1 15 110 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. 069 Folder The folder containing the original item. 1862 Series The series number of the original item. Series III 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/. Creator An entity primarily responsible for making the resource Bangert, Joseph V. Title A name given to the resource Letter: to Charles H. Hubbs from Joseph V. Bangert, January 30, 1987 Subject The topic of the resource state-funded Vietnam veterans study adipose tissue testing dioxin Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/32473a118ba4e3ebf1959e03b033cd90.pdf 456e7d0110ffd0d81c1f9f6d610856bd PDF Text Text ItoimDNunber 0181 Author Young, Alvin L. ° Corporate Author Rmnrt/Artidfl Titln Letter: from Alvin L. Young to Raymond Suskind, nqiui i/m uuu Febmary 23 1984 Journal/Book Title Year 000 ° Month/Day Color n Number of hianos 1 DeSCrlUton Notes Alvin L. Young filed this item under "Vietnam Veterans Twin Study." Enclosures mentioned in the letter are missing. Wednesday, July 11, 2001 Page 1811 of 1870 �EXECUTIVE OFFICE OF THE PRESIDENT OFFICE OF SCIENCE AND TECHNOLOGY POLICY WASHINGTON. O.C. 20600 February 23, 1984 Dear Ray: Thank you for the special hospitality shown to me during my February 1, 1984 visit to the Institute. I hope your students and staff enjoyed the exchange as much as I did. As a follow-up to our conversation, I have enclosed some documents that will be of interest to you. c 0 0 0 0 Abbreviated package on the results of the Air Force Health Study (RANCH HAND Epdemiologic Study). I presume that George Lathrop will be sending you a copy of the technical report. CDC Protocol for Health Studies of Vietnam Veterans. A 1969 Technical Report on Use of Herbicides in Southeast Asia. OSTP Cancer Document. NTP Cancer Document. The latter two documents on carcinogenesis are in the final review stages and, at least in the case of the OSTP document, will be submitted to the FEDERAL REGISTER in order to solicit public comment. Since my visit with you, I have had the opportunity to discuss with Seth Eisen your continued interests and concerns in the conduct of the Twin Study. I have encouraged him to pay you a visit in the near future. Best wishes. Alvin Young, Ph.D. LT COL USAF Senior Policy Analyst for Life Sciences Dr. Raymond Suskind Director Institute of Environmental Health University of Cincinnati College of Medicine 3223 Eden Avenue Cincinnati, Ohio 45267 � 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. 067 Folder The folder containing the original item. 1810 Series The series number of the original item. Series III 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/. Creator An entity primarily responsible for making the resource Young, Alvin L. Title A name given to the resource Letter: from Alvin L. Young to Raymond Suskind, February 23, 1984 Subject The topic of the resource Vietnam Experience Twin Study Air Force Health Study ao_seriesIII 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. 066 Folder The folder containing the original item. 1801 Series The series number of the original item. Series III 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/. Creator An entity primarily responsible for making the resource Custis, Donald L. Title A name given to the resource Letter: from Donald L. Custis to Max G. Bralliar, September 15, 1983 Subject The topic of the resource Vietnam Experience Twin Study study protocol CSEC Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/fde44ce7602419d46392cb1622e5d080.pdf 336e63644a2ca1469a06dadf926c5b63 PDF Text Text Item ID Number 01774 Author Corporate Author Report/Article TltlO Press Release: News from the National Research Council, Plan for Agent Orange Study of Veterans Needs "Considerable Revision," Research Council Committee Says, November 9,1982 Journal/Book Title Year 000 ° Month/Day Color Number of Images n 3 Desorlpton Notes Monday, June 11, 2001 Page 1775 of 1793 �(.news from the NATIONAL RESEARCH COUNCIL \\ ^ j J The National Research Council was organized by the National Academy of Sciences in 1916 in order to provide for a broader participation by American scientists and engineers in the work of the Academy. The Academy was chartered by the U.S. Congress in 1863 as a private organization with a responsibility for examining questions of science and technology at the request of the Federal Government. The N alional Academy of Engineering was organized in 1964 under the original NAS charter. The National Research Council now serves as the agent of both Academies in the conduct of studies and investigations in the public interest. 2101 C O N S T I T U T I O N A V E N U E , N . W . , W A S H I N G T O N , D.C. 2 0 4 1 8 A R E A CODE 2 0 2 3 3 4 - 2 0 0 0 Date: Nov. 9, 1982 Contact: Barbara Jorgenson or Gail Porter, (202) 33^-2138 Recommends delay until Air Force study completed PLAN FOR AGENT ORANGE STUDY "OF VETERANS' NEEDS "CONSIDERABLE REVISION," RESEARCH COUNCIL COMMITTEE SAYS' " " ~' FOR IMMEDIATE RELEASE WASHINGTON - Citing several design flaws in a research plan to identify possible health effects of the herbicide Agent Orange, a National Research Council committee advised* the Veterans Administration (VA) today to revise the plan and to delay the pilot study of Vietnam ground troops exposed to the chemical until results from a similar Air Force study are available. The Air Force's "Ranch Hand" study is examining veterans assigned to air crews that sprayed Agent Orange and other defoliants in Vietnam. Guidance from the results of this study "should have a significant impact on the directions, methods, and procedures" of the proposed VA study, the committee said. The committee recommended "considerable revision" of both a questionnaire to to be administered to selected Vietnam veterans through personal interviews and of proposed procedures to be used in follow-up physical examinations. It also told the VA that neither of the two methods currently proposed for selecting veterans to be included in the study was satisfactory. The selection method, it added, "requires much further investigation" before a final choice should be made. (OVER) •Copies of the committee's report are available from the Medical Follow-up Agency at the letterhead address. Reporters may obtain copies from the Office of Information, also at the letterhead address. �-2- The VA asked the committee to review a study plan prepared for the agency by the University of California, Los Angeles (UCLA), and to recommend improvements. Noting that the UCLA protocols have already been reviewed in detail by two other scientific panels, the committee chose to address broad issues "which the VA and other planners of this study must face in the next few months." SELECTION OF PARTICIPANTS The committee pointed out that the selection method proposed by the UCLA i researchers may be unnecessarily costly because it would require calculation of exposure levels to the herbicide for all Vietnam ground troops. An alternative method proposed by the Department of Defense (DOD), said the committee, would first estimate the exposure of military units and then select individual veterans with high and low exposures. The DOD method would be much less expensive, but also less valid, according to the committee. "It may be that an intermediate procedure can be identified which combines the advantages of the UCLA proposal with the (relative) economy of the DOD procedure." Enlisted men with multiple tours of duty, officers, and Air Force personnel should not be included in the study, the committee said, because differences between these groups and the majority of Army ground troops would "unnecessarily complicate the analysis." However, marines should be included, it continued, if enough participants are available to allow a separate analysis. Air and maintenance crews assigned to Army-based helicopters used in spraying operations should also be studied, if possible, the committee said. QUESTIONNAIRE AND CLINICAL PROTOCOLS Calling the proposed questionnaire "formidable," the committee recommended that it be focused more on known human and animal effects from exposure to Agent Orange and similar herbicides. Questions asked in the VA study, it emphasized, should be coordinated with those asked in the Air Force study so that data from the two projects will be compatible. Any attempt to study a broader array of possible health effects stemming from the "Vietnam experience," the committee commented, should be independent of the Agent Orange study. (MORE) �-3- Although the questionnaire has been kept confidential, the committee advised that it be provided to veterans groups and other interested parties. The possibility that public release of the survey might influence veterans' responses, said the committee, should not pose problems as long as participants do not know whether they are assigned to the high- or low-exposure groups. The committee also called for removal of ambiguous and esoteric terms from the questionnaire, greater emphasis on symptoms rather than on diagnoses, more detailed attention to quality control and standardization of clinical and laboratory examinations, and additional mortality or cause-of-death analyses to distinguish differences between veterans with high and low exposures. WHO SHOULD CONDUCT THE STUDY The committee concluded that "a stronger central scientific team to coordinate the whole effort can be assembled outside the VA than within it." Consequently, it recommended that the study be conducted by an academic coordinating center strong in biostatistics and epidemiology and with experience in multi-center collaborative studies. A subcommittee of the Committee on Epidemiology and Veterans Follow-up Studies of the Research Council's Commission on Life Sciences reviewed the VA Agent Orange study proposals. The subcommittee was chaired by Brian MacMahon, department of epidemiology, Harvard University School of Public Health, who also chairs the parent committee. Other subcommittee members were George C. Becking, health protection branch, Department of National Health and Welfare, Ottawa, Canada; Gary Friedman, medical methods research department, Kaiser-Permanente Medical Care Program, Oakland, Calif.; Allyn W. Kimball, department of biostatistics, School of Hygiene and Public Health, The Johns Hopkins University; and Leonard Kurland, department of epidemiology and medical statistics, Mayo Clinic, Rochester, Minn. C. Dennis Robinette of the Research Council's Medical Follow-up Agency served as the staff officer for the subcommittee. f # # gp: 1,10 � 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. 066 Folder The folder containing the original item. 1774 Series The series number of the original item. Series III 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 Press Release: News from the National Research Council, Plan for Agent Orange Study of Veterans Needs "Considerable Revision," Research Council Committee Says, November 9, 1982 Subject The topic of the resource Agent Orange Exposure Study Air Force Health Study study protocol study criticism ao_seriesIII 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. 084 Folder The folder containing the original item. 2098 Series The series number of the original item. Series III Subseries IV 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 1985 Title A name given to the resource Australian and American Newspaper Clippings on Agent Orange Royal Commission report, the US Air Force Health Study and veteran issues, November and December 1985, January 1986 Subject The topic of the resource Australian Royal Commission hearings popular press Agent Orange controversy Air Force Health Study ao_seriesIII 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. 079 Folder The folder containing the original item. 2051 Series The series number of the original item. Series III Subseries IV 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 1984 Title A name given to the resource Australian Newspaper Clippings on Australian Royal Commission Hearings, September 1984. Subject The topic of the resource Australian Royal Commission Hearings popular press Air Force Health Study litigation ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/6b5de55c8dd1c26fbfeeb7ce992ec00d.pdf b2b4e844da87d25a222df6031a40a834 PDF Text Text Item ID Number 01724 Author Jemison, Terry Corporate Author RODOrt/ArtiClO TltlO 4 Year JOIirnal/BOOk Title U.S. Medicine Year 1983 Month/Day September 1 Review Complete: Key Agent Orange Study Set to Go Color ° Number of Images 6 Doscrlpton Notes Monday, June 11, 2001 Page 1725 of 1793 �WASHINGTON—Many nurses and doctors in anesthesia training programs— as well as their instructors—have a problem with drug dependence, a new survey of that specialty has found. The survey, published in the JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, was prompted by problems observed in the University of California's San Diego Medical Center anesthesia training program, researchers Dr. C.F. Ward, Gretchen C. Ward, RN, and Dr. Lawrence J. Saidman related. In general, the researchers found that there is more of a temptation for anesthesiologists to use drugs than for other specialties. One rehabilitated drug user commented that "working in the OR was like working in the candy store." "Of the 247 programs which responded to the survey questions, 74 per cent identified at least one suspected episode of abuse, with the program incidence of at least one instance of confirmed abuse being 64 per cent," the researchers related. (Continued on page 12) (Continued on page 11) Key Agent Orange Study Set To Go By Terry Jemison WASHINGTON—The first comprehensive series of agent orange studies involving American ground troops in Vietnam has cleared peer review. E D I C I N E" PERRY L. JEMISON Managing Editor BRA (Continued on page 12) 4-Year Review Complete FRANK M. BEST Publisher (USPS 650-120) "In the western United States a signif- pate in the decentralization program, icant increase in the number of heroin however, but instead will receive emergency room visits was noted in commerical "integrated hospital sys1982 compared to 1977, but the number tems" purchased from software firms. (The software for the decentralized of emergencies is less than half the 1974program was developed within the VA. 1976 peak," the NIDA work group It is in a common language and can be report said. NANCY TOMICH Editor ANN CANNON FINCH Circulation Director U.S. Medicine is published semi-monthly by U.S. Medicine Inc., Suite 505, 2033 M St. N.W., Washington, D.C. 20036-3362. Telephone 463-6000. Subscription price is $55 per year. Second-class postage paid: original entry, Washington, D.C.; additional entry, Baltimore, Md. Postmaster: send address changes to U.S. Medicine, 2033 M St. N.W., Washington, D.C. 20036-3362. ®1983 U.S. Medicine Inc. JOHN A. GENTILE, JR. PHILIP KEUSCH PUBLISHING, REPRESENTATION Advertising RESEARCH, INC. Representative 800 Second Ave., New York, N.Y. 10017 Phone (212) 599-3166 Though one review panel's written comments are pending, which is a formality, the investigation appears ready to begin—nearly four years after Congress demanded it. While the Veterans Administration was wrangling over the ground troops study during most of that time (it eventually was relieved of responsibility for the work), other agencies got smaller studies of Vietnam veterans off the ground. In one, an Air Force study of 1,247 former flight crew members who sprayed the herbicide, data collection already has been completed with preliminary results clear: zero cases of several diseases of particular interest to compensation advocates. The Centers for Disease Control, which during the four years launched a birth defects study that now is nearly complete, this year took over VA's ground troops study. For years, some of the VA's strongest advocates in Congress, leaders of the House Veterans Affairs Committee, had stood by VA as it weathered storms of criticism. The CDC takeover occurred when some of those congressmen finally jumped ship and urged VA to give the study up. VA complied promptly. CDC, building upon the VA's work from late 1979 through the end of 1982, was able to complete a protocol in just a few months. After several additional months of peer review, two weeks ago the CDC ground troops study was approved by a White House work group, sources said. (Continued on page 28) Moving To DoD Alcohol, Drug Abuse & Mental Health Administration director, Dr. Willam £. Mayer, has reportedly been offered and has accepted the position of assistant secretary of defense for health affairs. The position is currently held by Dr. John F. Beary, who resigned his post effective mid-September. �U.S. MEDICINE 28 Agent Orange Study Clears Peer Review (Continued from page 2) A pilot phase is scheduled first, and according to the CDC timetable developed earlier this year, selection of veterans for the pilot study will be completed two months after peer review. CDC has "sole responsibility" for "all decisions" for interpreting the research results 4'/$ years from now under terms of a VA-CDC interagency agreement, according to a VA analysis of the pact. CDC will report its findings to VA. However, even when they controlled the study, VA leaders above the level of the Department of Medicine and Surgery avoided even general commitments to any policy action based on positive—or negative—findings. In contrast, Health and Human Services Department officials subsequently boasted that existing research and pending studies are expected to have the power to "wrap up" the agent orange issue. The House committee leaders' support for the shift of control to HHS followed their hearings where the HHS comment was made. Peer review of the study was completed in mid-August, when a White House work group approved the work of several peer review panels. One of the CDC investigators working on the project, Dr. Peter Layde, said before the White House meeting that no major shifts in focus had resulted from the tiers of peer review in recent months. One of the reviews was conducted by the congressional Office of Technology Assessment (OTA). President Carter, who was in office when the congressional mandate for the study was passed, previously had advised federal scientists to ignore a requirement in the law that OTA review the protocol, citing it as a "legislative veto" that he opposed in principle. The OTA review was not blocked by the Reagan administration, however, and in a report issued in July, OTA director John Gibbons praised the study design as "well constructed and strengthened by CDC's efforts to look ahead...." The study was required by Congress in Public Law 96-151—legislation reported by committee in May 1979 which became law that December. Since then, some of VA's delays in producing the study may be related to the disorder of Army records and litigation by veterans themselves who challenged VA's study methods. VA work on the study received considerable scrutiny from veterans groups active on agent orange, with some activists complaining VA was dragging its feet. By comparison, when the White House, through CDC's parent agency (Health and Human Services), recently conducted a publicly announced, open meeting for a panel of scientists and outside advisors to review the protocol, no veterans groups were in attendance among the handful of observers at the outset of the meeting. The head of that peer review committee, John A. Moore, DVM, described as a "critical question" one scientific issue that many say has been a great stumbling block to getting the study moving: quantification of exposure and selection of exposure cohorts. He and the CDC primary investigator, David Erickson, DDS, PhD, agreed at that meeting that the question is surrounded by uncertainty, and that while "most likely exposed" and "least likely exposed" cohorts may be separated on the scale of exposure as widely as possible, scientists may never know what the top and bottom of the scale is. Dr. Erickson, asked by peer reviewer and Mt. Sinai medical school environmental sciences director Dr. Irving J. Selikoff about ways to verify data on herbicide spraying, said the Ranch Hand Unit defoliation missions are documented—by time, space covered and quantities used—on computer tapes. He added there is "considerable doubt about the accuracy of these records in some quarters, particularly Air Force people." While others think the records are relatively good, Dr. Erickson said, scientists probably always will worry that some of the agent orange applications may be unknown, perhaps "buried" somewhere in records other than those of chemical units. Dr. Selikoff suggested that in the pilot study about to begin, 100 or 200 of the enrollees could be questioned about exposure and that recalled experience could be compared with the unit location in the Ranch Hand records. Dr. Erickson conceded such a test may be useful, but he noted that with the CDC birth-defects study already in progress he has found there is a lot of skepticism "particularly in the military" about what the veterans can tell epidemiologists. The popular insecticide malathion intentionally was sprayed on the jungle canopy in the vicinity of ground troops, he noted, and that may be the aerial spraying a veteran recalls. ........ �•en," —U.S. Medicine photo Dr. Peter Layde No major shifts in peer review Dr. Moore, director of the National Institute of Environmental Health Sciences (NIEHS) national toxicology program (and rumored to be in line for transfer to the Environmental Protection Agency), polled the peer reviewers on cohort selection and found no dissent on the concept of exposure classification. After the meeting, Dr. Moore declined to comment on the group's consensus on the sticky scientific issue of separation of exposure cohorts. (His secretary said he was too busy to make even 10-minute appointments for the indefinite future, and aides to both the directors of NIEHS and the National Institutes of Health indicated those program officials do not supervise his work on agent orange matters, but he reports directly to the White House group instead.) The White House panel, the Agent Orange Work Group of the Cabinet Council on Human Resources, was the last group to consider peer reviewers' reports. It always meets in secret. One protocol review obtained by U.S. MEDICINE—the OTA review— describes exposure cohorts that would be 6,000 Vietnam veterans each. �, Sources indicated that is unchanged. There would be three such cohorts in the main study: •Troops who served in combat areas located near an area where use of agent orange was recorded. •Servicemen in a combat area where I no such use was recorded. •Veterans who did not serve in combat areas and who were not thought to be exposed to agent orange. "Although it appears unlikely that the methods chosen will not allow some separation between exposed and nonexposed veterans, that possibility must be kept in mind," OTA said (emphasis . added). "In other words, it is still possible that studying associations between health effects and agent orange exposure may not be possible because the records will not provide information for meaningful exposure classification. "The protocol shows that CDC is aware of the problems in deciding about exposure status and provides assurance about the ability of the CDC to make appropriate decisions as the study goes along," OTA said. Another companion study, the "Viet| nam experience study," will contrast the health status of a cohort of 6,000 Vietnam veterans with another 6,000 veter- j ans who are not Vietnam veterans. It i may test for the health effects of ele- \ ments of the Vietnam environment, but I is not designed to examine any specific ; factors. • "This study, like the agent orange \ study, is 'hypothesis generating,'" Gib- \ bons of OTA said. "Currently, too little \ is known about possible health effects • • of Vietnam service to design a study to | test hypotheses that particular diseases j 1 are associated with Vietnam service," he 1 said. In the formal report, OTA said that in the absence of expectations of disease based on theoretical or empirical considerations, the studies are not justified "in terms ordinarily used by scientific review bodies." i However, OTA said, if the study of j the health experience of Vietnam veter- j ans is justified "on other than only ; scientific basis," then the research is ; appropriate. The VA's position is that no longterm health effects of exposure to dioxin have been demonstrated for diseases other than chloracne. Yet even before legally required to do so, it said its physicians' compassion for veterans compelled it to treat a veteran for a non-service-connected condition the veteran alleged was due to agent orange when hospital resources allowed it to do so. OTA's analysis of the protocol found that the agent orange study and the Vietnam experience study will have high sensitivity to detect a two-fold increase in risk "for health outcomes that occur in the control population at a \ rate of about 0.5 per cent—for outcomes based on the questionnaire phase." "For the medical, psychological and laboratory phases," OTA continued, "the studies will have high power to detect two-fold increases in outcomes that occur at the rate of 1.5 to 2 per cent in the control population. "For outcomes occurring more frequently, and for greater increases, the studies will have correspondingly greater power. "In comparison to most cohort studies that have been done, these studies are very powerful due to their large size. Even so, as CDC recognizes, the cohort design is not well-suited to detecting rare effects or those which occur at only slightly increased frequencies in the exposed group." In other developments in the agent orange issue: •A report issued by VA last month shows that nearly 6,000 veterans have �—U.S. Medicine photo Rep. James H. Scheuer AM A used 'loose and thoughtless' language filed disability compensation claims for skin conditions they relate to agent orange. Earlier, it was incorrectly reported that a third of skin condition claims had been granted (though not due to agent orange specifically). A VA newsletter on which the calculation was based did not qualify its statement that "3,200 claims (have been) filed by Vietnam veterans" as being only a partial total of claims, a sampling used to check the claims for chloracne cases. (In fact, only one case among the 6,000 now is considered possibly chloracne, an agent orange office researcher recently said.) i The 1,300 claims that had been allowed are among 6,000 claims, not 3,200. •According to a later issue of the same newsletter, "Agent Orange Review," chief medical director Dr. Donald L. Custis has reported that about 9,400 Vietnam veterans received care in approximately the first year of an agent orange medical care law raising their eligibility above most non-serviceconnected veterans. The VA's monitoring covered the period February 1982 to February 1983. The law, signed in November 1981, gives VA broad authority to treat veterans when the origin of their illness is uncertain and the possibility of a temporal relationship to Vietnam service cannot be ruled out. During the same period, there were 369,000 outpatient visits. •The House Veterans Affairs subcommittee on compensation and pensions reportedly advanced legislation that would provide compensation to Vietnam veterans suffering from chloracne, porphyria cutanea tarda and soft-tissue sarcoma if the disease appears within 20 years of discharge. Sponsor Rep. Thomas Daschle (D., S.D.) has maintained that scientific literature supports an association between the diseases and exposure to agent orange or its components. The Veterans Administration, which disagrees, opposed the bill, and according to press reports, the subcommittee split on party lines, with seven Democrats favoring it and four Republicans opposing the measure. •The American Medical Association, offering testimony at recent congressional hearings, is stressing the inadequacy of the science base to blame agent orange for long-term health effects other than chloracne, and it said legislation providing compensation should go no further than chloracne. AMA representative Dr. John R. Beljan, who chaired an association I I �advisory panel on toxic substances, has been kept busy explaining the association's action at a June meeting. The group accepted a resolution that AMA begin "an active public information campaign to get accurate information on dioxin before the public to prevent irrational reaction and unjustified public fright." Though not now part of AMA policy, a series of "whereas" clauses that precede the resolve drew, sh^irp reaction. They said in part, "The news media have made dioxin the focus of a 'witch hunt' by disseminating rumors, hearsay and unconfirmed, unscientific reports, including quotes attributed to scientists whose quote should have been, 'I don't know.'" Rep. James H. Scheuer (D., N.Y.), for example, in hearings of his House Science and Technology subcommittee, told Dr. Beljan that the AMA staff technically may dissociate itself from the colorful "whereas" clauses of the sponsoring (Missouri) delegation, but the language remains part of the AMA's "public posture." "lam really astonished that a professional organization as highly respected as the AMA...should have represented itself in such—well, to put it charitably— loose and thoughtless language," Rep. Scheuer said. He heads the subcommittee handling environmental matters. The controversial preamble to the resolution in the AMA house of delegates alleged the lives of people in areas of dioxin-contaminated sites have been ignorantly damaged "by this hysterical mal-reporting." "If one of my kids wrote such an irresponsible editorial in a high-school newspaper...! would whack their fannies," Rep. Scheuer said. Dr. Beljan said, "I regret the unfortunate continuing use of the words 'witch hunt.' That is not AMA policy." Another AMA witness explaining the AMA policy process—delegation proposals, reference committee review, and house of delegates action—told Rep. Scheuer that the clarification of just what part of the resolves were adopted by AMA was pursued in 75 media contacts in just the first week after the meeting. Explaining that the AMA recognizes chloracne as a possible long-term effect of dioxin exposure, Dr. Beljan added, "With respect to other alleged human health effects attributed to dioxin, the (AMA) Council on Scientific Affairs and its advisory panel concluded there was insufficient published data subject to peer review to establish a relationship between dioxin exposure and the adverse health effect." Two days before that hearing; Health and Human Services assistant secretary for health Edward N. Brandt Jr., MD, PhD, said in a letter to AMA president Frank J. Jirka that while he agreed with the policy to provide dioxin information to the public and the practicing physician, "we do not agree with some of the preparatory statements in that resolution." •Though the absence of any major unusual mortality patterns in the members of the Ranch Hand Unit that sprayed agent orange had been suggested earlier in raw data, the Air Force has released its detailed statistical comparison of study subjects and controls that formally affirms it. Morbidity analyses are continuing and only raw data have leaked out. "The mortality analyses described in the report have not revealed any statistical excess in the deaths recorded in the herbicide/dioxin-exposed group," the Defense Department said in a statement. "At this time, there is no indication that Operation Ranch Hand personnel have experienced any increased mortality or any unusual patterns of death in time or by cause. They are not dying in increased numbers, at earlier ages or by unexpected causes." �U.S. MEDICINE — U.S. Medicine photo Dr. John R. Beljan 'Whereases' are not AM A policy Statistically insignificant were findings of an increase in liver disorder deaths and a decrease in cancer deaths in the 1,247 defoliation pilots and flight crew members, compared to controls. "Highly significant" was lower mortality among Air Force members, both Ranch Hands and controls, compared to the average U.S. male, the Defense Department said. The statistical power of the study was criticized by some veterans. An attorney representing 20,000 Vietnam veterans or their families was quoted as calling the study "a patent fraud.... It has no power to detect anything short of a catastrophe." The 1,247 Ranch Hand unit members were compared to 6,171 controls who flew only cargo missions to, from or in Vietnam during the same period. "By a computerized 'nearest neighbor' selection process, up to 10 comparison individuals were matched to each Ranch Hander by job category, race, and age to the closest month of birth," the study summary reported. Five individuals were randomly chosen from each comparison set for a 1:5 design. "This baseline mortality report can in no way be regarded as conclusively negative because this small, young, and relatively healthy cohort may not have yet 29 reached the latency period wherein attributable fatal disease might be expected and detected within limited power boundaries of this study," the report cautioned. Principal investigators for the study, conducted at the School of Aerospace Medicine at Brooks AFB, Texas, are Col. George D. Lathrop, USAF, MC; Col. Patricia M. Moynahan, USAF, NC; Dr. Richard A. Albanese of the Data Sciences Division; and Lt. Col. William H. Wolfe, USAF, MC •A conference at the Centers for Disease Control in Atlanta has produced a consensus that a safe level of dioxin contamination in the soil of residential areas is 1 ppb. But Dr. Vernon N. Houk, director of the CDC Center for Environmental Health, cautioned, "There can't be a single national standard of any magic number." While the 1 ppb level can be used as an "action level," local demographics as well as the nature, pathways and lengths of exposure also must be considered, he said. "There may be levels of concern in each kind of situation," he said at a hearing following the conference. � 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. 