2 15 63 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. 028 Folder The folder containing the original item. 0437 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Source A related resource from which the described resource is derived Pesticide & Toxic Chemical News Date A point or period of time associated with an event in the lifecycle of the resource July 28 1982 Title A name given to the resource Dioxin Prisoner Testing Investigation Ended Due to Uncertainities Subject The topic of the resource Dow human testing Pennsylvania 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. 044 Folder The folder containing the original item. 1064 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Smith, A H. D.O. Fisher N. Pearce C.A. Teague Source A related resource from which the described resource is derived Community Health Studies Date A point or period of time associated with an event in the lifecycle of the resource 1982 Title A name given to the resource Do Agricultural Chemicals Cause Soft Tissue Sarcoma? Initial Findings of a Case-Control Study in New Zealand Subject The topic of the resource industrial exposure human testing 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. 048 Folder The folder containing the original item. 1230 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Shiplov, J. C. D. Graber J. E. Keil S. H. Sandifer Source A related resource from which the described resource is derived Immunological Communications Date A point or period of time associated with an event in the lifecycle of the resource 1972 Title A name given to the resource Effect of DDT on Antibody Response to Typhoid Vaccine in Rabbits and Man Subject The topic of the resource Human testing animal testing pesticide toxicology 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. 051 Folder The folder containing the original item. 1345 Series The series number of the original item. Series III Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Franklin, C. A. R. Grover J. W. Markham A. E. Smith K. Yoshida Description An account of the resource Corporate Author: American Conference of Governmental Industrial Hygienists, Inc. Source A related resource from which the described resource is derived Transactions of the Forty-Third Annual Meeting of the American Conference of Governmental Industrial Hygienists Date A point or period of time associated with an event in the lifecycle of the resource 1982 Title A name given to the resource Effect of Various Factors on Exposure of Workers Involved in the Aerial Application of Herbicides Subject The topic of the resource industrial exposure human testing protective clothing 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. 048 Folder The folder containing the original item. 1224 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Miller, H. J. Ita Aronovski Simi Cucos Dora Wasserman M. Wasserman Source A related resource from which the described resource is derived Bulletin of Environmental Contamination and Toxicology Date A point or period of time associated with an event in the lifecycle of the resource 1979 Title A name given to the resource Effects of Organochlorine Insecticides on Serum Proteins in Occupationally Exposed People Subject The topic of the resource DDT industrial exposure human testing pesticide toxicology 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. 048 Folder The folder containing the original item. 1234 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Wasserman, M. L. Tomatis Dora Wasserman N. E. Day Y. Groner S. Lazarovici Deborah Rosenfeld Source A related resource from which the described resource is derived Pesticides Monitoring Journal Date A point or period of time associated with an event in the lifecycle of the resource 1974-06-01 Title A name given to the resource Epidemiology of Organochloride Insecticides in the Adipose Tissue of Israelis Subject The topic of the resource DDT adipose tissue testing human testing 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. 048 Folder The folder containing the original item. 1207 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Hayes, Wayland J., Jr. William E. Dale Carl I Pirkle Source A related resource from which the described resource is derived Archives of Environmental Health Date A point or period of time associated with an event in the lifecycle of the resource 1971-01-01 Title A name given to the resource Evidence of Safety of Long-Term, High, Oral Doses of DDT for Man Subject The topic of the resource human testing 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. 040 Folder The folder containing the original item. 0929 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Nigg, H. N. J. H. Stamper Source A related resource from which the described resource is derived Chemosphere Date A point or period of time associated with an event in the lifecycle of the resource 1983 Title A name given to the resource Exposure of Florida Airboat Aquatic Weed Applicators to 2, 4 - Dichlorophenoxyacetic Acid (2, 4 -D) Subject The topic of the resource agricultural exposure herbicide application human testing protective clothing ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/9cf4c01c07645322adbadb01511544d6.pdf 18e58217ca8df06148ce403f5c5f2805 PDF Text Text Item ID Number °0979 Author Ramsey, J. C. Corporate Author Report/Article Title Exposure of Forest Workers to 2,4,5-T: Calculated Dose Levels Journal/Book Title Year 1979 Month/Day March Color Number of Images n 33 Alvin L. Young filed this item under the category "Human Exposure to Phenoxy Herbicides and TCDD" Friday, March 30, 2001 Page 979 of 1070 �ALVIN L YOUNG, Major, USAF Consultant, Environmental Sciences* EXPOSURE OF FOREST WORKERS TO 2,4,5-T: ' CALCULATED DOSE LEVELS J. C. Ramseyl, T. L. Lavy2 and W. H. Braun* ).- MAR 1979 MAR 1979 1 2 Toxicology Laboratory, Dow Chemical Company USA, Midland, Michigan. Altheimer Laboratory, University of Arkansas. �EXPOSURE OF FOREST WORKERS TO 2,4,5-T: CALCULATED DOSE LEVELS' SUMMARY This report presents calculated dose levels of 2,4,5-T in workers following application of 2,4,5-T in forestry operations. Experiments were conducted with 19 male and 2 female workers engaged in the application of the propylene glycol butyl ether (PGBE) ester of 2,4,5-T (ESTERON® 245 herbicide) by helicopter (both raindrop nozzle and microfoil boom), by backpack spraying, and by tractor-mounted mist blowers.1 No special instructions or safety precautions were used. Urine samples were collected following each application and analyzed for 2,4,5-T. The amount of 2,4,5-T absorbed by each worker was calculated by pharmacokinetic analyses of the urinary excretion data using three different methods. The results were classified by the worker's job description and the average dose levels of 2,4,5-T were as follows, calculated as mg 2,4,5-T per kg of body weight. Mixers, 0.073+0.046; backpack sprayers, 0.063+0.034; tractor drivers, 0.045+0.007; supervisors, O.OlliO.Oll; helicopter flagmen, 0.002±0.003. The two helicopter pilots had average calculated dose levels of 0.007 and 0.048 mg/kg. These dose levels of 1 T. L. Lavy, Altheimer Laboratory, University of Arkansas. ©Trademark of The Dow Chemical Company. �-2- 2,4,5-T are far below the 20 mg/kg no effect level for teratogenic or fetotoxic effects. Therefore, we conclude that under these conditions the absorption of 2,4,5-T presents a negligible toxic hazard to forest workers. INTRODUCTION Basic toxicological principles require a knowledge both of the inherent toxicity of a chemical and of the quantity actually absorbed into the body in order to assess its possible hazard. The quantity of chemical absorbed may be quite different from the quantity to which workers are exposed under field conditions. Therefore, a proper assess- ment of the potential hazard to workers during pesticide applications in the field is dependent on reliable estimates of the quantity of pesticide absorbed under these conditions. The amount of 2,4,5-T absorbed by applicators of 2,4,5-T formulations in forestry operations has never been directly measured. A study was recently conducted by T. L. Lavy (1) which provides urinary excretion data from which estimates can be made of the amount of 2,4,5-T absorbed by forestry workers during the application of 2,4,5-T. Four experiments were conducted with 19 male and 2 female workers engaged in the application of the propylene glycol butyl ether (PGBE) ester of 2,4,5-T (ESTERON® 245 herbicide) by helicopter �-* *3 _^ (both raindrop nozzle and microfoil boom), by backpack spraying, and by tractor-mounted mist blowers. Total voided urine samples were collected for each worker both prior to and following application, and measurements were made of the amount of 2,4,5-T excreted. The forest applications were made by personnel normally engaged in this type of work and all operations were carried out in the usual manner. No special instructions or safety precautions were used. The field conditions of the studies as well as the results of the analyses are reported in detail by Lavy (1). The total amount of 2,4,5-T excreted in the urine following exposure represents a minimum estimate of the amount of 2,4,5-T absorbed, since urinary excretion may not be complete at termination of the experiment. However, calculation of the absorbed dose of 2,4,5-T based on pharmacokinetic analysis of urinary excretion data is not dependent on total excretion and can therefore provide a more realistic estimate of the absorbed dose. Furthermore, this approach provides a sound statistical basis for evaluating the adequacy of the pharmacokinetic model to explain the observed data. It is the purpose of this paper to report estimates of the amount of 2,4,5-T absorbed by these workers, based on pharmacokinetic analyses of the amount of 2,4,5-T excreted in the urine. �-4- METHODS Pharmacokinetic Model In order to establish an adequate pharmacokinetic model for the absorption and excretion of 2,4,5-T, the following data were considered. Previous studies with 2,4,5-T ingested by human volunteers at a dose level of 5 mg per kg body weight showed that essentially all of the 2,4,5-T was quickly absorbed and excreted unchanged in the urine (2). Urinary excretion of 2,4,5-T occurred by an apparent first order process with a half life of 23.1 hr (0.96 day). The fecal route of excretion was shown to be negligible for 2,4,5-T in humans. In rats given a single oral dose of 5 mg/kg, the 2,4,5-T was excreted mainly in the urine by an apparent first order process with a half-life of 13.6 hr (3). In another study, in rats given a single intravenous dose of 5 mg/kg (4), urinary excretion of unchanged 2,4,5-T accounted for 96% of the administered dose and