Dioxin Registry Cohort which includes workers from 13 chemical production facilities in the United States, and who are known to have been exposed to pentachlorophenol or trichlorophenol and its derivatives over the past 40 years. Members of the Science Panel unanimously agreed that the Mortality Study, which will ascertain the fact and cause of death for all deceased members of the Registry, should proceed as designed and should be updated on a periodic basis. The investigators at NIOSH are strongly encouraged to continue to develop a quantitative exposure index based on available records for all of the identified members of the Dioxin Registry Cohort. The Morbidity Studies propose to measure current health status and reproductive outcome histories for several hundred workers from two of the facilities included among those in the Registry. These data will be compared to similar measurements on a group of unexposed persons matched for age, sex, race and current neighborhood of residence. The two facilities to be studied were chosen because of local interest in the possible health effects of dioxin exposure as well as the fact that they comprise a group of workers who may have been among the most heavily exposed individuals in the country. Members of the Science Panel pointed out some of the difficulties in conducting this study, particularly in the recruitment of appropriate comparison subjects, the collection of adequate information on reproductive outcomes and the interpretation of results where there is possible confounding with other chemical exposures. However, the Science Panel as well as NIOSH staff recognize the importance of studying this highly exposed group and recommend that the investigators continue their efforts. Results from the proposed pilot study are expected to resolve some of the difficulties, and as part of its review, the Science Panel is preparing detailed comments and suggestions for the NIOSH investigators which may be useful in conducting the proposed studies. cc: Dr. Edward N. Brandt, Jr. Dr. Marilyn Fingerhut � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5738 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Science Panel Review of Epidemiological Studies Proposed by the National Institute for Occupational Safety and Health Based on a Registry of Workers Known to Have Been Exposed to Polychlorinated Dibenzo Dioxins, Draft ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/bbf276965e06dc3308ff336014b18818.pdf 30d2b06640be391747c23579a1bc187c PDF Text Text Item D Number °5737 D Mscanned Author Corporate Author Cabinet Council on Human Resources, White House Ag RBDOrt/ArtlOlO TltlB Fact Sheet on Scientific Research of the Federal Government Journal/Book Title Yoar 000 ° Month/Day Color n Number of hnagos ° DOSCrlUton NOtOS Includes tables of Federally Sponsored Human Studies, Laboratory Studies, and Literature Surveys Related to Agent Orange. Tuesday, March 26, 2002 Page 5737 of 5743 �CABINET COUNCIL ON HUMAN RESOURCES WHITE HOUSE AGENT ORANGE WORKING (WHAOWG) GROUP FACT SHEET ON SCIENTIFIC RESEARCH OF THE FEDERAL GOVERNMENT Membership; o o o o o o o o o o o o Department of Health & Human Services (Lead Agency) White House Office of Policy Development White House Office of Science & Technology Policy Office of Management & Budget/ Executive Office of the President Council of Economic Advisors Department of State Department of Defense Department of Agriculture Department of Labor Veterans Administration Environmental Protection Agency ACTION Observer; o Congressional Office of Technology Assessment �This Fact Sheet of Agent Orange Research was compiled by the Agent Orange Working Group to inform the interested public about current U.S. Federal Government research on phenoxy herbicides and their contaminants. The list describes ongoing research and