064 Folder The folder containing the original item. 1724 Series The series number of the original item. Series III 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/. Creator An entity primarily responsible for making the resource Jemison, Terry L. Source A related resource from which the described resource is derived U.S. Medicine Date A point or period of time associated with an event in the lifecycle of the resource September 1 1983 Title A name given to the resource 4-Year Review Complete: Key Agent Orange Study Set to Go Subject The topic of the resource Agent Orange Exposure Study AMA Air Force Health Study Vietnam Experience Study ao_seriesIII 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. 078 Folder The folder containing the original item. 2007 Series The series number of the original item. Series III Subseries IV 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/. Creator An entity primarily responsible for making the resource Earley, Pete Source A related resource from which the described resource is derived The Washington Post Date A point or period of time associated with an event in the lifecycle of the resource March 9 1984 Title A name given to the resource Inside: The VA Subject The topic of the resource Australian Royal Commission hearings Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/c81ecbc866a23746c13a8abfeb0e46fa.pdf cf037bec869d77532e2280a7c52d9fcd PDF Text Text Item ID Number 01/12 Author Stellman, Steven D. Corporate Author ROpOrt/ArtlGlO TitlO Typescript: Estimation of Exposure to Agent Orange and Other Defoliants Among American Troops in Vietnam: a Methodological Approach [nd] Journal/Book Title Year 000 ° Month/Day Color Number of ImaBBs n 40 Descrlpton Notes Monday, June 11, 2001 Page 1713 of 1793 �ESTIMATION OF EXPOSURE TO AGENT ORANGE AND OTHER DEFOLIANTS AMONG AMERICAN TROOPS IN VIETNAM A Methodological Approach Steven D. Stellman, Ph.D. American Cancer Society 4 Nest 35th Street New York, NY 10001 Jeanne M. Stellman, Ph.D. School of Public Health Comprehensive Cancer Center Columbia University 21 Audubon Avenue New York, NY 10032 This work was partially supported by U.S. Service Grant NCI #5K07-CA-00730 <JMS) and by a from the National Council of Churches. Public Health special grant A preliminary account of this work was presented at the annual meeting of the American Public Health Association in Montreal, November, 1982. �ABSTRACT Two pivotal problems in determining whether exposure to herbicides has caused disease in Vietnam veterans or their offspring are definition of which troops were exposed and extent of exposure. The DoD HERBS tape is the most complete publicly available record of herbicide spraying in Vietnam. It contains about 17§000 records consisting of coordinates of spray missions, dates, chemical agent, quantity and area sprayed, and mission purpose. We have developed a set of discrete and con- tinuous indexes of exposure to herbicides for individual veterans. These indexes are based upon HERBS tape spray data, and upon locations and dates of service derived from a place-and-date matrix completed by the veteran. They can take into account environmental persistence of herbicide using first-order exponential decay kinetics with an estimated half-life of dioxin. Mean values for the continuous exposure indexes were significantly greater among veterans judged to be exposed according to self-reported job titles and specific military experiences, compared to men judged unlikely to have been exposed. Exposure indexes based upon the HERBS tape for classification of exposure to herbicides in South Vietnam during 1965 - 1971 appear to be well suited for use in epidemiologic studies. �AGENT ORANGE EXPOSURE INDEX Page 1 The possible human health effects associated with the systematic spraying of large portions of South Vietnam with defoliating chemicals carried out by the United States during 1962 to 1971 are a matter of great public and professional debate and concern. During that time nearly six million acres of land were sprayed. Agent Orange, a 1:1 mixture of the n-butyl esters of 2,4-D and 2,4,5-T, was the main herbicide used. Agents Nhite (2,4-D and picloram) and Blue (cacodylic acid) were also used but in lesser amounts [Young et al., 1978]. The ingredients of Agent Orange are known to be toxic. 2,4,5-T is embryotoxic and teratogenic to the mouse [Courtney and Moore, 1971; Neubert and Dillman, 1972; Hood et al., 1979], causes fetal anomalies in hamsters [Collins and Nilliams, 1971], and induces a variety of genotoxic effects in numerous animal and plant species [Grant, 1979]. 2,4-D in large doses can poison experimental animals and livestock [Rowe et al.,1954; Fenton, 1984], and is neurotoxic to humans [Goldstein et al., 1959]. When given orally to rats, 2,4-D was found to be embryotoxic and fetotoxic, but not teratogenic [Schwetz et al., 1971]. The 2,4,5-T used in Agent Orange was also heavily contaminated with 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) and its congeners [Young et al., 1978]. The mean concentration of TCDD in Agent Orange was 2 ppm. Individual concentrations ranged from 0.05 to about 30 ppm [Young et al., 1978]. In laboratory animals, TCDD was found to be extremely toxic [Huff et al., 1980]. The LD-50 for guinea pigs is less than 2 ug/kg of body weight [Huff et al., 1980; Schwetz et al., 1973]. At subacute �AGENT ORANGE EXPOSURE INDEX Page 2 doses it produces many other systemic effects. TCDD is also embryotoxic and teratogenic to several strains of rats and mice [Courtney and Moore, 1971], and has been found carcinogenic by several routes of administration [International Agency for Research on Cancer, 1977; Van Miller et al., 1977j Kociba et al., 1978]. The effects of TCDD on humans are not so well established as those for animals. Human health effects are known chiefly from studies following industrial accidents and other occupational exposures. Clinical evaluation of workers and others exposed to dioxins has produced a wide range of dermatological, metabolic, neurological, and behavioral effects [Huff et al., 1980]. The best known and most widely recognized of these is /• chloracne, which is often described as the "hallmark" of dioxin exposure. However, many of these other conditions can result from exposure without chloracne being present [May, 1973} Oliver, 1975} Pazderova-Vejlupkova et al., 1981]. These and other observations have led to the hypothesis that soldiers exposed to Agent Orange during military service in Vietnam may be at increased risk for various acute and chronic diseases and for fathering children with birth defects. �AGENT ORANGE EXPOSURE INDEX Page 3 Currently a number of studies are being conducted on the health of Vietnam veterans and their offspring. The majority are planned as long-term investigations and will not be completed for some years [American Medical Association, 1981], A prelimi- nary account of the Baseline Morbidity Study of Air Force personnel who conducted aerial herbicide dissemination missions in Vietnam (Operation Ranch Hand) showed no significant differences compared to control groups in conception outcomes such as prematurity, miscarriages, stillbirths, or "severe" birth defects, but did observe an excess of "minor" defects," as well as a significant excess of neonatal deaths and physical handicaps [Lathrop et al., 1984]. Among the studies now complete, a case-control study of babies born in the metropolitan Atlanta area concluded that Vietnam veterans in general did not have an increased risk of fathering babies with defects (all types combined) [Erickson et al., 1984a]. However, veterans judged to be "exposed" to Agent Orange had significantly higher risks of having children with birth defects including spina bifida, cleft lip with or without cleft palate, and a miscellaneous constellation of neoplasms. Donovan et al. [1984] have reported that the risk for Australian Vietnam veterans to have fathered a child with a birth defect was no different from that of other Australian men. �AGENT ORANGE EXPOSURE INDEX Page 4 In all of these studies, one of the most difficult problems has been that of defining exposure. Accurate data on individual exposure is not available. Information on general herbicide usage exists but has so far proved difficult to translate into individual exposures. Lathrop et al. [op. cit., Chapter M i l l ] computed an average exposure index for each Ranch Hand subject by dividing the total gallonage of TCDD-containing herbicide sprayed in the entire Vietnam theater during the subject's tour of duty by the number of airmen with duties equivalent to that subject during the same time period. This measure does not take into account individual exposures at specific times and places. Yet, even this index was largely ignored by the authors in their analysis. Instead, most epidemiological comparisons were made between the entire group of soldiers in Operation Ranch Hand and various nonRanch Hand control groups, in effect assuming a single presumably high average level of herbicide exposure for all those in Operation Ranch Hand and another, lesser level for the control group. Erickson et al. also used two different exposure indices. The first was a self-report obtained by asking the subject "Do you think you were ever exposed in any way to herbicides, like Agent Orange?" [Erickson et al., 1984b, p. 228] A more objective "Exposure Opportunity Index" (EOI), was also developed, whereby a "panel of specialists familiar with existing records of herbicide spraying in Vietnam used a mixture of objective and subjective methods" to estimate possible exposures for individual veterans [Erickson et al., 1984b, p. 2 ] Two separate 3. �AGENT ORANGE EXPOSURE INDEX Page 5 ECU scorings Mere done, one based on occupation, location, and time recorded in military records ("records-based score"), and one based on similar information obtained from direct interviews with the veterans ("interview-based score"). Despite this incorporation of external information, the EOI scoring system was judged by authors of the study to be "a generally subjective evaluation." Furthermore, Erickson et al. have commented that the mixture of effects reported could easily have resulted from errors of misclassification [Erickson et al., 1984a]. Thus, in contrast to the highly technology-intensive techniques for evaluating the medical status of veterans, the methods of estimating exposure to herbicides have remained fairly crude. Future studies of health and reproductive outcomes of Vietnam veterans will require development of more objective, valid exposure evaluation methods. One valuable source of objective, specific information on the patterns and extent of herbicide usage in Vietnam is the so-called HERBS tape, developed by the U.S. Army. This data source was used to derive the "records-based score" in the Atlanta birth defect study although the exact way in which the information was incorporated into the EOI was not described [Erickson et al., 1984b, p. 23]. The purpose of this paper is to investigate the use of the HERBS tape to see whether it can be an objective, valid source for exposure classification for individual veterans. The data file contained on this tape consists of an assembly of over 17,000 records, each describing a piece of a herbicide spray �AGENT ORANGE EXPOSURE INDEX Page 6 mission. The information provided within each tape record is summarized in Table It Besides location, the tape records also contain data on dates of spraying, the type of mission, which of the three herbicides was used, the volume used and the area sprayed. The HERBS tape was kindly made available to us by the Records Management Group of the office of the Adjutant General of the U.S. Army. MATERIALS AND METHODS Resourcei DoD HERBS Tape The 1980 version of the HERBS tape which we analyzed contained data on 6,475 distinct missions. A mission typically consisted of several legs, each one representing a continuous spray route, possibly including jogs. Each HERBS tape record refers to a single coordinate point on the map of Vietnam. Con- tinuity of spray runs from point to point on the map (and from one HERBS tape record to the next) is indicated by letter-numeral combinations called leg designators (1A, IB, etc.). The numeral of the leg indicates the number of the run within the mission to which the associated coordinate belongs, and the letter designates the leg within that run. The coordinates are keyed to the Universal Transverse Mercator (UTM) system, which is a rectangular grid ruled off in 100,000 meter sub-grids. The diagram in Figure 1 shows two legs of a mission flown near Pleiku. The plane turned its spray on at 1A, and continued to spray as it flew on to IB, 1C, ID, IE, and IF. It turned the spray off, flew to position 2A, and sprayed until 2B. �AGENT ORANGE EXPOSURE INDEX Page 7 For our calculations, we used established coordinates of vertices only, rather than center-points or average locations, since low-flying spray planes were frequently fired upon and forced to deviate from a straight-line course. Construction of Exposure Scales The method described here consists of several approaches used separately and in conjunction to provide different exposure indices for the Vietnam veteran in question. The parts are: (a) discrete exposure indices. Cg, CIQ, G ig , which are counts of the number of times a veteran was located within a specified radius (5, 10, or 15 km) from any of the spray locations on the HERBS tape, at times when spraying occurred; this index incorporates information supplied by the veteran using a pre-coded and tested Vietnam place-and-date matrix developed for this purpose; (b) Con t i nuQUs Exposure Indi ces t (i) E, , a continuous distance-weighted measure of how close in distance to actual defoliation missions the veteran was during his tour of duty, as calculated using the HERBS tape data and the veteran's military experience and place-and-date matrix; �AGENT ORANGE EXPOSURE INDEX Page 8 (ii) Eg, an integrated estimate combining both direct exposure, as in (i), and indirect exposure deriMed from residual herbicides, in an area of duty where spraying occurred prior to the veteran's service in that area, using the HERBS tape data and the veteran's place-and-date matrix; (iii) E-,, an integrated exposure index combining both (i) and (ii) above which allows for direct exposure, indirect exposure through environmental persistence, and distance from spraying missions during a veteran's tour of duty; (c) a self-reported history by the veteran of the dates and locations he served in Vietnam as recorded in the place-anddate matrix; (d) self-reported descriptions of military service, jobs and experiences using a pre-tested, pre-coded questionnaire. The discrete indices simply count the number of likely exposures which could have occurred within a specified radius of a veteran's location, while the continuous indices can take into account concurrent exposures plus potential exposures to residual herbicides from all previous spraying missions which took place within 15 km of a given location. �AGENT ORANGE EXPOSURE INDEX The discrete scales; C Page 9 (r_ - 5, 10, 15) is a count of the number of spray locations, represented by records on the HERBS tape, which fell within a specified distance, r_, place-and-date position reported by the veteran. of each Two hypotheti- cal examples of this calculation are shown in Figure 1 and in Table 3. In the example of Figure 1, a veteran reported that he was present in Pleiku on the date the diagrammed spray mission took place. As shown in the Figure, three vertices fall within 5 km of Pleiku, six fall within 10 km, and all eight fall within 15 km. We call these counts the "number of hits within 5, 10, and 15 km," respectively, and our scheme assigns the veteran exposures C5 = 3, C.Q = 6, and Cig = 8. This type of count can be computed for any location in Vietnam whose UTM coordinates are known. The con t i nuous scales; These indices are defined by i three related continuous exposure measures (E.-Eg). The first, represented by Equation 1, defines the index of exposure, E,, as the sum of the reciprocals of the distances of all spray locations from a given position. I E, = CoSd/D::) ._.._ " _. J (1) where C_ represents the initial concentration of the herbicide in each of the spraying missions, D.. is the distance from the veteran's i.th known location to the j.th coordinate on the tape, �AGENT ORANGE EXPOSURE INDEX Page 10 whose dates coincide with the veteran's assignment dates at location j . Distances closer than 10 m are counted as 10 m to . prevent the sum from approaching infinity. For the continuous index £<, , we only use spray dates included within the veteran's stay at location i,, which do not include the effects of spraying during previous missions. The use of reciprocal distances in this index gives higher weight to closer "hits" in the summation. For computational convenience, the sum is restricted to all distances less than or equal to 15 km, since hits at greater distances contribute negligbly to the sum. The second continuous measure of exposure, £„, is given by Equation 2. Eg has been constructed to consider the environ- mental persistence of an exposure over time. .. where X is a decay constant and t is time. For an individual veteran, the expression in Eq . (2) is integrated mathematically from t = t,, . . to t=tg . ., where t- . . is the first date he was stationed at location j and t,,, . . is the date he left it. The . <£fij integral is evaluated for each location j_ on the HERBS tape within 15 km of veteran location JL, provided the herbicide spraying occurred prior to t,, ... If the spraying occurred after ^ , ij time t, . ., then the lower limit of the integral is set to the J. , 1 3 actual date of spraying. �AGENT ORANGE EXPOSURE INDEX Page 11 Eg takes into account explicitly the fact that once sprayed Agent Orange and other herbicides will not instantaneously "disappear" but will be present in the environment, and will be degraded as time passes. He have used a first-order exponential decay, with rate constant A. . The choice of a first order decay law in the present study, that is, a constant halflife, is conservative since it assumes a more rapid disappearance than might actually have occurred. Studies of environmental persistence of TCDD in soil surrounding Seveso, Italy, the site of a large scale environmental release of TCDD, showed an increase in half-life with time [DiDomenico et al., 1980]. However, environmental degradation of TCDD in persistence studies conducted on heavily treated soils at test sites in Utah and Florida, observed by Young et al. [1976], demonstrated decay consistent with first order kinetics. In our calculations, we have assumed a half-life of one year, as suggested by several studies of TCDD persistence in soil [DiDomenico et al., 1980; Young et al., 1976$ Kearney et al., 1972]. The exposure index, E2, therefore gives higher weight to more recent sprayings, while "remembering" past sprayings, but weighting them according to an exponential decay law. As with any first-order decay, the half-life, tau, is given by i i I T i/z = In 2/X (3) �AGENT ORANGE EXPOSURE INDEX Page 12 A third index, Eg, given in Equation 4, is a composite of E. and Ep, which combines environmental persistence with reciprocal distance, to give higher weight to more recent sprayings as well as to closer hits. • * tst IJ ,,-, .. where the indices i and j. . - - -xt dt ar| d times t. . . and t 0 . . are defined A ,i j £,ij above. In these equations we have assigned a constant concen- tration CQ to the herbicide used in all missions. Self-Reported Exposure Data Self-reported history and place-and-date matrix formats were developed in consultation with numerous veterans and other experts on Vietnam geography. A matrix, divided into the four Combat Tactical Zones, or Corps, in Vietnam, 1,11,111,1V, was created in which major, villages, locations and areas heavily used by American troops were listed by the names used by the veterans. The printed matrix was accompanied by a map of Vietnam on which larger towns were also shown. The matrix was designed so that the respondent could indicate up to 98 specific places in Vietnam where he might have served and the dates that he was there. �AGENT ORANGE EXPOSURE INDEX Page 13 Subjects were asked whether or not they had experienced any of the following: been a sprayer on a C-123, helicopter, or boat, had worked at clearing vegetation, had worked as a sprayer or handler of herbicides during shipment, or had slept in or walked through obviously defoliated areas. Subjects were then classified as "exposed" or "not exposed" to each of these spray occupations or to recently sprayed terrain. This method of collecting location and date information data was pre-tested in 100 California veterans, and proved to be a satisfactory data collection instrument. Approximately 70% of questionnaires had sufficiently completed places and dates to calculate the above exposure measures, without assistance and without an interview. The questions used in the self-described exposure section are reproduced in Table 2. This information allowed us to compare the measures of exposure derived from the HERBS tape against the observations, experiences and military jobs reported by the soldiers. \ Application of Algorithms and Analysis of HERBS tape We have tested the exposure indices on a sample of 478 veterans selected from a study we have been conducting with the Veterans Education Project of the National Veterans Law Center, American University. Several thousand questionnaires were mailed to veterans participating in a nationwide outreach program sponsored by the Veterans Education Project. The questionnaires solicited information on veterans' health and reproductive outcomes, �AGENT ORANGE EXPOSURE INDEX Page 14 and contained the exposure instruments described above. This sample was clearly highly self-selected, so that it would not be appropriate to directly generalize associations of herbicide exposures with health outcomes from this population to all Vietnam veterans. However, since our present purpose is only to investigate our proposed exposure indices, and not health outcomes, there is nothing inherently biased in using this group to test and validate the exposure algorithms, of which the respondents had no knowledge. Finally, we have also carried out calculations on the aggregated data contained in the HERBS tape to obtain additional data on overall usage of defoliants and hence to provide more information about potential exposure of American troops in Vietnam during the 1965-1971. In addition we have made estimates of the relative concentration of herbicides used on each of the missions by calculating the ratio of gallons to area sprayed using the data recorded on the tapes. �AGENT ORANGE EXPOSURE INDEX Page 15 RESULTS Overall Patterns and Extent of Defoliation Activities Quantities of herbicides recorded on the HERBS tape can be compared with previously published estimates of herbicide use in Vietnam, as an indicator of the completeness of data available to us. The total volume of Agent Orange recorded on the HERBS tape was 11,197,929 gallons, which differs by less than Q.7% from the quantity reported by the National Academy of Sciences [Committee on the Effects of Herbicides in South Vietnam, 1974]. Similar levels of agreement were observed for Agents Blue and Nhite. Defoliants were used in Vietnam for a variety of purposes. Figure 2 shows the major reported uses of the three herbicides in Vietnam, defoliation and crop destruction, while Figure 3 shows the minor uses reported, related to Vietnamese r troop movement a,nd their interdiction. More than ten million gallons of Agent Orange were sprayed, in at least 3,000 separate defoliation missions. Nearly another million gallons of Agent Orange were used in crop destruction programs. About five million gallons of Agent Nhite and one million gallons of Agent Blue were also used for these purposes. Approximately 100,000 gallons of Agent Orange were sprayed around the perimeters of bases to deny cover to enemy troops. These latter uses of defoliants may also have led to significant exposure to U.S. troops. �AGENT ORANGE EXPOSURE INDEX Page 16 For more than Q0% of the missions, the calculated ratio of gallonage to area sprayed, which is a close approximation of concentration, is nearly constant. 15Ji of the missions with a substantially different gallon/area ratio occur among missions in the lowest gallonage classification (<500 gallons) and 5% of the missions dispensed less than 100 gallons. Although herbicide use in Vietnam had begun by January, 1962, the HERBS tape covers only those spray missions conducted after June, 1965. Limited amounts (less than 300,000 gallons) of other dioxin-contaminated herbicides, notably Agents Pink and Purple (active ingredient 2,4,5-T), were disseminated between January, 1962, and December, 1964 [Young et al., 1978]. Since these were years before major American troop involvement, the number of U.S. servicemen exposed would be extremely small. Figure 4 shows the total herbicide usage by calendar quarter. The precipitous drop in the first quarter of 1968 coincides with the Jet Offensive. As indicated in the Figure, usage tended to be \ most widespread when the largest numbers of U.S. soldiers were in the field. Application of Indices As an example, we have summed the indices C5, CIQ, and C,,g, which count the total number of "hits" within specific radii, in six towns or other places in Vietnam, where thousands of American troops were stationed: Chu Lai, Khe Sanh, Camp Evans, Pleiku, Tay Ninh, and Phuoc Vinh. Table 3 shows the total number of such hits falling within 5, 10, and 15 km of these locations, �AGENT ORANGE EXPOSURE INDEX Page 17 respectively, as well as the total index E,. , derived from all sprayings from 1965 through 1971. These represent upper limits to exposure indexes that would be calculated for veterans stationed at these locations for shorter periods of time. These sample calculations illustrate how the indices can differentiate exposure classification among combat troops. The equations were then applied to our study population. Of the 543 men sampled, 478 had sufficient information to compute exposure indices, and 303 of these judged themselves "exposed" within at least one of the categories queried in Table 2. Mean scores for the various discrete and continuous scales were computed separately for men designated as "exposed" within each of these six potential exposure categories, as well as for the remaining group of 175 men who said they did not think they •j were exposed, and who did not indicate that they had held any of the likely exposure jobs. Results are shown in Figure 5. All six of the "exposed" groups had Eg means higher than the mean of the "unexposed" group,average, and all categories but one (shipping handlers), a group for which we had few dbservations, had more "hits within 15 km", C» g , than the population average for that variable. Since a number of men belong to more than one nominally "exposed" category, the groups are not independent, so that it is not meaningful to make statistical comparisons between the group means. However, the mean values of the discrete exposure index, C 15' as weil as of the continuous indices E-, Eg» and E», in >,'."" - , '. ' ,'.!.'