excretion occurred by an apparent first-order process with a half-life of 10.7 hr. Thus, the urinary excretion of 2,4,5-T at this dose level occurs by a first order process that is essentially independent of the route of administration. �-5- A recent study conducted in this laboratory (5) showed that the PGBE ester of 2,4,5~T applied to the shaved skin of rats at a dose level of 5 mg/kg was virtually completely absorbed, and subsequently excreted in the urine as 2,4,5-T per se. Urinary excretion of 2,4,5-T appeared to be a first order process with a half-life of approximately 24 hr, indicating that the dermal absorption process may have been slow in relation to the urinary excretion of 2,4,5-T. The foregoing data demonstrate that measurement of the urinary excretion of 2,4,5-T can provide a reliable estimate of the amount of 2,4,5-T absorbed. Also, it is apparent that esters of 2,4,5-T are slowly but readily absorbed through the skin and are then excreted in the urine as 2,4,5-T acid. These considerations provide the basis for the pharmacokinetic model shown in Figure 1 for the absorption of 2,4,5-T or its esters and subsequent urinary excretion of 2,4,5-T in humans. A definition of symbols and terms is given in the legend of Figure 1. All calculations have been made on the basis of 2,4,5-T acid equivalents. �SCt)- 0, Bft) Figure 1. Schematic diagram of the pharmacokinetic model for the absorption of 2,4,5-T or its PGBE ester in humans, followed by urinary excretion of 2,4,5-T acid. S(t) - amount of 2,4,5-T remaining to be absorbed at time t. B(t) • amount of 2,4,5-T in body at time t. E(t) - amount of 2,4,5-T excreted in urine at time t. k and kje « first order rate constants for absorption and excretion of 2,4,5-T, respectively. The differential equations and initial conditions describing the dynamics of the pharmacokinetic model are shown in Figure 2. The half -life for the urinary excretion of 2,4,5-T in humans previously determined as 0.96 day (2) corresponds to an apparent first order elimination rate constant of 0.72 day" , the value we have used for k. 6 in the differential * equations of Figure 2. The value of S(t) at time zero represents the dose D , which is the total quantity of 2,4,5-T absorbed. Differential Equation Initial Condition dt dt dt Figure 2. Differential equations and initial conditions describing the pharmacokinetic model of Figure 1. �-7- Data Base The urinary excretion data reported by Lavy in Tables 6, 7, 8, and 9 of reference 1 were treated as follows. Since a large amount of diurnal variation was evident in the urine samples collected at 12-hr intervals, the values for successive 12-hr intervals were combined so that each value represents the amount of 2,4,5-T excreted per day. Urine samples collected on the day previous to either the first or the second application date were considered to be preexposure samples. The data thus arranged are shown in Table 1, with the same designation used by Lavy for each worker (1). The amount of 2,4,5-T in the pre-exposure samples fluctuated widely with no apparent pattern, therefore no background corrections were applied. The workers employed as mixers may have been exposed on the day previous to the application date (since the formulations are usually mixed the day before the actual application), but for purposes of pharmacokinetic analysis they were considered to be exposed only on the date of application.[ The duration of the application 1 procedures ranged from 55 minutes to approximately 4 hours (average 138 minutes). Since this is a short time span relative to the total duration of the experiments (up to seven days), the calculated dose was considered to be a single application to the skin at time zero. These assumptions have either a negligible or a maximizing influence on the calculated dose absorbed. �' -f* -8- TABLE 1. Daily and Total Amounts of 2,4,5-T Excreted in the Urine of Forest Workers Following Application of ESTERON® 245a Worker No. b 1A IB 2A 2B 3A 3B 4A 4B 5A 5B 6A 7A 7B 8A 8B 9A 9B 10A 10B 11A 11B 12A 12B 13A 13B 14A 14B ISA 15B 16A 16B 17A 17B 18A 18B 19A 19B 20A 20B 21A 21B mg 2,4,5-T Excreted Day 0 0.119 0,039 0.398 0.784 nd 0.246 0.146 0.749 0.033 0.098 0.373 0.796 0.314 0.088 c Day l " 0.182 0.169 0.611 2,067 0.472 1.142 0.254 0.402 0.133 0.193 0.572 0.211 0.931 0.698 - - 0.103 0.097 0.690 0.953 0.037 0.343 0.644 0.709 0.889 1.246 nd nd nd Day 2 0.210 0.122 1.458 0.911 1.100 0.237 0.913 1.101 0.772 0.367 1.027 3.701 0.708 0.858 0.277 1.500 0.716 0.748 1.068 2.272 1.632 Day 3 0.127 0.167 1.460 0.978 1.648 0.515 0.421 0.584 0.251 0.126 0.458 0.856 0.368 0.579 0.196 0.687 0.548 0.773 0.539 1.653 1.204 0.041 0.267 1.827 1.344 0.109 0.038 nd nd nd 0.012 0.020 0.099 0.008 0.310 1.409 1.397 0.029 0.060 0.035 nd nd nd 1.894 1.362 0.026 nd 0.288 0.324 0.715 0.960 nd 0.047 nd nd nd nd 0.230 2.430 1.470 0.008 0.020 0.467 0.370 1.610 1.112 0.014 0.018 0.070 nd nd nd 0.053 0.037 0.602 0.812 1.229 3.536 0.158 0.057 0.079 0.022 0.029 0.016 nd ' nd 0.107 0.014 0.383 0.600 0.883 2.229 0.113 0.032 0.064 Day 4 0.155 0.203 0.723 0.646 0.618 0.549 0.495 0.506 0.222 0.122 0.235 0.876 0.422 0.380 0.146 0.599 0.478 0.761 0.892 0.629 0.283 Day 5 0.085 0.198 0.422 0.464 0.218 0.214 0.279 0.597 0.101 0.074 0.214 0.760 0.334 0.259 0.134 0.372 0.278 0.498 0.893 0.408 0.279 nd nd 0.097 1.386 0.964 0.155 0.010 0.084 1.136 0.737 0.032 0.081 0.097 nd nd nd nd nd nd nd Day 6 0.075 - 1.212 - 0.267 - 0.494 - 0.142 - 0.566 _ - 0.069 - 0.773 - 0.031 nd nd 0.255 0.409 0.602 0.916 2.428 0.073 0.365 0.455 0.804 1.650 0.067 nd nd nd nd nd 0.022 0.089 - 0.016 nd nd 0.033 0.022 0.032 0.011 - 0.465 0.116 nd - Totald 0.834 0.859 5.886 5.066 4.323 2.657 2.856 3.190 1.621 0.882 2.506 6.970 2.763 2.775 0.753 3.501 2.664 3.489 4.281 6.208 3.398 0.041 1.057 8.188 6.685 0.325 0.319 0.140 nd 0.168 0.071 2.481 2.839 5.907 10.955 0.541 0.107 0.229 0.022 0.116 0.138 Data taken from Lavy ( ) 1. A and B refer to the first and second exposure, respectively. cThe beginning of day 1 is designated as the beginning of the exposure. Excluding the 2,4,5-T excreted on day 0 (the "pre-exposure" sample). e - means no data available; nd means 2,4,5-T below detection limit in urine. �-9- In order to estimate the actual amount of 2,4,5-T absorbed (calculated as mg 2,4,5-T) during each application, the following three methods were used. Method A This method is based on pharmacokinetic parameter estimation techniques in which the best parameter estimates are considered to be those that yield the closest fit of the calculated data to the observed data (using the least squares criterion). In this case, parameter estimates were desired for the absorption rate constant (k absorbed dose of 2,4,5-T (DQ). ) and for the total The excretion rate constant (kle) was set at the previously established value of 0.72 observed data consisted of mg 2,4,5-T excreted day~ , and the observ< in the urine per day. The data for each worker following both exposures were plotted on semi-logarithmic graph paper. Visual inspection of all these plots showed that there were 12 exposures for 10 different workers in which (a) the data were complete (no missing data points), and (b) the time course of urinary excretion of 2,4,5-T followed a kinetically consistent pattern (i.e., a rise following the application date and a subsequent log-linear decline). These data sets were consistent with the model shown in Figure 1. �I,* V-' -10- Pharmacokinetic parameter estimation for these 12 data sets was accomplished with a digital computer, and the average percent variation explained was 69.0% (range 29.5% to 93.5%). The results of these analyses are shown in Figures 3 (a) through 3(&) in which the points • and o represent the observed and calculated data points, respectively, As expected, the estimated values of D varied considerably between individuals. However, the apparent first-order absorption rate constant k was reasonably consistent between individuals, the average value being 0.92 day~ with a standard deviation of 0.21 day" (n = 12) . The foregoing analyses thus provided an estimate of the absorbed dose of 2,4,5-T for 12 of the 41 exposures comprising the complete study. The results are shown in column A of Table 2. Also, the average value of the absorption rate constant determined here was used in the following two methods to obtain further estimates of the absorbed dose. Method B Integration of the differential equations of Figure 2 and solution for the total amount of 2,4,5-T excreted in the urine t days following exposure, designated as E(t), results in equation 1. CD �• Observe O Calculi : "TV: * : , ••. ; ' i i ... | Q) i : • .• : . . { . ; • ; • Cu O bO e . ;. i j • i •- • ~'T f ' .... . - ; i " j i ; T '• - >-. cO : T3 i •. I O : 1. - : • : • 4-1 0) 0 o.io- i ' 9 S i-o- • . . : O : • s; 60 • . j • t . - O.I;;. . : :: i '. t i . • \ i i J 0.10 i i 0 Day Day Worker No. 1(A) D (CalcJ = 0.90 mg o Figure 3a • : . 1 . ;'"'.'' . i . 0.01 j. j . 1 •" - -.;:• . ". ' • - '• • ' ;. . - . 3 • j l ' . ; ' ! ' ' ••»• -| - ... .. • j.j . " ~^ \ , .., .!.. _;. „ ; :. O . i : '• : • : ' !Mi - i; ! o e 1 ; \ f .';"• __... - i-4 :. | ' •••-,-.; . .. T) Oi . • L ^ J' ; ' ': f| ':" i i ' i ! -- H — : a! 9 ' : j .• . 1 : : 1 i : :; -i ; T-;- r ; , : : : i . : : ; .: : ! • . : •; 0 0) H • : , = : i • ! • •• •-.-;---• T -,'r -- 0: - 0) 4J (!) ,A -* ; i i- : Oi4§liP;Ul4^fe^ .. •. : . ... 1 ......... ^._ .. : ! |. :. ; : 1 ; 1 ---- - . ; . , . . . . j l l , ! - . . ^ . •; Observed •"•" --q i - . • ' . i - u : ;rr . ni •u 10. - 1 ... .• j i .... .._ ;„_!_...: . ..._. Worker No. 2(A) alcj) = 5.15 D (CalcD =5.1 mg Figure 3b i c �.LIT 1(T !.:.*< "oh 1 i • I : , • ._: : M 0) • ; L , -:•:-. '....; ; '• \ i "• 0) 4J 0) '• ':.'. ! t-t U : i:] i ; ,.|J : ! - i ! i ; ' • ' 1 : * ! j • ' • ' • ' • * cd •d i 1 1 i ' : ; 9 : . . . j g 1.0 - ; :j i O .. . .:.. ! • :' : - 60 s a : : . i. ...; ._ - •[ : ;.. ;"! • 1 0.10 i 1 i ..i :..;. '- i " ; " • ; ; ; : 1.0.L .:-•-... bO e 0 0 o .... .: ; . ; ...• : ' ; r- • • C ' /. O i ; . i • • . ' - .. j .. . .: • 0.10. i - - _|.. . .. ; : : : i -:..-- • ': ;..[. !. ..i - .. . - j _ ". • : • i ! ' CM i ..'. ; ! _*.„ H : :i . • ; ' . 1 ' ; 4-1 ." o \ • - . . - ' . ; : - CN : - •o <u . ! : - . i-iiPTi j j : : ' H i i :-' i : '• ' ' : ' • —• : ; • ••.n\ - 1-L i- i i : ; - ; : • . ._; ;.. ,.|._ _.!_ Cl . : O Ga1 Lil|te d —L _ T-P1™: i J '= • J •: • ' ! • Ob serve d id ; \ : . ! . j : . . J .! . U..I..J. . • . 3^^^^ _:...: .L...L L! ll.^.._ .• .... :aicbijite'd: ;_[ ; ' I": : p i ' : 1 i 1 0 Day Day Worker No. 3(A) DQ (Calc) = 4.26 mg Calc) 4. Worker No. 4 (A) D (Calc) = 2.76 mg Figure 3c Figure 3d 1 ' : �: 'A * • .._ ' ; r ; ' TI^I cEitiii flf• 1 - { '• '. ! '• '• [J: ; 4"r-~- :~^5-- _l_ i 0: 13 (U ' 1 alculbted ' i | .: f | (1) ! v : "i • 0) ; •p (U n U : : ; - ' ! . •. 