demonstrates the breadth of research efforts. Interested persons may obtain further information on these studies by contacting the representative, as listed in the Fact Sheet, from each Federal agency conducting research. This Fact Sheet, describing the sixty-four federal studies and research projects completed and underway, is a clear illustration of the time and effort and funding that has been expended in the Federal arena and demonstrates the government's positive effort to seek answers to the Agent Orange question. The Agent Orange Working Group has the responsibility for overseeing such research and disseminating information to the public as it becomes available. In light of this mandate, the Working Group has compiled this list. The Working Group will also assure that research findings are promptly made available to the public as data are gathered and analyses are completed. �CABINET COUNCIL ON HUMAN RESOURCES AGENT ORANGE WORKING GROUP FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE AGENCY STUDY TITLE T Y P E Mortality O F S T U D Y Morbidity Cancer S T A T U S Reproduction Analytical Completed Ongoing Estimated Completion Date DEPARTMENT OF HEALTH AND HUMAN SERVICES NIOSH Investigation of Leukemia Cluster in Madison County, Kentucky Allegedly Associated with Pentachlorophenol Treated Ammunition Boxes Publication Oct 83 CDC Birth Defects and Military Service in Vietnam Study X Late 1983 NIOSH Dioxin Registry X X X Late 85 NIEHS Establishment and Maintenance of an International Register of Persons Exposed to Phenoxy Acid Herbicides and Contaminants X X X Indefinite NIOSH Soft Tissue Sarcoma Investigation X Indefinite NCI Case Control Study of Lymphoma and Soft Tissue Sarcoma NCI Study of Mortality Among Pesticide Applicators from Florida Late 84 X Publications in Press �Page 2 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE TYPE AGENCY STUDY TITLE Mortality Morbidity OP S T U D Y Cancer Reproduction STATUS Analytical Completed Ongoing Estimated Completion Date DEPARTMENT OF HEALTH AND HUMAN SERVICES cont'd X *CDC Epidemiologic Study of Ground Troops Exposed to Agent Orange during the Vietnam Conflict 1987 VETERANS ADMINISTRATION Vietnam Veteran Mortality Studies Vietnam Veteran Identical Twin Studies Survey of Patient Treatment File for Vietnam Veteran In-Patient Care Late X Protocol X Retrospective Study of Dioxins and Furans in Adipose Tissue of Vietnam-Era Veterans Initial 1984 Initial 1983 Survey X Agent Orange Registry Examinations TCDD in Body Fat of Vietnam Veterans and Other Men 1984 X Indefinite Publication in Preparation X 1985 *Mandated to the VA by P.L. 96-151 Sec. 307. Transferred from VA to CDC under Interagency Agreement January 14, �Page 3 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE TYPE AGENCY STUDY TITLE Mortality Morbidity OF S T U D Y Cancer Reproduction STATUS Analytical Completed Ongoing Estimated Completion Date DEPARTMENT OF DEFENSE Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicide Orange (Air Force Health Study) Armed Forces Institute of Pathology Agent Orange Registry of Vietnam Veteran Biopsy Tissues Baseline 1983 Complete 1999 X X Indefinite X Indefinite (Annual Reports) ENVIRONMENTAL PROTECTION AGENCY Report of Assessment of a Field Investigation of Six-Year Spontaneous Abortion Rates in Three Oregon Areas of Relation to Forest 2,4,5-T Spray Practices National Pesticide Monitoring Project of Human Adipose Tissue (Published) X �Page 4 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE TYPE AGENCY STUDY TITLE Mortality OF Morbidity S T U D Y Cancer Reproduction STATUS Analytical Completed Ongoing Estimated Completion Date DEPARTMENT OF AGRICULTURE A Case Control Study of the Relationship Between Exposure -to 2,4-D and Spontaneous Abortions in Humans X Exposure Measurements of Mixers, Loaders and Applicators of 2,4-D