.'". . " .' '" ^ ' ' " .".' V ' exposed and unexposed groups as a whole are compared in Table 4. Mean values for E« and E3 were significantly higher in the ex- '- �AGENT ORANGE EXPOSURE INDEX Page 18 posed compared to the unexposed: mean E2 was 41% higher (p<.01) and mean £„ was 32% higher in the exposed. Using a Mann-Hhitney U O test for the discrete variable Cig, the mean rank among the exposed was significantly higher than in the unexposed (p<.05). DISCUSSION As illustrated in Figure 5 and Table 4, HERBS tapederived exposure indices vary widely among individual troops, ranging from no exposure to a high probability of having been directly sprayed upon, and are consistent with likely exposures associated with specific military jobs and experiences in Vietnam. It is particularly noteworthy that there is little difference in mean Ew values for men whose self-reports indicated 0 that they cleared vegetation, slept, or walked through fields, and men who reported no exposure. Ne believe this to be reflective of the uncertainty and confusion which exists in the minds of many veterans about whether or not they were exposed to Agent —i Orange. Many sources of defoliation in Vietnam in addition to chemical herbicides have been documented by the National Academy of Sciences [Committee on the Effects of Herbicides in South Vietnam, 1974], such as bombing and shelling, use of Rome plows (super-bulldozers), resettlement, cutting of trees for lumber and firewood, and local agricultural practices (swidden agriculture)j it is difficult to see how a soldier under the stress of combat could be expected to distinguish one cause of defoliation from another. Our method can sort out those individuals who �AGENT ORANGE EXPOSURE INDEX Page 19 erroneously believe themselves to have been exposed and whose misclassification might thereby dilute any potentially observable effect in an epidemiological study. On the other hand, a self-report might miss important sources of contact with defoliants because the soldier was unaware of previous spraying in the area. Note, for example, the statistically significant differences in £„ and Eg between groups in Table 4, which take into account prior spraying at a given location, compared to the lack of statistical significance of differences among values for £„, which includes only current exposure. This demonstrates the importance of considering the residual effects of herbicide spraying encountered by troops long after the actual date of herbicide application. In a previous survey of veterans [Stellman and Stellman, 1980] we recorded reports of hundreds of servicemen who had entered freshly denuded forests, and who camped within defoliated areas, either in the jungle or near the perimeters of their base camps, in areas which were recently sprayed. In addition, men could have been exposed by spending time in areas long after spraying took place. Men on extended jungle patrols often swam in and drank water from streams that drained defoliated areas. The possibility of exposure from the latter source cannot be ruled out. Tissue samples from rodents, birds, fish, and reptiles trapped several years after spray tests were halted at a Florida test site for Agent Orange (Table 5) contained traces of dioxin [Young et al.,1978, p. 111-19]. �AGENT ORANGE EXPOSURE INDEX Page 20 It is precisely for these reasons,that jit is impossible to give credence to any health effects study in which assignment of herbicide exposure levels to individual veterans is based „ solely upon self-reports, We are aware, of course, of limitations associated with surveys of self-selected individuals. In health surveys subjects can be self-selected for a variety of reasons, including concern over possible exposure to Agent Orange, and concern about their own health. For this reason, any studies relating exposures to health outcomes in this population are likely to be highly biased. However, since no veteran could possibly know the thousands of dates and places of missions on the tape, there can be very little selection bias in this measure. Therefore, we believe this to be an independent and objective source of exposure information, despite the fact that our data was elicited from participants who selected themselves to participate in our survey. Furthermore, from the wide varia/ bility of the aggregated indices for these specific locations, we infer that it would be quite difficult for a subject to deliber—i ately fabricate a high score for himself. That is, a subject is highly unlikely to be able to identify places at random, and expect that the scores for those places, restricted to the time period he served in Vietnam, would be especially high. �AGENT ORANGE EXPOSURE INDEX Page 21 Because questionnaires are all self-administered, there is the usual problem of how to handle missing or obviously incorrect information. Our evaluation algorithms are biased towards minimizing exposure by truncating Vietnam location dates according to overall dates of service in Vietnam, and eliminating records with no dates at all. The majority of respondents took great pains to fill out the exposure related section and the Vietnam location and date section with care. Fewer than five questionnaires from obviously unreliable subjects were eliminated. Recent experience with another, non-self-selected group, comprising a random sample of several state membership lists of the American Legion, convinces us that veterans possess and utilize many resources to recall just where they were in Vietnam and what they did there. (Study in progress.) A still more accurate exposure method would, in addition, assign different exposure values to each mission, according to the actual number of gallons dispersed, the area sprayed, the rate of dispersion and even the meterological conditions, if this data were available. For the great majority of missions the results obtained here would not change because, as indicated above, the ratio of gallons to area was nearly constant. Nithout taking differing concentrations into account, the method is, at worst, a conservative approach to exposure estimation because the small number of concentration outliers are concentrated in the missions carried out over the smallest acreage, hence possibly representing the most intense exposure. �AGENT ORANGE EXPOSURE INDEX Page 22 It is probable that we are underestimating exposure arising from backpacking and other small, but intense uses of herbicides since we know that most of the missions with a substantially different gallons/area ratio from the calculated average fall in the low gallonage category. Refinement of the method, with variations in concentration and in different types of spray missions taken into account, is currently underway. The U.S. Army is revising the 1980 HERBS tape to provide still more accurate data on backpacking missions. This new information will be incorporated into our method as soon as it becomes available. It may, of course, be possible for other researchers, particularly those engaged in large, government-sponsored studies, to obtain complete military records of troop movements in Vietnam, as has been attempted by Erickson et al. [1984b], and to apply this or similar methods to derive still more accurate exposure information, thereby possibly eliminating many of the drawbacks associated with personal recall and use of self-administered questionnaires and approximations of concentration. On a more modest level, the method outlined in this article can be readily applied at minimal expense by the many registries and projects now being carried out by state agencies and private research groups. The obvious next step is to examine the prevalence of adverse health conditions in relation to the values of the herbicide exposure indices described in this paper. Such studies are ". now in progress. •' ^s 5 �ACKNOWLEDGMENTS This study was made possible through the help of many individuals and institutions: Lawrence Qarfinkel, American Cancer Society. John Jordan, Louise Ransom, Robert Morris, Andy Smith, Tim Smith, Chris losso, National Council of Churches. Keith Snyder, Lew Milford, Ron Simon, National Veterans Law Center, American University. Mike Gold, City University of New York Department of Veterans Affairs. Steve Zoloth, Hunter College of the City University of New York. John F. Sommer, Jr., The American Legion. Richard Christian, U. S. Army Records Management Group. �REFERENCES American Medical Association (1981): The health effects of "Agent Or an qe" an d Po1v chl o r i n a t edL.p i o x i n Co n t am i n ant s. Technical Report. Council on Scientific Affairs. Chicago, Illinois. Collins TFX, Williams CH (1971): Teratogenic Studies with 2,4,5-T and 2,4-D in the Hamster. Bull Environ Con tarn Toxicol 6:559567. Committee on the Effects of Herbicides in South Vietnam (1974)s Part A. Summary and Conclusions. National Academy of Sciences, Washington, DC. Courtney KD, Moore JA (1971): Teratology Studies with 2,4,5Trichlorophenoxyacetic Acid and 2,3,7,8-Tetrachlorodibenzo-pDioxin. Toxicol Appl Pharmacol 2fi.: 396-403. DiDomenico A, Silano V, Viviano G, Zapponi G (1980): Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy. V. Environmental persistence of TCDD in soil. Ecotoxicol Environ Safety 4.:339-345. Donovan JW, MacLennan R, Adena M (1984): Vietnam service and the risk of congenital anomalies. A case-control study. Med J Austral 140;394-397. Erickson JD, Mulinare J, McClain PW, Fitch TO, James LM, McClearn AB, Adams MJ (1984a): Vietnam veterans" risks for fathering babies with birth defects. J Amer Med Assocn 252;903-912. Erickson JD, Mulinare J, McClain PW, Fitch TQ, James LM, McClearn AB, Adams MJ (1984b): Vietnam veterans" risks for fathering babies with birth defects, Atlanta: Centers for Disease Control. Fenton BK (1984): A fatal case of 2,4-D toxicity? Vet Record, June 16, 1984, p. 599. Goldstein NP, Jones PH, Brown JR (1959): Peripheral Neuropathy after Exposure to an Ester of Dichlorophenoxyacetic Acid. J Amer Med Assocn 171:1306-1309. Grant WF (1979): The Genotoxic Effects of 2,4,5-T. Mutat Res 65 ; 83Hood RD, Patterson BL, Thacker 6T, Sloan GL, Szczech GM (1979): Prenatal Effects of 2,4,5-T, 2,4,5-Trichlorophenol , and Phenoxyacetic Acid in Mice. J Environ Sci Health Cl g : 189-204. �Huff JE, Moore JA, Saracci ft, Tomatis L (1980): Long-Term Hazards of Polychlorinated Dibenzodioxins and Polychlor inated Dibenzof urans. Env Health Persp 36; 221 -240. International Agency for Research on Cancer ( 9 7 : Some fumigants, 17) the herbicides 2,4-D and 2,4,5-T, chlorinated dibenzodioxins and miscellaneous industrial chemicals. IARC Monograph 15: Evaluation of the Carcinogenic Risk of Chemicals to Man. Lyon, France. Kearney PC, Noolson EA, Ellington CP Jr (1972): Persistence and metabolism of chlorodioxins in soils. Environ Sci Technol 6:1017-1019. Kociba RJ, Keyes D6, Beyer JE, Carreon RM, Hade CE, Dittenber DA, Kalnins RP, Frauson LE, Park CN, Barnard SD, Hummel RA, and Humiston CG ( 9 8 : Results of a two-year chronic toxi17) city and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-pdioxin in rats. Toxicol Appl Pharmacol 46:279-303. Lathrop GD, Wolfe WH, Albanese RA, Moynahan PM ( 9 4 : An epidemic18) logic investigation of health effects in Air Force personnel following exposure to herbicides. Baseline morbidity study results. USAF School of Aerospace Medicine, Brooks Air Force Base. May G (1973): Chloracne from the accidental production of tetrachloridibenzodioxin. Brit J Indus Med 30:276-283. Neubert D, Dillmann, I (1972): Embryotoxic Effects in Mice Treated with 2,4,5-Trichlorophenoxyacetic Acid and 2,3,7,8-Tetrachlorodibenzo-p-Dioxin. Arch Pharmacol 272:243-264. Oliver RM ( 9 5 : Toxic effects of 2,3,7,8-tetrachlorodibenzo-l ,417) dioxin in laboratory workers. Brit J Indus Med 32 ; 49-53 . "1 Pazderova-Vejlupkova J, Nemcova M, Pickova J, Jirasek L, Lukas E (1981): The development and prognosis of chronic intoxication by tetrachlorodibenzo-p-dioxin in men. Arch Env Hlth 36 ; 5-1 1 . Rowe VK, Hymas TA (1954): Summary of Toxicological Information on 2,4-D and 2,4,5-T Type Herbicides and an Evaluation of the Hazards to Livestock Associated With Their Use. Amer J Yet Res 15:622-629. Schwetz BA, Sparschu GL, Gehring PJ (1971) i The Effect of 2,4Dichlorophenoxyacetic Acid (2,4-D) and Ester of 2,4-D on Rat Embryonal, Foetal and Neonatal Growth and Development. Fd Cosmet Toxicol 9:801-817. . . . ;v;.ji*v.£ ••&...,.....^Vavl' ' ' ' ' '' Schwetz BA, Morris JM, Sparschu GL, Rowe VK, Gehring PJ, Emerson JL, Gerbig CG ( 9 3 : Toxicology of chlorinated dibenzo-p17) dioxins. Env Hlth Persp §: 87-99. �Stellman SD, Stellman JM ( 9 0 : Health problems among 535 Vietnam 18) veterans potentially exposed to toxic herbicides. Paper presented at the Society for Epidemiologic Research, Minneapolis, June, 1980. Man Miller JP, Lalich JJ, Allen JR ( 9 7 : Increased incidence of 17) neoplasms in rats exposed to low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemosphere 9:537-544. Young AL, Thalken CE, Arnold EL, Cupello JM, Cockerham LG ( 9 6 : 17) Fate of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the environment: Summary and decontamination recommendations. USAFA-TR-76-18. Department of Chemistry and Biological Sciences. U.S. Air Force Academy, Colorado. Young AL, Calcagani JA, Thalken CE, Tremblay JW ( 9 8 : The 17) Toxicology, Environmental Fate and Human Risk of Herbicide Orange and its Associated Dioxin. USAF Occupational and Environmental Health Laboratory (OEHL), Technical Report No. TR-78-92, Final Report, Brooks Air Force Base, Texas, Medical Division. �TABLE 1 DATA CONTAINED ON HERBS TAPE Date (Month/Day/Year) Combat Tactical Zone (I, II, III, Mission Number Agent (Orange, White, Blue) No. of Gallons Type of Mission (Defoliation, Crop Destruction, etc.) Area Sprayed (Hectares) Leg Designator! 1A, IB, etc. UTM Coordinate of Leg . . . i �TABLE 2 Hording of Questions on Self-Described Exposure to Agent Orange In this section we are interested in finding what you remember about being exposed to defoliating herbicides, such as Agent Orange, which were used to kill jungle cover in Southeast Asia. If you believe you were exposed to such a chemical agent, either by directly loading it, spraying it, or entering a freshly sprayed area, we would like you to describe how you were exposed and when. If you don't remember being directly exposed to herbicides, check here: and go on to next page. No Sprayer on C-123 Sprayer on Helicopter Sprayer on boat Loader/handler of spray on any of the above Job involved clearing vegetation and/or patrolling around camp, roads, or clearing free-fire zones Slept/walked through sprayed areas. Exposed to herbicides used near camp or on roads you traveled on Handler of spray during storage or shipment Yes If yes, No. of weeks �TABLE 3 Number of Herbicide Spray "Hits" within 5, 10, and 15 km of Six Selected Sites in Vietnam (1965-1971) Place No. of spray hi ts wi thi n: 5 km 10 km 15 km Exposure Index EI' Jay Ninh 0 5 33 2.814 Chu Lai 2 33 55 6.304 15 23 55 8.264 Camp Evans 3 35 110 10.609 Phuoc Vinh 27 144 356 38.958 Pleiku 69 74 121 43.600 Khe Sanh *Defined by Eq. (1) �TABLE 4 Statistical Comparisons Between Mean Exposure Indices For Veterans Self-Described as "Exposed" and "Not Exposed" to Agent Orange VARIABLE Average Value of Variable for Veterans Reporting Exposure Average Value of Variable for Veterans Not Reporting Exposure (Numbers of veterans are given in parentheses) 8.94 (303) 8.39 (175) N.S. (303) 5.85 (175) <.01 0.98 (303) 0.74 (175) <.05 8.25 Mean Rank '15 248.9 (303) Mean Rank 223.2 (175) MannWhi tney U 2364.5 <.05 �TABLE 5 Levels of TCDD Found in Animals 3 to 8 Years After Heavy Spraying of Agent Orange at Eglin Air Force Base, Florida SPECIES TISSUE CONCENTRATION (ppt) Mammals: Beachmouse Hispid Cotton Rat Liver Liver 300 - 2400 <10 - 210 Birds! Meadowlark Mourning Dove Savannah Sparrow Liver Liver Liver 100 - 1020 50 69 Fishs Spotted Sunfish Mosquito Fish Sailfin Shiner Liver Nhole Body Whole Body Amphibia: 6-Lined Racerunner Muscle Source: Young et al., 1978 86 12 12 360 - 430 �CAPTIONS FOR FIGURES Figure 1. Representation of a typical spray mission flown near Pleiku. Plane sprayed continously front 1A to IF, flew without spraying to 2A, then sprayed from 2A to 2B. Number of vertices or "hits" falling within radii of 5, 10, and 15 km are 3, 6, and 8, respectively. Figure 2. Quantities of Herbicides Orange, White, and Blue used in Defoliation and Crop Destruction missions in South Vietnam, 1965-1971. Figure 3. Quantities of Herbicides Orange, Nhite, and Blue use in five minor types of missions in South Vietnam, 1965-1971. Figure 4. Quantities of three herbicides used in South Vietnam, 1965-1971, by calendar quarter. Figure 5. (a) Mean discrete exposure index Cig computed for men with six different job categories with probable Agent Orange exposure, and for men not likely to have been exposed, (b) Same for continuous exposure index E0.''' • • ", -' .' - ,' •' • . e v a -£' --'•"•.»?'" .'.,'-«. ,„'.'•*?£ t" '' �Figure 1 NUMBER OF "HITS" 5 km 10 km 15 km 8 15 km �Figure 2 MAJOR USES OF HERBICIDES IN VIETNAMJ965-7I PURPOSE AGENT ORANGE DEFOLIATION WHITE NO. OF MISSIONS 3038 4.96 1348 BLUE 159 ORANGE 474 09 .6 'V < CROP DESTRUCTION WHITE 56 BLUE 310 V*'3 0.06 0.58 6 MILLIONS OF GALLONS �Figure 3 MINOR USES OF HERBICIDES IN VIETNAM, 1965-71 PURPOSE AGENT BASE PERIMETERS ORANGE WHITE BLUE ENEMY CACHE v SITES ORANGE WHITE BLUE' WATERWAYS. ORANGE WHITE BLUE COMMUNICATION LINES ORANGE WHITE BLUE ENEMY SUPPLY ROUTES NO. OF MISSIONS ORANGE WHITE BLUE 20 30 40 50 60 70 80 THOUSANDS OF GALLONS 90 100 �Figure 4 HERBICIDE USE IN VIETNAM,I965-I97I CO o o li. o (O AGENT ORANGE I 234 1965 I 234 1966 I 234 1967 I 234 1968 I 234 1969 YEAR AND QUARTER I 234 1970 I 234 1971 �Figure 5 (a) C.CAJ * 2 200 * 180 1O ^^•^M ^•MiM 160 M^M» 140 ^••M* b 120 I^^H* 5 X frig ^•» I^M» ^•H MM CO X & 100 UJ a: & 80 ___ ( 1 ( ^M^V u. 0 60 0* ID o 40 20 •MM- _ ' MM " "MEAN T " -1- T J_ <> 1 __ 1 I — 1 n SPRAYER ON COPTER LOADER OR HANDLER 1 SPRAYER CLEARING SLEPT OR HANDLER ON VEGETATION WALKED DURING C-123 THROUGH SHIPMENT SPRAYED AREAS MODE OF EXPOSURE TO AGENT ORANGE 1 NONE MEAN �Figure 5 (b) 2.2 er 2 20 -° X UJ UJ O ,.4 CL a! <r o _j UJ < I- O zo cc MEAN 0.8 0.6 o UJ cr 0.2 0 1 SPRAYER ON COPTER LOADER OR HANDLER I I SPRAYER CLEARING SLEPT OR HANDLER ON VEGETATION WALKED DURING C-123 "" " THROUGH SHIPMENT SPRAYED AREAS 1 NONE MODE OF EXPOSURE TO AGENT ORANGE � 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. 063 Folder The folder containing the original item. 1712 Series The series number of the original item. Series III 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/. Creator An entity primarily responsible for making the resource Stellman, Steven D. Jeanne M. Stellman Title A name given to the resource Typescript: Estimation of Exposure to Agent Orange and Other Defoliants Among American Troops in Vietnam: a Methodological Approach [nd] Subject The topic of the resource Agent Orange Exposure Study HERBS database Air Force Health Study study protocol ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/56d514a7011f45363c2d2088fb18f434.pdf ceebfb72a56e554f4b0099f140c7d89c PDF Text Text Item ID Number 01874 Author Corporate Author ROPQPt/ArtlCiO TitlO "ineraryf°r Mr. K. D. A. Medbury, Commissioner, Australian Repatriation Commission, Department of Veterans Affairs, Australian Government, March 3-4, 1980 Journal/Book Title Year 000 ° Month/Day Color Number of Images 2 Doscripton Notes Wednesday, July 18, 2001 Pago 1874 of 1908 �ITINERARY for MR. K. D. A. MEDBURY Commissiorir-r, Australian RepatriaLion Commission Department of Veterans Affairs Australian Government MONDAY. 3 March 1980 0!OO Colonel Lathrop and Lt Colonel Moynahan meet Mr. Medbury at VIP Suite 240. Escort to Officers' Mess for breakfast. 085fj Transport to Headquarters, Aerospace Medical Division (Bldg 150) 0900 Meet with Colonel Mohr (Bldg 150) 0930 Meet with Colonel Enders (Rldg 125) 0955 Transport to Eplcenrioloyy Division (Bldg 930) 1000 Introduction to Project RANCH HAND II (Colonel Lathrop) 1015 U.S. Air Force Experience with Herbicide Orange (Major Young) 1015 Break 1100 Environmental Fate of Herbicide Orange (Major Young) il'jfj Transport to Officers' Mess 15:00 Lunch - Officers' Mess l?f>5 Transport to Epidemiology Division (Bldg 930) I.';30 Literature Review (Major Sauri) 1400 L'pideriiiolofiic Approach (Lt Colonel Wolfe) l'-30 Break IMS Data Collection (Lt Colonel Moynahan/ Captain Pennington) l!»l'i Physical Examination (Lt Colonel Wolfe) IM r > Statistical Methodology (Dr. Albanese) 16T) Resources (Major Daves) \Wh Transport U> Officers' Mess 1630 Social Hour - Officers' Mess �TUESDAYj. 1 —~" March""J 9fJO - - - ""' ~~ -™™ 1 •" 0800 Colonel Lathrop and Lt Colonel Moynahan meet Mr. Medbury at VIP Suite 240. Escort to Officers' Mess for breakfast. OR55 Transport to Headquarters, USAI" School of Aerospace Medicine (Bldg 125} 0900 -USAF School of Aerospace Medicine Briefing (Bldg 125, Conference Room) and tour of facilities (Mr. Berry) 4 112b Transport to Officers' Mess 1130 Lunch - Officers' Moss 12J.5 Transport to Epidemiology Division (Bldg 930) 1300 Sunmary/Questions and Answers (Colonel Lathrop) Transportation on standby � 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. 069 Folder The folder containing the original item. 1874 Series The series number of the original item. Series III Subseries IV 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 Itinerary for Mr. K. D. A. Medbury, Commissioner, Australian Repatriation Commission, Department of Veterans Affairs, Australian Government, March 3-4, 1980 Subject The topic of the resource international cooperation AVHS Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/4aecc3ebad3217a7449af6e8e627429d.pdf 70ae6ebf7eeeed19bcd75e8b0722e182 PDF Text Text Item ID Number °1607 Author Corporate Author Roport/Artido TltlO Typescript: Synopsis of Background Journal/Book Title Year 000 ° Month/Day Color a Number of Images ^ DeSOrlptOn NOtOS Sections of an Air Force Working Paper. Wednesday, June 06, 2001 Page 1608 of 1688 �II. Synopsis of Background A. Current News media presentations have recently focused medical, political and lay attention on possible adverse health effects in military personnel, allegedly due to Herbicide Orange [a mixture of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)] which was used as a defoliant during the Vietnam Conflict. Other herbicides containing 2,4,5-T were also used extensively, and as commonly used by the news media, the term "Herbicide Orange" refers to all of these 2,4,5-T products (a convention used throughout this protocol). This defoliant was later found to have been contaminated with the toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (Figure A-l, Section XII). Claims for compensation have been filed against the Veterans Administration (VA), by 625 veterans. In response to Congress, the General Accounting Office (GAO) investigated the issue and subsequently recommended that the Department of Defense (DOD) conduct a long-term epidemiologic study of the problem. The Department of the Air Force has made a formal commitment to the Congress and the White House to conduct such a study. B. Use of Herbicides Research and development on phenoxy herbicides began in the early 1940s. Most of the initial phytotoxic screening programs and the development of application technologies were sponsored by the DOD. The herbicide, 2,4,5-T, was first commercially produced in the United States in 1944. During the years from 1961 through 1969, the Department of Defense procured approximately 34 percent (53 million pounds) of the total US production for use in South Vietnam. However, 8.9 million pounds of that amount were not sprayed inSputh Vietnam, but were destroyed by at-sea incineration »The first Sustained DOD operational use of herbicides was initiated during the Vietnam Conflict (Operation RANCH HAND) and the first shipment of herbicides used in RANCH HAND was received at Tan Son Nhut Air Base, Republic of Vietnam (RVN), on 9 January 1962. These compounds were intended to accomplish two objectives: (1) the defoliation of vegetation to improve visibility and thus decrease the risk of ambush, and (2) the destruction of enemy crops. Four 2,4,5-T containing herbicides were used by the military during the period 1962-1970. These four included: (1) Herbicide Purple (used from 1962 through 1964) n-butyl 2,4-D n-butyl 2,4,5-T iso-butyl 2,4,5-T AIR FORCE WORKING PAPER II-l 50% 30% 2Q% �(2) Herbicide Pink (used from 1962 through 1964) n-butyl 2,4,5-T 60% iso-butyl 2,4,5-T 40% (3) Herbicide Green (used from 1962 through 1964) n-butyl 2,4,5-T 100% (4) Herbicide 15 April 1970)• Orange (used from early n-butyl n-butyl 2,4-D 2,4,5-T 1965 through 50% 50% Analysis of archived samples of Herbicide Purple suggest that the mean concentration of TCDD may have been approximately 33 ppm (Range 17 to 47 ppm TCDD) while archived samples of Herbicide Orange may have had a mean concentration of approximately 2 ppm (Range: <0.02 to 15 ppm TCDD). In addition, two other herbicides were widely used in South Vietnam. These were Herbicide Blue (an organic arsenical formulated from the sodium salt of cacodylic acid), and Herbicide White (a water soluable triisopropanolamine salt formulation of 2,4-D and picloram). The amounts of the vartaus herbicides used in South Vietnam from January 1962 throughfWi I is/to are shown in Table 1. ^ i i i T^^^^^^> f I Hi i i %rf%*^^ ^T t Table 1. Estimated Quantities of Herbicides and TCDD Sprayed in South Vietnam, Jan 1962-Feb CHEMICAL POUNDS 2,4-D 2,4,5-T TCDD Picloram Cacodylic Acid 55,940,150 44,232,600 368 3,041,800 3,548,710 106,763,260 Herbicide Total Ninety-six percent of all 2,4,5-T was contained in Herbicide Orange; the remaining 4 percent in Herbicides Green, Pink, and Purple. However, Herbicides Green, Pink and Purple contained approximately 40 percent of the estimated amount of TCDD disseminated in South Vietnam. Green, Pink and Purple were sprayed as defoliants on less than 90,000 acres from 1962 through 1964, a period when only a small force of U.S. military personnel were in South Vietnam. Ninety percent of all the Herbicide Orange (containing 38.3 million pounds of 2,4,5-T and 203 Ib of TCDD) was used in defoliation operations on 2.9 million acres of inland forests and mangrove forests of South Vietnam. AIR FORCE WORKING PAPER 11-2 �Most of the herbicides used in South Vietnam were sprayed from aircraft. RANCH HAND aircraft, the C-123, disseminated 88 percent of all herbicides. Helicopters and ground application equipment used by personnel from all branches of the U.S. Armed Forces applied the remaining 12 percent of herbicides (primarily Herbicide Blue). Concurrent with the change to Herbicide Orange, the scope of aerial use shifted from four rotating aircrews to 30 permanently assigned aircrews and additional support personnel. Following the announcement in October 1969 that the administration of 2,4,5-T to pregnant rodents caused an increase in the rate of congenital abnormalities, the DOD confined Herbicide Orange spray operations to nonpopulated areas and in April 1970, all uses of the herbicide were halted. In March 1972, all remaining stocks of 2,4,5-T containing herbicides were removed from South Vietnam, and transported to Johnston Island, Pacific Ocean, for open storage (Project PACER IVY), and incinerated at sea in 1977 (Project PACER HO). In 1979, the Environmental Protection Agency (EPA) suspended the use of herbicides containing 2,4,5-T because an epidemiologic study in the United States attributed abortogenic effects to its use. AIR FORCE WORKING PAPER II-3 �III. Goals of the Investigation From the above background, three interdependent study goals emerge: A. Health (1) To identify veteran and active duty individuals with adverse health effects (physical and psychological) if any, which are attributable to herbicide exposure, and (2) To identify other individuals at risk of developing future adverse health effects, if any. B. Political To satisfy the social concern for proper investigation voiced by lay and scientific communities, both national and international. C. Legal To clarify the question of compensation awards to the 625 claimants. With regard to the goal of legal clarification, it is apparent that data and conclusions arising from this investigation, positive, negative, or indeterminant, will probably be used to better assess the issue of long-term health effects and resultant compensation. The operational assumption of this study, therefore, is: Air Force Operation RANCH HAND personnel probably received a greater average occupational exposure to 2,4,5-T and TCDD than US Army ground personnel, implying that RANCH HAND personnel should develop greater numbers of acute and chronic clinical signs/symptoms from the exposure, and should manifest them sooner than US Army personnel, if indeed there are any adverse long-term health effects at all. This dose-response notion suggests that although the Air Force population is not the best one to study, it is probably better than the Army population. The overall scientific thrust of this investigation is to define the natural history of disease, if any, and its spectrum of illness, by direct and indirect methodology. AIR FORCE WORKING PAPER III-l �IV. Synopsis and Discussion of Literature A. Overview More than 20,000 scientific articles relating to the phenoxy herbicides have been published since the 1940's. Many of the articles cite herbicide-caused health effects in a variety of animal species. Most early studies used a myriad of herbicide formulations and unknowingly dealt with physically and chemically impure compounds, and the assay technology was far short of today's state-ofthe-art. Many human studies have ascribed cause and effect relationships but have suffered from problems of clinical empiricism or questionable methodology. The only consistent chronic clinical finding associated with exposure to 2,4,5-T herbicide has been chloracne, recognized by most workers as the herald sign of overexposure to the herbicide. It is now recognized that the chloracne was caused by the presence of TCDD rather than the 2,4,5-T. Sequaelae from chloracne, localized or systemic, appear to be unusual according to the preponderance of the literature. It is appropriate to note that sustained worldwide usage of herbicides for 30 years has not evoked a readily identifiable disease state. It is clear from the literature and the usage history of herbicides that if there are significant attributable long-term health effects, they are either reasonably rare, or of such nonspecific commonality that they blend unnoticeably into the symptoms, syndromes, or diseases associated with increasing age or other such factors. B. Pharmacokinetics of 2.4-D. 2.4.5-T and TCDD The pharmocokinetics of 2,4-D have been well studied in animals. 