'O't :• . : ' : : a •- -r; • '.-pH-1- ' •• .i ; H • ___.^[_:^.l .' ; • i_j 6. 1 ; '• : (U _ ! "I 1.0- ' i i --— T— -|.-rr - ~p ' :. I. • ' .! ' \' : — --^ 1 tO ' ' . i. Observed Q) H . • i CM " • : = ; . -.« 0.10. r 0.10i* j f 0.01 c) | 1 1 2 Day Worker No. 5(A) DQ (Gale) = 1.56 mg Figure 3e t 3 • 1 4 0.01 •; Day Worker No. 5(B) D (Calcj = 0.95 mg Figure 3f �10 . : ; ; ; ; . 1 < i ; : • Observed ' i • ; •. ; : : : : -; . •:-M 1 : : : i i • ; U-^- ! • 0) 4J 01 M O ; - • i . : i ! ' ! - •* -• ! H • : i 1 : ' i i • t 1 , ' • . ! i : , . i '• i : :. : . L i . i ' ' - « -. • - . . ! ... i.. . 1 ' . • !• - 1 3 0) - 4-1 i V •••i ' ' "^ -t- -~ ~-i~t- _ - _ m " . - •f O -t: i ~n: - : . . . . .. ; t — .. i 1 i i i .I i; j-.i \ J_ i j s ; \.. .. • t- ' i • - : ~ j • \ : • ~ "1~ " r~ j : - i 1 -- 'I j .. T i '•I- • .- '•- ' | ...(..-j. - 60 _ .... i: -i 10 ,. i 1 i r 1". i 1 1 ! ...j_.i_ CM . . . . . . . ~ T" '. . f T.: J-l j: r : i j ; -'--- P. ;. ' -• .-! \ | 1 O .1. uLite d ! ! 01 .:-;-;:,• . -: . _.{..- i M S i ^HxC - - • : 1 •-•- i i 1 *L i ! !*> i : • ' • : : ; } ; .! ,; ; ' > - • U .- i \ : '• I i i j :' M 01 •. Xbse,r: .01 i •: ...j ' • 1 V . ' , w ... ! - 1.0 - • • ; : ; -p " "T * ; i ; : '. i i i i i 1 i 1 i ; 1' i :' ; -H .- - t \ : i : ! • '• oU al cu! 8 t3ed; i ; : t (5 <» o i:-o:-^\\[ • 1 i ! . .'— Q ^ .... i ; : I •; ; T i c ; c i i 0.10 1 | 2 I i 0.10 | () 1 Figure 3g 3 ])a> r Day Worker No. 6 (A) D 2.64 mg I | 2 Worker No. 8(A) D = 3.09 mg Figure 3h i /*. 5 �10 - 2 - ' • } j.u- ] ' « Observed: ; : j ; ; ; . O |. .- ._.:... ..j........ •-..,.. i . . .. ,. iCalculjated i [ . '. fl • ! : : • : '; 'O ' ", ; ."• • \ I ' : "!' ' ' i i : . ! • I • i " . ;" " • '. I ' • — . ' • j ! i ' [ I i '. • ;• i : "!'" j" j" "; ~"~ . ; ; • : ; : ' i ' to .. PL, :. . 1 ; : ' : . j .•.-.. T3 <U n o : . . , 8 : : i ' • »v 1-0 .... ' ... . .. . . . ._!.. ..-._ :. ... " i( . ; j - . • • : . . : , . i • ' . : j i ' : ; • :. : ! ) i . ; _ .. ..; ; . i . .. * • J • '."• !" ' ".' i . ! | ': • • : ' ^, . . ' ; ' - : • ] : : • j •~ : : ~: '~ 1 ~ " • •" : ' . : : '• i : '• : \ I ;• 1 -; •;• : .: - . :. .' . _ - 4 1 . . . . -.-: 1 • ' " i . ^> .:.., ,/.- 6 : L 0' : " | " "" •; " ~": """" ; , . . . . _ , ; . : '- . . " CN) .. 1 0 X *U - 1 '.-&.". •'"":. 60 6 - - ; • '- -:• * d '- £ " 6 (g- "!*>"•'.:" ; '.' : 1 I1 Cl 1 :"7 " " • : ... _. o * • ; ' : ~"-- ' ' - "i T~ [ ' • • ; . i • • ; : : • • : i ' ' ; • i_.i_ - -4-.- i- .;. :. .i 1 . ; ' M j • i '. iA^ ; . .-.:'.• 1 ' 1 i ' H ' i i : : ..:..:.:.. 0) • : i . . . ' . i : Q) -. -• !• • : ; ; • • • ; • ' —; • [--;- I — • ?—!-••• • i •;•-'•-: 4; •a 0) •u - -r - j - : -;— : • . ! • : ! :alculated M '. i I ! T;~: 7 • ( - - ; - ; - - : • - : - . - • - ; - - p, , : ..... . . . j.. .. f\ ' ^ • r ' '•. 1 i _». e . :••;•-.— ... ...i..-..;|.0. , E-i 1 csT j 1 j — ~ -;_ ; . . . . . . . ...._= • . ' - . . • ' - . -'-:-.-[ 0) .. •..! . 4J :. . . . O • : <u : v "=":T":1": "": V.. i ;..-• Obse'rvfed^ ; • -| -J--i-' ^ ...:-_-..•:..!_....'. :. !.._.L_L.:...L:..,..L_.... i 6 : i ' : i i ; 6 : i i n t in 0 I 1 ' : I i 2 3 1 4 , 0.10 5 0 1 1 2 Day Worker No. 9 A ( ) D ale) =3.& ( a c C l ) = 3 8 mg . 4 Figure 31 1 3 Day Worker No. 9 B ( ) DQ ( a c C l ) = 3 0 mg . 9 Figure 3j i 4 5 �10 t 1 i. : • : L..:.f> Obsieirye ^ : : : ] j ; , ' 1. ..__ . : . : i 1 i —; . i ~t :~i— ^p'QalbulE ted: . i .., ... I — . \ T---- .• ; U_j ! 1— ; ' •' . ... j .. ( —; — 1. * ' • .... f ,; . .. . . " iii - ii: '••'•• - 1 H ••• : i ! • 1° • : :- :.- - : • ! J ' r : i ! - _, 8 V 1 ; : ; ^^ : ; ' . ' ;.: m f : 4 i 1 - " 1. ; : ... -.. • ! ,! :! (! .i :' .._J._. ...;.,_., ..... ;_ ; ! . , _j.... _;. QJ (X 13 0) 4-1 0) l-i O ! ' ; ;. i ^ :' : ._J ;—L. ;_ -L. .— .'—. — _:...;___ j.. Q 8 Galciilc 'pgjj .. :._ .:... CD T3 <U 4J 0) M O — L<|b served -~ -—-! i ; :. . 1.0 • • : i : j t 0.10- . •. . :~ 00 o B ° ""' ;•....' ..... < • 1 0.10 0 1 1 1 2 3 4 1 1 0.01 5 i 0 2 Figure 3k 3 Day Day Worker No. 11(A) D (Calc) = 6.4? mg ale) 6.45 1 Worker No. 12 (B) D (Gale) = 1.06 mg le) 1.06 Figure 31 i �-17- TABLE: 2. Calculated Amount of 2,4,5-T Absorbed by Forest Workers During Application of ESTERON® 245 wortter No. a 1A IB 2A 2B 3A 3B 4A 4B 5A 5B 6A 7A 7B 8A 8B 9A 9B 10A 10B 11A 11B 12A 12B 13A 13B 14A 14B 15A 15B 16A 16B 17A 17B ISA 18B 19A 19B 20A 20B 21A 21B Method A 0.898 - 5.153 - 4.262 - 2.755 - 1.561 0.947 2.644 - 3.086 Method B 0.875 0.943 6.175 5.564 4.535 2.918 2.996 3.504 1.701 0.969 2.752 7.312 3.035 3.048 - - 3.844 3.085 3.845 2.926 3.832 4.702 6.818 - 6.450 - 1.063 nd - - 0.059 1.109 8.993 7.013 0.357 0.335 0.154 nd 0.241 0.102 2.603 3.118 6.197 12.032 0.568 0.153 0.275 0.112 0.113 0.152 Method Cb "y""~i.040 ± 0.408 (6) 1*221 ± 0.833 (5) 1 9.016 ± 9.539 (6) 5.804 ± 2 . 8 4 0 (5) 4.585 ± 2.030 (6) 3.173 ± 1.884 (5) 4.206 ± 3.720 (6) 4.003 ± 2.175 (5) 1.800 ± 1.005 (6) 0.941 ± 0.248 (5) 2.624 ± 0.719 (5) 6.842 ± 4.667 (6) 3.270 ± 1.260 (5) 3.077 ± 0.365 (5) 1.169 ± 0.373 (4) 3.877 ± 1.410 (5) 3.088 ± 0.527 (5) 4.369 ± 1.574 (5) .766 ± 3.513 (5) .373 ± 1.449 C5) .240 ± 1.732 (4) 0.190 '(1) 1.151 ± 0.290 (6) 1(T.130 ± 3.704 (5) L_ 8.882 ± 4.750 (6) 0.541 ± 0.439 (4) 0.455 ± 0.374 (6) 0.469 ± 0.673 (3) d nd 0.241 0.099 3.323 3.560 7.431 13.501 0.877 0.147 0.262 0.077 0.251 0.345 ± ± ± ± ± ± ± ± ± 0.233 0.032 1.653 1.572 2.905 6.143 0.934 0.054 0.102 (3) (3) (6) (5) (6) (5) (6) (3) (4) (1) ± 0.184 (4) ± 0.532 (4) A and B refer to the first and second exposure, respectively. The number of individual determinations of D by Method C is shown in parentheses. 3 �-18- Solution of equation (1) using the previously determined values of k01 and k ie at successive values of t reveals the cumulative fraction of the absorbed dose of 2,4,5-T that is excreted in the urine following exposure. The values of this fraction obtained from 1 through 7 days following exposure are given in Table 3. TABLE 3. Cumulative Fraction of the Absorbed Dose of 2,4,5-T Excreted in the Urine Days Following Exposure Cumulative Fraction of Dose ExcretedV: 1 0.1956 2 3 4 5 6 7 0.4819 0.6974 0.8326 0.9105 0.9532 0.9760 The absorbed dose D was calculated by dividing the cumulative quantity of 2,4,5-T excreted in the urine by the appropriate fraction at that time. This procedure provided a single estimate of the absorbed dose for 39 of the 41 exposures, shown in column B of Table 2. Method C By using the integrated form of the equation for the cumulative quantity of a chemical excreted as a function of time, an equation can be derived with which the absorbed dose can be �•f V- •*• -v -19- calculated based on the interval (in this case, daily1 amount of 2,4,5-T excreted using the previously esta- blished values for Ic and k ie (7) . This calculation is based on equation 2 where E. is the amount of 2,4,5-T excreted during the i-th day following exposure, d. is the length of the collection interval (1 day), and t. is the total number of days following exposure. D The calculation of by this method is independent of the total (cumulative) quantity of urine collected. C2) Application of equation 2 therefore provided an estimate of the absorbed dose every day on which urine was collected following each of the 41 exposures comprising the study. The results shown in column C of Table 2 are the average calculated dose (± standard deviation) for each exposure by this method. �-20- RESULTS Table 2 shows the calculated dose of 2,4,5-T following each exposure to the 21 workers in this study. A comparison of the data in Table 2 reveals similar results by all three methods used to calculate the dose. As expected, these calculated doses are almost always greater than the total mg of 2,4,5-T excreted in the urine at the end of 5 or 6 days following exposure (last column in Table 1). The maximum (i.e., worst case) estimated dose shown in Table 2 for each exposure was used to calculate the dose in mg 2,4,5-T per kg body weight for each worker. These dose levels are shown in Table 4, 5, 6 and 7 for the four types of spray application included in this study. It is apparent from inspection of these tables that the quantity of 2,4,5-T absorbed by the workers was usually less than 0.1 mg/kg. In fact, only two doses exceeded this level; a backpack sprayer (No. 2, second exposure) with a calculated dose of 0.132 mg/kg, and a mixer (No. 18, second exposure) with a calculated dose of 0.156 mg/kg. The lowest dose level of 0.001 mg/kg was received by flagmen for helicopter applications. Since there was an obvious correlation between the job descriptions of the workers and the calculated dose levels of 2,4,5-T, the results were grouped on the basis of job descriptions. The average dose levels thus obtained are �-21- TABLE 4. WORKER CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: BACKPACK SPRAYER APPLICATION BODY WEIGHT MAXIMUM CALCULATED DOSE OF 2,4,5-T (Kg) JOB DESCRIPTION EXPOSURE 1 (M) 72.6 Mixer/Supervisor First Second 0.014 0.017 2 (M) 68.1 Sprayer First Second 0.132 0.085 3 (F) 49.9 Sprayer First Second 0.092 0.064 4 (M) 95.3 Sprayer First Second 0.044 0.042 5 (F) 52.2 Sprayer First Second 0.034 0.019 6 (M) 65.8 Sprayer First 0.042 7 (M) 74.9 Sprayer First Second 0.098 0.044 (a ex ) �-22- TABLE 5. CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: TRACTOR MOUNTED MIST BLOWER APPLICATION WORKER (sex) BODY WEIGHT _ (kg) JOB DESCRIPTION EXPOSURE MAXIMUM CALCULATED DOSE OF 2,4,5-T Cmg/kg) 8 (M) 95.3 Supervisor First Second 0.032 0.012 9 (M) 84.0 Driver First 0.046 0.037 Second 10 (M) 106.7 Driver First Second 11 (M) 79 . 