on Wheat X 1982 Exposure of Forest Workers to Ground Applications of 2,4-D X 1983 �CABINET COUNCIL ON HUMAN RESOURCES AGENT ORANGE WORKING GROUP FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE AGENCY STUDY TITLE T Y P E D F Mortality STUDY ReproMorbidity Cancer duction Analytical STATUS Estimated Completed Ongoing Completion Date DEPARTMENT OF HEALTH AND HUMAN SERVICES Publications in Press NIEHS Investigation of Leukemia Cluster in Madison County, Kentucky Allegedly Associated with Pentachlorophenol Treated Ammunition Boxes CDC Birth Defects and Military Service in Vietnam Study * NIOSH Dioxin Registry NIOSH Establishment and Maintenance of an International Register of Persons Exposed to Phenoxy Acid Herbicides and Contaminants X Late 1 8 93 X X X Indefinite X X X Indefinite NIOSH Soft Tissue Sarcoma Investigation Indefinite NCI Case Control Study of Lymphoma and Soft Tissue Sarcoma Indefinite NCI Study of Mortality Among Pesticide Applicators from Florida Publications _in Press �FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE AGENCY TYPE OF STUDY Mortality STUDY TITLE STATUS ReproMorbidity Cancer duction Analytical Estimated Completed Ongoing Completion Date DEPARTMENT OF HEflLTH AND HUMAN SERVICES cont'd *CDC Epidemiologic Study of Ground Troops Exposed to Agent Orange during the Vietnam Conflict X X X X X 18 97 VETERANS ADMINISTRATION Vietnam Veteran Mortality Studies Vietnam Veteran^ Identical Twin Studies Survey o f Patient Treatment File for Vietnam Veteran In-Patient Care Agent Orange Registry Examinations X X X X X TCDD i n Body F a t o f Vietnam Veterans and Other Men Retrospective Study o X f Protocol X X X X Late X X Initial 1 8 94 Initial 1 8 93 Survey Indefinite , Publication in Preparation X X 18 94 X 1985 Dioxins and Furans in Adipose Tissue of Vietnam-Era Veterans *Mandated to the VA by P.L. 96-151 Sec. 307. Transferred from VA to CDC under Interagency Agreement January 14, 1983. �Page 3 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE TYPE OF STUDY AGENCY STUDY TITLE Mortality ReproMorbidity Cancer duction Analytical STATUS Estimated Completed Ongoing Completion Date DEPARTMENT OF Epidemiolcgic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicide Orange (Air Force Health Study) Baseline 1963 Complete 1 9 99 Armed Forces Institute of Pathology Agent Orange Registry of Vietnam Veteran Biopsy Tissues Indefinite EWIRONMENTAL PROTECTION AGENCY Report of Assessment of a Field Investigation of Six-Year Spontaneous Abortion Rates in Three Oregon Areas of Relation to Forest 2,4,5-T Spray Practices National Pesticide Monitoring Project of Human Adipose Tissue (Published) Indefinite (Annual Reports) �Page 4 FEDERALLY SPONSORED HUMAN STUDIES RELATED TO AGENT ORANGE T Y P E OF S T U DY AGENCY STUDY TITLE Mortality STATUS ReproMorbidity Cancer duction Analytical Estimated Completed Ongoing Completion Date DEPARTtffiMT OF AGRICULTURE A Case Control Study of the Relationship Between Exposure to 2,4-D and Spontaneous Abortions in Humans 1982 Exposure Measurements of Mixers, Loaders and Applicators of 2,4-D on Wheat Exposure of Forest Workers to Ground Applications of 2,4-D X 1983 �Page 5 FEDERALLY SPONSORED LABORATORY STUDIES AND LITERATURE SURVEYS RELATED TO AGENT ORANGE TYPE OF STUDY AGENCY STUDY Animal DEPARTMENT OF HEALTH AND HUMAN SERVICES Bioassay of Octachlorodibenzo-p-dioxin Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzo-pdioxin in Swiss Webster Mice Carcinogenesis Bioassay of 2,3,7,8-Tetrachlorodibenzc-pdioxin in Osborne-Mendel Rats and B6C3F1 Mice Bioassay of a Mixture of 1,2,3,6,7,8- and a Mixture of 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxins for Possible Carcinogenicity Comparative species Evaluation of Chemical Disposition and Metabolism of 2,3,7,8Tetrachlorodibenzofuran (TCDF) in Rat, Monkey, Guinea Pig and Two Strains of