2,4-D is readily absorbed on oral administration. Initially, it is distributed in high concentrations to the central nervous system and liver. Eventually, all tissues are involved, with the kidneys accumulating twenty times the concentration of the other tissues. The plasma half-life of 2,4-D is approximately 3 to 12 hours, with elimination from the body through the kidneys at a dose-dependent rate. Generally, high doses or repeated lower doses result in tissue accumulation. The majority of 2,4-D is eliminated unmetabolized; however, esters of 2,4-D have been shown to undergo hydrolysis prior to excretion. Muscle and fat show the lowest accumulation of 2,4-D on repeated exposure, whereas the kidneys and liver show the highest accumulations. Within 24 hours of a single dose administration of 2,4-D, 16.8% was present in the uterus, placenta, fetus and amniotic fluid in gravid rats. In addition, 2,4-D was found in the milk of lactating rats for up to six days following single-dose exposure. AIR FORCE WORKING PAPER IV-1 �(2) 2,4,5-T The pharmacokinetics of 2,4,5-T have been well studied in animals. In all animals, 2,4,5-T has been shown to be readily absorbed upon oral administration. However, beyond this point, 2,4,5-T has shown marked variations in its pharmacokinetics in the various animals. These differences are thought to be due to variations in species, age, dosage levels, routes of administration and chemical formulations used in the various studies. The distribution is generally ubiquitous throughout the body except in hamsters, which show no placental passage, and in mice, which show placenta! passage only in late gestation. Clearance from plasma and the body varies greatly among animals with rats showing faster clearance than dogs, mice and man. In addition, this clearance appears to be generally dose-dependent. The biological half-life of 2,4,5-T in rats, as estimated by tissue analyses and urinary clearance at administered dosages of 5 mg/kg, is 4.7 hours. However, at 200 mg/kg, the half-life in rats is prolonged to 25 hours. Excretion of 2,4,5-T is primarily via the kidneys. The elimination of 2,4,5-T at low doses is essentially achieved in an unmetabolized form. However, at higher or more chronic doses, elimination involves the liver in a more active role (i.e., conjugation). Higher doses and repeated lower doses appear to result in accumulation in animal tissues. (3) TCDD The information on the absorption, distribution and excretion of TCDD has been mostly derived from animal models. The only reported human study dealing with pharmacokinetics of TCDD dealt with the analysis of TCDD in tissues at necropsy of one case of confirmed TCDD exposure subsequent to the accidental release of TCDD in Seveso, Italy in July 1976. Studies in rats, mice and guinea pigs generally show that intestinal absorption of TCDD is relatively complete, with a large proportion of TCDD remaining unmetabolized in the liver. The majority of this TCDD is assumed to be localized in the liver microsomes (centrifugation techniques). Initially, adipose tissue accumulates TCDD, followed later by accumulation in the liver, adrenals, kidneys and lungs. The level of TCDD in the liver and adipose tissue is about ten-fold greater than in other body tissues; however, significant species variability has been observed. The biological half-life of TCDD varies by species, but is reported to range from 12 to 50 days. The major route of excretion is via the feces with urinary excretion occurring at a much reduced rate. (4) Phenoxy Herbicides in Humans Relatively few studies have dealt with the pharmacokinetics of 2,4-D and 2,4,5-T in humans. Numerous reports of occupational exposures in industry and in commercial and private herbicide applications have supported percutaneous entry. Rapid absorption AIR FORCE WORKING PAPER IV-2 �has been observed after oral administration of 2,4-D or 2,4,5-T. The primary mode of excretion of the phenoxy herbicides is via the urine with 74% of 2,4-D and 63%-72% of 2,4,5-T being cleared from the body within the first 96 hours. The majority of phenoxy herbicides are unmetabolized prior to excretion. The biological halflife of 2,4-D and 2,4,5-T in humans (as estimated by tissue analyses and urinary excretion) is 33 hours and 18 hours, respectively. Tissue analysis has revealed a ubiquitous distribution of the herbicides after absorption. Limited studies on the accumulation of the phenoxy herbicides following repeated doses suggest that such accumulation in humans is unlikely. This is in contrast to numerous animal studies on 2,4-D and 2,4,5-T which show that such accumulation does occur. No specific data are available on the odor threshold of Herbicide Orange. Data are available however, on the odor threshold of a butyl ester formulation of 2,4,5-T. The odor threshold was found to be about 0.3 ppb (the taste threshold was 1.3 ppb). A Threshold Limit Value (TLV) of 10 mg/m3 for both 2,4-D or 2,4,5-T has been adopted by the American Conference of Governmental Industrial Hygienists. The TLV is a time-weighted average concentration for a normal 8-hour workday/40-hour workweek to which workers may be repeatedly exposed, day after day, without adverse effect. Analysis of ambient air samples collected adjacent to and downwind from actual dedrumming operations involving Herbicide Orange were at least two orders of magnitude below the TLVs. C. Proposed Cellular Mechanisms of Action for TCDD TCDD has, in general, three proposed mechanisms of action by which its variety of effects, both documented and suspected, can be understood. All currently available information in this area is derived from animal, plant, and bacterial models. The few human studies dealing with mechanisms are limited to the clinical manifestation of chloracne. (1) Microsomal Enzyme Induction TCDD's ability to induce a variety of microsomal enzymes is well documented. The induction of aryl hydrocarbon hydroxylase, delta-aminolevulinic acid synthetase and cytochrome P-448/P-450 associated enzymes are implicated in the development of cutaneous porphyria. The induction of aryl hydrocarbon hydroxylase and other mixed-function oxygenases/oxidases have been associated with carcinogenesis and tumorogenesis. In addition, TCDD has been shown to be a possible promoter or cocarcinogen of known carcinogens. In some nonhuman studies, TCDD produced a protective effect against endocrine tumors (e.g., pituitary, uterine, pancreatic, adrenal and mammary tumors). TCDD's induction of UDP-glucuronyl transferase, an important enzyme in steroid metabolism, may explain this peculiar effect. The induction of DT-diaphorase and lysosomal acid proteinases have been implicated in TCDD's neuropathic effects. AIR FORCE WORKING PAPER IV-3 �These and other biochemical alterations may account for TCDD's clinical manifestation of chloracne resulting from an over production of keratin in the sebaceous ducts. (2) DNA/TCDD Interaction. Alterations in the structure and fidelity of transcription of DNA due to 'TCDD have been indirectly demonstrated. TCDD, because of its planar ring structure, is felt to "intercalate" with DNA causing "frame-shift" mutations in a manner similar to that seen with the acridine family of compounds. A few laboratory studies with bacterial systems (Escherichia coli and Salmonella typhimurium) and one plant system (the African Blood Lily) have implicated TCDD as being capable of producing chromosomal aberrations and perhaps a weak dominant lethal effect. This hypothesized DNA/TCDD interaction could explain the development of chloracne, as well as the suggested mutagenic and carcinogenic effects, if similar mechanisms occur in mammalian species. (3) Toxicity. A nonspecific or as yet unspecified toxicity continues to serve as a reasonable mechanism for TCDD's hepatic and thymus toxicity. TCDD has been described by some as "one of the most potent, low molecular weight toxins known", with extremely low concentrations producing severe liver damage and death in various animal studies. The immune suppression effect of TCDD has been shown to result specifically from its T-cell (thymus) toxicity. In addition, TCDD's concentration in adipose tissue suggests the possibility that under situations of weight loss (e.g., life style, medical indications, or disease), TCDD may be released into the circulation. Such hypothesized reemergence of the agent could result in low doses being either detectable and/or toxic at some later point in time. If TCDD's primary toxicity results from low doses (e.g., a mutagenic/carcinogenic effect) rather than high doses (e.g., cellular poisoning and cell death), then the deposition of TCDD in the adipose tissue may have greater significance with respect to delayed effects on the long-term health of the exposed individual. This possibility raises a theoretical dose-response paradox which might "explain" the prevailing preponderance of symptoms in populations which may have been exposed to relatively low doses of TCDD (see Section IV D). D * Animal Studies A comparison of animal toxicity studies is difficult due to variations in experimental designs which include differences in (1) the species, age, and sex of animals used; (2) the level, route, and length of exposure to chemicals; (3) the purity of the chemicals used; and (4) the criteria measured and the time sequence of data IV_4 AIR FORCE WORKING PAPER �collection. Animals have shown a wide range of toxic effects. This range may serve as a guide to anticipate the potential toxic effects in humans following exposure to Herbicide Orange. A summarization of the literature is presented in Table A-l of the Appendf& It is apparent that the toxic effects of 2,4-D and 2,4,5-T are markedly different than the effects of TCDD. TCDD is approximately 1000 times more toxic in acute studies. In addition, the slower clearance time of TCDD may account for the significantly lower daily doses required to elicit chronic toxicity. A consistent finding in TCDD toxicity is depletion of the lymphoid tissues throughout the host. This is readily characterized by involution of the thymus in all species studied. In relation to the chronic maternal toxic dose, the embryotoxic dose is markedly lower for TCDD than for 2,4-D and 2,4,5-T. Both 2,4,5-T and 2,4-D appear to be very weak teratogens and/or carcinogens at best, but these evaluations are complicated by varying levels of contamination by various dibenzo-p-dioxins. TCDD appears to have significant teratogenic and carcinogenic potentials which appear to be species specific. The most striking observation noted in the literature is a marked variation in response among species. Examples of these variations are in the areas of acute toxicity (TCDD's LDso in the guinea pig is 1 yg/kg compared to 1000 yg/kg in the dog), excretion (2,4,5-T plasma half-life in rats is 4.7 hrs compared to 77 hrs in dog), and oncogenicity (TCDD is oncogenic in rats but has not been shown to be oncogenic in mice under similar conditions). Even among strains of the same species (rats) variations in oncogenicity were noted following 2,4,5-T exposures. As noted earlier, this high variability between species is an important consideration in designing human studies. A second area of interest noted in the literature is a possible dose-response paradox in nonhuman primates (rhesus monkey) following exposure to TCDD. Animals in chronic exposure studies fed a low level of TCDD in feed [e.g., 50-500 parts per trillion (ppt)] have shown signs of disease only after several months when, tv-f0-' was approximately 1 yg/kg body weight. Unfortunately, animals'* receiving comparable amounts of TCDD in single-dose acute toxicity studies (LD5Q determinations) have not been observed for the emergence of chronic effects. Therefore, it remains unclear whether the toxicity demonstrated in chronic exposure studies is dependent upon repetitive exposure accumulated to 1 yg/kg or whether similar toxicity would also be demonstrated following a single dose of 1 yg/kg after a comparable observation period. E. Case Reports Much of the medical literature on 2,4-D, 2,4,5-T and TCDD exposures in humans is based on individual case reports. Most of the patients discussed in these reports were exposed to multiple chemical agents and, therefore, it is difficult to determine which AIR FORCE WORKING PAPER IV-5 �agents were responsible for specific symptoms. Nevertheless, the general areas of dermatologic and neuropsychiatric disease have been of primary interest to most investigations. Since the neuropsychiatric symptoms of herbicide exposure are numerous and largely subjective in nature, they have been extremely difficult to assess from a clinical standpoint. In addition, hepatic dysfunction, and renal, gastrointestinal and cardiac disturbances are "linked" to exposures to these chlorophenolic compounds. (1) 2,4-D A multitude of symptoms have been attributed to 2,4-D, and the ones reported most consistently are listed in the Appendix, Table A-2. Components of some of these selected symptoms/signs are described in Table A-3 of the Appendix. The asthenic syndrome, peripheral neuropathy and hepatic dysfunction are of particular interest. Other symptoms of systemic toxicity occur, but usually resolve within 4-6 weeks. The acute peripheral neuropathy associated with 2,4-D exposure has been extensively described. It has an early onset, causes prolonged disability of variable degree, and recovery has been incomplete in many cases. Electromyography in some patients has demonstrated deneryation, and some studies have detected decreases in nerve conduction velocities. One autopsy study demonstrated a demyelination process within the brain of a 76year-old male who committed suicide by ingesting 2,4-D in kerosene. (2) 2,4,5-T/TCDD The human effects of 2,4,5-T are difficult to evaluate since the chemical is contaminated with TCDD in the manufacturing process. The effects of TCDD have been determined from studies of trichlorophenol workers, and from laboratory workers using TCDD. Symptom/sign complexes attributable to exposure to 2,4,5-T and TCDD are listed in Tables A-2 and A-3 of the Appendix. Chloracne usually begins in the zygomatic/temporal region and is often found on and behind the pinna of the ear. This is an oily acne-like skin condition characterized by comedones and inclusion cysts which may result in extensive scarring. In severe cases spread of lesions to the throat, back and inguinal areas has been noted. This skin condition is frequently preceded by erythema and blepharoconjunctivitis. Active lesions usually disappear within two years, but have been found 30 years after exposure. Porphyria cutanea tarda and hypothyroidism have also been linked to 2,4,5-T/TCDD exposure. Other symptoms such as asthenia, liver and renal dysfunction, neuropathy, and gastrointestinal and cardiac disturbances are probably due to mechanisms similar or identical to those of 2,4-D. Numerous instances of alleged disease due to 2,4-D/ 2,4,5-T exposure have been the subject of heavy media attention, particularly an episode of alleged 2,4,5-T exposure in Globe, Arizona, AIR FORCE WORKING PAPER IV-6 �in 1969. Despite extensive scientific review and analysis with negative findings, the Globe incident continues to be cited in current news media presentations. An incident in Missouri in 1971 in which six children, two adults and numerous animals were exposed to TCDD contaminated oil is frequently described as well. Many of the animals died and the humans developed chloracne and other acute toxic effects; however, all humans were healthy after five years of follow-up study. A final .prospective assessment of fertility, teratogenesis and carcinogenesis will probably be made in the future. F. Veteran Complaints The Veterans Administration Compensation and Pension Service, Washington, DC, provided the USAF with data on the first 361 claims filed by veterans alleging altered health status due to exposure to Herbicide Orange. A review of these claims revealed that less than half of the veterans received detailed physical examinations to evaluate the claims. Numerous media presentations emphasizing both military and civilian herbicide exposures have described a remarkably wide spectrum of health effects being claimed by the veterans. Based on current guidelines established by the Veterans Administration (Program Guide 21-1, Section 0-18 and Title 38 USC), none of the symptoms cited in these claims could be shown to be secondary to exposure to Herbicide Orange. Based on a review of military personnel and medical records, the vast majority of the exposure claims remained unsubstantiated/*£he guidelines state that the only chronic residual of defoliant exposure ever incriminated by clinical history has been chloracne. Furthermore, chloracne has been associated with prolonged intensive exposure and all other toxic effects of the herbicide were viewed to be rapid in onset and to run a brief course followed by recovery without residual disease. In fact, the vast majority of the claims alleging exposure to Herbicide Orange were not for chloracne and, as a result, did not satisfy the criteria set forth for compensation. Three of the first 361 claims cited chloracne, but none could be confirmed by physical examination. Table 2 summarizes the descriptive characteristics of the first 361 claimants, while Table 3 summarizes the distribution of these complaints by symptom category. Appendix Table A-4 displays similar data from a VA review of 625 claims received by 30 June 1979. AIR FORCE WORKING PAPER IV-7 �Table 2 SUMMARY OF DESCRIPTIVE CHARACTERISTICS OF HERBICIDE RELATED CLAIMS SUBMITTED TO THE VETERANS ADMINISTRATION AS OF 30 APRIL 1979* Total Number of Claims: Sex: 100% Male Mean Age: 34 years Mean Number of Alleged Symptoms per Veteran: 2.3 Branch of Service: (Service history identified in 66.8% of claims) US Army 66.4% US Marine Corp 17.4% US Air Force 11.2% _ US Navy_ 5.0% _ _ ^ *Exact racial distribution unknown; anecdotal information suggests the majority of claimants are non-Caucasian. Table 3 HERBICIDE RELATED CLAIMS SUBMITTED TO THE VETERANS ADMINISTRATION BY SYMPTOM CATEGORY AS OF 30 APRIL 1979 Total Number of Claims: 361-13 = 348* PERCENT DERMATOLOGIC (hairloss; chloracne; tinea, eczema, 48.9 contact dermatitis, keloid, vitiligo, tumors, porphyria) PSYCHIATRIC (personality disorders, anxiety neurosis, 27.6 depression, psychoses, pedophilia, alcoholism, adjustment reactions) 'EAR, NOSE, & THROAT (hearing loss, tinnitus, voice loss, 14.4 sinusitis) CANCER (lung, bone, pancreas, brain, thyroid, 13.8 larynx, colon, skin, soft palate, leukemia, lymphomas, Hodgkins Disease) PERIPHERAL NEUROPATHY (numbness, paresthesia, weakness, 12.1 tingling, Guillan-Barre Syndrome, Multiple Sclerosis, Amyotrophic Lateral Sclerosis) ASTHENIA (headache, weight loss/gain, dizziness, 11.2 fainting/blackouts, fatigue, lethargy) GASTRO-INTESTINAL (pain, ulcers, diarrhea, bleeding, 10.9 hemorrhoids, colitis, achalasia, regional enteritis) REPRODUCTIVE (decreased sex drive, impotence, decreased 10.1 fertility, miscarriages, sterility; genetic defects in offspring) PULMONARY (asthma, shortness of breath, infiltrates, 9.2 chest pain, bronchitis, pulmonary hypertension, lung disease) AIR FORCE WORKING PAPER IV-8 �Table 3 (CONTINUED) PERCENT OPHTHALMOL06IC (conjunctivitis, visual loss, pterygium, O~ blurred vision, light sensitivity, optic atrophy) MUSCULO-SKELETAL (arthritis, gout, fractures, stiffness, 8.1 spasm, -hernia, bone disease, strains) CARD10-VASCULAR (hypertension, arrhythmias, myocardial 7.5 Infarction, peripheral vascular disease, heart problems) 6ENITO-URINARY (urethritis, stones, renal disease, 4.0 prostatitis, epididymitis, testicular mass) CENTRAL NERVOUS SYSTEM (strokes, loss of memory, seizures, 3.7 tremors, meningoencephalitis,speech impairment) HEPATIC (hepatitis, liver disease, gall-bladder 3.5 disease, jaundice) PANCREATIC (Diabetes Mellitus, pancreatitis, reactive 2.3 hypoglycemia, increased amylase levels) HEMATOLQGIC (Pernicious Anemia, blood disorders, 1.4 lymphnode disease, spleen disease, Polycythemia Vera) COLLAGEN-VASCULAR (Systemic Lupus Erythematosis, Rheu1.2 matoid Arthritis, Polymyositis, Sarcoidosis) ALLERGIC (allergic reactions) 0.9 F E V E R ( l o w - g r a d e fever, fever of unknown origin) 0.9 POISONING (lateritic soils) 0.3 PERIODONTITIS AMYLOIDOSIS~ HYPERTHYROIDISM 0.3 0.3 0.3 *NOTE: 13 CLAIMS ALLEGED EXPOSURE ONLY (WITHOUT SYMPTOMS) AS BASIS FOR COMPENSATION Study design implications that can be drawn from these tables are limited due to the lack of knowledge concerning denominator data. Overall, the group of claimants exhibited a high frequency of readily identifiable disorders (e.g., dermatologic, psychiatric, and cancer). Further evaluation of the claims revealed that of the total number of claimants, 16.3%, had previous diagnoses of psychiatric disorders (20% of these diagnosed with schizophrenia). Table 4 summarizes information from those claims submitted by USAF veterans. AIR FORCE WORKING PAPER IV-9 �Table 4 HERBICIDE RELATED CLAIMS SUBMITTED BY USAF VETERANS BY SYMPTOM CATEGORY AS OF 30 APRIL 1979 Number of USAF Veterans: 28 (Mean age = 35.4 years) Symptom Psychiatric Dermatologic Reproductive Peripheral Neuropathy Cancer Miscellaneous Percent 50 39 25 14 7 7 The demonstrated lack of an easily identifiable symptom complex on review of the veteran claims clearly requires a comprehensive evaluation of individual symptoms. G. Epi demi ologic Studies Epidemiologic studies of occupational groups have validated links between exposure to TCDD and the development of chloracne. Associations between TCDD and psychological abnormalities have also been suggested. A 1978 study by Hardell and Sandstrom in Sweden evaluated occupational exposure to chlorophenolic compounds in soft tissue cancer patients by a case-control design. They found an association between cancer and exposure, but methodologic problems have raised questions concerning the value of these findings. Tung (1973) reported an abnormal increase in the occurrence of primary carcinoma of the liver in Vietnam (26 cases per year during 1955-1961 versus 144 cases per year during 1962-1968). He attributed the increase to a suspected carcinogenic effect of TCDD. His published study, however, has been criticized for failure to contain sufficient data and descriptions of methodology to verify his conclusions. The role of aflatoxin as an alternative cause of liver cancer was not addressed. His study was largely an empiric clinical report. A study sponsored by the EPA in 1979 in A!sea, Oregon, found a statistically significant increase in spontaneous abortion in areas where 2,4,5-T herbicide was routinely used in reforestation programs. EPA concluded, however, that "for all its complexity, this analysis is a correlation analysis, and correlation does not necessarily mean causation." This report is currently the subject of intense scientific criticism. Differences in the availability of specialty obstetrical care and in the patterns of health care delivery existed between the exposed and control areas; these differences were not taken into consideration by the researchers. Variations in the ascertainment of spontaneous abortions in each of AIR FORCE WORKING PAPER IV-10 �the areas severely limited the validity of the data, and of the conclusions derived from them. A recent study conducted in Australia (1978) was unable to find an association between birth defects (neural tube abnormalities) and the use of 2,4,5-T herbicide. Epidemiologic studies are continuing in Seveso, Italy where a population of 220,000 was potentially exposed to TCDD following an industrial accident in July 1976. These studies have involved investigations of more than 30,000 children and detailed clinical examinations of 1,024 persons, including the most severely exposed children and adults. Recent data (Homberger, et al., 1979) indicated that most cases of chloracne from this incident cleared rapidly. To date, the growth and development of newborn infants and children, immunological response, chromosomal aberrations, the response to the challenges of infectious diseases, and the morbidity and mortality patterns of the study population have not been significantly altered by TCDD exposure. Thirty-eight cases of birth defects were reported in early 1977, approximately 6-8 months after the industrial accident. However, the authors ascribe this increase to an artifact of surveillance. The social pressures operating in the Seveso population prior to the accident fostered underreporting of birth defects, while the atmosphere after the accident made the occurrence of a birth defect more socially acceptable. The post accident congenital malformation rate is not significantly different than the rate in similar areas of Central Europe. Similarly, ascertainment and surveillance of spontaneous abortions after July 1976 is hampered by the lack of valid baselines for the pre-accident period. Another progress report on the aftermath of the Seveso accident (Pocchiari, et al. 1979) has revealed: (1) a decrease in the prevalence and severity of chloracne in the exposed population; (2) an increase in idiopathic clinical and subclinical neurologic disease as demonstrated by delayed peripheral nerve conduction velocities; and (3) increases in the prevalence of idiopathic hepatomegaly (8%) and alterations in liver function tests which returned to normal over an 18 month period of follow-up. Thus far, immunologic, cytogenetic, and embryomorphologic analyses have been unable to detect significant differences between exposed and nonexposed individuals. A 2,4,5-T Dispute Resolution Conference was held in Arlington, Virginia, from 3 to 7 June 1979. Fifty-six recognized experts from the United States and seven foreign nations were actively involved in the deliberations of the conference. Human Exposure, Carcinogenicity/Mutagenicity, and Teratogenicity Working Groups independently reached the conclusions that there was no valid scientific evidence linking fetotoxicity, teratogenicity or carcinogenic! ty in humans to 2,4,5-T/TCDD exposures. The Human Exposure Working Group also concluded that there were no epidemiologic data associating TCDD with any long-term health effect in humans other than persistent chloracne. While they did not find evidence of serious long-term health effects, neither could they find strong AIR FORCE WORKING PAPER IV-11 �evidence for lack of effect. Most previous epidemic!ogic studies have not had sufficient statistical power to detect increased risks of low incidence/prevalence conditions in the observed populations, and the period of observation in many prospective studies has been less than ideal. Several potentially valuable epidemiologic studies are currently in progress. -Two independent and comprehensive studies of workers exposed to TCDD at a Monsanto manufacturing plant in Nitro, West Virginia, are currently being conducted (Mt. Sinai Medical Center, New York, and the Kettering Laboratory, University of Cincinnati, Ohio). These chemical industry workers were exposed over long periods of time and were previously evaluated in 1953 and 1956, following an industrial accident which occurred in 1949. In a personal communication, Dr. Raymond Suskind of the Kettering Laboratory has reported a follow-up study of 122 workers 28 years after heavy exposures to TCDD. There were 32 deaths in the group, and the relative risks of death were 0.69 for all causes, and 1.0 for malignancy; however, no firm conclusions can be drawn due to the small numbers involved. The Dow Chemical Company is currently analyzing data from a reproductive survey of the spouses of 2,4,5-T/TCDD exposed workers. A Czechoslovakian study involving a 10 year followup of TCDD exposed workers, and a US National Cancer Institute (NCI) mortality study of 4,400 structural pest control workers are also underway. Preliminary reports of a larger study of long-term morbidity by Suskind at the Nitro site have failed to reveal significant abnormalities other than persistent mild chloracne and decreased nerve conduction velocities, possibly associated with alcohol intake. These new studies, and the continuing evaluations of the Seveso, Italy, population, should provide valuable