5 Mixer 0.041 0.054 First Second 0.086 0.053 �-23- TABLE 6. CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: HELICOPTER (MICROFOIL BOOM) APPLICATION MAXIMUM CALCULATED DOSE OF 2,4,5-' (mg/kg) WORKER (sex) BODY WEIGHT (kg) 12 (M) 95.3 Pilot First Second 0.002 0.012 13 (M) 109. Q Mixer First Second 0.092 0.081 14 (M) 84.0 Supervisor First Second 0.006 0.005 15 (M) 61.3 Flagman First Second 0.008 nd* 16 (M) 74.9 Flagman First Second 0.003 0.001 *Not detected. JOB DESCRIPTION EXPOSURE �-24- TABLE 7. (e. sx) CALCULATED DOSE OF 2,4,5-T TO FOREST WORKERS: HELICOPTER (RAINDROP NOZZLE) APPLICATION MAXIMUM BODY CALCULATED DOSE OF 2,4,5-' JOB WEIGHT EXPOSURE DESCRIPTION (ma/ka) (ka> 17 (M) 72.6 Pilot First Second 0.046 0.049 18 (M) 86.3 Mixer First Second 0.086 0.156 19 (M) 81.7 Supervisor First Second 0.011 0.002 20 (M) 86.3 Flagman First Second 0.003 0.001 21 (M) 95.3 Flagman First Second 0.001 0.002 �-25- TABLE 8. AVERAGE CALCULATED DOSES OF 2,4,5-T TO FOREST WORKERS JOB DESCRIPTION TOTAL NUMBER OF EXPOSURES Mixers AVERAGE CALCULATED DOSE OF 2,4,5-T(mg/kg) Dev. 8 0.07310.046 11 0.06310.034 Tractor Drivers 4 0.04510.007 Supervisors 6 0.01110.011 Helicopter Flagmen 8 0.00210.003 Backpack Sprayers Helicopter Pilot (No. 12) 2 0.007 Helicopter Pilot (No. 17) 2 0.048 �-26- shown in Table 8. The mixers, backpack sprayers, and tractor drivers had average dose levels of 0.073±0.046, 0.063±0.034, and 0.045±0.007 mg/kg respectively. The average dose level calculated for all the workers in these groups (n=23 exposures) was 0.063+0.036 mg/kg. The super- visors and helicopter flagmen showed average dose levels of O.OlliO.Oll and 0.002+0.003 mg/kg respectively. The two helicopter pilots had average dose levels during the two applications of 0.007 and 0.048 mg/kg. DISCUSSION The general validity of the linear pharmacokinetic model used to obtain the dose estimates reported here is attested by the reasonable fit of the observed and theoretical data points shown in Figures 3(a) through 3(£). three methods of calculating D While any of the should provide a valid estimate, Method C (the use of the interval amounts of 2,4,5-T excreted) is believed to yield the best overall value, since each daily urinary output of 2,4,5-T carries equal weight in calculation of the average dose absorbed for a given exposure. The generally excellent agreement between the three methods of calculating D support to the above conclusions. (Table 2) lends further �-27- The pattern of the daily amount of 2,4,5-T excreted in the urine following exposure is characterized by a maximum on day 2, followed by a steady log-linear decline thereafter (see the calculated data points in Figure 3) . However, an examination of the data in Table 1 shows that, in many j cases, there is a significant increase in the amount of 2,4,5-T excreted after the second day following exposure. These data are inconsistent with the excretion pattern expected from a single exposure (2) , and may indicate subsequent exposure to 2,4,5-T or to its ester after the actual application date. The speculation that such ex- posures might arise from the use of contaminated clothing or footgear should be verified by further experiments and observations. In each case, these increased amounts of urinary 2,4,5-T have the effect of increasing the calculated dose, and therefore result in maximized estimates of the dose absorbed on the application date. Since the data reported by Lavy (1) indicate clearly that the respiratory route of exposure to 2,4,5-T is virtually negligible, we have assumed that most of the absorbed dose of 2,4,5-T is the result of dermal exposure to ESTERON 245 herbicide formulations. However, the methods used here to calculate the absorbed dose are, in effect, independent of the actual route of administration and will reflect the total amount of 2,4,5-T absorbed by all possible routes. �-28- The pharmacokinetic model describing the absorption and excretion of 2,4,5-T in humans can also be used to predict the accumulated body burden of 2,4,5-T that would result from repeated daily exposures (6). The results of this mathematical simulation are shown by the solid line in Figure 4. These simulated data predict that the maximum accumulated body burden of 2,4,5-T resulting from repeated daily exposures would be 1.4x the daily dose D . In other words, if a worker absorbed a dose of 0.05 mg/kg each day, the maximum body burden attained would be 0.07 mg/kg and this maximum would be reached after approximately 7 daily exposures. However, if the 2,4,5-T remaining to be absorbed were removed 6 hr after each exposure (e.g., by washing or changing clothing), the predicted accumulated body burden would be represented by the dotted line in figure 4. In this case, the maximum body burden would be 0.3x the daily dose D , and this maximum would be reached after approximately 3 daily exposures. In summary, the amount of 2,4,5-T absorbed by forest workers during the application of ESTERON® 245 has been shown to be generally less than 0.1 mg 2,4,5-T per kg of body weight. Since this dose level is far below the no effect level of 20 �-29- mg/kg for fetotoxic or teratogenic effects cited by EPA (8), we conclude that under these conditions the absorption of 2,4,5-T presents a negligible toxic hazard to forest workers, WRITTEN BY: //i a./?? JoHn C . Rams ey , Ph . D Bio trans format ion Group Terry L. Lavy^ Ph.D. Altheimer Laboratory University of Arkansas Werner H. Braun Group Leader, Biotransformation REVIEWED BY: Group �2.8 2.6 2.4 2.2 2.0 - D 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 I oo o I 0.2 0 0 3 4 8 9 10 11 12 13 14 15 16 17 18 19 20 Days Simulated body burden of 2,475-T following 13 repeated daily exposures in units of the daily dose D . Solid Line=body burden if, 2,4,5rT continuously absorbed. Dotted Line=body burden if 2,4,5-T remaining to be absorbed is removed 6 hours after each exposure. Figure 4 �-31REFERENCES (1) T. L. Lavy. Measurement of 2,4,5-T Exposure of Forest Workers. Project Completion Report to National Forest Products Association. November, 1978. (2) P. J. Gehring, C. G. Kramer, B. A. Schwetz, J. Q. Rose, and V. K. Rowe. The Fate of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) Following Oral Administration to Man Tox. Appl. Pharmacol. 26, 352-361 (1973). (3) W. N. Piper, J. A. Rose, M. L. Leng, and P. J. Gehring. The Fate of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) Following Oral Administration to Rats and Dogs. Tox. Appl. Pharmacol. 26_, 339-351 (1973) . (4) M. W. Sauerholf, W. H. Braun, G. E. Blau, and P. J. Gehring. The Dose-Dependent Pharmacokinetic Profile of 2,4,5-Trichlorophenoxyacetic Adid Following Intravenous Administration in Rats. Tox. Appl. Pharmacol 3_6_, 491- 501 (1976). (5) J. D. Young, J. C. Ramsey, and W. H. Braun. Pharmaco- kinetics of 2,4,5-T PGBE Ester Applied Dermally to Rats. The Dow Chemical Company, Midland, Mich. Manuscript in Preparation - �-32- (6) Continuous System Modeling Program III. Reference Manual. IBM No. SH 19-7001-2. Program 1972. (7) J. C. Ramsey, G. E. Blau, and P. J. Gehring. Pharmacokinetic Modeling Based on Interval Excretion Data. The Dow Chemical Company, Midland, Mich. Manuscript in Preparation. (8) EPA. Rebuttable Presumption Against Registration and Continued Registration of Products Containing 2,4,5-T, Federal Register 43 (78), 17116-17157, April 21, 1978. � 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. 042 Folder The folder containing the original item. 0979 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Ramsey, J. C. T. L. Lavy W. H. Braun Date A point or period of time associated with an event in the lifecycle of the resource 1979-03-01 Title A name given to the resource Exposure of Forest Workers to 2,4,5-T: Calculated Dose Levels Subject The topic of the resource industrial exposure human testing 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. 043 Folder The folder containing the original item. 1038 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Sauerhoff, M. W. M. B. Chenoweth R. J. Karbowski W. H. Braun J. C. Ramsey P. J. Gehring G. E. Blau Source A related resource from which the described resource is derived Journal of Toxicology and Environmental Health Date A point or period of time associated with an event in the lifecycle of the resource 1977 Title A name given to the resource Fate of Silvex Following Oral Administration to Humans Subject The topic of the resource human testing ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/c0208aa220ef749ca2646df751f7681e.pdf c1fd91136b3c2e8c6913738e5cb32d39 PDF Text Text Item ID Number Author Brown, Marry D. Corporate Author Final Report/Article TltlB Report: Herbicide (2,4-D) Applicator Exposure Measurements Journal/Book Title 000 Year ° Month/Day Color n Number of Images 48 DBSCrlptOn Notes Supported by USDA Agreement No. USDA-TPSU-RU-0191 and New Jersey Agricultural Experiment Station Project No. NJ04502. Tuesday, May 15, 2001 Page 1466 of 1514 �FINAL REPORT HERBICIDE (2,4-D) APPLICATOR EXPOSURE MEASUREMENTS Harry D. Brown 106 Administration Bldg. New Jersey Agricultural Experiment Station Cook College, Rutgers University New Brunswick, N.J. 08903 Supported by USDA Agreement No. USDA-TPSU-RU-0-191 and New Jersey Agricul tural Experiment Station Project No. NJ04502. �INTRODUCTION The phenoxy herbicides have been used to control broad-leafed weeds in crops, water sources, forests, pastures, range lands, gardens, lawns, urban and industrial sites. Because of the efficiency, economy and safety, the phenoxy herbicides, especially 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D), besides other herbicides, remain essential for agricultural and other uses (Diaz-Colon and Bovey, 1976). Use of 2,4,5-T and 2,4-D on a large scale to defoliate vegetation has resulted in controversy about the fate of the chemicals. Many of the hazardous properties ascribed to 2,4,5-T are to a lesser extent shared by 2,4-D. As a result, a number of papers dealing with the fate in the environment, toxicological effects on living organisms (Diaz-Colon and Bovey, 1976; Sauerhoff et al., 1977; Piper et al. , 1973) have been published. Cooper (1974) compared 2,4,5,-T and 2,4-D. He has reported that commercial samples of 2,4-D in mice were teratogenic and embryotoxic. Increasing controversy about their safe use has raised doubt about their utility in achieving vegetation management objectives. A Dow Chemical report on Forestry Applicators exposure to 2,4-D has recently been published (Levy, 1980). Nonetheless, in total, only meager information regarding human (e.g. gardeners, small farmers, etc.) exposure to 2,4-D is available. This study reports an investigation conducted under conditions characteristic of actual use pattern to determine the quantity of body surface contact of applicator with the commercial 2,4-D formulation and the quantity of the chemical measurable in serum and urine. MATERIALS AND METHODS Applicator Eleven healthy young male (ages 19 to 31 years) human volunteers were selected and were examined by the University physician prior to the work. Each subject was examined for blood pressure, pulse rate and body temperature on the day of work, both before and after the work period, and similar examinations were made every morning for the next three days (Table 1). Sterile gauze pads (size 0.67 sq. ft.) were attached on the back and chest of each volunteer. A paper cap (area 0.44 sq. ft.) was used to cover the head. Location The study was carried out either on the campus of Rutgers University or near the campus in New Brunswick, New Jersey during the period from May, 1981 to August, 1981. The location was covered with weeds and grass. Each area was roughly between one-half to one acre. Spray Material and Equipment The spraying material consisted of DMA-4 concentrate (obtained as a gift from Dow Chemical, U.S.A.) which contained 3.8 Ib acid equivalent/gal 2,4-D. The