Mice Neurotoxicity of 2,4,-D in Rodents Environmental Analytical Literature STATUS Completed Ongoing Estimated Completion Date �Page 6 FEDERALLY SPONSORED LABORATORY STUDIES AND LITERATURE SURVEYS RELATED TO AGENT ORANGE AGENCY STUDY TYPE Animal OF Environmental STUDY Analytical Literature STATUS Completed Ongoing DEPARTMENT OF HEALTH AND HUMAN SERVICES cont'd Studies of the Chemical Disposition and Metabolism of Octachlorcdibenzodioxin (OCDD) Effects of Agent Orange Compo•nents on Male Fertility and Reproduction Mutagenicity Studies of TCDD, 2,4-D; 2,4,5-^ and Esters of 2,4-D and 2,4,5-T Implications of Low Level Exposure of Dioxins X Mechanisms of Toxicity of the Chlorinated* p-dioxins X Research Toward Understanding the Molecular Level Mechanisms of Toxicity of TCDD and Related Compounds Synthesis of Selected Tetrachlorcdibenzo-p-dioxins and Related compounds as Analytical Standards Estimated Completion Date �FEDERALLY SPONSORED LABORATORY STUDIES AND LITERATUFE SURVEYS RELATED TO AGENT ORANGE TYPE AGENCY STUDY EFFORT Animal OF STUDY Environmental Analytical Literature STATUS Completed Ongoing DEPARTMENT OF HEALTH AND HUMftN SERVICES cont'd Matrix Effect and Sub Partsper-billion Quantitative Analysis of TCDD by Mass . Spectrometry - With Special Reference to Milk Toxic Actions of Tetrachloroazobenzene Dioxins X Xenobiotic Induction of Pleiotropic Responses in Liver X Molecular, Biochemical Actions of Chlorinated-pdioxins Mechanism(s) for Toxicity of Chlorinated Dibenzodioxins Estimated Completion. Date �Page 8 FEDERALLY SPONSORED LABORATORY STUDIES AND LITERATURE SURVEYS RELATED TO AGENT ORANGE TYPE OF AGENCY STUDY Animal Environmental STUDY Analytical Literature STATUS Completed ongoing Estimated Completion Date ENVIROflCNTAL PROTECTION AGENCY Evaluation of Large Scale Combustion Sources • X X Evaluation of Municipal Waste Combustors X X Bacterial Decomposition of TCDD X Investigation of Bioavailability to Fresh Water Fish of TCDDs in Fly Ash X Analysis of Environmental Samples for PCDDs and PCDFs DEPARTMENT OF AGRICULTURE Survey of Phenoxy Herbicide Use by Agricultural Commodity Survey of Phenoxy Herbicide Literature Annaul Bibliographies . Published �FEDERALLY SPONSORED LABORATORY STUDIES AND LITERATURE SURVEYS RELATED TO AGENT ORANGE TYPE AGENCY STUDY Animal OF Environmental STUDY Analytical Literature STATUS Completed Ongoing Estimated Completion Date DEPARTMENT OF AGRICULTURE confd Photolysis of 2,4,5-T X Biological and Economic Assessment of 2,4,5-T and Si1vex X Report in Preparation TCDD Residue Monitoring in Deer DEPARTMENT OF Dtsnabttas Indefinite Environmental Chemistry of Herbicide orange and TCDD VETERANS ADMINISTRATION Review of Literature on Herbicides, Including Phenoxy Herbicides and Associated Dioxins Published 18 91 Annual Update Approved • Urinary 6-Hydroxy Cortisol: Physiological and Pharmacologic Studies (Including Agent Orange) 1982 Effect of TCDD on Lipid Metabolism 1983 �I10 FEDERALLY SPONSORED LABORATORY STUDIES AND LITERATURE SURVEYS RELATED TO AGENT ORANGE T Y P E flGENCY STUDY fefrfeukr Animal OF Environmental STATUS S T U D Y Analytical Literature Completed Ongoing Estimated Completion Date VETERANS ADMINISTRATION cant1 d Mechanisms of Dioxin Induced Toxicity Using the Chloracne Model - Phase I Publication in Press Behavioral Toxicity of An Agent orange Component 2,4-D X 18 94 Effects of 2,3,7,8-Tetrachlorodibenzodioxin on Hepatobiliary Function in Animals \* Mechanism of TCDD Absorption and Toxicity on Lipid and Lipoprotein Metabolism X 1985 1985 Metabolism of the Herbicides Present in Agent Orange and Agent White 1985 TCDD Exposed Rhesus Monkeys: Effects on Behavior and Stress Hormones 1985 �Page 11 BEDERRLLY SPONSORED LABORATORY STUDIES AMD LITERATURE SURVEYS RELATED TO AGENT ORANGE A G E N C Y ! : T Y P E OF S T U D Y STATUS : * STUDY EFFORT, • V;' Animal ' Environmental Analytical Literature Completed Ongoing . Estimated Completion Date '• VETEKJlls ADMJBMISTRR.TION o p n t ' d 4 Neurcmuscular Toxicity of Agent Orange X X 18 95 Mechanisms of Dioxin Induced Toxicity Using the Chloracne Model - Phase II X X 18 95 Effects of Low Dose TCDD on Mammalian Chromosomes and Liver Cells \» Mechanism of Porpfoyria Caused by TCDD and Belated Chemicals X X 18 96 X X 18 96 Effects of Agent Orange on Sleep X X 18 96 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5737 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource Corporate Author: Cabinet Council on Human Resources, White House Agent Orange Working Group Title A name given to the resource Fact Sheet on Scientific Research of the Federal Government ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/4fff6934a4dc21aed906b7d399435add.pdf 7d153694ebb57f8571b464dd982ad8f8 PDF Text Text Item D Number os >™ D Author Gorporete Author Report/Article Title Table 1: Major Epidemiologic Studies of U. 8. Vietnam Veterans, Agent Orange and TCDD Exposure and the Vietnam Experience Currently Ongoing in the United States Journal/Book Title Yeer 000 ° Month/Day Color Number of Images n ° Doscrfyton Notes Tuesday, March 26,2002 Page 5736 of 5743 �Table 1 Major Epidemiologic Studies of U.S. Vietnam Veterans, Agent Orange and TCDD Exposure and the Vietnam Experience Currently Ongoing in the United States Title Responsible Federal Agency and Study Location Type of Study Total Study Population Size Completion Date Air Force Health Study United States Air Force School of Aerospace Medicine, San Antonio, Texas Matched Cohort Study of Ranch Hand Personnel and Controls. Mortality, Morbidity and Reproduction. VA Mortality Study Veterans Administration, Agent Orange Projects Office, Washington, D.C. Mortality Study of 60,000 Vietnam-Era Veterans Early 1985 Vietnam Experience Twin Study Veterans Administration, VA Medical Center, St. Louis, Missouri Morbidity Study of Identical Twins 1,200 1986 Birth Defects Study Centers for Disease Case-Control study 8,400 Control, Atlanta, Georgia of Anatomical Birth Defects 1984 Agent Orange Epidemiologic Study of Ground Troops Centers for Disease Three-Cohort MorControl, Atlanta, Georgia bidity Study of Vietnam Veterans 18,000 1987 Centers for Disease Matched Cohort Mor- 12,000 Control, Atlanta, Georgia bidity Study of Vietnam and nonVietnam Veterans 1987 ^Vietnam Experience Epidemiologic Study 2,500 a) Baseline Reports 1983-1984 b) Long-term followup planned Selected Cancers Case-Control Study Centers for Disease Case-Control study Control, Atlanta, Georgia 2,000-Cases 1988 1,300-Controls Dioxin Registry NIOSH, Cincinnati, Ohio 6,000 Registry Study 1985 �Total Study Population Size Responsible Federal Agency and Study Location Type of Study VA/AFIP Soft Tissue Sarcoma Study Veterans Administration, Agent Orange Projects Officef Washington, D.C. Case-Control Study 500-Cases a) Vietnam Service of Soft Tissue 1,000-Controls Data 1984 Sarcomas b) Total Study 1985 Kansas Soft Tissue Sarcoma Study National Cancer Institute, Case-Control Study of Soft Tissue Washington, O.C. Sarcomas 100-Cases 1984 300-Controls National Cancer Institute, Case-Control Study Washington, D.C. 100-Cases 1986 300-Controls Title ^/Washington Soft Tissue Sarcoma Study " TCDD in Human Fat Veterans Administration Environmental Protection Agency, Washington, D.C. Completion Date 555 samples 1985 Analytical Study of TCDD in demographically collected Human Tissue � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5736 Series The series number of the original item. Series VIII Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Table 1: Major Epidemiologic Studies of U. S. Vietnam Veterans, Agent Orange and TCDD Exposure and the Vietnam Experience Currently Ongoing in the United States ao_seriesVIII