data. The large study groups involved in the Seveso and NCI studies should provide good statistical power, and the Nitro, West Virginia, and Czechoslovakian efforts will evaluate the effects of exposure after prolonged periods of time (10-30 years). The results of these studies should fill major gaps in the knowledge of 2,4,5-T/TCDD epidemiology, and should prove to be useful in evaluating the long-term effects of these compounds on health and reproductive outcomes. AIR FORCE WORKING PAPER IV-12 �V. Epidemiologlc Study Design: A. Matched Cohort Design Considerations The proposed goals for this study clearly mandate a comprehensive epidemiologic approach, incorporating mortality, morbidity and follow-up studies. Exposure to herbicides during the 1962-1970 time period may have initiated long-term health effects that may or may not be progressive. If such effects are detectable by past history, and can be verified, direct links to the compensation^can be made. Current health status, as mirrored by the large number of recent VA claims, becomes of major interest, because such claims may indicate medical conditions that might be confirmed by a comprehensive physical examination. If both the mortality and morbidity studies yield only indeterminant or weakly suggestive findings, it may be that sufficient time has not yet passed for substantial emergence of longterm health effects. This dictates a requirement for a follow-up element to the study. Methodological shortcomings are inherent in each element of this comprehensive study. To some extent, the classical deficiencies of each particular epidemiologic approach are compensated by the concurrent use of the other elements. For example, the low chance of identifying a relatively uncommon disease solely by the use of a follow-up study is offset by the inclusion of the mortality and morbidity studies. The relatively quick feedback that can be attained from these studies will serve to better define the follow-up study and will help to alleviate problems that arise as a result of changes in diagnostic criteria and methods over time. Nevertheless, problems that can affect ascertainment of disease in all phases of the study will remain. Inaccurate patient recall of antecedent events, the distortion of information by knowledge of anticipated symptomatology and participant or observer knowledge of their exposure status can only be corrected to a limited extent by review of records for symptom validation and "blind" assessment protocols. In addition, fundamental problems dealing with adequate selection of a control group and limiting loss to study can influence even the most comprehensive epidemiologic investigation. These and other pitfalls in study design will be discussed in more detail in Section VIII. Since the study has three elements and confronts a health issue with undefined endpoints, strong bias, and political pressure with severe time constraints, the following design represents the best overall framework for achieving validity. The design process is complex and in itself time dependent. The epidemiologic techniques used are time-compressed. Unique record searching systems within the Air Force, and computer and clinical capabilities, as well as bias and loss-to-study correctors, will work toward making this effort achievable. AIR V-l FORCE WORKING PAPER �B. Ascertainment of Exposed and Control Group Populations (1) Exposed Group Operation RANCH HAND personnel flew C-123 aircraft in Vietnam during 1962-1970. Data from hand-compiled lists obtained through the RANCH HAND Association (a reunion organization), Air Force personnel computer entries, historical records and actual C-123 flight orders, place the estimated study population at approximately 1200 individuals. Of those personnel confirmed by the USAF computer system, 25% are still on active duty, with the remainder being composed of retired or separated persons. An indepth search to identify all RANCH HAND participants is being conducted of all organizational records stored at the Military Records Division, National Personnel Records Center (NPRC), St. Louis, Missouri. Detailed advertisements in active/retired military trade journals, VA publications, and local newspapers will be pursued in the near future to insure maximal ascertainment/identification of the exposed group. Introductory letters will be sent to the last known address of all identified persons, and nonresponse will be pursued by cross-locator systems available within the government (e.g., Social Security Administration, VA, Internal Revenue Service). Significant efforts will be made to account for at least 99% of the total population (see Figure A-2, Section XII).Because of the limited number of estimated RANCH HAND personnel (1200), no subsampling of the exposed group is planned in any phase of the study. All members will be strongly encouraged to participate in all phases of the investigation. (a) Known or Predicted Characteristics of the Exposed Group All exposed aircrew personnel are males currently ranging in age from approximately 28-58 years. The normal C-123 crew composition was one pilot and one copilot/navigator (both officers) and one spray equipment console operator in the rear of the aircraft (enlisted); thus, the aircrew officer-enlisted ratio will be approximately 2:1. The inclusion of RANCH HAND support personnel in the study will make the overall officer-enlisted ratio approximately 1:2. While almost all officers were Caucasian, approximately 10-14% of the enlisted men were Black. Attempts will be made to identify all maintenance personnel assigned to the RANCH HAND units. Maintenance of the RANCH HAND aircraft was performed within a step-wise organizational structure. Routine daily maintenance (primary) was conducted by flight line support personnel who were often dedicated exclusively to RANCH . HAND operations. More extensive maintenance (secondary) was carried out by consolidated support units at the base level, which were also responsible for non-RANCH HAND C-123s as well. Major aircraft overhauls and modification were conducted by maintenance units at Clark Air Base, Philippines. The maintenance personnel in these centralized units were not directly assigned to RANCH HAND, and their exposures to RANCH HAND C-123 aircraft and herbicide cannot be validated. From AIR FORCE WORKING PAPER V-2 �1962 through 1964, the primary flight line maintenance teams were dedicated to RANCH HAND aircraft and these individuals can be identified by the mechanisms described above. In 1965, flight line maintenance was performed by personnel of the centralized maintenance organization (secondary) and it may not be feasible to adequately identify these individuals from available records. After 1966, the RANCH HAND organization transferred their base of operations to a new location, and primary maintenance was once again performed by personnel assigned specifically to RANCH HAND. These individuals can again be readily identified. Thus, maintenance personnel directly assigned to RANCH HAND will be included in the study. These complexities are summarized in Table 5. Table 5 FEASIBILITY OF IDENTIFYING AIRCRAFT MAINTENANCE PERSONNEL (TOTAL POPULATION) EXPOSED TO HERBICIDE ORANGE Primary Mai nt Personnel •*• Time Jan 1962-Jul 1964 Aug 1964-Dec 1966 Jan 1967-Apr 1970 Yes Yes/No 3 Yes Secondary Maint Personnel No No No ^individual assigned to RH; denominator known Individual not assigned specifically to RH, although may have serviced the aircraft; denominator not ascertainable 3 "Morning Reports" may permit ascertainment of this group. Because of the significant combat hazard associated with low, slow flying missions, all early RANCH HAND crewmembers were elite volunteers (see Risk-Taking Bias, Section VIII). In fact, RANCH HAND crew members comprised one of the most highly decorated units during the Vietnam Conflict. Anecdotal stories reveal that most crew members were, on occasion, heavily exposed to Herbicide Orange due to normal or combat induced equipment malfunctions within the aircraft. Many former RANCH HAND personnel are expected to be currently employed in the aerospace industry as commercial airline pilots, airline managers, and flight mechanics. RANCH HAND personnel still on active duty are expected to be found in senior management positions. (2) Ancillary Study Groups (Non-RANCH HAND personnel) Air Force handlers of herbicide drums in Vietnam were exposed to herbicides because of drum leakage. Advertisements AIR FORCE WORKING PAPER V-3 �similar to those proposed for the RANCH HAND personnel will be issued in attempts to define this population. As the drum handlers were ad lib participants, no personnel designator was assigned to these individuals, thus prohibiting computer tracking and identification. The population is unknown, but expected to be small (less than 200) as the majority of drum handlers were known to be Vietnamese. Additional .groups such as US Army personnel (officer and enlisted) who flew as observers, US Army helicopter crews, as well as experimental fighter-bomber spray personnel, may be included in the study. Specific epidemiologic/clinical studies for these groups must be planned by a separate protocol following their ascertainment since control group selection will be difficult or moot. It is intended that all data derived from the ancillary study groups will be subsetted for separate analysi^and these data will be treated as anecdotal to the primary study. The members of these groups are expected to be males, ranging in age from 28-68 years. The officerenlisted ratio is estimated at 1:10. Approximately 10-18% of these populations are expected to be Black. Low numbers of respondents are expected and population at risk ascertainments will not be possible. (3) Control Group (Not exposed to Herbicide Orange) Total ascertainment of the C-130 population is being conducted by computer selection for specific military flying organizations, foreign country service and years of service. Over 2.3 million personnel records have already been scanned and the approximate C-130 sample size is 25,000 individuals. Aircrew members who flew C-130 aircraft in RVN during 1962-1970 will be selected as controls for the RANCH HAND aircrew population and the C-130 flight line maintenance population will be ascertained from personnel records by similar mechanisms, and will serve as the specific control population for the RANCH HAND support personnel. The proportions on active duty, and non-active duty status are expected to parallel the patterns in the exposed group. Another possible control group, the non-RANCH HAND C-123 population, is known to be too small (approximately 3000) to provide adequate sampling flexibility and replacement under the proposed best .match variable concept (see below and Section VI, A). Many of the RANCH HAND aircraft were reconfigured for transport and insecticide missions and thus, non-RANCH HAND crews responsible for these other missions, may have been exposed to Herbicide Orange residues in these aircraft. This group may not be truly unexposed to herbicides and therefore is not |fe an appropriate control population. The C-7 crewmembers have also been considered as a potential control group; however, this latter group was comprised of only 1000 to 1200 individuals. AIR FORCE WORKING V-4 PAPER �(a) Known or Predicted Characteristics of the Control Group The normal crew composition of a C-130 is three officers and two enlisted personnel. The control group will be "pure" from the standpoint of lack of occupational exposure to herbicide. The entire control group will be considered "nonvolunteer" with respect to abnormally high combat risk. While in general they will possess lifestyle characteristics and socio-economic backgrounds^ similar to the^ exposed group, their overall combat morbidity /mortality andXresultant .stress influences upon general health may be slightly less than'^the exposed group. For those separated and retired C-130 controls, similar proportions to the exposed group are expected to be employed in the aerospace industry. Known and estimated factors of the control and exposed populations are summarized in Table 6. (4) Matching Procedures and Rationale Each member of the exposed group will be computer matched to a set of C-130 controls comprised of at least 10 individuals using four variables. Since the two groups are highly selected and inherently similar with respect to many variables, very close matches are feasible. This epidemiologic design incorporates a matched concept because: (1) a matched cohort design will provide maximum test power throughout the entire study, (2) statistical intergroup comparisons may be made without normalization by four key variables known to effect symptom frequencies of interest, thus providing greater power for complex statistical testing, and (3) close matching is feasible and necessary for some of the anticipated analyses of the physical examination findings. Matches will not necessarily be rigidly maintained throughout the analytic phase, depending upon the particular analysis. It is apparent that following the match, both exposed and control populations will be very nearly identical with respect to the four influencing variables so that a replacement concept is feasible (see E below). In the event that frequent match breaks still occur, stratification techniques can be used. Matching will be conducted for (1) age, by year of birth, and closest month possible, (2) Air Force Speciality Code (AFSC) as an absolute match, (3) length of time spent in Vietnam, to the closest six month period, and (4) race (Caucasian versus nonCaucasian) as an absolute match. These variables are listed in priority order of the match sequence. Specific rationale for these variables is as follows: (1) many clinical symptoms and signs allegedly attributed to herbicide exposure (see literature review) can also be attributed to an aging effect, or to collateral diseases more commonly associated with advancing age, (2) AFSC controls specifically for officer-enlisted status (as well as crewmember or noncrewmember status), a variable strongly linked to educational background, current socio-economic status, and moderately linked to AIR V-5 FORCE WORKING PAPER �Table 6 COMPARISON OF THE STUDY GROUP TO POSSIBLE CONTROL GROUPS BY KNOWN AND ESTIMATED FACTORS KNOWN FACTORS STUDY GROUP POSSIBLE CONTROL GROUPS RANCH HAND C-123 POPULATION SIZE OFFICER/ENLISTED RATIO Non-RANCH HAND C-123 C-7 C-13Q 800-1200 3000 1:2 1:2 1:2 1:2 YES NO (JP-4) 1200 18,000-25,000 AIRCRAFT FUEL (AV-GAS) YES (+JP-4)* YES (+JP-4)* OCCUPATIONAL HERBICIDE EXPOSURE YES YES/NO ** NO 1+ to 4+ 0 0 NO ESTIMATED FACTORS OCCUPATIONAL INSECTICIDE EXPOSURE 2+ COMBAT HAZARD 4+ 3+ 3+ 2+ RVN-IN COUNTRY ASSIGNMENT 4+ 4+ 4+ 2+ *In 1968, aircraft were modified with a JP-4 booster. **Contaminated aircraft reconfigured for transport may have resulted in exposure to non-RANCH HAND personnel V-6 AIR FORCE WORKING PAPER �age (5 year median difference) and socio-economic background, (3) total length of tour in RVN (measured in six month intervals, or actual flying hours, if feasible) will control for the generalized probability of combat morbidity, mortality, and for combat induced neuro-psychiatric disorders; additionally, length of tour may reflect effects real ted to intensity of alcohol consumption, drug consumption (chemoprophyTactic or illicit), and degree of tropical disease acquisition and (4) race controls for difficulty in diagnosis of dermatitis, socio-economic background, etc. {note: There is possible racial discordance for VA claimants). (5) Study Group Selection Procedures (a) Mortality Analysis For the mortality analysis, the ten controls will be selected for each exposed subject, regardless of current vital status (Figure 1). The control individuals will be randomly assigned to one of 10 cohorts, C^ through C^Q. All of the exposed individuals and a 50% random sample of each set of controls will be included in the mortality analysis. The current vital status of each exposed-control set will be determined, and their mortality experience will be followed throughout the duration of this study. In addition to providing a 1:5 mortality analysis, this technique will characterize the mortality experience of each control cohort. Figure 1. Mortality Analysis Cohorts RH COHORT CONTROL COHORTS E l C 2 C E E C E l,l C l,2 C l,3 c 2,l C 2,2 C 2,3 C 2,4 C 2,10 3,l C 3,2 C 3,3 C 3,4 C 3,lO 4,l C 4,2 C 4,3 C 4,4 C 4,lO C J,2 C 3 C 4 C E E j C j,l j,3 AIR FORCE WORKING PAPER V-7 l,4 C j,4 c l,10 C j,10 �(b) Questionnaire, Physical Examination and Follow-up Study In the questionnaire and physical examination phases of the study, a 1:1 match between each living exposed subject and his C} (primary) control will be attempted. If the primary control is deceased, unaccountable, or unwilling to participate in the morbidity and follow-up studies, the next control ( C o ) will be selected and so on until a willing subject is found (Figure 2). Since the control's vital status and volunteerism should be independent of the matching sequence, many primary controls should enter the study. The remaining members of the control set will be used as replacement candidates for possible use later in the study (see section E below). All replacement controls will be clearly identified for the purposes of subset analysis so that any inadvertent bias created by the replacement strategy can be assessed. Figure 2. Selection Procedure for the Questionnaire, Physical Examination, and Follow-up Study LIVING RANCH HAND INDIVIDUAL CONTROL INDIVIDUALS c t o - * r > C10 l ** 1:1 t Deceased o Unaccounted - Unwilling * Volunteer ** Replacement Candidates C. Mortality Study (1) Introduction The mortality, morbidity, and follow-up studies are components of a "non-concurrent" prospective study used in the observation of a specially exposed group or industrial population starting from some date in the past. The initial exposures occurred 8-17 years ago and varied in intensity and duration from one RANCH HAND member to another. Access to employment, medical and other AIR V-8 FORCE WORKING PAPER �types of records is an obvious requisite for such a study. The classical "case-control", retrospective study is not operative in this protocol due to the lack of defined clinical endpoints. The mortality study will be conducted in two phases; a review of past mortality, and a continuing assessment of the death experience in the exposed and control cohorts over the duration of the RANCH HAND II project. (2) Data Collection Methods The mortality status of the exposed cohort and the randomly selected controls will be ascertained using multiple techniques including; telephone interviews with subjects or their families, a review of Death Benefits claims filed with the VA, acquisition of death certificates on all known deceased individuals and reviews of autopsy reports and medical records whenever possible. D. Morbidity Study (1) General Considerations A vigorous attempt to determine the morbidity experience of all exposed subjects and their primary controls will be undertaken using questionnaires, indepth personal interviews, and physical examinations. The schedule and method of contact with the study subjects is depicted in the Appendix, Table A-5. (2) Questionnaire Methods All exposed members and their matched primary controls will be offered a comprehensive personal and family health questionnaire via telephone. The questionnaire is an important part of this study because non-compliance rates for the physical examination and its face-to-face interview are expected to be substantially greater than non-compliance with telephone questionnaire. As depicted in the Appendix, Figure A-2, only an estimated 40% of the RANCH HAND population will participate in the examination, while 65% will respond to the telephone questionnaire. The information collected by questionnaire from these additional 309 individuals and their controls will provide valuable morbidity data which would otherwise be lost. The questionnaire (see Section XIII) will emphasize identification data, RVN tour history, dermatologic conditions, neuropsychiatric conditions, fertility aberrations, genetic defects in offspring, sensory defects, and personality factors, including assessments of risk-taking behavior. A review of medical systems will be included in the questionnaire, and will inventory symptoms prior to, during, and after duty in Vietnam as well as currently. The questionnaire will be limited to a 30-45 minute telephonic interaction with participants, and it will take 10 to 12 months to complete all initial questionnaires on both groups. It may be necessary to conduct the questionnaire in two telephone sessions to AIR FORCE WORKING PAPER V-9 �minimize fatigue and maximize validity of response. The questionnaire will be "field-tested" on a group of 25 to 30 former Air Force pilots with Vietnam combat experience. Specific questions on the questionnaire will be directed to verifiable information, wherever possible. Specific response verification and bias indicator questions (nonsense symptoms), and indicators of risk-taking behavior are being developed. They w i l l be added and appropriately sequenced immediately prior to the start of the study. Questionnaire data will be cross-linked and integrated with medical record information and physical examination findings. Questionnaire data from individuals not completing all phases of the study w i l l not be discarded, but will be incorporated within the entire data base where statistically appropriate. Each participant will be asked to sign release forms so that all civilian health records, including those of dependents, can be obtained and reviewed as necessary. Federal health records on all family members on file in the NPRC will be retrieved. For retired members, and separated members with VA priviledges, all available VA medical records will be obtained. All retrieved medical records will be reviewed, scored, compared to questionnaire data for reliability, and then be entered into a repository system. Identified participants who are non-responsive to questionnaire will be pursued to determine status, disinterest, moribund state or death, etc. These individuals will be cross-referenced in other federal record systems in an attempt to achieve total ascertainment. Death certificates and autopsy reports will be retrieved on all dead exposed and matched control subjects for the mortality analysis. Birth/death certificates will be sought for all offspring, born subsequent to the study subject's Vietnam duty. (3) Physical Examination A voluntary comprehensive physical examination will be offered to all individuals in both the exposed and primary control groups. The condition for entry into the examination phase of the study will be the completion of the baseline questionnaire. In ^—•—CTTe event that the*control does not complete both the questionnaire and the physical examination, the Cg control will be selected, and so on, until a w i l l i n g control is obtained. (See Figure 2). Statistical testing will be conducted by a variety of techniques on both questionnaire and examination findings (see V I , Statistical Methodology below). At the time of physical examination, an extensive face-to-face interview will be conducted. A standardized protocol will be used to insure comparability of inteview data. This will provide cross-reference data to the initial questionnaire and to medical record data, if retrievable. Specific response verification and bias indicator questions will be included during the interview as well. (4) Examination Parameters A comprehensive physical examination will be conducted on all willing participants. The examination will be structured as outlined below and in Section XIV. AIR FORCE WORKING PAPER V-10 �General Physical Examination FBS, 2 Hr Post Prandial Urinalysis BUN/Creatinine Cholesterol/HDL Cholesterol Triglycerides Serum Protein Electrophoresis Hemoglobin Hematocrit White Blood Cell Count Platelet Count RBC Indices Sedimentation Rate Cortisol Differential Thyroid Profile (RIA) CPK ECG Chest X-Ray VDRL/FTA Dermatologic Examination Urine Porphyrins Urine Porphobilinogen Delta-ami no!evulenic Acid Neuro-Psychiatric Nerve Conduction Velocities Psychological Battery MMPI WAIS WRAT Halstead-Reitan Wechsler Memory Scale Subtests Cornell Index Reproducti ve Exami nati on LH, FSH, Testosterone Semen Analysis Neoplasti c/Hepati c E xami nati on SGOT SGPT GGTP Alkaline Phosphatase LDH (Isoenzymes if elevated) Additional Studies (Individuals with abnormal history or examination) Karyotyping Hepatitis Antigens/ Antibodies (A and B) Additional Consultations as Required Anti-Nuclear Antibody Immunoelectrophoresi s Monilia Skin Test Quantitative Immunoglobulins Examinations will be performed at a single USAF medical facility having dermatologic, neurologic and electromyogram/ nerve conduction capabilities. Special Air Force authorization will be obtained to conduct such examinations on individuals separated from the service and informed consent forms will be obtained for nerve conduction tests. Physicians and technicians AIR FORCE WORKING PAPER V-ll �will handle all participants without a knowledge of exposed or control status, and will conduct the examinations by standardized protocols to minimize variability. Medical students and interns will not perform these examinations, and specialty trained neurologists and dermatologists will perform the appropriate portions of the examination. An onsite monitor will insure that the examination protocol is followed. . Clinical specimens will be forwarded to USAFSAM where most of the laboratory procedures will be conducted. The only laboratory procedures to be accomplished at the examining facility will be those which require immediate processing (see Section XIV, D(5)). All laboratory tests will thus be subject to the same technology and rigid quality control. Laboratory and physical examination data will be measured on a continuous scale whenever possible in order to improve statistical power in the analysis. Special contingencies will be made for unusal laboratory testing. Karyotyping of the individual and his family members will be performed if clinical history or physical examination findings are suggestive of this need. Most well conducted studies have shown that, when present, chromosomal abnormalities due to TCDD are transient. If on detailed analysis of the baseline examination and questionnaire, reproductive areas are heavily affected, routine karyotyping may be included in the test battery for the follow-up study. TCDD analysis on blood and urine will be considered in the future provided that (1) strong cause and effect relationships can be ascribed to Herbicide Orange and (2) high resolution mass spectrometry technology achieves 10 femtogram sensitivity with high specificity. Appropriate specimens will be obtained from all participants, aliquoted, and preserved at -70°C for possible analysis in the future. Physical examination and laboratory data will be placed in the member's coded master file for detailed cross-analysis to questionnaire data. Information identifiable to the subject will not be released without his consent in accordance with the Privacy Act. (Exceptions: In accordance with Air Force regulations, all active duty flying personnel and air traffic controllers found to have disqualifying defects will be temporarily "grounded" pending resolution; in accordance with federal regulations, all commercial airline pilots and air traffic controllers found to have disqualifying defects will be reported to the Federal Aviation Administration.) E. Follow-up Study (1) Study Adaptations Following complete data analysis of the mortality and morbidity studies, an adaptive or restrictive health survey will be developed and administered to all follow-up study subjects three and five years after the initial questionnaire. Similarly, a condensed physical examination profile that will achieve adequate sensitivity and specificity for prospective diagnosis will be AIR FORCE WORKING PAPER V-12 �developed. The adaptive physical examination will be offered to all follow-up participants, and w i l l also be conducted in years three and five (see Appendix, Table A-5). An interim examination is essential in this study because the age group under study is approaching that portion of the mortality/illness incidence curve /"*""^tRSfsteepest slope. A lapse of five years between examinations would easily miss significant development of disease in the intervening years. Ample precedent for interim examinations can be found Tn the^frarvl'inglvam, cardiovascular disease study and the follow-up evaluation of West Point graduates being conducted by the Air Force. (2) Entry Criteria All exposed or control i n d i v i d u a l s completing the baseline questionnaire and physical examination will be entered into the follow-up; further continuation will depend upon the member's willingness/ability to participate in additional health surveys and condensed examinations. (3) Loss to Study Loss of participants over time adversely affects any epidemologic study in two ways. As the sizes of the study groups decrease, statistical power also declines, and bias is injected into the study if losses are not randomly distributed in the study populations. It is reasonable to assume that in this study, losses will be non-random with greater non-compliance among individuals who perceive their health as "well," since there is less incentive for this group to continue participation. As shown in Figure 3, such a differential pattern of loss will alter the population and skew the frequency distribution curve. Most previous epidemiologic studies have approached the problem of declining statistical power by beginning the study with a "multiple to one" control group, and passively *Hew^aTtrT= tion to occur throughout the study period. However, this approach does not address the problem of bias. This study will taken an active approach to bpth*These problems by using a replacement concept. As a control is Tost to study, a replacement will be chosen from the original set of 10 matched