herbicide was mixed with tap water prior to use and the resulting mixture was applied at a rate of approximately 1 gal/30 min. by a hand sprayer held at hip level. A DuPont air sampler was attached to the applicator and was kept running during the spraying operation. The areas were covered by spraying six gallons in about three hours as per label instruction. �Weather Conditions Weather conditions during this study were moderate, temperature ranging between 65° to 78° F with humidity from 50 to 89%. Wind was fairly calm throughout this study except on one occasion, when it gusted to 10 miles per hour. Sample Collection for Analysis • To ascertain body surface exposure, gauze pads and caps were collected immediately after the work and washed in methanol. Air filter absorbents were also washed in methanol. Residue separated by methanol was evaporated to dryness and then treated with 15% BF, in methanol. Finally, it was extracted with n-hexane (Yip, 1975). Blood samples were drawn before the work and at the end of the day's work. Three more blood samples were drawn on the following three mornings. Overnight pooled urine samples were collected before the work and the day's collections were made during and/or after the treatment. Then the pooled urine samples were collected twice a day for the next 4 to 7 days. Blood sera and urine samples were treated, extracted and analyzed by the method of Sauerhoff et al.5^ (1977). Vegetation samples and soil samples from the treated area were collected before the treatment and then once every 24 hours for the next 4 days after the treatment. Samples were treated and analyzed by the methods of Davidonis et al. (1980) and Olson et al. (1978). Analytical Procedures 2,4-D residue extracted in n-hexane was analyzed on a pas chromatograph (Tracer Model No. 560, equipped with electron capture detector and a six foot glass column packed with 3% OV-101 on 80/100 supelcoport). Clinical determinations on blood serum and urine were made through the automated procedures of a commercial diagnostic laboratory. RESULTS AND DISCUSSION The various data are summarized in tables 1-13 and figures 1-22. At the end of a day's work, an applicator had an average 2,4-D residue of 49.39 yg/sq. ft. on the back, 52.41 yg on the head. The average value of 2,4-D residue on vegetation in the exposed areas was 27.93 yg/g of tissue at the end of the working day (i.e. first day). The residue fell to 8.57 yg/g tissue after four days. On the other hand, the average soil residue value was 2.68 yg/g soil at the end of the first working day, which Increased to 5v12*yg/soil (87.6%) on the fourth day. The average base level for phenolic compounds in serum was 70.7 ng/ml at zero level exposure. Immediately after the day's work, the value went up to 165.3 ng/ml and again went up to 267.7 ng/ml on the second. The difference between the base level and the measured level we take to be a specific measurement of the test material, 2,4-D. The value came down to 123.7 ng/ml on the third day. The average amount of phenolics ranged from 3.45 yg (zero level exposure) to 7.85 yg (fifth day) for the 12 hours of pooled urine. *Appendix A is a more extensive discussion of methodology. �Some changes were noticed in clinical analysis made on blood aerum and urine. Analysis of 2,4-D retained by the air monitor filter revealed detectable residue. The amount of air drawn through the filter was calculated to be 56.6 to 84.96 liters, and the calculated 2,4~D residue was 43.1 to 60.1 parts per trillion. Results of this study indicate that there was a considerable amount of 2,4-D in the air, on vegetation and soil surface of the treated areas. An appreciable quantity of 2,4-D also landed on the body surface, All serum and urine samples showed measurable 2,4-D residue. Statistical Analysis * The clinical residue and weather data were critically scrutinized by both linear models and regression models. The primary emphasis of the analysis was to identify the parameters that recorded any significant change. This was accomplished by subtracting the baseling value from the observed value and then dividing it by the baseline. Analysis of the resulting values revealed highly significant (a=0.01) changes in the serum creatinine and total protein levels, and significant ( H . 5 change in the urine specific gravity. It was also seen o)0) that the total protein and BUN/creatinine were positively correlated with the residue on the chest of the volunteers and with their height. When the peak residue in the body fluids was related with the external factors, it was seen that the serum residue was positively correlated with the 2,4-D concentration in the air and the amount of chemical that had landed on the head and back. Likewise, the urine residue was positively correlated with the air volume and the height of the volunteers. Precipitation (rainfall-high humidity) was negatively correlated with the serum residue, presumably due to decreased chances of vaporization and subsequent inhalation. *Analysis done by Dr. Robert Trout, Statistician for the NJAES. CONCLUSION Our observations, therefore, indicate that during normal working conditions, an appreciable amount of 2,4-D can enter into the applicator's body through inhalation and/or through body surface (dermal) absorption. Lengthy retention times have been observed in some subjects (Table 6). These findings are consonant with the report of Levy et al. (1980) for foresters. Clinical physiology data obtained here are consistent with long retention times for this chemical. We surmise, but have no specific evidence, that the 2,4-D molecule or some portion (phenolic), binds to serum protein and is eliminated as a function of the turnover of the protein molecules. Other than the clinical (chemical) changes noted above, we have seen no pronounced adverse effect of 2,4-D exposure. REFERENCES 1. Sauerhoff, M.W., Braun, W.H., Blau, G.E. and Gehring, P.J. (1977). The Fate of 2,4-Dichlorophenoxyacetic Acid (2,4-D) Following Oral Administration to Man. Toxicology 8:3-11. 2. Piper, W.N., Rose, J.Q., Lang, M.L. and Gehring, P.J. (1973). The Fate of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) Following Oral Administration to Rats and Dogs. Toxicol. Appl. Pharmacol. 26:339-351. �3. Levy, T.L. (1980). Determination of 2,4-D Exposure Received by Forestry Applicators. Dow Chemical, U.S.A. Report. October, 1980. 4. Diaz-Colon, J.D. and Bovey, R.W. (1976). Selected bibliography of the phenoxy herbicides. I. Fate in the Environment. MP 1303. Texas Agric. Exp. Stn., College Station. 5. Cooper, P. (1974). Food Cosmet. Toxicol. 12:418-421. 6. Davidonis, G.H., Hamilton, R.H. and Mumma, R.O. ( 9 0 . Comparative Meta18) bolism of 2,4-Dichlorophenoxyacetic Acid in Cotyledon and Leaf Callus from Two Varieties of Soybean. Plant Physiol. 65:94-97. 7. Olson, B.A., Sneath, T.C. and Jain, N.C. ( 9 8 . Rapid Simple Procedure 17) for the Simultaneous Gas Chromatographic Analysis of Four Chlorophenoxy Herbicides in Water and Soil Samples. J. Agric. Fd. Chem. 26:640. 8. Yip, G. (1975). Analysis for Herbicides and Metabolites. J. Chromatographic Sciences 13:225-230. �CLINICAL XXX DATA �Table 1 PHYSICAL EXAMINATION Temp ( F °) Blood Pressure Pulse Rate Applicators 0 X 1 2 3 0 X 1 2 3 0 X 1 2 3 No. 1 98.0 98.4 97.8 98.4 98.4 128/74 114/70 120/78 120/60 120/78 76 60 80 78 72 No. 2 97.6 98.0 98.0 98.0 97.8 110/78 118/78 110/78 110/72 120/80 60 72 80 68 64 No. 3 97.4 97.6 97.8 97.0 97.8 112/82 120/70 110/74 118/6?. 120/76 60 72 60 61 64 No. 4 98.2 99.4 97.4 98.0 98.0 90/60 100/68 100/64 96/68 92/60 80 100 76 76 84 No. 5 97.6 98.8 98.0 98.2 98.2 112/74 124/80 120/82 120/80 110/80 72 84 84 80 84 No. 6 97.0 98.6 97.2 97.0 97.4 120/80 110/74 108/78 112/78 112/74 84 88 96 92 100 No. 7 97.4 98.4 97.0 97.0 98.2 104/64 100/60 110/64 120/64 110/70 78 78 80 78 80 No. 8 98.4 98.4 98.6 97.8 98.0 140/76 120/80 112/70 130/68 130/76 80 64 96 80 68 No. 9 98.6 98.4 97.0 98.0 97.2 110/70 110/70 110/80 120/80 120/74 60 60 68 80 64 No. 10 97.8 98.0 97.4 98.2 97.8 104/60 100/70 108/60 112/70 102/60 84 68 84 88 88 No. 11 97.4 9 . 97.2 97.2 97.0 86 120/68 110/70 110/80 112/70 110/76 80 80 80 68 80 Legend 0 = Pretreatment X = Posttreatment 1-3 = Days after treatment �Table 2 Detection of 2,4-D Residue from Gauge Patch (= Body Surface) yg/sq. ft. 1 Applicator No. Head Chest Back 1 8.55 7.81 5.10 2 14.06 11.68 10.60 3 7.06 3.37 3.77 4 222.20 171.50 99.63 5 34.22 94.53 41.16 6 141.80 111.50 74.23 7 76.16 68.39 46.64 8 16.99 13.56 11.86 9 19.12 14.58 10.29 10 18.55 31.46 4.46 11 17.80 14.95 18.63 �Table 3 2,*i-D Residue on Vegetation Treated Area 2,4-D yg/g Vegetation 0 X X+1 X+2 X+3 1 0.59 28.85 16.15 16.67 20.16 2 14.74 29.60 22. A3 4.32 2.13 3 00.00 25.35 7.70 1.92 3.44 2.47 X+4 Amount of 2,^-D on Soil Surface Treated Area 2,4-D -fjg/g Soil X+1 X+2 X+3 «* 3.70 1.90 2.80 7.30 - 3.58 4.21 0.72 1.59 7.25 - 0.00 0.13 0.15 0.27 0.80 0.93 0 1 1.24 2 3 X X X X X 0 X 1 2 3 1» = = = = = *s Pretreatment Posttreatment 1 day after treatment 2 days after treatment 3 days after treatment ^ days after treatment �Table 4 Amount of 2,4-D Residue and Endogenous Phenolic Compounds in Serum Applicator No. 1 2 3 k 5 6 7 8 9 10 11 0 2,4-D Residue (ng/ml ) X+1 X 75.1 826.6 114.4 170.1 131.5 112.8 112.3 54.0 93.5 157.8 56.3 221.9 208.3 123.5 44.5 3.5 29.0 19.0 224.4 00.0 00.0 443.2 538.3 19.1 50.2 7.8 496.9 862.9 119.3 55.7 41.8 93.3 55.6 X+2 311.0 250.1 74.6 92.4 169.9 94.3 194.7 43.6 43.0 58.8 27.9 X+3 . 112.3 102.3 479.6 84.2 245.1 674.6 178.6 83.4 25.7 36.3 114.8 • 0 = Pretreatment X - Posttreatment X+1 «= 1 day after treatment X+2 = 2 days after treatment X+3 = 3 days after treatment Note: Because phenoxy and other phenolic compounds have liquid chromatographic migrations similar to that of 2,4-D, there is a variation in the base for specific measurement of the test compound. �\0 Table 5 Amount of 2,4-D in Serum Applicator No. X i X+l 2,4-D (ng/rol) X+2 714.3 198.7 0 196.1 48.3 2 60.4 116.1 3 128.4 38.0 4 285.4 5 X+3 482.0 — 440.6 654.6 6 — — 113.6 386.1 — 188.8 466.3 7 179.9 74.8 — 150.2 8 15.6 52.2 40.1 9 21.2 12.8 14.0 10 74.3 39.8 — 17.3 11 55.6 27.9 114.8 Legend X = X+l X+2 X+3 Posttreatment = 1 day after treatment = 2 days after treatment = 3 days after treatment 134.1 79.9 �Table 6 Total Amount of 2,4-D and Endogenous ^henolic Comnounds Excreted in the Urine yg 2,4-D Excreted per 12 hours Applicator No. 0 1 12 2k 36 48 60 1 3.73 7.12 2.38 2.58 6.49 5.70 2.93 21.20 28.96 - - - - 2 3.22 7.17 1.22 2.85 6.00 5.75 4.46 6.44 - - - 3 2.85 4.25 10.00 8.87 1.75 0.60 1.33 10.79 1.09 4.07 - - - - 4 8.11 15.44 21.38 7.66 9.56 5 0.32 1.31 1.79 1.60 1.31 6 9.95 7 9.91 8 0.00 0.11 9 10 72 84 96 108 120 132 144 156 - - - - - - 30.55 24.87 13.09 6.23 - - - - 2.62 3.32 2.27 7.39 - - - - - I*. 56 15.62 5.04 23.39 13.87 6.28 8.46 13.16 10.81 15.25 2.73 3.12 2.89 0.91 5.00 8.84 - - - - - 0.57 2.77 1.34 3.46 2.84 3.08 5.30 1.97 1.49 2.68 0.00 0.00 0.00 0.00 0.75 0,00 0.85 2.46 8.28 6.57 1.46 4.09 1.42 2.10 3.73 2.21 4,31 4.47 0.00 1.9* 1.73 1.63 2.83 2.21 2.73 8.48 4.35 - 0 • Pretreatment 1 • Posttreatment - - - - - - - - - �Table 7 HEMATOLOGY WBC x 103 liters 0 X 1 RBC x 106 RGB (g/dl) 2 3 0 X 1 2 3 HCT (%) 0 X 1 2 3 0 X I 2 3 3. 1 6.0 7.1 6.3 7.0 5.5 4.78 j, 4.68 j, 4761 j, 4*50 j. 4.43 15.5 15.1 14.8 14.6 14.6 44.4 43.7 44.8 441.6 441.5 3. 2 5.7 6.8 5.9 5.2 5.2 4.99 5.06 5.15 4.85 4.89 15.9 15.6 16.2 15.0 15.3 43.2 43.8 44.7 42.0 42.4 3. 3 6.7 6.1 5.2 5.6 5.0 4*69 4*64 4*63 4.71 4*65 14.9 14.8 14.5 14.6 14.9 41*2 41*2 41*2 40*9 40*6 ! 3. 4 6.5 7.6 6.6 6.7 6.5 5.72 5.76 5.75 5.85 5.50 15.5 15.6 15.3 16.8 14.8 43.9 44.0 43.5 44.6 41*8 ! 3. 5 6.3 6.5 5.9 7.0 6.2 5.34 5.22 5.23 5.56 5.27 15.9 15.7 15.7 16.8 15.6 44.6 44.1 44.7 46.5 43.6 D. 6 6.7 7.8 6.7 8.4 6.9 5.39 5.23 5.46 5.43 5.03 16.8 16.9 17.1 17.8 16.2 47.6 46.3 48.5 47.8 44.9 3. 7 6.6 8.1 9.8 8.2 7.9 5.45 5.20 5.42 5.33 5.29 16.5 15.9 16.3 17.0 16.3 48.0 47.3 46.9 46.0 o. 8 8.3 8.3 6.2 6.3 6.1 4.97 4.75 4.99 4.99 5.04 8.1 7.8 5.21 4.76 5.07 5.42 5.14 15.8 413.2 44.1 6.0 15.7 413.9 42.6 6.2 15.7 413.2 42.8 6.1 15.2 412.4 42.9 o. 9 15.8 413.3 44.9 441.0 37*4 40*3 38.1 o. 10 7.8 7.5 8.1 7.6 7.7 4.97 5.06 5.33 5.14 16.4 17.1 16.3 4.8 6.0 6.0 5.9 4.99 4.81 4.95 5.11 14.8 14.4 14.9 14.9 45.0 43.0 45.0 4 - 4 - 4 41.2 37.8 39.3 47.1 4 40.7 45.9 5.0 15.8 •l 13*5 16.5 0. 4.80 44.54 11 Legend 0 = Pretreatment X = Posttreatment 1-3 = Days after treatment J. 3877 J. 35*3 X 4, 4- 42.0 J �Table 7 (cont.) HEMATOLOGY MCV ( 3 y) MCH (yyg) MCHC (%) Platelet Estimate Applicators 0 X 1 2 3 No. 1 93 93 97 92 94 32J4 32^0 No. 2 87 87 87 87 87 3lt7 30.8 3lts No. 3 88 89 89 87 87 31J8 3ll8 3ll3 No. 4 7*4 7*4 7*3 7*4 7*6 27.0 26t9 26*6 No. 5 81 81 82 81 83 29.6 No. 6 85 85 86 85 89 3l7l 32.2 31.1 32.6 No. 7 85 83 84 85 87 30.2 30.4 40.0 3lt? No. 8 87 87 87 86 87 30.9 No. 9 7*5 7*5 7*5 7*5 7*5 24*8 No. 10 91 90 90 89 90 No. 11 83 84 83 83 83 A 0 A X = Posttreatment 1-3 » Days after treatment A. 2 3 A. 0 X 1 2 3 0 X 1 2 3 A. 34.7 34.3 32.9 34.9 35.1 N N N N N 31.0 31^2 36.6 35.5 36?1 N N N N N 30.8 32lO 36.0 35.9 35.1 35.4 36;6 N N N N N 28.5 27.6 35.2 35.2 34.9 37t4 35.8 N N N N N 30.0 29.7 30.1 30.3 35.4 35.5 35.0 35.8 36.2 N N N N N 35.2 36J 3 Dec N N N N 31^4 34.2 35.2 34.3 35.9 35.7 N N N N 3ltl 30.4 30.6 30.1 36.3 36t4 Dec N N N N 25*3 25t2 33.9 34.6 34.6 33.9 34.0 N N N N N 3itg sitg site 3it2 so. 8 35.7 36.1 35.8 35.6 34.9 N N N N N 28.8 35.2 35.1 36.0 3etl 35.0 N N N N N A 0 = Pretreatment A, 1 32J9 A Legend X A 32?0 32J3 A A 35.6 36.0 A A 24*9 A A A 33.0 24*9 28.9 29.1 29.2 28.3 •f A 34.9 36l9 A 36^4 35.9 3ets 35.2 N �Table 8 BLOOD CHEMISTRY Glucose (mg/dl) BUN (mg/dl) Creatinine (mg/dl) Uric Acid (mg/dl) Applicators 0 X 1 2 3 0 X 1 2 3 No. 1 93 88 79 81 76 12 12 13 11 No. 2 78 83 63* 80 75 18 17 17 19 No. 3 93 94 92 95 87 21 21 22 No. 4 87 112+ 86 92 86 12 14 No. 5 197+ 149+ 166+ 163+ 149+ 13 No. 6 111+ No. 7 81 0 X 1 2 3 0 X 1 2 3 11 0.9 1.0 0.9 0.8 0.8 6.4 6.5 6.1 4.9 5.2 16 1.2 1.3 1.2 1.2 1.0 6.1 6.3 6.6 6.3 5.5 27+ 26+ 1.0 1.0 1.0 1.1 0.9 3.8 4.5 3.9 4.8 4.1 12 13 15 1.1 1.2 1.2 1.1 1.1 7.6 7.9 7.5 8.4+ 8.1+ 14 12 13 15 1.0 1.0 1.0 0.9 0.9 6.6 7.7 6.6 7.0 6.9 95 91 92 18 19 18 16 18 1.2 1.3 1.2 1.1 1.2 6.3 6.6 6.4 5.8 6.8 137+ 76 88 91 14 15 16 18 15 1.2 1.5+ 1.2 1.1 1.2 7.0 7.1 7.1 7.2 7.3 107 15 15 17 13 13 1.1 1.0 1.0 1.0 0.9 5.6 5.3 5.1 5.4 4.4 81 No. 8 122+ 102 127+ 81 No. 9 118+ 90 107 79 122+ 17 16 15 17 17 1.1 1.0 1.2 1.0 0.8 5.7 5.8 5.4 6.0 4.9 No. 10 101 84 134+ 99 140+ 15 15 16 15 14 1.0 1.1 1.2 1.1 1.0 6.3 7.0 7.3 6.9 5.9 No. 11 148+ 124+ 112+ 98 111+ 20 19 17 14 12 1.5+ 1.0 1.0 1.0 0.9 7.3 5.1 4.8 5.0 4.7 Legend 0 = Pretreatment X = Posttreatment 1-3 = Days after treatment �Table 8 (cont.) BLOOD CHEMISTRY A/G Ratio Globulin (g/dl) Calcium4"1" (mg/dl) Bun/Great Applicators 1 0 1 0 0 No. 1 2.7 2.6 2.6 2.3 2.3 1.7 1.8 1.8 1.5 2.0 13.3 12.0 14.6 14.5 14.2 4.3 4.3 4.3 4.5 4.2 No. 2 2.5 2.5 2.4 2.5 2.2 1.9 1.9 1.9 1.8 2.1 15.0 13.1 14.2 15.6 16.2 4.3 4.2 4.1 4.1 4.2 No. 3 2.4 2.4 2.3 2.4 2.2 2.1 2.0 2.2 2.0 2.2 21.0 21.0 22.0 24.5 28.5 4.4 4.5 4.5 4.3 4.5 No. 4 2.5 2.5 2.6 2.3 2.2 1.6 1.7 1.6 1.8 1.9 10.5 11.2 9.7 12.0 14.3 4.4 4.4 4.3 4.4 4.3 No. 5 3.2 3.5 3.4 3.2 2.8 1.4 1.3 1.3 1.4 1.7 12.4 13.5 12.8 13.6 16.2 3.8 3.8 3.9 4.0 4.0 No. 6 3.0 2.8 2.9 2.6 2.2 1.6 1.7 1.6 1.8 2.1 14.7 14.1 14.2 14.2 14.5 4.2 4.5 4.3 4.4 4.4 No. 7 3.1 3.1 2.9 2.7 2.5 1.6 1.4 1.5 1.6 1.8 11.7 10.1 13.6 15.7 12.7 4.2 4.2 4.3 4.4 4.3 No. 8 2.5 2.6 2.4 2.4 2.6 1.9 1.4 1.9 2.0 1.7 14.7 15.2 16.9 13.9 15.4 4.3 4.3 4.2 4.4 4.3 No. 9 2.8 2.7 2.5 2.7 2.5 1.6 1.7 1.8 1.7 1.7 15.9 15.6 12.6 17.1 "20.4 4.2 4.1 4.3 4.3 4.2 No. 10 2.8 2.7 2.8 2.5 2.6 1.6 1.8 1.8 2.0 1.8 16.0 13.3 13.4 13.3 14.1 4.2 4.2 4.2 4.4 4.2 No. 11 2.5 2.7 2.8 2.7 3.0 1.9 1.7 1.6 1.7 1.5 13.3 18.3 17.3 14.2 13.7 4.3 4.2 4.3 4.3 Legend 0 = Pretreatment X = Posttreatment 1-3 = Days after treatment 4.1 �Table 8 (cont.) BLOOD CHEMISTRY Applicators LDH (IU/1) SCOT (IU/1) ' Alk. Phos. ( U 1 I/) GGT (IU/1) T. Bill, (mg/dl) 0 X 1 2 3 0 X 1 2 3 21 160 175 201 140 164 23 23 22 20 22 23 209 224 2$7 2$1 235 16 16 15 25 24 26 151 161 157 177 172 10 10 11 16 16 15 136 152 157 144 164 24 20 23 20 29 28 154 167 153 150 148 70 26 23 23 36 23 166 153 176 146 114 117 28 33 23 26 24 160 148 152 4*4 46 45 31 32 31 20 20 152 154 6*4 80 67 68 32 40 34 33 40 183 96 111 103 99 41 32 34 23 26 58 58 31 32 32 22 24 0 X 1 2 3 0 X 1 2 3 No. 1 42 40 43 45 39 22 22 20 22 No. 2 79 79 80 82 79 25 26 24 No. 3 69 61 71 79 79 22 24 No. 4 64 62 63 63 63 11 No. 5 90 81 88 87 87 No. 6 75 68 76 75 No. 7 116 111 115 No. 8 4*6 5*1 No. 9 5*2 No. 10 6*9 No. 11 116 5*8 6*1 Legend 0 = Pretreatment X = Posttreatment 1-3 = Days after treatment ! 0 X 1 2 3 20 0.6 0.7 0.4 0.3 0.8 15 15 0.7 0.7 . . 0.7 08 0.6 11 12 12 0.4 0.6 0.5 0.7 0.4 24 24 23 21 0.5 0.5 0.7 0.6 0.4 36 36 36 39 38 0.2 0.2 0.5 0.5 0.5 145 16 15 16 14 14 0.9 0.8 1.0 its itl 136 129 15 17 14 14 14 0.6 0.9 0.3 0.2 0.2 157 151 154 13 14 13 17 15 0.9 0.7 0.9 0.8 0.5 201 191 2$8 197 10 14 21 18 17 itl 0.8 0.9 0.7 0.9 195 179 187 169 165 16 10 11 14 12 itl 0.8 0.9 0.9 0.8 213 189 202 191 159 10 10 10 13 13 0.5 0.6 0.6 itl 1?3 �Table 8 (cont.) BLOOD CHEMISTRY Cholesterol (mg/dl) T. Protein (g/dl) Calcium (mg/dl) Albumin (g/dl) Applicators 0 X 1 2 3 0 X 1 2 3 0 X No. 1 179 173 177 1(1)8 169 9.9 9.8 9.7 9.1 9.4 7.3 7.2 No. 2 223 221 215 219 175 9.8 9.6 9.3 9.5 9.3 7.2 7.2 7.0 7.2 6.7 4.7 No. 3 its its 151 lt7 10.2 10.4 10.3 10.0 10.2 7.4 7.3 7.3 5.0 4.9 5.0 4.9 4.9 No:. 4 170 180 170 172 172 .9.6 9.7 9.4 9.7 9.2 6.7 6.8 6.7 6.6 6.4 4.1 No. 5 202 222 218 218 208 9.0 9.4 9.5 9.5 9.4 7.7 8^2 7.9 4.4 4.7 No. 6 210 208 209 208 192 10.0 9.7 7.7 7.6 7.5 7.3 6.9 4.7 4.8 4.6 4.7 4.7 No. 7 154 152 its it? 150 10.3 9.9 9.8 9.6 stl 7.4 7.2 7.0 6.8 5to 4.4 4.3 4.3 4.4 No. 8 165 169 170 180 172 9.7 9.9 9.7 10.1 9.7 7.1 7.3 7.2 7.1 4.6 No. 9 153 160 163 163 itg 9.7 9.5 9.6 10.0 9.4 7.3 7.3 7.0 7.5 6.4 4.5 4.6 4.4 4.8 4.4 No. 10 158 168 170 168 155 9.6 10.0 10.0 10.5 9.7 7.3 7.6 7.6 7.5 7.3 4.5 No. 11 161 lt9 160 160 157 9.9 9.9 7.3 7.1 7.3 7.3 7.4 4.8 4.5 4.5 4.6 4.4 its Legend 0 = Pretreatment X = Posttreatment 1-3 = Days after treatment 10.6 10.2 10.1 9.6 9.5 9.9 9.9 1 2 7.1 ste 7.1 3 6.7 7.4 7.1 7.8 7.6 0 X 1 2 4.6 4.6 4.6 3t3 3 4.5 4.7 4.6 4.7 4.6 4.3 4.1 4.3 4.2 4.5 4.6 4.7 4.8 4.7 4.8 4.5 4.9 4.9 4.9 4.7 �Table 9 ACID PHOSPHATASE AND HAPTOGLOBIN HAPTOGLOBIN (mg/dl) ACID PHOSPHATASE (IU/1) Applicators 0 X 1 2 3 1 2 3 4 5 No. 1 0.2 0.3 0.0 0.0 0.0 22 17 20 21 25 No. 2 0.3 0.3 0.4 0.0 0.0 24 26 24 25 18 No. 3 0.2 0.1 0.1 0.0 0.0 71 89 87 82 85 No. 4 0.0 0.0 0.0 0.0 0.04 92 113 111 76 108 No. 5 0.0 0.0 0.0 0.0 Missing 109 105 108 99 122 No. 6 0.0 0.0 0.0 0.02 0.12 189 197 204 174 238 No. 7 0.0 0.0 0.0 0.0 0.16 87 95 85 118 134 No. 8 0.2 0.0 0.0 Missing Missing 79 157 81 91 72 No. 9 0.0 0.0 0.0 Missing 0.2 90 90 91 165 80 No. 10 0.0 0.0 0.0 Missing 0.1 95 154 173 86 161 No. 11 0.0 0.0 0.0 Missing 0.6 159 114 118 118 128 Legend 0 «= Pretreatment X = Posttreatment 1-3 «= Days after treatment �\<\ URINALYSIS Table 10 pH Applicators 0 X la Ib 2a 2b 3a 3b No. 1 5.0 6.0 5.0 8.0 6.0 8.0 5.0 5.0 6.0 No. 2 6.0 6.0 5.0 6.0 6.0 6.0 6.0 6.0 5.0 No. 3 5.0 8.0 6.0 6.0 8.0 5.0 7.0 5.0 6.0 No. 4 5.0 5.0 5.0 5.0 6.0 5.0 7.0 5.0 6.0 No. 5 7.0 6.0 6.0 6.0 7.0 6.0 6.0 6.0 5.0 No. 6 5.0 6.0 6.0 6.0 6.0 8.0 6.0 6.0 6.0 No. 7 7.0 6.0 6.0 5.0 7.0 5.0 5.0 6.0 7.0 No. 8 6.0 6.0 6.0 5.0 5.0 6.0 6.0 7.0 5.0 7.0 5.0 8.0 No. 9 6.0 6.0 6.0 5.0 5.0 5.0 6.0 6.0 6.0 6.0 6.0 6.0 No. 10 6.0 6.0 6.0 5.0 6.0 5.0 5.0 5.0 6.0 No. 11 6.0 6.0 6.0 6.0 5.0 6.0 6.0 6.0 5.0 Legend 0 = Pretreatment X « Posttreatment 1-7 = Days after treatment a « 7:00 a.m. collection b « 7:00 p.m. collection 4a 4b 5a 5b 6a 6b 7a 5.0 6.0 6.0 6.0 5.0 6.0 — �Table 11 \ppll:ators So. 1 Sto. 2 So. 3 No. 4 No. 5 No. 6 No. 7 No. 8 No. 9 No. 10 No. 11 0 Amber Clear Amber Clear Amber Clear Straw Cloudy Straw Clear Straw Cloudy Straw Clear Yellow SI. cloudy Yellow Clear Yellow Clear Yellow Cloudy URINALYSIS COLOR X la Ib Yellow Clear Amber Turbid Yellow Turbid Straw Clear Straw Cloudy Straw Cloudy Straw Clear Yellow Clear Amber Clear Yellow Clear Yellow Clear Yellow Cloudy Amber Turbid Amber Clear Straw Clear Amber Clear Yellow Clear Yellow Cloudy Yellow Clear Straw Cloudy Straw Cloudy Straw Cloudy Straw Clear Straw Hazy Straw Hazy Straw Clear Straw Clear Straw Clear Yellow Hazy Yellow Clear Yellow Clear Yellow Cloudy Yellow Clear Legend 0 = Pretreatment X = Posttreatment 2a 2b Yellow Yellow Clear Clear Yellow Yellow Cloudy Cloudy Yellow Yellow Clear Clear Straw Yellow Clear Cloudy Yellow Yellow Cloudy Hazy Straw Yellow Cloudy Hazy Straw Yellow Clear Clear Straw Yellow Cloudy Hazy Straw Yellow Cloudy Hazy Straw Straw Clear Clear Straw Yellow Clear Clear 1-7 = Days after treatment a = 7:00 a.m. collection 3a 3b Yellow Clear Yellow Clear Yellow Clear Yellow Clear Yellow Clear Yellow Cloudy Yellow Clear Yellow Clear Yellow Clear Yellow Clear Yellow Clear Yellow Clear Yellow Turbid Yellow Clear Yellow Cloudy Yellow Cloudy Yellow Cloudy Yellow Cloudy Yellow Clear Yellow Cloudy Yellow Clear Yellow Clear 4a 4b 5a 5b 6a . 6b 7a Yellow i Clear Yellow ;— Turbid Yellow —_ Turbid Yellow —;_• Cloudy Yellow Cl Dudy Yellow Cloudy Yellow Cloudy Yellow Yellow Yellow Yellow Yellow Yellow Yello Clear Hazy Cloudy Hazy Clear Clear Hazy Yellow Yellow Yellow Yellow Yellow Yellow Yello Clear Clear Clear Clear Clear Clear Hazy Yellow Clear Yellow Turbid 7:00 p.m. collection �Table 12 URINALYSIS SPECIFIC GRAVITY Applicators 4a 4b 5a 5b X la Ib 2a 2b No. 1 1.022 1.010 1.026 1.007 1.015 1.010 1.023 1.010 1.015 1.028 1.027 1.028 1.028 1.024 1.024 1.026 1.033 1.028 1.033 1.023 1.030 1.026 1.033 1.020 1.024 1.015 1.022 1.008 1.020 1.020 1.020 1.018 1.024 1.019 1.022 1.018 1.020 1.022 1.022 1. 