controls. The replacement will be selected from the control set, and will have a perception of health similar to that of the lost control (Figure 4). The replacement strategy will maintain statistical power and the integrity of the matched design despite loss to study in the control group, and will correct anticipated bias while minimizing the number of required physical examinations. At the initiation of the follow-up study loss of an exposed member will not be cause to cease surveillance of his primary matched control. In the event of a control loss (for reasons other than death), the next control of the set will be brought to study (Figure 5), the comprehensive questionnaire will be administered, and a baseline physical examination performed. Medical data AIR FORCE WORKING PAPER V-13 �EFFECT OF NON-RANDOM LOSS TO STUDY IN THE CONTROL POPULATION N WELL ILL HEALTH SPECTRUM IF CONTROL LOSSES ARE ILL, A SPURIOUS EFFECT ' IS ATTRIBUTED TO HERBICIDE EXPOSURE. IF CONTROL LOSSES ARE WELL, A TRUE/VALID HEALTH EFFECT IS DILUTED. �«" / ANALYSIS OF REPLACEMENT SCHEME yL, \j\jw REPLACEMENTS MATCHED FOR HEALTH STATUS (DEAD CONTROLS NOT REPLACED] �iiqure CONTROL REPLACEMENT FOR THE MORBIDITY AND FOLLOW UP STUDIES EXPOSED 1000 CONTRO 1000 YEAR 0 YEAR 1 YEAR 2 YEAR 3 YEAR 4 YEAR 5 YEAR 6 O V-'M AIR QUESTIONNAIRE DATA RECONSTRUCTED DATA LOSS TO STUDY PHYSICAL EXAMINATION DATA FORCE HORKIMfi PAPER 3 1 OCT 1979 �for the intervening years will be reconstructed from the questionnaire and interview responses. IN ALL CASES OF LOSS-TO-LOSS STUDY, INTENSIVE EFFORTS WILL BE MADE TO DETERMINE THE SPECIFIC REASONS FOR NON-COMPLIANCE, AND DATA FROM REPLACEMENT CONTROLS WILL BE REVIEWED TO ASSESS COMPARABILITY WITH THE LOST INDIVIDUALS. Medical record reviews of new entrants will continue throughout the follow-up period. (4) Study Length The follow-up study is initially planned for five consecutive years. Results of the entire effort will be presented to a neutral scientific body. Their recommendation for continuance/ discontinuance of the study will be forwarded to the Air Force Surgeon General for final decision. F. Determination of "Disease" (1) Introduction Since this study is dealing with an unknown clinical endpoint with unknown latency, determination of a disease state by statistical methodology is a prime scientific thrust of the investigation. From the literature, chloracne is the only recognized chronic disease associated with high exposure to dioxin. The questions of primary interest are: (1) Does a history of chloracne invariably lead to future disease? and (2) In the absence of chloracne, is there emergence of other attributable diseases? Under a broad concept of "spectrum of illness", either or both of these conditions are possible. The clarification of their respective contributions to the natural history of past or of subsequent "disease" becomes extremely difficult. (2) Discussion Inferences about a disease state from this study can be derived from several logical approaches. These approaches can be grouped into two categories: (1) those dealing with symptoms which can be used to construct a symptom complex that may represent disease, and (2) those dealing with physical signs which in themselves represent disease. In the former, one can form a subset of individuals that have symptoms (e.g., infertility) and study them during the morbidity and follow-up studies. Focusing on the overall patterns of alleged symptoms and categorizing them into a symptom complex may identify those individuals with a disease syndrome, or those at higher risk of developing disease (e.g., genetic disorders, cancer). In the latter approach, data on abnormal physical signs (e.g., genetic defects in offspring) and laboratory results can be compared between exposed and non-exposed groups in an attempt to again establish the presence or absence of disease. By putting this array of data into a logical decision-making scheme, specific relative risks can be calculated in the follow-up study. AIR FORCE WORKING V-17 PAPER �By the use of combinational and correlational analyses, statements about the probability of a disease state, a subclinical state, and over-reporting bias can be attempted. If the development of symptoms in the exposed group is positively correlated with physical findings, and this correlation is absent in the control group, a statement concerning the existence of a possible disease state can be made. By taking these possible combinations of observations and viewing them in the context of associated positive verifiers, negative bias indicators, and positive exposure index, the probability of over-reporting bias acting in these circumstances can be substantially reduced and, as a result, any statement concerning the existence of disease is strengthened. Similarly, if symptoms in the exposed group do not correlate with the development of findings, but are associated with positive laboratory results, a statement concerning the existence of a subclinical disease state can be made. However, if comparisons within the RANCH HAND group reveal a negative correlation between reported symptoms and the presence of abnormal physical signs, then an over-reporting bias and/or subclinical disease state is suggested. Another method to assist in the determination of a disease state is the use of normalized exposure index and the application of regression techniques to the resulting curve. If there is a positive correlation between increased exposure and the presence of various abnormal physical signs and/or verifiable symptoms, then a symptom complex or disease syndrome is suggested. Factors suspected of altering the classical dose-response curve include cellular repair mechanisms and the hypothesized release of TCDD from adipose tissue following weight loss. The addition of multivariate techniques to the regression analyses will strengthen statements about the presence of disease. Beyond these pair-wise and group comparisons, newer techniques of pattern recognition, such as Factor Analysis and Cluster Theory, are being considered in order to achieve a more automatic and objective analysis. The strength of any inferences made from these analyses is dependent upon the statistical power inherent in the study. In addition, due to the possibility of latency being a factor in this study, a negative analysis at any time within the study does not categorically imply lack of disease, since sufficient time for emergence may not have passed. G. Determinations of Exposure Indices; (1) Exposure Concepts A major concern in conducting this study is the lack of accurate exposure data. Although most personnel assigned to RANCH HAND squadrons were undoubtedly exposed to Herbicide Orange and TCDD, the exposures within the group must have varied widely. AIR FORCE WORKING PAPER V-18 �Exposure to herbicides and TCDD by RANCH HAND personnel occurred almost daily. Anecdotal information suggests that many had direct skin contact which was repetitive over a long period of time (one-year tour for most individuals). Further, it is also suggested that most RANCH HAND personnel felt that the herbicides employed in the operations were not toxic to animals and man and hence, they did not exercise the caution' in handling these chemicals that is recommended today. Several individuals have, in fact, repetitively tasted or drunk Herbicide Orange to convince their colleagues or the press of its safety. m~-#nG> historical review of RANCH HAND operations, most individuals can be classified into one of three groups based on their likely potential for exposure to the herbicides: (1) Pilots, Co-pilots and Navigators: (2)_ Console Operators and Flight Engineers Crew Chiefs, Aircraft Mechanic, and other Support Personnel: low potential ^-^ high potential" moderate potential The "pilot" group probably received most of their exposure during pre-flight checks as well as during the actual dissemination missions. The console operator group was exposed while supervising the loading of the aircraft, during ground testing the equipment, and by tank leakage during dissemination missions. The crew chief group experienced contact with herbicides during dedrumming and aircraft loading operations as well as during on-site repair of the aircraft and spray equipment. The available historical records on Operation RANCH HAND indicate that personnel assigned to the project seldom had a "routine" work schedule or environment, thus complicating estimates of the level of herbicide and dioxin exposure. Since actual exposure data (e.g., mg of herbicide/kg body wt) are not available, the establishment of an exposure index will be attempted. The exposure index will be calculated for each RANCH HAND individual to obtain a standardized frequency distribution. The exposure index will be calculated by evaluating the known factors that would have influenced exposure. /These will include such factors as:, 1 £*."*( (1) (2) A , *\fL f\ . \ J*A/I ..A/* Irt 0 Iv&J A ' Date of tour with RANCH HAND in Vietnam. Number and lengths of tours in Vietnam with RANCH HAND. (3) Number of herbicide dissemination missions (as reflected by flying hours and air medals). (4) Herbicides employed (yearly records are available that reflect the amount of each herbicide sprayed). (5) Crew position. AIR FORCE WORKING PAPER V-19 �6) /Time ter^and /rom m>*fsi on I'Ocati on,*7 (length mi ssio w a s n mi ted/by ai ref^aft fu^l coris-Cimpti op^most missions ~~ were"Trom ,to two" hours -fn duration). ' " " © Routes of exposure (the major route of exposure for most RANCH HAND personnel was probably percutaneous, although for the console operator, exposure through inhalation may have also been important). An exposure index may be derived from consideration of the above factors, i.e., it is a function of the factors: E! = (D,T,P,C,R,H) Where Ej = Exposure Index D = Dioxin Concentration Estimate During RANCH HAND tour The date of tour with RANCH HAND is important since mean dioxin concentrations in the herbicides changed by a factor of 16 between pre-1965 and post-1965. In 1965, both high and low dioxin formulations were available. Thus, a scale of values for TCDD are: Pre-1965 T • = P 32 1965 Post-1965 16 2 Duration of = The ratio value of the amount of 2,4,5-T containing Herbicide applied for any given year against total amount of the herbicide applied during thej»ame_jy_£ai Data on herbicide expenditures by year travail able. For example in 1962, Purple comprised 88 percent all herbicides used that year, while in 1966, Herbicide Orange accounted for 66 percent of the total amount of herbicide applied. = Crew Position/AFSC Relative exposure values for this determined by separate studies. factor will be Route of Exposure Relative values for exposures via ingestion, inhalation or percutaneous absorption will need to be evaluated from literature, computer modeling, and inflight determinations using a Herbicide Orange simulant. AIR FORCE WORKING PAPER V-20 �H = Exposure History A relative value based upon the subject's preception as to the magnitude of his own exposure. This will be obtained from the questionnaire and may reflect no exposure, a light exposure, a moderate exposure or a heavy exposure. A weighted value will be assigned to each exposure estimate, if possible. (2) Proposed Studies Within the exposure index equation, relative exposure values for two factors are lacking; crew position within the C-123 aircraft and the route of exposure. Approaches which will be used in obtaining estimates for these two factors include (1) use of a diffusion model which would consider the internal aircraft volume and configuration in computing specified source strengths and concentration levels; (2) use of quantitative data obtained at specified points within the aircraft following actual C-123A/A 45Y-1 dissemination missions using a Herbicide Orange Simulant; and (3) use of a combination of the above two methods. Discussion with personnel of the U.S. Army Environmental Hygiene Agency and the Chemical Systems Laboratory, Edgewood Area, Aberdeen Proving Grounds, Maryland, suggest that the dispersion of herbicide vapors and particles within the C-123 aircraft could be modeled provided data could be obtained for selected parameters. These parameters include: (1) Air flow measurements within the aircraft under flying conditions simulating those encountered during actual RANCH HAND missions. (2) Physical properties of Herbicide Orange components. (3) Internal volume of aircraft and individual compartments. (4) Temperatures of internal surfaces. (5) Estimate of surface area on the floor of the aircraft. Given a specific scenario, for example, a 25 sq ft spill involving two gallons of Herbicide Orange on the aircraft floor during a mission, the model could determine the magnitude and duration of the chemical concentration in the areas near the console operator versus the air concentration in the cockpit. They key to determining the magnitude and route of exposure of C-123 aircrew members is obviously selecting the most likely aircraft configuration used during RANCH HAND and determining the frequency and magnitude of spills within the aircraft. These observations will come from the recollection of personal observations by RANCH HAND personnel. AIR FORCE WORKING PAPER V-21 �The 355th TAS/Spray Branch, Rickenbacker AFB OH is presently using the C-123 aircraft configured with the A/A 45 Y-l Internal Dispenser. Air flow measurements, volume determinations, and surface temperature data will be obtained for modeling and simulant studies. A suitable Herbicide Orange Simulant was developed by the USAF in 1965 and consisted of glycerine, water, and sodium thiosulfate in a ratio of 68:16.8:15.2, respectively. Since physical and chemical data are available on the simulant, the addition of a sodium fluorescein tracer may permit particulate sizing and quantitative determinations of the extent of contamination in the air of the aircraft and on the surfaces of the aircraft and on aircrew members. An estimate of relative exposure for non-flying personnel will be developed in a different manner. The Air Force conducted extensive industrial hygiene monitoring programs during the dedrumming and incineration of Herbicide Orange, Project PACER HO, (See Young, et al., 1978). These monitoring data (e.g., breathing zone data) and recently conducted, but as yet unpublished data on percutaneous absorption of 2,4,5-T in humans during actual spray operations in reforestation programs (Dow Chemical U.S.A., Midland MI, 1979), will permit more refined calculations of exposure estimates for this group of individuals. When these concepts are used to calculate an exposure estimate, there will be a group of RANCH HAND individuals with an exposure index of zero (clerical/ administrative personnel with little or no flight line duties). In the event that these more "elegant" exposure index calculations are not feasible, two other approaches to the exposure estimate are available. A crude index can be constructed, based solely on the duration of RVN duty and the TCDD concentration of the herbicides used each year. While such an index would be less precise in defining an individual's estimated level of exposure, it would still permit valid comparisons within the RANCH HAND population. Stratification techniques could also be employed using AFSC and duration of exposure (RVN duty) as the grouping criteria. AIR V-22 FORCE WORKING PAPER �VIII. Recognized Study Difficulties and Corrective Measures A> Medical Precedence (1) Problem A departure from the usual methodological approach characterizes this particular epidemiological investigation. Clearly there is no historical "roadmap of methodology" to conduct this study. Most occupational exposure studies use the presentation of an unusual disease to justify the initiation of a comprehensive study. A rare disease or a common disease in an uncommon site, or one with an unusual presentation appearing in space-time clusters, often in an ujiusual_population or age group, usually generates the requirement for a new study. In the case of Herbicide Orange, the evidence for long-term human effects is tenuous and controversial. Despite the unique problems that this study possesses, such as the lack of clinically defined endpoints, there are many problems that it shares with other occupationally related exposure studies. For example, the question of a latent period in the development of symptoms/signs, the lack of accurate dose-response relationships, and the possibility of a synergistic effect with other toxins/carcinogens are all operating in this study. Since most cohort studies of occupational mortality use the general population as a standard for deriving the expected number of deaths, preemployment selection ("healthy worker" bias) affects the comparative experience. Age-standardized mortality ratios (SMR's) in general are 60-90 percent of the standard in the working population. Similar conflicting results can occur using the matched cohort method proposed in this study design. Statistical verification of the validity of utilizing such a control for a summary mortality index (e.g., SMR) has been .infrequently attempted in the past. Inability to verify the validity of the more classical methods of comparing mortality will necessitate the use of multiplicative and/or logistic models to obtain a valid standardized mortality ratio. (2) Corrective Measures Unprecedented study designs forced by unprecedented occurences of occupationally related medical complaints require novel approaches, and reorientation and standardization of thinking; all of which require an effective Peer Review system. Beyond even the immediacy of the current study is the growing problem of a myriad of occupationally-related exposures, both in the military and civilian sector, which will require similar epidemiological studies in the future in order to make some judgment as to whether or not an association is of causal significance. AIR FORCE WORKING PAPER VIII-1 3 1 OCT 1979 �B. Group Accountability Bias (1) Problem The numerous media presentations on "Herbicide Orange" Issues have focused attention on the RANCH HAND group. Several attempts have been made to construct lists of former members of this group and thus the RANCH HAND population should be easier to locate and contact than the control population. This difference will be particularly evident with respect to reported mortality experience. The incentives for cooperation and study participation ,are likely to be greater in the exposed group than in the controls. Also, the close knit reunion association of former RANCH HAND personnel will lead to a more precise reporting of morbidity and mortality in that group. Such group identity tends to decrease the degree of unaccountability in the exposed group while its absence in the controls may lead to under ascertainment of mortality. This could then lead to the attribution of excess mortality in the exposed population. (2) Corrective Measures Unaccountability bias w i l l be minimized by attempting to keep the percentages of unaccounted for study subjects below 1% in both exposed and control groups. The morbidity and mortality status of all i n d i v i d u a l s selected for the study w i l l be strongly pursued u t i l i z i n g a variety of techniques previously described. C. "Risk Taking" Behavior Bias (1) Problem The early RANCH HAND aircrew population was an exclusively volunteer group; the C-130 control population, while volunteers in the Air Force, were not volunteers for special hazardous missions. RANCH HAND mission conditions were considered to be more dangerous than those encountered in the normal combat environment. This suggests that some differences may exist in the psychological profiles of the two groups. A sensation seeking or risk taking psychological orientation may have altered the accident mortality or morbidity patterns of the exposed group. In addition, an accident rate affected by peripheral neuropathy could be masked by undetected risk taking behavior bias. (2) Corrective Measures In an attempt to correct for the unique psychological factors that affect the choice of an aeronautical career, and to adjust for the effects of combat stress, transport aircrew members were matched with crewmembers of s i m i l a r transport aircraft. However, the volunteer .nature of the early RANCH HAND AIR FORCE W O R K I N G PAPER VIII-2 3 I �operation casts doubt on the adequacy of this basic matching as an attempt to control for the psychological effects of combat stress. The factors of volunteerism and risk-taking behavior must be considered from both the i n d i v i d u a l and group perspectives. The assessment of individual risk-taking behavior has been quantified by psychological instruments such as the Sensation Seeking Scale (SSS) of Zuckerman, et al. and the Life Experience Inventory (Torrance). The SSS has been demonstrated to have considerable validity in measuring a variety of phenomena i n c l u d i n g volunteerism and participation in risky activities and has been applied to naval aviation trainees (Waters). This study was unable to demonstrate an increased accident-related mortality in this group of individuals. These models w i l l be adapted for use throughout all phases of the study. D. Response Bias (1) Problem False positive response is anticipated as the primary bias operating in this study. Compensation issues arising from individual claims to the VA or from class action suits, heightened health concern generated by extensive publicity, disenchantment with military service, and the simple desire to please the interviewer may introduce positive responses that exceed the study's ability to correct or adjust. False negative response w i l l also operate, and such bias is even more d i f f i c u l t to assess than the spurious response in a positive direction. Significant factors in this direction include: issues of patriotism and loyalty, personal conviction as to the propriety of the defoliation program and their participation in it, the strong v i r i l i t y orientation of the pilot/aircrew population (particularly with reference to questions of libido and fertility), personal inconvenience caused by study participation, errors of memory, and fear of the adverse effects on career goals that abnormal physical examination results could produce (a s i g n i f i cant problem for active c i v i l i a n and military p i l o t s ) . (2) Pending Retirement Bias The military retirement system also creates a potential source of bias. A "pending-retirement phenomenon" occurs when personnel who are approaching the end of their careers exaggerate their symptoms so that they may become eligible for disability benefits. (3) Corrective Measures The primary correction technique for questionnaire response bias w i l l be a carefully constructed and standardized physical examination. Multiple verification and bias indicator questions w i l l be designed and included in the i n i t i a l questionnaire. Memory verification w i l l be conducted by cross-referencing responses AIR FORCE WORKING PAPERS VIII-3 3: �to medical and personnel records. Detailed statistical correlations between the questionnaire responses and the physical examination results w i l l be conducted. All telephone interviews and physical examinations w i l l be conducted on a " b l i n d " basis to the maximum extent possible. Self-administered and group-administered questionnaires, which would allow for uncontrolled response changes, w i l l not be conducted. Models of anticipated biases and their estimated impact on the study w i l l be attempted prior to the final analysis of any phase in order to justify the analytic methods used. Conclusions drawn from this study will be predicated and coupled to a bias estimate. E. Interview Bias (1) Problem Voice inflection, speed of interview, intonation and ethnicity are recognized factors which can affect positive or negative interview response. These factors will definitely operate in this study. (2) Corrective Measures An extensive interviewer training program will be conducted in order to limit the effects of interviewer bias. The Survey Research Center of the University of Illinois and the Center for Disease Control, Venereal Disease Training Branch, Atlanta, Georgia, will assist in this effort. The training will concentrate on techniques to elicit sensitive personal and medical information in an accurate manner, while minimizing discomfort to the subject and the interviewer. Quality assurance methodology and information verification techniques will also be included in the training. •Interviewers will be randomly monitored by the supervisor in an unannounced manner. For particularly sensitive questions (e.g. illicit drug usage), randomized response techniques (coin flip method) will be used, recognizing that responses will be valid on a group basis only. F. Political Implications (1) Problem The question of adverse health effects due to Herbicide Orange exposure in Vietnam has evoked many strong emotions. The actions of consumer groups, environmentalists, and other special interest groups have generated defensive responses on the part of some governmental agencies, and reactive decisions by others. Frequently, these responses have been based on unsubstantiated claims and/or scientific evidence of questionable validity. As a result of these governmental actions, the political impact on the planning of this study has been substantial. Suggestions to increase the scope • AIR FORCE WORKING PAPER VIII-4 3: '•-0 �of the effort to include other "exposed" individuals or poorly defined ancillary groups continue to surface. However, monumental problems of group ascertainment, exposure validation, control group selection, and control of additional bias make the inclusion of such individuals undesirable from a sound scientific perspective. If such decisions are made without regard for their scientific impact, compromise of study validity is assured. (2) Corrective Measures The dilution of the scientific credibility of this effort by politically motivated decisions will be diplomatically resisted. While all suggested improvements will be considered, any alterations or corrections to the study protocol will be based on sound scientific assessments of the proposed changes. Such issues will be clearly presented to appropriate peer review agencies for comment. If studied, ancillary groups will be analyzed separately from the main study group and reported anecdotally. G. Loss to Study/Statistical and Bias Considerations (1) Problem Loss to study in the RANCH HAND group poses a major problem to the validity of the inferences that can be made from any subsequent comparisons between or within groups. The avenues of loss will conceivably arise from individual apathy (volunteer bias), lack of appropriate financial reimbursement for loss of salary, the presence or absence of illness (perception of health), and the lack of a desire for "treatment". Losses of matched controls during the questionnaire and physical examination phases of the study, though predictably greater than in the exposed group may be managed by replacement from the predetermined set of controls. The estimated participation of individuals is shown in Section XII, Figure A-3. It is estimated that the overall response rate of the exposed group will be 65% in the initial questionnaire and 40% in the physical examination phase of the study. These high non-compliance rates are expected to occur despite great efforts to keep the questionnaire at an acceptable length, and to coordinate questionnaire administration and physical examination with the subject's personal schedule. Losses to study in either the exposed or control groups will obviously lead to decrements in statistical power, while losses in the control group could cause severe bias in the analytic phases of the study. Such losses would skew the distribution of controls, (Figures 3 and 4) and thus alter the characteristics of the population available for study. If differential losses in the control group occur (i.e., "well" controls dropout more frequently than "ill" controls), a "true" herbicide effect would be diluted (Figure 10). Conversely, if "ill" controls are differentially lost, a spurious effect would be attributed to herbicide exposure. To a lesser extent, losses in the exposed group could create similar effects; however, loss to study in the RANCH HAND population should be much less of a problem then in controls, due to their vested interest. AIR FORCE WORKING PAPER VIII-5 �RATIONALE OF REPLACEMENT EXPOSED -4-1:1 LOSSES "" P[L/WJ > PIL/IJ PIL/WJ DILUTIONAL BIAS -t �(2) Corrective Measures The USAF is committed to expending maximal effort to encourage participation. Loss to study problems in the study participants will be avoided as much as possible by detailed and exhaustive efforts to contact and followup each identified participant. NON-PARTICIPANTS WILL BE STRONGLY ENCOURAGED TO RECONSIDER THEIR INITIAL DECISIONS. • Design considerations have been made to minimize loss to study in both the exposed and control populations. Although the USAF can not compensate study subjects for lost wages during the physical examination, transportation costs, per diem, and lodging costs will be reimbursed. The replacement concept will help to counteract the decrement in statistical power, and offset the bias created by differential patterns of loss. The exposed group is already of maximum size and cannot be increased, but non-compliant controls can be replaced. This will maximize the degree of pairing between the two study groups. If a non-compliant control is replaced by a control with a similar perception of his own state of health, the alteration of the control group distribution is offset; (i.e., an "ill" control is replaced with an "ill" individual, and a "well" control with another "well" individual.) This concept of replacement, coupled with extensive efforts to encourage compliance will minimize losses to study and offset the adverse effects of those losses that do occur. H. Statistical Power Limitations (1) Probl em As discussed above, statistical power considerations