016 No. 6 1.029 1.028 1.025 1.024 1.026 1.017 1.029 1.024 1.012 1.014 1.016 1.016 1.017 1.014 1.020 1.014 1.026 1.026 1.020 1.022 1.026 1.027 1.027 1.012 1. 015 1.017 1.023 1.024 No. 9 1.013 1.027 1.025 1.025 1.031 1.031 1.030 1.032 1. 015 1.030 1.025 1.020 No. 10 1.017 1.018 1.026 1.007 1.008 1.006 1.021 1.011 1. 018 No. 11 1.025 1.016 1.017 1.020 1.022 1.012 1.016 1.012 1. 025 1.026 1.015 1.023 1.023 1. 012 No. 8 1.026 1. 028 'No. 7 1.030 1. 016 No. 5 _— 1. 030 No. 4 7a 1. 029 No. 3 6a 1. 006 No. 2 6b — _. 0 Legend 0 = Pretreatment X = Posttreatment 1-7 = Days after treatment a = 7:00 a.m. collection b = 7:00 p.m. collection 3a 3b . — �Table 13 U « I * AL » I I S Appllcatort 0 1 l a II BACTERIA ?ew CRYSTALS Calcium Oxalete tPITH-. Occet. CRYSTALS vValet I t la CRYSTALS IPITHi Uric Rare acid. Urates Jb 3a CPITH: fPtTH' wnc-0-l 1-1 b-r Jo tfitiji. Occet. IPIIH: CRYSTALS Occas. k-» Cal- It BACTERIA BACTERIA CRYSTALS CPITNi CRYSTALS XBCiO-l WBC Few Few Calcium Few Urates IVTTHi Rare . Oxalate CRYSTALS TI ' CPITHj Urates CRYSTALS TT"^ 8-1 Cal- CRYSTALS clue 0-1 Calctum OxaUta 1 1 BACTERIA BACTERIA UBC:J-J Few Few rRYS~TAL$ CRYSTALS PROTEIN: clum Calcium ~\ Oulata Oxalata PROTEIN; (PITHs UBC:0-I Few RaTe Ful 1 0-1 VBC; 0-1 UBC:0-I £r*- WBC: 0-1 WBC:0-t tpTTHi V3C:0-I W)C:l-2 laVTTALS IFfTH: VBC:0-2 trTTrli WBC:0-1 BTTH: Few ~* Few ?S few CRYSTALS Celclio Few 11 IJ Oxalates. many amor- It EPITH, WSC:0-I few— CTiYTTALS CRYSTALS Hi>|c CRYSTALS CRYSTALS CRYSTALS Calcium acid. Calcium AmorFew Cal- OxaCalcium Ouclum phous late, Oxalate late. •rates Oxalate, Uretas CLUCOSE Few CLUCOSE •wny Trace amorTrace phous 0-1 WBC:0-I tf»C:0-l UBC:0-I UBC:0-t CRYSTALS EPITH: CTiV5TAts Calcium Few cat - few Oxalase, CRYSTALS Clum AmorCalcium Oxalate phous Oxa late- CASTS: 0-fc urates Few. byline Amorphous casts •rates tPITH; Occas. CRYSTALS CRYSTALS Phos• Few cel- phetes clum BLOOO: Oxalate. TI Few mucus threads WDC:0-I EPITH: Few UBCiO-t WBC:0-I UBC:0-I ViCiO-l UDC:0-t WBC:0-I tpTTH: IfTTH: IFTTB: Few Few FI BACTERIA Few CRYSTALS Urates tPTTn: msa in— w«C:0-t tTTTH: IF7TH: Rare CRYSTALS CRYSTALS Occas. liare Calcium Calcium Oxalate 2* Amorphous Urates. 2» Hucus VtC:l-l n w«c!o-i l^rt W!C:0-I t?ll«: Rare YSTALS re Calcium Oxalate, tPITHl . Occas. CRYSTALS WBC:0-I |ljre ' W8C:0-I IPlTH; Rare EPITH: CRYSTALS - . Occas. CRYSTALS Urates {PITH: WBC-.I-J CRYSTALS . Occas . CRYSTALS Urates acid. Urates Urates nvTTALs urn CRYSTALS WBC:I-J tfTTHs phOUS Occas. SediCRYSTALS ments Urates JLOOD-.I* *zr-— WBC:0-I CRYSTALS CRYSTALS EPITH: Calcium Occas. Full Oxalate BACTERIA Field itoJ: Amor•mount, phous SediFew ment mucus threads CRYSTALS - ' . . . . . . . . . . . . . . . . . . . . . . RBC:Rara ITtTH: Occas. Few awicus threads rcq< threads yjCup-l JSCj.O-1 tflTH: CPITHi Rare Rare BACTERIA. Full field MliOO tPITHL Rare W1C;0-I VlCiO-t ITTTH; Rare iTTfHi m phous Urates MICWft VtC:0-l VBCJM I?TlHj. PTfrl: lire Rare BACTERIA :TERIA . Im- S V»C:0-1 CRYSTAL!I f requenlt Calcium Oxalate,i I* IhlCUS 1* rtocuiI Threads Threads fit . BACTERIA WK:0-t IACTERIA PROTEIN BACTERIA V>C:0-I 1+ Hoderate P.BC:Rare Many TRYTTAIS Many HlYS~TALS CRYSTALS Calciun CRYSTALS BACTERIA Few • Celclum Calcium Oulate AmorCRYSTALS Oxalate. phous Oxalate Amor1* Mucus Phosthreads . phates phous Urates, Calcium Oxalate CRYSTALS YSTALS tPITH: CPITH^ tPITH; CRYSTALS tPITH: tPITH; OccaOcca- ' Moderate Calcium ! T P Calcium Iclim Few Oulate CRYSTALS slonal Oxalate, Oxalate BACTtRIA slonal Calcium CASTS; AmorOxalate Calcium phous Field CRYSTALS Oxalate Sediment Moderate PROTEIN; «t amount Calcium Oxalate. Few wfit1 f frequent S IPITH: CfltH: Rare Rare fRYSTALlHYSTAlS frequent Rare Calcium Calcium Oxalate Oxalate - t.| phous •rates amorphous 7a Occat. BACTERIA UBCil-J W»C:»-1 . ITTTH; Occas. CRYSTALS ilralts CRYSTALS Few BLOOD I* Urates Urates CRYSTALS PROTEIN Orates ITTTH: JP1 CRYSTALS r^ field amorphous •rates K »b «o» • VBC:0-I WBClO-l CTlTTALS (a amorewcus • threads. phous sperurates ewto- CRYSTALS CRYSTALS Urates >hos- Ik Sb WIT EPITH; CftWAlS • Occas. Lg. «Mt. CRYSTALS I CJTV amorphous few uric «rates, < few calcium mulata tPTTH; Occas. vn* mucus- . threads ten ia <*- VBC 'o-i +1 WBC: 1-2 Occas. BACTERIA IFfTHl <* VBC- clum Oulata i Ve VBCiO-l tMTH! Rare tPITH; tPITH; Rare Rare BACTtRIA Faw - tPITM: Rare UO&i. Bcce llonal tPITH: tPITH; Occa- CRYSTALS Calcium slonal Oxalate �Figure 1. 2,4-D and Endogenous Phenolic Compounds Measured in Serum 1.0 _ 0.6 _ 0.4 0 X 1 2 3 ,- 0.8 Subject No. 1 _ <u CO C£ 0.2 . Day = Pretreatment • Posttreatment = 1 day after treatment = 2 days after treatment = 3 days after treatment �Figure 2. 2,4-D and Endogenous Phenolic Compounds Measured in Serum 0 X 1 2 3 1.0 0.8 M <U Subject No. 2 0.6 cn Q 0.4 00 0.2 \_ 1 Day « » = = = Pretreatment Posttreatment 1 day after treatment 2 days after treatment 3 days after treatment �Figure 3. 1.0 2,4-D and Endogenous Phenolic Compounds Measured in Serum Subject No. 3 0 X 1 2 3 i- 0.8 0) CO 0.4 60 0.2 1 Day = Pretreatment = Posttreatment = 1 day after treatment = 2 days after treatment = 3 days after treatment �Figure 4. 2,4-D and Endogenous Phenoli: Compounds Measured In Serum 1.0 r. 0.8 0.6 CO a 0.4 00 0.2 I 1 Day Subject No. 4 0 = Pretreatment X « Posttreatment 1 = 1 day after treatment 2 = 2 days after treatment 3 = 3 days after treatment �Figure 5. 2,4-D rahd Endogenous Phenolic Compounds Measured in Serum 1.0 _ 0.8 0.6 0.4 0.2 1 Day Subject No. 5 0 = Pretreatment X = Posttreatment 1 = 1 day after treatment 2 = 2 days after treatment 3 = 3 days after treatment �Figure 6. 0.8 0.6 p 0.4 0.2 Subject No. 6 0 X 1 2 3 1.0 <u 2,4-D and Endogenous Phenolic Compounds Measured in Serum - = = = = = Pretreatment Posttreatment 1 day after treatment 2 days after treatment 3 days after treatment �Figure 7. 2,4-D and Endogenous Phenolic Compounds Measured in Serum 0 = Pretreatment X = Posttreatment 1 « a day after treatment 2 * 2 days after treatment 3 = 3 days after treatment 1.0 0.8 to 0.6 en H 0 00 Subject No. 7 0.4 3. 0.2 1 Day �Figure 8. 2,4-D and Endogenous Phenolic Compounds Measured in Serum 1.0 0.8 0.6 <u en 0.4 OC 0.2 1 Day Subject No. 8 0 » Pretreatment X = Posttreatment 1 = 1 day after treatment 2 = 2 days after treatment 3 = 3 days after treatment �Figure 9. 2,4-D and Endogenous Phenolic Compounds Measured in Serum 0 « Pretreatment X = Posttreatment 1 = 1 day after treatment 2 = 2 days after treatment 3 = 3 days after treatment 1.0 0.8 g to Subject No. 9 0.6 0.2 1 Day �Figure 10. 1.0 0.8 S> 0.6 CO o sf «M tn 0.4 0.2 2,4-D and Endogenous Phenolic Compounds Measured in Serum Subject No. 10 0 X 1 2 3 » Pretreatment » Posttreatment = 1 day after treatment = 2 days after treatment = 3 days after treatment �Figure 11. 2,4-D and Endogenous Phenolic Compounds Measured in Serum 1.0 0.8 $ 0.6 V) C5 CM be 04 . 0.2 Subject No 0 X 1 2 3 11 Pretreattnent Posttreatment 1 day after treatment 2 days after treatment 3 days after treatment �Applicator No. 1 0 » Pretreatment X « Posttreatment Figure 12. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine 30 20 12 24 36 48 60 Hour 72 84 96 108 120 132 144 �30 Figure 13. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine Applicator No. 2 0 «• Pretreatment X = Posttreatment 20 o •ato * 10 12 24 36 48 60 Hour 72 84 96 108 120 132 144 �30 Figure 14. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine 20 p L 10 Hour Applicator No. 3 0 - Pretreatment X = Posttreatment �Figure 15. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine Applicator No. 4 0 = Pretreatment X = Posttreatment 30 20 . cd 4J o CM t>0 10 12 24 36 48 60 Hour 72 84 96 108 120 132 144 �30 Figure 16. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine Applicator No. 5 0 - Pretreatment X = Posttreatment 20 JC 10 120 Hour 132 144 �Figure 17. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine 12 24 36 48 72 60 Hour 84 Applicator No. 6 0 Pretreatment X Posttreatment 96 108 120 132 144 �30 Figure 18. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine Applicator No. 7 0 = Pretreatment X = Posttreatment 20 o H CM 00 X 12 24 36 48 60 Hour 72 84 96 108 120 132 i 144 �30 Figure 19. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine 20 rt jj o 6C 10 Hour Applicator No. 8 0 * Pretreatment X = Posttreatment �30r Figure 20. Amount of Total 2,4-B and Endogenous Phenolic Compounds Excreted in Urine Applicator No. 9 0 * Pretreatment X » Posttreatment 20- «8 •U Q CM 00 10- X 12 24 36 48 60 72 Hour 84 96 108 120 132 144 �30 r Figure 21. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine Applicator No. 10 0 = Pretreatment X - Posttreatment 20 O H (50 3- 10 I 12 24 36 48 60 72 Hour 84 96 108 120 132 144 �30 r Applicator No. 11 0 » Pretreatment X = Posttreatment Figure 22. Amount of Total 2,4-D and Endogenous Phenolic Compounds Excreted in Urine 20 10 12 24 36 48 60 72 Hour 84 96 108 120 132 144 �MS* Appendix Methodology for 2,4-D Analysis �Methods for Analysis of 2,4-D In order to select the most recent analytic techniques for 2,4-D assay in urine, serum, gauze patches, vegetation and soil samples, a literature survey was done. The following methods were used in our investigation: a. Urine: Out of the total volume of urine samples, 10 ml was taken and 2 ml of IN HC1 was added to it. The acidified urine was then mixed with 5 ml of diethyl ether and was shaken for 10 minutes on a Buchler-Vortex -evaporator (Vortex setting was kept at 5). This extraction method was followed three times. The ether extracts were pooled together and evaporated to complete dryness at a temperature not higher than 45°C. The dry residue was dissolved in 1 ml of methanol first and then mixed thoroughly with 1 ml of 15% solution of BF3 in methanol. The resultant mixture was heated in a water bath at 70°C for 10 minutes for complete methylation. The methylated solution was cooled and again extracted thrice with 1 ml of n-hexane. N-hexane extracts were either injected (1 yl) immediately in a G.C. or stored at -20°C. b. Blood Serum: One ml of isolated serum was diluted with 4 ml of distilled water and then acidified with 1 ml of IN HC1. The acidified serum was then treated (i.e. extracted and methylated) in exactly the same manner as was the urine. One yl of n-hexane extract was injected in a G.C. c. Gauze Patches: Immediately after the day's work, the patches (from the front, back and head cover) were soaked separately in 100 ml of methanol and kept overnight at 4°C. After washing the patches thoroughly with methanol, 50 ml of the wash (from each group) was evaporated to dryness