are heavily dependent on loss to study rates. Since the design of the study is also limited by the small exposed population, statistical power for identifying the relative risk of an uncommon disease or symptom-complex (<1/100) is very low (<.50), (See Section VI F). This study will, to a greater extent, be able to detect increased risks only in common diseases or symptom-complexes (2) Discussion The "herald sign" of TCDD exposure, chloracne, is expected to have the greatest likelihood of achieving adequate statistical power in this study. Recent findings from Seveso, Italy, support the importance of chloracne as the primary marker symptom. The incidence of chloracne has been reported by Reggiani (personal communication) and Homberger, et al., to be 14.9 cases per 1000 residents in the region of highest contamination of Seveso (Zone A) and 6 to 12 cases per 1000 in the Seveso community as a whole. These rates vary by age group, with children being at highest risk. Only 1 to 5 cases per 1000 were seen in other regions of Northern Italy (Milan, Como, and Lecco). The incidence of adolescent acne in all AIR FORCE WORKING PAPER VIII-7 �of these populations varies between 21 and 30%. These incidence rates probably place chloracne at the lower limit of adequate statistical power within the constraints imposed on this study. In the Nitro, West Virginia studies, residuals of chloracne, as well as exacerbations of previously active disease, continue to be seen 10 years after the most recent exposures, and 30 years after the industrial accident. Thus, it is likely that any chloracne in the exposed population may be' detected, despite the intervening years since RANCH HAND exposures. In addition to chloracne, other recently reported human effects of TCDD exposure at Seveso, Italy, appear to fall within the capabilities of this study design (e.g., peripheral neuropathy, neuropsychiatric effects, and liver dysfunction). In general, with respect to statistical from relatively small samples fair much ical or dichotomous data. Consequently, made to obtain physical examination data ous manner. I. power, continuous data even better than either categora concerted effort will be in a scored and/or continu- Variability of Procedures (1) Problem The variance of physical examination findings from differences in technique and the random errors inherent in laboratory testing are items of concern, particularly if attributable health effects are subtle or of low magnitude. Nonstandardized procedures and techniques are major contributors to this variance. (2) Corrective Measures Variability in examination procedures will be minimized by the use of standardized procedures, examination protocols, similar equipment, and training. Most laboratory procedures will be conducted centrally at the USAFSAM, and quality control will be stressed at all times. J. Confounding Exposure Factors (1) Problem While virtually all of the media attention has been directed toward the 2,4,5-T containing herbicide formulations, other herbicides were applied concurrently by the C-123 aircrews in Vietnam. Herbicide Blue (Cacodylic acid with 15.4% pentavalent arsenic) and Herbicide White (2,4-D and Picloram) were used throughout the 1962-1970 time period. Any long-term health effects from these AIR FORCE WORKING PAPER VIII-8 �additional compounds may confound the results of the study. Peripheral neuritis, tremors, skin and lung cancer, loss of hair and nails, skin rashes, and gastric symptoms have been alleged after exposure to arsenical pesticides. The organophosphate insecticide, Malathion, was also sprayed by many of these same aircrewmembers when RANCH HAND duties permitted their temporary assignment to mosquito/malaria control units. Many of these individuals were involved in the aerial spray application of these and other pesti cides both before, during, and after their Vietnam service. Longterm effects from these chemicals would confound the study results. The small size of the RANCH HAND population will allow very little opportunity for analytic stratification for these confounding variables. Differing patterns of exposure to aircraft fuels in the study populations have been suggested as confounding factors. The C-130 aircraft were powered by turbo-prop engines which used jet fuel (JP-4), while the C-123 and C-7 aircraft were powered by standard reciprocating engines which used leaded aviation fuel (AV-GAS). After June 1968, many C-123s were modified by the addition of auxilliary jet engine boosters for added power on takeoffs and emergencies. (2) Discussion and Corrective Measures While the extent of confounding caused by exposure to these other pesticides is undetermined at this time, assessment of its magnitude must rely on responses of the subjects to that portion of the questionnaire dealing with other occupational exposures. For this reason, information concerning exposures to other herbicides/insecticides used in Vietnam will be collected. Whenever possible, stratification techniques will be used to adjust for these confounding variables during data analysis. Variations in fuel between C-130 and C-123 aircraft would be significant factors if individuals in the study were heavily and repetitively exposed. However, the normal duties of the study participants did not involve aircraft refueling or other fuel handling activities. Thus, fuel exposures can be minimized as a significant confounding factors. AIR FORCE WORKING PAPER VIII-9 �IX. Reporting Procedures Interim synoptic progress reports will be provided to the Surgeon General through Quarterly Management Reviews conducted each January, April, July and October. Key data analyses will be displayed, but inferences and conclusions will await full data analysis at the conclusion of each phase. A formal report for each of the three phases will be completed with forecasted submission dates of: Mortality Study, July 1981; Morbidity Study, October 1981; and Follow-up Study, April 1986. Findings and conclusions of each phase will be published in a journal of stature. Total study design, findings, and conclusions will be published in the USAFSAM Aeromedical Reviews or Technical Reports. AIR IX-1 FORCE WORKING PAPER �XII. APPENDIX TABLE'A-l SUMMARY OF 2,4-D, 2,4,5-T AND TCDD ANIMAL STUDIES TABLE A-2 "SYMPTOM COMPLEX" DERIVED FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D, 2,4,5-T AND/OR TCDD TABLE A-3 DETAILED LISTING OF SYMPTOMS/ SIGNS BY MAJOR CATEGORY FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D, 2,4,5-T AND/OR TCDD TABLE A-4 HERBICIDE RELATED CLAIMS SUBMITTED TO THE VETERANS ADMINISTRATION BY SYMPTOM CATEGORY AS OF 30 JUNE 1979 TABLE A-5 SCHEDULE AND MODE OF CONTACTS WITH STUDY SUBJECTS TABLE A-6 MONTE CARLO SIMULATION FIGURE A-l 2,3,7,8-TETRACHLORODIBENZO-PDIOXIN (TCDD) FIGURE A-2 ESTIMATED IDENTIFICATION/ PARTICIPATION OF RANCH HAND POPULATION AIR FORCE WORKING PAPER XII-1 3 1 DOT 1379 �i r\u»w L. n - A. SUMMARY OF 2,4-D, 2,4,5-T, AND TCDD ANIMAL STUDIES 2,4-D 2,4,5-T TCDD LD50 RANGE (ACUTE) 100-1000 mg/kg 100-1000 mg/kg 1-1000 pg/kg CHRONIC TOXIC DOSE APPROACHES ACUTE LEVEL RAPID CLEARANCE 1/2 ACUTE LEVEL; VARIABLE CLEARANCE MARKEDLY LOWER LEVEL BIOACCUMULATION SIGNS OF ACUTE/ CHRONIC TOXICITY ANOREXIA ANOREXIA WEIGHT LOSS WEIGHT LOSS ATAXIA INVOLUTION OF THYMUS MUSCULAR WEAKNESS G.I. INJURY ALOPECIA IRRITATED G.I. -TRACT LIVER CONGESTION EPITHELIAL CHANGES - MINOR LIVER INJURY KIDNEY CONGESTION LIVER LESIONS (VARIABLE) HYPOTHYROIDISM MINOR KIDNEY INJURY MINOR LUNG CONGESTION EMBRYO TOXIC DOSE APPROACHES TOXIC LEVEL APPROACHES TOXIC LEVEL MARKEDLY BELOW TOXI.C MATERNAL LEVELS TERATOGENICITY QUESTIONABLE; WEAK AT BEST *LOW INCIDENCE ONLY IN MICE (CLEFT PALATES a DILITATED RENAL PELVIS) SPECIES VARIATIONS: YES MICE NO RATS CARCINOGENICITY QUESTIONABLE WEAK AT BEST ONE STUDY: YES NUMEROUS STUDIES: NO EPITHELIAL CHANGES IN PRIMATES: YES IN RATS *TCDD CONTAMINATION OF 2,4,5-T HAS BEEN SHOWN TO BE A CONTRIBUTOR TO TERATOGENIC EFFECT IN MICE AIR FORCE WORKING PAPER XII-2 3 1 OCT 1979 �TABLE A-2 "SYMPTOM COMPLEX" DERIVED FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D; 2,4,5-T AND/OR TCDD 2,4-D 2,4,5-T (+ TCDD) TCDD CHLORACNE CHLORACNE PORPHYRIA PORPHYRIA HYPERPIGMENTATION HYPERPIGMENTATION ASTHENIA ASTHENIA ASTHENIA PERIPHERAL NEUROPATHY PERIPHERAL NEUROPATHY PERIPHERAL NEUROPATHY CARDIAC DISTURBANCE CARDIAC DISTURBANCE SWEATING/FEVER CARDIAC DISTURBANCE RENAL DYSFUNCTION RENAL DYSFUNCTION LIVER DYSFUNCTION LIVER DYSFUNCTION LIVER DYSFUNCTION GI DISTURBANCE GI DISTURBANCE GI DISTURBANCE HEADACHE PNEUMONITIS CSF PROTEIN ALTERATIONS HYPOTHYROIDISM CONVULSIONS HEARING/SMELL DISTURBANCES AIR FORCE WORKING PAPER XII-3 3 1 OCT 1979 �TABLE A-3 DETAILED LISTING OF SYMPTOMS/SIGNS BY MAJOR CATEGORY FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D; 2,4,5-T AND/OR TCDD NEURO-PSYCHIATRIC ABNORMALITIES AESTHENIA PERIPHERAL NEUROPATHY ANXIETY HYPOREFLEXIA DEPRESSION WEAKNESS FATIGUE PARESTHESIAS APATHY EXTREMITY NUMBNESS LOSS OF DRIVE MYALGIA LIBIDO GAIT DISTURBANCE IMPOTENCY "MILD" PARESIS SLEEPLESSNESS EMOTIONAL INSTABILITY ANOREXIA DIZZINESS DECREASED LEARNING ABILITY AIR FORCE WORKING PAPER XII-4 3 1 OCT 1979 �TABLE A-3 (CONTINUED) DETAILED LISTING OF SYMPTOMS/SIGNS BY MAJOR CATEGORY FROM LITERATURE REVIEW OF CASE STUDIES EXPOSED TO 2,4-D,2,4,5-T AND/OR TCDD DERMATOLOGIC DISEASE CHLORACNE PORPHYRIA CUTANEA TARDA HYPERPIGMENTATION HIRSUTISM (BODY) ALOPECIA OF THE SCALP OTHER DISORDERS HEPATIC DYSFUNCTION RENAL DYSFUNCTION INCREASED CHOLESTEROL AND TRIGLYCERIDE PROTEINURIA DECREASED OUTPUT INCREASED LIVER FUNCTIONAL TESTS TUBULAR DEGENERATION GLOMERULAR DEGENERATION RENAL GLUCOSURIA GI DISTURBANCE CARDIAC DISTURBANCE NAUSEA BRADYCARDIA VOMITING TACHYCARDIA DIARRHEA ATRIAL FIBRILLATION GASTRITIS ABDOMINAL PAIN AIR FORCE WORKING PAPER , XII-5 3 1 OCT �TABLE A-4 HERBICIDE RELATED CLAIMS SUBMITTED TO THE VETERANS ADMINISTRATION BY SYMPTOM CATEGORY AS OF 30 JUNE 1979 (N=417) SYMPTOM CATEGORY PERCENT Dermatologic 49.9 •Nervousness/Headache/Fatigue 23.0 Neuritis 14.6 Gastroi ntesti nal/Geni touri nary 13.4 Malignancy 11.0 Decreased Libido 5.8 Respiratory 5.3 Ear/Nose/Throat 5.0 Cardi ovascular/Hypertensi on 4.1 NOTES: 625 total claims 190 claimed exposure without symptoms 18 claims paid for non-herbicide related conditions 1 claim paid for documented chloracne AIR FORCE W O R K I N G PAPER XII-6 �TABLE 5 SCHEDULE AND MODE OF CONTACTS WITH STUDY SUBJECTS STUDY PHASE CONTACT MADE TIME Morbidity Study Introductory Letters Dec 79 - Jul 80 Morbidity Study Comprehensive Telephone Questionnaire Jan 80 - Dec 80 Baseline Physical Exam Mar 80 - Mar 81 Confirmation Face-to-Face Interview during Baseline PE Mar 80 - Mar 81 Fol 1 ow-up Study Adaptive Phone Questionnaire Adaptive Physical Examination Jan 83 Mar 83 Dec 83 Mar 84 Fol 1 ow-up Study Adaptive Phone Questionnaire Adaptive Physical Examination Jan 85 Mar 85 Dec 85 Mar 86 AIR FORCE WORKING PAPER XII-7 �TABLE A-6 MONTE CARLO SIMULATION PROGRAM 10 20 30 40 210 220 230 240 250 260 270 280 290 DIM C(10,3) DIM A(10,3) P2=.25 Dl=.45 50 M=0 60 N=0 70 FOR I=1TO 10 80 FOR J=1TO 3 90 A ( I , J ) = 0 100 C ( I , J ) = 0 110 NEXT J 120 NEXT I 130 M=M+1 140 PRINT M 150 IF M=1001 THEN 330 160 F=l 170 1=1 180 J=l 190 C ( I , J ) = R N D ( 1 ) 200 X=P2+F*D1 IF C(I,J) > X THEN 270 1=1+1: F=l IF I > 10 THEN 250 GOTO 190 N=N+1 GOTO 130 A(I,J)=A(I,J)+1 J=J+1 IF J>3 THEN 320 300 F=0 310 320 330 340 GOTO 190 GOTO 130 STOP SELECT PRINT 215 350 FOR 1=1 TO 10 360 370 380 390 400 410 PRINT A ( I , 1 ) , A ( I , 2 ) , NEXT I PRINT PRINT "N(l)" } N(l) PRINT " N ( 2 ) " , N(2) PRINT "N(3)", N(3) 420 END GLOSSARY I = Control individual index J = Examination number index = Attendance array = number of times the ith control was used for the jth examination C ( I S J ) = Testing variable array N = number of times no control was available M = number of matches attempted Dl = preselected probabilities. Pj = Dl + P2 and P2 Po = P2 AIR FORCE WORKING PAPER XII-8 �Figure A-l 2, 3, 7, 8-TETRACHLORODIBENZO-p-DIOXIN (TCDD) • MOLECULAR WEIGHT 321.8935 • MELTING POINT 303-305°C • DECOMPOSITION POINT 980-1,000°C • SOLUBILITY, GRAMS/LITER ORTHO-DICHLOROBENZENE 1.40 CHLOROBENZENE 0.72 ORANGE HERBICIDE 0.58 BENZENE 0.57 CHLOROFORM 0.37 ACETONE 0.11 METHANOL 0.01 2*10" 7 WATER XI1 H 3 1 OCT 1979 o AIR FORCE WORKING PAPER ' �figure A-2 ESTIMATED IDENTIFICATION/PARTICIPATION OF THE RANCH HAND POPULATION ESTIMATED RESPONSE ESTIMATE RANCH HAND POPULATION NUMBER OF PARTICIPANTS 1200 1188 UNACCOUNTABLE < 1% ACCOUNTABLE 99% NON-PARTICIPANTS DEAD/MORIBUND 10% UNWILLING 25% QUESTIONNAIRE PARTICIPANTS 65% 772 NON-PARTICIPANTS BASELINE EXAM PARTICIPANTS 60% 463 40% — i NON-PARTiciPANTS^ 20% 80% 371 NON-PARTICIPANTS 20% XII-10 1st FOLLOW-UP EXAM PARTICIPANTS 2nd FOLLOW-UP EXAM PARTICIPANTS 80% 297 AIR FORCE WORKING PAPER 3 1 OCT 1979 �XIII. QUESTIONNAIRE The release of the actual questions within the questionnaire could possibly result in irreparable damage to the study from an avoidable source of responder bias. Consequently, the following is a summary of the general subjects to be covered as well as those specific areas that will receive particular emphasis.. Preliminary information will be obtained from a short mail-back questionnaire during the first contact with the study subjects. Personal identification data, RVN tour information, willingness to participate, acknowledgement of the Privacy Act Statement and an Informed Consent for release of records and medical evaluation/emergency treatment will be obtained at that time. This information will be verified by review of the individual's military personnel records. Addresses and telephone numbers will be verified and updated by use of several sources (i.e., Worldwide Locator Service, Social Security Service, Credit Bureaus, Rosters of RANCH HAND Association, Veterans Administration Benefits Records, the Internal Revenue Service, and other available sources). In addition, at this time a request will be made to have the wife present for the telephone interview in order to obtain an accurate obstetrical history. The telephone questionnaire will, of necessity, be quite lengthy, but it will be convenient to the subject, and given in two interviews if necessary. It will verify personal identification data such as name, SSAN/AFSN, date of birth, address, telephone numbers, race, military status, effective date of status, location of military medical records and marital history information. RVN tour information will be rechecked and expanded to include data such as date of tour, tour end date, AFSC, organization of assignment, PCS and TOY status, combat missions, medal(s) awarded (i.e., Air Medal, Distinguished Flying Cross, Purple Heart), and whether or not the tour was a RANCH HAND affiliated tour. Pre and Post-RVN exposure information, both occupational and avocational, to asbestos, radiation, herbicides, pesticides, will be elicited, including the frequency and time of the exposure. RVN exposure to these chemical and physical agents will also be collected. Medical information obtained during this telephone interview will include of a statement of general health, smoking history, alcohol consumption history and long-term medication/drug use. In addition, questions dealing with infertility, birth defects of offspring, as well as the wife's obstetrical history (i.e., total conceptions, live births, miscarriages, stillbirths and premature pregnancies) will be asked. A family history specifying cancer, heart disease, liver disease and inherited disorders in both the subject's and wive's families will be collected. A review of systems will be attempted, specifically emphasizing the neurologic, dermatologic, reproductive, and hepatic systems as well as specific symptoms associated with a neoplastic condition. AIR FORCE WORKING PAPER XIII-1 �Specific questions will address the personality makdup of the individual in order to assess his potential risk-taking behavior (see Section VIII.C). Information verification and bias indicator questions will also be integrated into the questionnaire. During this initial telephone questionnaire, those participants agreeing to undergo a physical examination will be instructed to insure that the medical examiners are "blind" as to whether or not they were former RANCH HAND personnel. At the time of physical examination(s), the subject will receive a comprehensive face-to-face questionnaire which will expand and verify the information that was obtained in the telephone questionnaire and records review. An extensive review of systems will be covered at that time, including a more extensive occupational and avocational exposure history. Just prior to the time of follow-up physical examinations (FY 1982 and FY 1984), a preliminary telephone contact will establish the subject's current health status and his willingness to continue participation in the study. An appointment for the followup examination will also be arranged. An adaptive telephone questionnaire will be given emphasizing those symptoms and systems that were found to be significantly associated with the exposed population on statistical analysis of the first year's results. If the subject expresses a desire to cease participation at this time, he will be encouraged to reconsider his decision and reasons for dropping out of the study will be sought. AIR FORCE WORKING PAPER XIII-2 �XIV. Physical Examination Design A. General Comments This phase of Project RANCH HAND II is a cross sectional study of the subject's health at the time of examination. It is important that examiners remain unaware of the subject's status as a RANCH HAND participant or as a control subject. The physician exam^ iner is tasked to examine and objectively record his findings. The examining physician is not, and cannot be expected to arrive at any definitive diagnosis as the full history and laboratory results are not available to him. The compilation and analysis of data will be performed by the study investigators at Brooks Air Force Base, Texas. They will notify the subject and the physician of his choice of the results of the examination. These examinations will define the health status of the subjects at a point in time, and will establish the presence of physical findings, if any exist. After statistical review of the study groups, these findings may permit definition of a chronic effect due to exposure. An inaccurate examination may lead to falacious study results in two ways: a presumed syndrome may be defined which does not in fact exist, or a syndrome which in fact exists may not be defined with enough validity to warrant further actions. The examining physician is responsible for recording a complete and detailed report of the physical examination. In this role, the examining physician is tasked to collect evidence of the presence or absence of physical signs of abnormality only. Formulation of impressions is not requested nor desired. If, during the examination, the physician discovers evidence of acute serious illness requiring immediate treatment, the normal emergency or urgent care procedures of the medical facility would apply. If during the examination, the examining physician finds evidence of present illness requiring further medical attention, he should so state to the subject and offer to forward or have forwarded pertinent information to the subject's physician. A clear record of any such advice and treatment should be recorded. The ultimate value of the RANCH HAND II Study will lie in complete accurate and, whenever possible, quantitative data permitting the most stringent and powerful statistical analysis. For that reason, the physical examination protocol requires exact measurements in many instances, and the use of defined meanings of semi quantitative indicators in other places. AIR XIV-1 FORCE WORKING PAPER �^; Conduct of the Examination SUBJECT SECTIOK PHYSICAL EXAMINATION 1. GENERAL APPEARANCE eph c. f^--rnrlnmrpfc dL. /"/Undernourished -Ectomorph b. r~? Well-nourished tf. f~J Obese ^f. Appearance (1) /~~7 Younger (2) /~7 Same (3) /~7 Older as stated age. Appearance of illness or distress /~7 Yes f~7 No Hair Distribution /~7 Normal £V Abnormal / 7 Hirsuitism /~7 Alopecia " 2. M F I C J H T SITTING BLOOD PRESSURE RIGHT ARM AT HEART LEVEL W E I G H T fUndr.»«»d) SYSTOLU J. PULSE R A T E REGULAR; LJ YES .DIASTOLIC. Describe any irregularities. [J NO a. Irregular /*7 b. Irregularly irregular /~7 c. VPBs per minute 4. EYE G R O U N D S [~] N O R M A L f D ABNORMAL /-y A-V nicking" £7 'P light reflex /~7 Arteriolar spasm !. 6. E N T [""] N O R M A L 5a ABSENT PRESENT ARCUS SENILIS Describe any vascular lesions, hemorrhages, exudates, /~7 Hemorrhage^ papiiiedema, f~J Exudates /"/ Papilledema f~J Disk Pallor /~7 7" Cupping \~~\ A B N O R M A L - Describe any abnormality. Tympanic membranes intact /~J Yes f~J No Nasal ulcerations /~7 No /~7 Yes 7. N E C K r£«r>«c/«Jly rhrrold tfl«nrf) ( [NORMAL 9. H E A R T [_J NORMAL J ABNORMAL. A7 R [2]] N O R M A L r~7 Asymmetrical expansion f~~J Hyperresonance f~~7 Dullness I R /~7 L /~7 Describe any abnormality. / / Parotid gland enlargement " Thyroid gland palpable f~7 Enlarged /~~jf Nodules /"7 Tenderness 8. T H O R A X AND L U N G S Abnonral Ocular Pigmentation £7 Yes £7 No _ £7L QJ A B N O R M A L /""/ Wheezes /~7 Rales [^ABNORMAL Displacement of apical impulse /~7 No Heart sounds normal /~7 Yes f~J No Describe any abnormality, especially basilar rales. Circumference at nipple level Expiration cm Inspiration cm Describe any enl*rgement, irregvilarity of rate, murmurs, or thrills. f~J Yes Precordial thrust f~7 No /~7Si /~7S2 f~~7 Yes (Continued in Item 18 on Reverse) 1 0 . ABDOMEN \ \ NORMAL /~~7 Heptomegaly cm Liver Span f~~7 Splenomegaly tl. r'XTRfMlTlFS I "1 N O R M A L Tl'l ABHOSMAL D*«cribe arry-Mmormality Vrt*i special attention to the /~~7 Other mass - «pie«n "nd liver. Record waist measurement Specify: on attached form. / 7 Tenderness " Liver f~7 Spleen /~7 Other, specify: '~'\ A B N O R M A L /~7 Absence, specify: Edema /~J Pitting f~7 Non-pitting Loss of hair on toes Describe an y edema or siRns o f vnscular insufficif ncy. A7 Clubbing of nails f~J Varicosities �(p? SECTION PHYSICAL EXAMIMATIOH (Continued) iz. PERIPHERAL PULSES DIMIN. NORMAL ABSENT COMMENTS RADIAL FEMORAL POPLITEAL DORSALIS PEDIS POSTERIOR TIBIAL 13. /~7 f~7 f~7 f~~7 1A. CD ABNORMAL NORMAL SKIN Indicate type and location of lesions on attached anatomical figure. Hyperpigmentation / 7 Jaundice " f~7 Petechiae /~7 Spider angiomata A7 Ecchymoses /~7 Palmar erythema Lesions Woods Light Comedones Acneiform lesions Acneiform scars Depigmentation Inclusion cysts (UV) Positive Cutis Rhomboidalis (Obtain photographs of major lesions) Spine / 7 Scoliosis " f~7 Kyphosis f~7 Tenderness , Level _ f~J Decreased range of motion Muscle - Specify: /~7 /7 " f~7 /~7 ABNORMAL [ j NORMAL MUSCULOSKELETAL Weakness Tenderness Abnormal Consistency Atrophy f~7 Pelvic tilt £7 Straight Leg ,,, is. GENITOURINARY - RECTAL - HERNIA £7 / 7 Inguinal hernia £VR " £ L 7 NORMAL Testes £7R Absent £7 £7 Enlarged Atr.ophic £7 £7 £7 £7 Stool Hemacult: KM sing: Right /.Left.. AT ABNORMAL /~7 Varicocele /~7 Hemorrhoids f~J Epididycis /~7 Prostatic ZZ7 Scotal nass - Specify Enlargement cin dia £7 Rectal mass /~7 Positive £Z7 Negative 16. LYMPH NODES - CHECK ALL AREAS. f~J NORMAL f~7 ABNORI"IAL - SPECIFY CERVICAL, OCCIPITAL, SUPRACLAVICULAR, AXILLARY, EPITRACHLEAR, INGUINAL, FEMORAL / 7 Enlarged ~ / 7 Tender ~ / 7 Hard . " / 7 Fixed ~ /~7 Confluent 17. NERVOUS SYSTEM - SEE ATTACHED FORMS '18. HEART A*rp OTH^R OBSERVATIONS (Continued from Item 9) t Murmur £J.No /"7 Yes Area /^7 Ao £~/ Pu /~7 Apex £J 54 sys £7 Dia DATE OF EXAMINATION D*Y £7 £7 £7 T Y P E D OR £7 • £Y p m u T E D N A M E OP" £7 £7 £'. A M I N t N G P H Y M C ! * N RETURN FORM TO; USAFSAM ~ BROOKS > rE TX 7E235 AIR FORCE �CLINICAL RECORD NEUROLOGICAL EXAMINATION HEAD AND NECK - Normal to Palpations/Inspection £7Y £7N Specify Scar Asymmetry £7 Depression JT] Carotid Bruit £7No £7R ZZ7L Neck Range of Motion £J Normal or Decreased to £7 Lef't EH Right £J Forward £J Backward TRUNK MOTOR SYSTEM.- Handedness Right £7 Left Gait /"/ Normal or £J Broad Based £7 Ataxic /^/Small Stepped ^/Other-Specify Associated Movements £7Arm Swing £7Norma^ or Abnormal £7R £}L Muscle Status (strength, tone, volume, tenderness, fibrillations) Bulk £7 Normal /^Abnormal Tone Upper Extremities £7Normal or /^/Increased /"^Decreased £7Right £7Left Lower Extremities /27Normal or /^/Increased £7Decreasecl Strength - Distal wrist extensors £JNorm^ ^Decreased Ankle/Toe Dors/Flexors ^JNorma} /^/Decreased Proximal Deltoids £7Normal /^Decreased Hip Flexors /^Normal /^/Decreased Abnormal Movements (tremors, tics, choreas, etc.) Fasiculations £JNo Tenderness £7No EJYes (1-4+) /^/Yes (1-4+) Tremor £7^° O Yes ~ s P ec i f y Upper Extremity £JR [JL\[J Res ting /^Essential /^/Intention Lower Extremity /^/R £}Lj£JQther Coordination (a) Equilibratory - Eyes Open Eyes Closed - Romberg £7Positive (Abnormal) /^/Negative (Normal) Right Foot Left Foot (b) Nonequi libra to ry (F to N; F to F; H to K) Finger-to-nose-to-finger £7Normal /^/Abnormal ORignt ZI7Left /I7BothLeft Heel -Knee-Shin ONorma1 £7 Abnormal £7Ri ght /J (c) Succession Movements (including check, rebound, posture-holding) If indicated, check /JNormal £7 Abnormal £7R £7R Rapidly alternative movements fcJNorma] /^/Abnormal /^/R £JL Skilled Acts (a) Praxis (b) H a n d w r i t i n g . If indicated, £JNormal /27^bnorma'1 (c) Speech (articulation, aphasia, agnosia) Grossly /^/Normal [jl Abnormal - Specify Dysarthria £J Aphasia £7 XIV_4 AIR FORCE WORKING PAPER 3 1 OCT 1979 �p.'.i Reflexes (0-absent; 1-sluggish; 2-active; 3-very active; 4-transient clonus; 5-sustained clonus) R L R L Abnormal Other R LR L Deep Deep Babinski Patellar Biceps Triceps • Achilles Remarks MENINGEAL IRRITATION Spurling Maneuver of Neck £7Normal £7Abnormal £7R £7L £7Both Straight Leg Raising £7Normal £7Abnormal £JR £7L £7Both NERVE STATUS (tenderness, tumors, etc.) SENSORY SYSTEM (tactile, pain, vibration, position. If positive sensory signs are present, summarize below and indicate details on Anatomical Figure, Std. Form 531) Light Touch £7Normal £7Abnormal o - i r-TH i /—r«u i (Map on Anatomical Figure) y n. Pin Prick £7Normal £7Abnormal <• K ' Vibration (at ankle, 128 hz tuning fork): £7Normal £7Abnormal £JR Position (Great toe): £7Normal £7Abnormal £7R L £7 £7L Both ZI7 CRANIAL NERVES I R Smell L II Smell £7Present £7Absent £7Present £7Absent . Fundus R Normal £7 Abnormal £7 Disk Pallor/atrophy £7Exudate £7Papi 11 edema £7Hemorrna9e Fundus L Normal £7 Abnormal £7 Disk pallor/atrophy £7Exudate £7 Papi 11 edema £7Hemorrhage Fields (to confrontation) Right £7Normal £7Abnormal Left £7Normal £7Abnormal I I Normal £7 £7Abnormal - Specify I Pupils-Size (mm) Equal £7 Unequal £7 Difference mm Shape, position Round £7 Other £7 £7R £7L Light, Reaction Normal £7 Abnormal £7 £7R Position of Eyeballs Movements R Nystagmus Rotary £7 (Draw position) L Horizontal £7 Vertical AIR FORCE'WORKING PAPER XIV-5 3 1 CCT 1S79 �xi Ptosis R/^7 L £7 ' V Motor R Clench Jaw - Symmetric [J L Sensory R Normal £7 L Normal £7 Cornea! Reflex VII v Abnormal £7 Abnormal £7 R Yes No Z7 R£7 L£7 V l£7 V-|£7 L Motor R Normal smile £7 L Deviated £7 2 V2 - Palpebral Fissure O Yes ZI7No Normal smile O Yes OMo Palpebral Fissure £7Yes ZI7No IX Palate and Uvula X Movement Normal £J Deviation to £7R Palatal Reflex R £7Normal fcJKbnorma /"/Abnormal XII Tongue-Protruded-Central £7 Atrophy £7No ZI7Yes R £7 L MENTAL STATUS (alert, clear, cooperative, etc.) /~7Yes - Specify Subjective Gross abnormalities: SUMMARY OF POSITIVE FINDINGS Objective Diagnostic Impression Date Signature AIR XIV-6 FORCE WORKING PAPER �C. Special Procedures (1) Nerve Conduction Velocities (NCV) (a) These studies have been determined to be an important parameter in long-term follow-up studies of persons thought to have been exposed to Herbicide Orange Components. (b) The Nerve Conduction Velocities should be performed by a physician or by a specialty qualified technician under the supervision of a physician trained .in neurophysiological methods. (c) Specific NCVs (1) Dinar Nerve (one side only) (a_) motor (above elbow, below elbow) (b) values recorded (i) (11) (2) distal latency NCV Peroneal Nerve (one side only) (a_) motor (b) values recorded (i) distal latency (11) NCV (3_) Sural Nerve (one side only) (a_) (b) (d) sensory: orthodromic values recorded: NCV Methods (U Standardized, published methods will be used (e.g., Smorto, Marcio P., and John V. Besmajian; Electrodiagnosis; Harper and Row; NY, 1977). AIR FDRCE WORKING PAPER XIV-7 3 1 CCT 1979 �(2) Psychological Test Battery (a) General (!_) This battery yields objective numerical data, and is well-standardized and clinically validated. The individual tests were chosen to insure an adequate analysis of the major alleged manifestations of Herbicide Orange toxicity. Each test either validates the other tests or is considered to be a "definitive" test for analysis of a suspected psycho-neuropathic effect under study. (2) Compare to the general civilian population, characteristic response tendencies are observed on the MMPI and Cornell Index among active duty aircrewmen being evaluated in an aeromedical setting. It is also important to consider the effect that pending retirement has exerted on the reporting of medical history and symptomatology. This may also alter responses to psychological testing. (b) Specific Tests (lj Wechsler Adult Intelligence Scale (WAIS): Individually-administered collection of verbal and nonverbal intellectual measures; also useful for clinical inferences when combined with the neuropsychological battery below. (2) Reading subtest of the Hide Range Achievement Test (WRAT): Individually-administered measure of word recognition ability. Important so as to rule-out reading inefficiency should response to personality instruments below be of questionable validity (e.g., high F Scale on MMPI). (3) Halstead-Reitan Neuropsychological Test Battery: Individually-administered collection of brain behavior relationship measures for establishing the functional integrity of the cerebral hemispheres. The battery must include the following subtests: Category, Tactual performance, Speech-Sounds, Seashore Rhythm, Finger Tapping, Trail Making, and Grip Strengths. The Aphasia Screening and Sensory-Perceptual Exams are considered optional in view of their redundancy with the clinical neurologic exam included in this project. Individualized test debriefing is conducted to clarify test performances in the WAIS and Neuropsychological Battery. (4_) Three subtests of the Wechsler Memory Scale I (WMS I); Individually-administered measures of immediate and delayed recall of verbal and visual materials. The Local Memory, Associate Learning and Visual Reproduction subtests are to be administered in the standard, immediate-recall fashion initially. After 30 minutes has elapsed, the examinee is asked, without prior alerting, to recall as much as he can about the Logical Memory and AIR XIV-8 FORCE WORKING PAPER �Visual Reproduction subtest stimuli. both test-retest administrations. Standard scoring is used for ($) Cornell Index ( C I ) : Self-administered and standardized neuropsychiatric symptom and complain inventory, i n c l u d i n g items i n v o l v i n g asthenia, depression, anxiety, fatigue, and GI symptoms in lay language. Endorsement of items are to be explored and clarified in test-debriefing. (6) Minnesota Multiphasic Personality Inventory (MMPI): Self-administered clinical psychiatric screening .instrument; also capable of estimating response biases (e.g., "fake good," or "fake bad"). The shortened version of Form R (i.e., items 1 to 399) may be substituted for the 566-item Long Form. Standard scoring and Minnesota norms are to be used, with the possible exception of active duty examinees where USAFSAM aircrew norms may be applied. Clarification of profiles showing response biases, questionable validity, and/or unusual item endorsements w i l l be conducted in individual test debriefing. (3) 12-Lead Electrocardiogram (a) A standard 12-1ead scalar electrogram is required. If an arrhythmia is observed, a one minute rhythm strip is requested, in addition. (b) Interpretation; The electrocardiograms will be interpreted by physicians in the USAF Central ECG Library and compared to previous individual ECG records in the case of rated (pilot or navigator) subjects. (c) Disposition (USAF Central ECG Library): (1_) Pilots and Navigators - The original tracings will be microfisched and a permanent record established for each individual. (2) Enlisted Subjects - The original tracings will be microfisched and a permanent record established for each individual. (4) Radiographic Examination (a) A standard 14x17 i n . , standing, teleroenthgenogram in the PA position using small n i p p l e markers. AIR FORCE W O R K I N G PAPER XIV-9 �(5) Laboratory (a) Specific Tests (I) Performed at the Local Examining Facility (a_) Hematocrit (b) Hemoglobin (£) RBC Indices (<d) While Blood Cell Count (e_) Platelet Count (f) Erythrocyte Sedimentation Rate Urinalysis (h_) (2) Semen Analysis (Number, Motility, Morphology) Performed by USAFSAM Clinical Pathology Laboratory (a_) Blood Urea Nitrogen (b) Fasting Plasma Glucose (£) Creatinine (d_) 2-hour Post Prandial Plasma Glucose (e_) Differential Cortisol (f) Cholesterol & HDL cholesterol (j.) Triglycerides (hi) S60T (i_) SGPT (j_) GGTP (k_) Alkaline Phosphatase (U (m) AIR XIV-10 LDH 'Serum Protein Electrophoresis FORCE WORKING PAPER �(rO (o) (3_) ' CPK VDRL Performed by USAFSAM Epidemiology Division Reference Laboratory LH (Ib) FSH (£) Testosterone U) Thyroid Profile (RIA) (e_) Delta-ami no! evulinic Acid (fV (£) (a.) Urine Porphyrins Performed at USAFSAM if liver function studies are abnormal (a_) (bj (5) Anti-nuclear Antibody Hepatitis Antigens/Antibodies (A and B) Performed if medical history indicates an increase in infectious diseases: (a_) (bi) Monilia Skin Test (c_) (b) Immuno electrophoresis Quantitative Immunoglobulin Determinations Rationale for Laboratory Procedures (I) Studies on the toxicity of TCDD in animals have shown that the following organ systems are damaged: (a_) Liver: Hepatic necrosis, liver enzyme changes, hypoproteinemia, hypercholesterolemia, hypertriglyceridemia. (b) Reticuloendothelial System: Thymic atrophy, altered cellular Tmmunity, decreased lymphocyte counts. (c_) Hemopoietic System: thrombocytopenia, leukopenia, pancytopenia. AIR XIV-11 FORCE WORKING PAPER Anemia, �(d_) Endocrine System: Hemorrhage and atrophy of adrenal cortex, hypothyroidism. (e) Renal: Increase in blood urea nitrogen. In addition, statistically significant increases in hepatocellular carcinomas (liver) and squamocellular carcinomas of the lung were found. (2_) Studies on the toxic effects of TCDD in .man have shown that the following organ systems are damaged: (aj Skin: Chloracne, hirsutism. (bj Liver: Porphyria cutanea tarda. Increased levels of transaminase and of GGTP. Enlarged, tender liver, hyperlipidemia. (c_) Renal: Hemorrhagic cystitis, focal Pyelonephritis. (d_) Neuromuscular System: Asthenia, i.e., headache, apathy, fatigue, anorexia, weitht loss, sleep disturbances, decreased learning ability, decreased memory, dyspepsia, sweating, muscle pain, joint pain and sexual dysfunction. (e) Endocrine System: Hypothyroidism. (3_) Based upon the reports of toxic effects in animal and human exposures, the following organ panels are recommended: (a) (_b) Reticuloendothelial (£) Renal (d) Endocrine (e) (4J Hemopoietic Neuromuscular Hemopoietic screening should include: (aj (tO AIR Hemoglobin (c) XIV-12 Hematocrit RBC indices FORCE WORKING PAPER �Erythrocyte sedimentation rate (&) (_5) Platelet count Reticuloendothelial system: (a_) White blood cell count (b) Differential (£) Serum protein electrophoresis (_d) .Selective use of skin testing, immunoelectrophoresis, and quantitative immunoglobulin determinations (6) Hepatic screen: (a_) (b) SGPT (c_) GGTP (d) Alkaline phosphatase (e.) LDH (_f) Cholesterol (3) HDL cholesterol (h_) Triglyceride (i_) Urine prophyrins (j_) (7_) SGOT Urine porphobilinogen Renal screen: (a_) (bi) BUN (c) (8_) Urinalysis Creati ni ne Endocrine screen (a_) AIR XIY-13 Differential cortisol (0730 and 0930 hours) FORCE WORKING PAPER �(b.) (£) (9) Thyroid profile (RIA) Fasting plasma glucose Neuromuscular system: CPK (10) The following tests should be peformed only as follow-up for abnormalities in the liver panel: U) (b.) HBsAg (£) Anti HBcAg (id) Anti HB s A g (e.) (11) HA s A g ANA Elucidation of sympoms of asthenia: (a) (b_) AIR LH (c) XIV-14 Testosterone FSH FORCE WORKING PAPER �: ESTIMATED COST OF A CONTRACT OPTION < ; : ,. * •I i. I These estimates are based on the costs of a study conducted at a 2,4,5-T "j production plant by the Kettering Laboratory at the University of Cini cinatti under the supervision of Raymond Suskind, M.D. A mortality '• i ;s | study of 122 workers (conducted 28 years after exposure) arid a morbidity j study based on questionnaire, physical examination,and laboratory data from ! ii 437 Individuals were conducted. £/€^T"~CONTRACT COSTS (IN 1977-78 KETTERIN6 # OF SUBJECTS PHASE 122 Mortality Study i Baseline ' Physical Examination COST $100K DOLLARS) C^T/SUBJECT $819.67 RANCH: HAND II ; ^;COST # OF SU1INJECTS I 7200 j j Ii i 5.9M i $200K $457.66 f\f\f 926 ' i . 4.ZM . •j 437 v !i ':i 225.00 608 i | $220K 503.43 ' v ztf K { i L j K4ft-Tj | /5"? r :i i i^ 1 */££> K 1 926 250.00 437 Baseline Laboratory Procedures 608 j i 1 ; Follow-up : Examinations Follow-up i i i: ii ; , Jr ^r '•*> ^[g^^_ ) b ^^** ^** » «» 4 i i ! 7-1 i H : I i j ii j: i i j [ i 1 ii i i j , �1 * i; t: 1 . ' i- : ; ii '• li : : ' i • i i, •! j 3 0 OCT \ i' 1 , • . ': ; > ! = 1 i: ; i: : j • :i ji ' Hi • ;' i ESTIMATED COST OF A CONTRACT OPTION i' i| \\ ; 1 i ' i \ These ( • ,inmatesiare based on the costs of a study conducted at a 2,4,5-T f mates ja S ' : : i |i , !: • j i production plant by the Kettering Laboratory at the University of Cincinatti under the supervision of Raymond Suskind, M.D. A mortality I j li :• |! study !of;122 workers (conducted 28 years after exposure) and a morbidity study based on questionnaire, physical examination,and laboratory data from •TV> /; ; Uail vvCl • 1 1 ] ! ! f- i . 1 :• i : ! ' 1; i •'• \ ny ii y i uuu j j> il :i 1 •! j 1 • ; ! ; j |, ! j i • f |; ' : : ' '' \''i ^ ! M | ; i ; ' A ' ! ;; i V»UIIVIU^.^t.U . .i '• I , ': | :' ' CONTRACT COSTS (IN DOLLARS) KETTERING ^•iiisyBJJCJS__COST £ti. li|i.- 1977-78 i : C COST/SyBJE_CT RANCH HAND II £_OF JUBJECTS COST i Mortality Study ; Baseline ; Physical Examination : 122 $100K $819.67 7200 $5.9M 437 $200K $457.66 926 4.2M 225.00 608 1.4M 503.43 ' 926 4.7M 250.00 608 1.5M Follow-up : Examinations Baseline I Laboratory ! Procedures Follow-up 437 $220K $T7".7M . �i OF BY ! ' CATE60gY_ ' 50 23 . " 19 13 - : 41? CLAIWS MLLE6BD1 "EXPOSURE1 ? f s • . IS " " S 5 � 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. 060 Folder The folder containing the original item. 1607 Series The series number of the original item. Series III 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 Typescript: Synopsis of Background Subject The topic of the resource Air Force Health Study dioxin ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/487f9f52184542c0c8d9e8db08ba0ee7.pdf 11bbf1a3de9a8ac52c86879de5657e4f PDF Text Text Item ID Number °1606 Author Corporate Author Report/Article TltiB Typescript: General Dettinger's Responses to Questions, 11 Oct 78, House Vet's Affairs Committee Journal/Book Title Year 000 ° Month/Day Color Number of Images n 1 Dflscrlpton Notes Wednesday, May 23, 2001 Page 1607 of 1608 �5?.$ w h a t is s c i e n t i f i c a l l y r e p o r t e d i»i t h i s e i c a , '5*7 tl-.ir !".;;.- tc t';* '.''i t* ?:?ns .Vir, i:;i?ti a t i o n . Us a r a sit»ir,- We lir.vc O'lfnt-i-tl • £?5 • t}*,a s r r v i n - s of o n e o c c u r c::+. s o f - a l y cc^-.ijs t e n t rl'.j-'si =in:i.v 5 2 9 ; halj> in their £ v c lviatj.cn ox tjia i i r c h l c n . I to We c e r t a i n l y iJT.t i £30 | to get to the bottom oi1 it, there is no qussticn. 53 t : 7?: ere is a l o t __p3e^ c.'ijoir.g ____s_t\j.fiy_. inn 532 1 the D c r p . s tr-fiii t ol D a f a n s e r i j h t n o - ? , a a a 210 1 .'ix hin cl t h o u g h i,1^ h a v e 533 P ccl l e c t c d t h a n c i c s of r.ll ^ar,il;?ic:n;5--tivc-ri e r a 531* s^ho i.'are i n v o l v e d '.:i-!;h tlic- s p t £ . > ' i n j o;;era t i c n - - U ' 3 h a v e - 536 nany 537 the £r.:'.chhands P.arjuijg^a (,]J^JliV—«JLiL1-' '*- "ill be g a t t i n ? to / 533 ' s -it^E. HP h a ^ B a l s o c s j i ' a c t e d t h & u t a s i d ;^p<;i,t? locate all,- «£ the peopli * - — . — m _ _ , ^— _. . .. . u :;?. th J ' The re -; OZ 1 � 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. 060 Folder The folder containing the original item. 1606 Series The series number of the original item. Series III 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 Typescript: General Dettinger's Responses to Questions, 11 Oct 78, House Vet's Affairs Committee Subject The topic of the resource Air Force Health Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/2907a36115142782c019a4b81982ad26.pdf e931c00bd64cbfdbfe735e63b5faed09 PDF Text Text Item ID Number °1605 Author Corporate Author Report/Article TitlQ Typescript: Medical Examination of Personnel with Possible Exposure to Herbicide Orange,- A Proposed Protocol Journal/Book Title Year 000 ° Month/Day Color n Number of Images s DOSCrlpton Notes Includes editorial notes. Wednesday, May 23, 2001 Page 1606 of 1608 �MEDICAL EXAMINATION OF PERSONNEL WITH POSSIBLE EXPOSURE. TO HERBICIDE ORANGE - A PROPOSED PROTOCOL There is little information on the residual or chronic effects of the constituents of Herbicide Orange, 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,3,7,8 tetrachlorodi\Y* yx^w • benzo-p-dioxin (TCDD)A Evaluation must, therefore, be based on the acute effects that have been described for these substances or their precursers yj** fMlOI-e, U5€. SW >r _—— ^-N tn- flormal 4ft4tt*trnrt u&agfe, industrial accidents «gr(commercial usey The organ systems of primary concern are the skin, central nervous system, peripheral nervous system, liver, kidney and hematopoetic. In addition, asthenic and other constitutional sysmptoms have been described. Prominent among these are headache, malaise, gastrointestinal and sexual dysfunction. There have been unsubstantiated reports of teratogenesis, increased fetal wastage, and lung, liver and mesenchymal tumors. II. EXPOSURE HISTORY . l* * / --JC prof& A careful history to ascertain the time and degree of exposure ^haJJ be $h& f! obtained. Enclosure I is a suggested questionaire to aid in obtaining this information. r A thorough medical history /hal) be obtained with emphasis on the systems both preceding and following possible exposure, whether the dysfunction was evaluated by a physician, the diagnosis if known, and treatment given. Pertinent family history should be investigated and a thorough ,.•*' work history from the time of the first job should be obtained. A history of chloracne following possible exposure should be carefully . d iv«cJn \" MEDICAL HISTORY described in paragraph I. It should include information on dysfunction .' �searched for, as evidence indicates that without chloracne other acute disorders are unlikely. IV. PH YS.IJC AL_EXAMINATI ON A complete physical examination^shajjybe performed with special emphasis directed towards disorders of the skin, liver, lungs and kidney. A very thorough neurological examination shall be conducted paying particular attention to evidence of peripheral nervous system disease. V. LABORATORY Laboratory studies ^ha.])* include the following. Other studies should be done as indicated by the history and physical examination. 1. Complete hemogram a. Red Blood Cell Count b. Red Blood Cell Indices c. Hemoglobin d. Hematocrit e. White Blood Cell Count f. Differential Count g. Reticulocyte Count h. Platelet Count 2. Urinalysis including microscopic and specific gravity 3. Renal Function Studies a. Serum Creatinine b. Blood Urea Nitrogen (BUN) 4. Liver Function Studies a. Serum Glutamic-oxaloacetic Transaminase (SGOT) b. Serum Glutamic-pyruvic Transaminase (SGPT) �c. Gamnia-glutamyl Transpeptidase (GGT) d. Alkaline Phosphatase e. Serum Bilirubin f. Prothrombin Time g. Serum Uroporphyrins 5. Serum Protein 6. Serum Triglycerides 7. Serum Cholesterol 8. Fasting Blood Sugar 9. 14"xl7" Posterior-Anterior X-ray of the chest 10. Sputum cytology 11. Stool for occult blood 12. Visual Acuity Screening a. near b. far 13. Air conduction audiogram VI. All positive findings in the history, physical examination, or laboratory studies /sriaTp result in appropriate follow up investigation. Special consultaion will be liberally utilized. A copy of all examinations 'will be forwarded to the Office of the Surgeon General and to the Occupational and Environmental Health Laboratory, Brooks AFB, TX. �-IRE-EXAMINATION QUESTIONNAIRE 1. Name 2. Present 3. Dates in Vietnam 4. Units assigned to when in Vietnam 5. Specific location of units 6. Jour job in the unit: describe •*'' '^ you work with -pes ^ tJTd =if-yes, what "«jifiLSti cide? a. Blue b. White c. Purple d. Orange •e^—hisecticides * f. Other q /<5> s* y. How often did you work with the-pesticide? 10. What type of contact occurred? a. spray d. soil b. liquid e. plants c. vapor 11. Did you develop symptoms following exposure? 12. If yes, describe 13. Did you seek help: Yes ____ Yes 14. If yes, was a diagnosis made? „____, No Yes No 15. If yes, what? 16. Was treatment given? 17. If yes, what? , Yes No _^ . No �18. Did symptoms disappear? _________ Yes _____ No 19. If yes, how long did they persist? _ _______________________ _2tL— Are- you having symptoms now? i:;~r^es m " ~™^^ ,0 s Sine* I tK *.-\ fy / (..-' J^ .X* _ I * -X- ' I • IJ t � 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. 060 Folder The folder containing the original item. 1605 Series The series number of the original item. Series III 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 Typescript: Medical Examination of Personnel with Possible Exposure to Herbicide Orange - A Proposed Protocol Subject The topic of the resource Air Force Health Study study protocol ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/5605e5a6a27b16b9fca7221018cc7904.pdf d27c233dcd99c635eb516f8ae3f924c6 PDF Text Text Item ID Number oieo4 Author Corporate Author Report/Article Title Typescript: Project Ranch Hand II Journal/Book Title Year 000 ° Month/Day Color rj Number of linages 35 DOSCrlptOU NOtOS Appears to be printouts from a slide presentation. Wednesday, May 23, 2001 Page 1605 of 1608 �PROJECT RANCH HAND II A WHITE HOUSE DIRECTED EPIDEMIOLOGIC INVESTIGATION OF POSSIBLE ADVERSE HEALTH EFFECTS ATTRIBUTABLE TO HERBICIDE EXPOSURE AMONG OPERATION RANCH HAND PERSONNEL �STUDY DESIGN IDENTIFY EXPOSED POPULATION SELECT COMPARISON POPULATION DETERMINE BASELINE HEALTH STATUS OF THE TWO GROUPS • MORTALITY » DISEASE OR ABNORMALITY (MORBIDITY) COMPARE FINDINGS STATISTICALLY TO DELINEATE POSSIBLE HERBICIDE EFFECTS ACCOMPLISH FOLLOW UP STUDIES OF POPULATIONS �STUDY POPULATIONS ALL RANCH HAND MEMBERS WHO SERVED IN VIETNAM DURING 1962-1971 IDENTIFIED (1,200+) COMPARISON GROUP COMPOSED OF CARGO FLIGHT CREW MEMBERS AND SUPPORT PERSONNEL IN SOUTHEAST ASIA DURING SAME PERIOD BUT NOT OCCUPATIONALLY EXPOSED TO HERBICIDE (19,000+) EIGHT COMPARISON SUBJECTS MATCHED TO EACH RANCH HANDER BY: • JOB CATEGORY RANCH HAND _ DAPr RACE INDIVIDUAL • • AGE COMPARISON INDIVIDUALS , JJI 1:8 EXPOSURE INDEX DEVELOPED FOR RANCH HAND POPULATION �MORTALITY PORTION FIVE INDIVIDUALS RANDOMLY ORDERED IN EACH COMPARISON SET MORTALITY EXPERIENCE OF THE FIVE COMPARISON SUBJECTS COMPARED TO A RANCH HANDER RANCH HAND INDIVIDUAL COMPARISON INDIVIDUALS RANDOMLY ORDERED MORTALITY COMPARISONS 1-5 t �MORBIDITY PORTION FIRST INDIVIDUAL IN 5 MEMBER MORTALITY SET USED FDR COMPARISON STUDY • IF COMPARISON SUBJECT DECEASED OR NON-COMPLIANT, NEXT COMPLIANT SUBJECT SELECTED LIVING RANCH HAND INDIVIDUAL COMPARISON INDIVIDUALS RANDOMLY ORDERED MORTALITY COMPARISONS I 4- 1:1 - DEAD + UNWILLING (NONCOMPLIANT) I — I * I I I V A * I I J ** VOLUNTEER * * REPLACEMENT CANDIDATES �MATCHING PROCEDURES INITIAL MATCH COMPARISON INDIVIDUALS RANCH HAND INDIVIDUAL 1 :8 I I I I I I I COMPARISON INDIVIDUALS RANDOMLY ORDERED MORTALITY COMPARISON MATCH FOR MORTALITY PORTION RANCH HAND INDIVIDUAL 1 :5 lllliDOD COMPARISON INDIVIDUALS RANDOMLY ORDERED MORTALITY COMPARISONS MATCH FOR MORBIDITY PORTION LIVING RANCH HAND INDIVIDUAL + - * ** * ~ UNWILLING * * VOLUNTEER REPLACEMENT CANDIDATES �QUESTIONNAIRES DEVELOPED AND ADMINISTERED UNDER CONTRACT • INCORPORATED DATA FROM EXTENSIVE LITERATURE REVIEW AND VETERANS' COMPLAINTS AND CONCERNS QUESTIONNAIRES DEVELOPED FOR STUDY SUBJECTS, SPOUSES, AND NEXT OF KIN ADMINISTERED FACE-TO-FACE IN HOME BY OVER 80 ESPECIALLY SELECTED AND TRAINED PERSONNEL REQUIRED UP TO 3 HOURS TO COMPLETE PROVIDED OVER 300 ITEMS FROM EACH STUDY SUBJECT FOR ANALYSES OVER 5000 QUESTIONNAIRES ADMINISTERED �PHYSICAL EXAMINATION ACCOMPLISHED BY CONTRACT • CIVILIAN ORGANIZATION OF NATIONAL STATURE • EXAMINERS UNAWARE OF EXPOSURE HISTORY PARTICULAR EMPHASIS ON DERMATOLOGIC, NEUROPSYCHIATRIC, HEPATIC, IMMUNOLOGIC, REPRODUCTIVE, AND NEOPLASTIC ASPECTS • BASED ON EXTENSIVE SCIENTIFIC LITERATURE REVIEW EXAMINATION REQUIRED THREE DAYS PROVIDED OVER 1100 ITEMS FROM EACH STUDY SUBJECT FOR ANALYSES OVER 2200 EXAMINATIONS ACCOMPLISHED �MORBIDITY PORTION PARTICIPATION RANCH HAND 1206 POTENTIAL SUBJECTS COMPARISON ORIGINAL REPLACEMENTS QUESTIONNAIRE 1174 (97%) 956 (93%) 576 (90%) EXAMINATION 1045 (87%) 774 (76%) 450 (71%) �BASELINE MORTALITY PORTION RESULTS RELEASED JUNE 1983 EVALUATED 50 RANCH HAND AND 250 COMPARISON SUBJECTS WHO DIED FROM NONCOMBAT CAUSES SMALL NUMBER EMPHASIZES PRELIMINARY NATURE OF RESULTS RESULTS • MORTALITY EXPERIENCE NEARLY IDENTICAL IN RANCH HAND AND COMPARISON GROUPS • CAUSE SPECIFIC ANALYSES NOT STATISTICALLY DIFFERENT �MORBIDITY PORTION RESULTS LACK OF CLEAR CUT HALLMARKS REQUIRED COMPREHENSIVE EVALUATION OF NUMEROUS SYSTEMS • GENERAL PHYSICAL HEALTH • MALIGNANCY • FERTILITY/REPRODUCTIVE • NEUROLOGY • PSYCHOLOGY • HEPATIC • DERMATOLOGY • CARDIOVASCULAR • IMMUNOLOGY • HEMATOLOGY • PULMONARY • RENAL • ENDOCRINE • INDIVIDUAL HEALTH �GENERAL PHYSICAL HEALTH SIGNIFICANT GROUP DIFFERENCE FOUND IN SELF-PERCEPTION OF HEALTH WITH MORE RANCH HANDERS PERCEIVING THEMSELVES TO BE IN FAIR OR POOR HEALTH • NOT SUPPORTED BY EXPOSURE INDEX ANALYSES BORDERLINE SIGNIFICANT GROUP DIFFERENCE IN THE EXAMINER'S ASSESSMENT OF ILLNESS OR DISTRESS (RH=>C) • NOT SUPPORTED BY EXPOSURE INDEX ANALYSES NO SIGNIFICANT GROUP DIFFERENCES IN PERCENT BODY FAT OR HEMATOCRIT SIGNIFICANTLY MORE INDIVIDUALS WITH SEDIMENTATION RATE ABNORMALITIES IN THE YOUNGER COMPARISONS THAN IN THE RANCH HANDERS • NO OVERALL GROUP DIFFERENCES OBSERVED �MALIGNANCY NO SIGNIFICANT DIFFERENCE IN THE OCCURRENCE OF "SYSTEMIC" CANCER NO SOFT TISSUE SARCOMA FOUND RANCH HANDERS • ONE CASE FOUND IN COMPARISONS SIGNIFICANTLY MORE POST-SEA SKIN CANCER IN THE RANCH HAND GROUP THAN IN THE ORIGINAL COMPARISONS WHO COMPLETED PHYSICAL EXAMINATION • DIFFERENCE ONLY BORDERLINE WITH TOTAL COMPARISON GROUP • ANALYSES NOT FULLY ADJUSTED FOR SUN EXPOSURE (GEOGRAPHIC AREA OF RESIDENCE) • NON-MELANOMA CELL TYPE PREDOMINATES • FACE, HEAD AND NECK PREDOMINANT DISTRIBUTION �MALIGNANCY (CONTD) ANALYSES DEMONSTRATED ASSOCIATION BETWEEN SMOKING AND "SYSTEMIC" CANCER AND INDUSTRIAL CHEMICAL EXPOSURE AND SKIN CANCER IN BOTH GROUPS SLIGHTLY MORE GENITOURINARY CANCER (6 TO 3), MORE OROPHARYNGEAL CANCER (4 TO 2), AND LESS GASTROINTESTINAL CANCER (0 TO 5) IN RANCH HAND GROUP, BUT DIFFERENCE NOT SIGNIFICANT EXPOSURE INDEX ANALYSES REVEALED NO STATISTICALLY SIGNIFICANT OR SUGGESTIVE ASSOCIATIONS BETWEEN HERBICIDE EXPOSURE AND EITHER SKIN OR "SYSTEMIC" MALIGNANCY �VERIFIED SKIN AND SYSTEMIC CANCER • RANCH HAND ALL COMPARISONS NUMBER (%) SKIN CANCER ORIGINAL COMPARISONS NUMBER (%) NUMBER (%) 35 (3.3) 11 (1.4) 25 (2.1) SYSTEMIC SITE LIP, MOUTH, THROAT 4 2 2 DIGESTIVE SYSTEM 0 4 5 RESPIRATORY 3 1 2 GENITOURINARY BLOOD, LYMPH 6 2 3 0 0 1 OTHER 1 1 1 TOTAL 14 (1.3) 10 (1.3) 14 (1.2) �FERTILITY/REPRODUCTIVE OVER 7000 CONCEPTIONS EVALUATED NO SIGNIFICANT GROUP DIFFERENCES • SPERM COUNT, PERCENT ABNORMAL • FERTILITY/INFERTILITY • MISCARRIAGE, STILLBIRTH, LIVE BIRTH SIGNIFICANT GROUP DIFFERENCE (RH > C) • REPORTED BIRTH DEFECTS - NO SIGNIFICANT DIFFERENCE WHEN SKIN ANOMALIES (BIRTH MARKS, BLEMISHES, etc.) REMOVED • REPORTED PHYSICAL HANDICAPS • REPORTED NEONATAL DEATH MEDICAL RECORD VERIFICATION OF REPORTED EVENTS UNDER WAY NO CONSISTENT PATTERN WITH INCREASING EXPOSURE �REPORTED POST-SEA DEFECTS BY SEVERITY RANCH HANDERS (RH) VERSUS ORIGINALS (0) RH 0 SEVERE Y N 32 885 18 726 P 0.20 MODERATE Y N 22 895 20 724 P 0.71 LIMITED Y N 26 891 io P 0.04 734 RANCH HANDERS (RH) VERSUS ALL COMPARISONS (A) SEVERE Y N 32 885 34 1,275 P 0.22 MODERATE Y N 22 895 34 1,275 P 0.77 LIMITED Y N 26 891 18 1,291 P 0.01 �INDIVIDUAL HEALTH (CONT'D) NO SIGNIFICANT DIFFERENCE IN DISTRIBUTION OF ILL INDIVIDUALS GROUP DIFFERENCES ONLY FOR • SKIN CANCERS, NOT CORRECTED FOR SUN EXPOSURE • PULMONARY FUNCTION (MORE ABNORMALITIES IN COMPARISON) BOTH GROUPS IN GOOD HEALTH FOR AGE �NEUROLOGY NO SIGNIFICANT GROUP DIFFERENCES IN CRANIAL NERVE FUNCTION NO SIGNIFICANT GROUP DIFFERENCES IN TESTS OF PERIPHERAL NERVES EXCEPT FOR A BORDERLINE DIFFERENCE IN BABINSKI REFLEX • EFFECTS OF ALCOHOL USE AND ABNORMAL GLUCOSE METABOLISM DEMONSTRATED IN BOTH GROUPS NO GROUP DIFFERENCES IN CENTRAL FUNCTION (TREMOR, COORDINATION, ROMBERG, GAIT) NO SIGNIFICANT GROUP DIFFERENCES IN NERVE CONDUCTION VELOCITY NO DOSE RESPONSE EFFECT OBSERVED FOR PERIPHERAL NERVES, CRANIAL NERVES, CONDUCTION VELOCITY, OR CENTRAL FUNCTION �PSYCHOLOGY COMPREHENSIVE GROUP OF VALIDATED TESTS USED ANALYSES STRATIFIED BY EDUCATION • REFLECTED KNOWN SUBSTANTIAL EFFECT OF EDUCATION ON PSYCHOLOGICAL TESTING SUBJECTIVE MEASURES SHOWED SIGNIFICANT GROUP DIFFERENCES FOR HIGH SCHOOL EDUCATED PERSONNEL (QUESTIONNAIRE, CORNELL INDEX, MMPI) • NOT OBSERVED IN THE COLLEGE EDUCATED INDIVIDUALS NO DIFFERENCES IN IQ OR PERFORMANCE TESTING NO DOSE RESPONSE EFFECTS OBSERVED �HEPATIC RANCH HANGERS REPORTED MORE LIVER SYMPTOMS IN PAST • NO CLINICAL EVIDENCE OF SIGNIFICANT GROUP DIFFERENCES AT EXAMINATION OVERALL BIOCHEMICAL GROUP DIFFERENCES: GGPT (RH=>C), LDH (RH=>«, CHOLESTEROL (RH<C) NO OVERALL GROUP DIFFERENCES: SGOT, SGPT, ALK. PHOS. T. BILI, D. BILI, TRIGLYCERIDES, UROPORPHYRIN, CQPRQPQRPHYRIN, D-ALA NO PORPHYRIA CUTANEA TARDA DETECTED NO DOSE RESPONSE EFFECT OBSERVED �DERMATOLOGY QUESTIONNAIRE RESPONSES SHOWED NO GROUP DIFFERENCES FOR • OCCURRENCE OF PAST ACNE • OCCURRENCE OF PAST ACNE RELATIVE TO INDIVIDUAL'S SEA TOUR • SEVERITY OR DURATION OF PAST ACNE • ANATOMIC LOCATION OF PAST ACNE SUGGESTING CHLORACNE �DERMATOLOGY (CONT'D) PHYSICAL EXAMINATION SHOWED • NO CLINICAL DIAGNOSES OF CHLORACNE • NO POSITIVE BIOPSIES FOR CHLORACNE • NO GROUP DIFFERENCES IN THE PREVALENCE OF THE 5 MOST COMMON DERMATOLOGIC DIAGNOSES EXPOSURE INDEX ANALYSES WERE NEGATIVE �CARDIOVASCULAR PHYSICAL EXAMINATION SHOWED SIMILAR GROUP FINDINGS FOR • SYSTOLIC, DIASTOLIC BLOOD PRESSURES • ABNORMAL ECG'S • COMPARISON OF PAST ECG'S TO THE EXAM ECG • HEART SOUNDS • FUNDUSCOPIC ABNORMALITIES • CAROTID BRUITS NO PREMATURE HEART DISEASE IN THE RANCH HANDERS �CARDIOVASCULAR (CONT'D) SOME PERIPHERAL PULSES DECREASED IN RANCH HANDERS • SIGNIFICANCE UNCERTAIN ANALYSES DEMONSTRATED EFFECTS OF • AGE • SMOKING, PAST ANDPRESENT HERBICIDE EXPOSURE ANALYSES WERE ESSENTIALLY NEGATIVE FOR CARDIOVASCULAR ABNORMALITIES �IMMUNOLOGY NO GROUP DIFFERENCES SMOKING, ALCOHOL, AGE EFFECTS DEMONSTRATED IN BOTH GROUPS HEMATOLOGY NO DIFFERENCE IN CLINICALLY SIGNIFICANT BLOOD ABNORMALITIES DIFFERENCES IN CELL HEMOGLOBIN CONCENTRATION PRESENT • MOST VALUES STILL WITHIN NORMAL LIMITS �PULMONARY NO GROUP DIFFERENCES IN REPORTED DISEASE, FORCED VITAL CAPACITY, FORCED EXPIRATORY VOLUME (1 SECOND) OR FEV^FVC RATIO NO CONSISTENT ASSOCIATIONS BETWEEN PULMONARY FUNCTION AND EXPOSURE LEVELS EXPECTED EFFECTS OF SMOKING HISTORY SEEN IN BOTH GROUPS NO INDICATION THAT CURRENT PULMONARY FUNCTION WAS AFFECTED BY EXPOSURE TO HERBICIDES �RENAL NO SIGNIFICANT DIFFERENCES IN TESTS OF RENAL FUNCTION NO CLINICAL EVIDENCE OF HERBICIDE EFFECT EXPOSURE INDEX ANALYSES ESSENTIALLY NEGATIVE �ENDOCRINE SOME THYROID HORMONE GROUP DIFFERENCES • MOST VALUES STILL WITHIN NORMAL LIMITS TESTOSTERONE LEVELS INCREASED IN RANCH HANDERS • MOST VALUES STILL WITHIN NORMAL LIMITS BLOOD GLUCOSE LEVELS NOT SIGNIFICANTLY DIFFERENT �INDIVIDUAL HEALTH BOTH GROUPS SIMILAR IN • RISK TAKING ACTIVITIES • RELIGIOUS PREFERENCE • EDUCATION • PERSONAL AND FAMILY INCOME • MILITARY STATUS • REPORTED INJURIES AND POISONINGS • CURRENT AND PAST USE OF ALCOHOL • PAST HISTORY OF CIGARETTE, PIPE, CIGAR, USAGE MORE RANCH HANDERS CURRENTLY SMOKE THAN COMPARISONS �INTERPRETIVE COMPLEXITIES STATISTICAL ASSOCIATIONS DO NOT MEAN CAUSATION NO ANALOGOUS HUMAN STUDIES MANY STATISTICALLY SIGNIFICANT RANCH HAND-COMPARISON GROUP DIFFERENCES ARE NOT OF CLINICAL RELEVANCE EXPOSURE INDEX ANALYSES ARE UNREFINED POSITIVE AND NEGATIVE FINDINGS REQUIRE FOLLOW-UP �SUMMARY BASELINE MORBIDITY PORTION DID NDT DEMONSTRATE DEFINITIVE CLINICAL END POINTS CONCLUSIVELY ATTRIBUTABLE TO HERBICIDE EXPOSURE NO STS, PCT, CHLORACNE DIAGNOSED IN RANCH HANDERS DID FIND A NUMBER OF CLINICAL AND SUBCUNICAL DIFFERENCES • DEFINING SIGNIFICANCE OF SOME DEPENDENT ON ANALYSES OF DATA NOT YET COLLECTED (SUN EXPOSURE, BIRTH RECORDS) • MOST VALUES STILL WITHIN NORMAL RANGES SCHEDULED FOLLOW UP EXAMINATIONS WILL PROVIDE ESSENTIAL DATA NECESSARY TO DEFINE BOTH FALSE POSITIVES AND ANY FALSE NEGATIVES �PROJECT RANCH HAND II BASELINE MORTALITY AND MORBIDITY STUDIES ACCOMPLISHED RESULTS CONFIRM EFFECTIVENESS OF PROTOCOL DESIGN AND IMPLEMENTATION INITIAL FINDINGS UNDERSCORE NEED FOR FOLLOW UP OVER TIME EXTENSIVE DATA BASE ALREADY OBTAINED WILL ALLOW CONTINUING DATA ANALYSES �CONCLUSIONS STUDY MEASURED TRUE HEALTH STATUS TO MAXIMUM EXTENT POSSIBLE ALL SIGNIFICANT FINDINGS ARE BEING FOLLOWED UP INSUFFICIENT EVIDENCE TO SUPPORT HERBICIDE CAUSALITY AT THIS TIME FINDINGS TO DATE SHOULD BE REASSURING TO RANCH HANDERS • NO CHLORACNE MEANS LOW EXPOSURE VERSUS CHEMICAL WORKER POPULATIONS • NO MAJOR CLINICAL HEALTH PROBLEMS • OVERALL GOOD GENERAL HEALTH FOR AGE �STUDY COMPLEXITIES ENORMOUS DATA BASE (4 MILLION ITEMS) VALIDITY OF SELF REPORTING IN ABSENCE OF COMPLETE MEDICAL RECORD VERIFICATION EFFECTS OF MULTIPLE RISK FACTORS (AGE, SMOKING, etc.) POTENTIAL BIASES STUDY SCHEDULE � 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. 060 Folder The folder containing the original item. 1604 Series The series number of the original item. Series III 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 Typescript: Project Ranch Hand II Subject The topic of the resource Air Force Health Study mortality trends morbidity trends ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/d9ac158c2b33f282e4cdf130097db61d.pdf c17ac476eae7cf0b1c0922c39b3cc22a PDF Text Text Item ID Number °1603 Author Corporate Author Roport/Artido TltlO Typescript: Differences Between Annual Flying Physical Examination and the Herbicide Orange Examination Journal/Book Title Year 000 ° Month/Day Color D Number of Images 1 Doscrlpton Notes Wednesday, May 23, 2001 Page 1604 of 1608 �Differences Between Annual Flying */ Physical Examination and the Herbicide Orange Examination Routine Flying Chest X-Ray Cardiogram VD Tests Urinalysis 3 Blood Counts 9 Blood Chemistries Diabetes Tests Herbicide Orange Yes Yes Yes/No Yes Yes No Yes/No Yes Yes Yes/Yes Yes Yes Yes Yes/Yes Areas. Dermatologic Exam No with 3 blood chemistries Yes Neuro-Psychiatric Exam Psychological Battery Nerve Conduction Tests No No Yes Yes Reproductive Exam Semen Analysis 3 Hormone Tests No No Yes Yes Cancer/Liver Exam No 5 Blood Chemistry Tests Yes 8 additional specialized tests Performed if indicated by other tests Not ever performed Attachment 1 � 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. 060 Folder The folder containing the original item. 1603 Series The series number of the original item. Series III 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 Typescript: Differences Between Annual Flying Physical Examination and the Herbicide Orange Examination Subject The topic of the resource Air Force Health Study ao_seriesIII