at less than 45°C temperature. The dry residue was dissolved in 1 ml of methanol and then methylated and finally extracted as above. The methylated compound, however, was attracted three times with 4 ml, 3 ml and finally 3 ml of n-hexane. The pooled extractant was diluted when needed before G.C. analysis or stored as before at -20°C. d. Air Filter: Each air filter was washed with 50 ml of methanol immediately after the day's work and was kept at 5°C overnight. Clear methanol was removed and the filter was further rinsed twice with 10 ml of methanol. The pooled methanol was treated in the same way as the gauze patches. e. Vegetation: Ten grams of freshly collected leaves were chopped and homogenized in 50 ml of 95% hot ethanol. The homogenate was centrifuged at 5,000 rpm in a fixed angle rotar for 30 minutes. Supernatant was carefully removed and saved. The pellet was thoroughly washed with 50 ml of 80% hot ethanol and recentrifuged three times as before. Each supernatant fraction was pooled together in a round bottom flask and was evaporated to bring the final volume to 20 ml. The concentrated supernatant was adjusted to pH 3 by adding exactly 10 drops of H3PO^. This acidified solution was extracted first with 50 ml of diethyl ether and then with 25 ml and finally with 25 ml of diethyl ether. The total extractant was evaporated to dryness under a current of nitrogen at 45°C. The dry residue was again extracted three times with 3ml, 1 ml and 1 ml of methanol. The combined methanol extract was treated with 1 ml of 15% BF2 in methanol and kept under a nitrogen atmosphere in a water bath at 70°C until concentrated to 2 ml. This methylated solution was further extracted with nhexane as described above. N-hexane was diluted when needed for G.C. analysis. �f. Soil: Fifty prams of soil sample was mixed with 40 ml of IN H^SO, to prepare a slurr. To the acidified soil, 45 ml of diethyl ether was added and was taken in a separating funnel for extraction. The separating funnel containing the soil sample was shaken for a total of fifteen minutes, but for not more than one minute at a time. The solvent layer was decanted and passed through glass wool and the aqueous layer containing soil particles was rejected. The clear solvent layer was then mixed with 25 ml of IN NaOH and shaken vigorously in a separating funnel for 1 minute. The organic layer was rejected and the alkaline aqueous layer was cleaned by partition method with 25.ml chloroform. The clean aqueous layer was further acidified with 1 ml of cone. l^SO^ and extracted with 25 ml of ether. The ether extract was dried completely and redissolved in 5 ml of methanol. Methylation and final n-hexane extraction were made as in the case of the vegetation samples. The following gas chromatographic conditions were used: Detector, Electron capture Ni 63 temperature: 350°C Gas: Methane: Argon (5:95) Flow rate through the column 25 ml/min Sample volume injected 1 yl Column material 3% 0V 101 on 80/100 supelcoport Length of the column 6 ft I.D. of the column 2 mm Column temperature 187°C Injection port temperature 200°C � 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. 055 Folder The folder containing the original item. 1466 Series The series number of the original item. Series III Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Brown, Harry D. Title A name given to the resource Final Report: Herbicide (2,4-D) Applicator Exposure Measurements Subject The topic of the resource human testing agricultural exposure industrial exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/7dc6e538c6e9bc368d14f0ed36fab353.pdf 45c49c8f66f3ac02fea392a3d9a306c7 PDF Text Text Item ID Number °1291 Author Rose, Richard J. Corporate Author Report/Article Title Genetic Variance In Nonverbal Intelligence: Data From the Kinships of Identical Twins Journal/Book Title Scienco Year 1979 Month/Day September 14 Color n Number of Images 3 DoSCrlpton NotOS Alvin L Youn 9 fi'ecl this item under the category "DDT/Human Toxicology and Environmental Fate" Thursday, April 26, 2001 Page 1291 of 1328 �man, M. Kupcrsmith, E. Estcy, M. Goldstein, Lancet 1976-11, 515 (1976); A. Licbcrman, T. Miyamoto, A. F. Batlista, M. Goldstein, Neurology 25, 459 (1975); A. Liebcrman el al., N. Engl J. Med. 295, 1400 (1976); H. L. Klawans, W. J. Weiner, P. A. Nausieda, P. Volkman, C. Goetz, M. D. Lupton, Neurology 27, 390 (1977). 3. M. O. Thorner, S. M. Ryan, J. A. H. Wass, A. Jones, P. Bouloux, S. Williams, G. M. Besser, J. Clin. Endocrinol. Melab. 47, 372 (1978); L. Lemberger, R. Crabtree, J. Clemens, R. W. Dyke, R. T. Woodburn, ibid. 39, 579 (1974). 4. After the administration of uC-labeled pcrgolide, total radiation in plasma reached its peaked concentration at 1 to 2 hours, indicating that the drug was absorbed during this period of pharmacologic activity (A. Rubin el al,, unpublished observations). 5. Blood was drawn i» heparinized tubes daily at 8:00 a.m. and 9:30 a.m. for the determination of prolactin, LH, FSH, growth hormone, cortisol, and TSH. 6. V. N. Sinha, F. W. Selby, U. J. Lewis, W. P, Vanderlaan,/. Clin. Endocrinol. Metab. 36, 509 (1973). The prolactin standard (V-L-S No. 1) and specific antiserum were kindly provided by the National Pituitary Agency, NIAMDD. Sensitivity of the assay is 0.5 ng/nil, and the coefficient of variation is 6 percent between 8 to 30 ng/ ml. A computer program was used for analysis of the counting data. Control serum assayed with each set of samples had an interassay variability of ± 5 percent. 7. R. W. Fuller, J. A. Clemens, E. C. Kornfeld, H. D. Snoddy, E. B. Smalstig, N. J. Bach, Life Sci., in press. 2 April 1979; revised 21 June 1979 Genetic Variance in Nonverbal Intelligence: Data from the Kinships of Identical Twins Abstract. The multiple relationships within kinships of adult monozygotic twins permit incisive analyses to be made of genetic and environmental effects on behavioral traits. Data from families of 65 monozygotic twin pairs yield evidence of geneticvariance on the Block Design Test, a nonverbal measure of general intelligence. A comparison of mental ability of foster children with that of their biological and their adoptive parents was first reported in 1924 (/), and 1 year later H. J. Mullet presented the first case report of intellectual resemblance in monozygotic (MZ) co-twins who had been separated in infancy (2). In the succeeding halfcentury, studies of adopted children and separated identical twins have had a central role in research on genetic and environmental determinants of cognitive abilities. The resultant data have generated a continuing controversy (5), and its resolution may require new research designs. The families of adult identical twins provide a new paradigm of particular promise for behavior-genetic study (4). In this report we describe the paradigm and illustrate its application. In Fig. 1 the multiple parent-offspring relationships found within families of adult identical twins arc diagramed. Children in each of the nuclear families derive half their genes from a twin parent, those genes being identical with genes of the parent's twin sister or brother (the children's "twin aunt" or "twin uncle"). Since the children and the twin aunt or uncle do not live in the same households, their relationship is somewhat comparable to that between foster children and their biological mother or father. In this way, studies of children of MZ twins provide a parallel to studies of adopted children, with two important advantages: (i) There is no disruption of the nuclear family milieu; the children arc reared by their biological parents in their SCIENCE, VOL. 205, 14 SEPTEMBER 1979 own homes, (ii) In adoption studies biological fathers are rarely available for study (5); the relationship of nephew or niece to twin uncle parallels that of foster children to their biological father. The environmental covariance of a nephew or niece and the twin aunt or uncle will be markedly less than that of a parent and child living in a common household, it may not be zero, however, because MZ twins may select or create similar postmarital environments. An estimate of such effects can be obtained from the resemblance of nephew or niece to the spouse aunt in kinships of male twins and to the spouse uncle in kinships of female twins. In the absence of assorlative mating, the children share neither genes nor a household environment with the spouse aunt or uncle, and any behavioral resemblance would therefore suggest an environmental covariance common to all members of the kinship. Because their twin parents have identical sets of nuclear genes, children of MZ twins are genetically related to one another as half-siblings; socially, they are reared as cousins in separate homes. Further, in contrast to conventional halfsiblings resulting from divorce, death of a parent, or illegitimacy, MZ half-siblings are expected to be of the same age and size. Accordingly, offspring of MZ twins afford a unique human parallel to methods employed in animal genetics, where controlled matings of sires to multiple dams yield estimates of genetic, environmental, and maternal effects from a nested analysis of variance of the fulland half-sib progeny. Better still, half-sib progeny occur with equal frequency among maternal and paternal MZ twins, providing a balanced research paradigm that cannot be achieved in lower animals even with controlled matings. To illustrate the paradigm, we here present a study in which it is applied to the Block Design Subtest of the Wechsler Intelligence Scales. Wechsler's Block Design Test is an adaptation of one introduced in 1923 by Kohs (6), who presented evidence that results from his test correlated highly with results from the Stanford Binet but, unlike the Binet, had only a modest relation to level of education. Research with Wechsler's adaptation supports Kohs's assertion that the block test provides a measure of general intelligence. Across a wide age range, block design is highly related to the general factor common to all Wechsler subtcsts (7); it is the most reliable of the nonverbal subtests, and no Fig. 1. Parent-offA spring relationships in families of identical twins. (A) The offspring of identical twin mothers comprise a maternal halfsibship who genetically relate to their twin aunt as closely as Kinship of twin mothers Kinship of twin fathers they do to their own mother. (B) In the abTwin mother or father—son/daughter sence of assortative Male mating, offspring in a illustrated for mother Female paternal half-sibship Twin aunt or uncle—nephew/niece Twin share neither comillustrated for twin aunt mon genes nor a comSpouse aunt or uncle—nephew/niece mon environment with their spouse illustrated for spouse aunt aunt. In a parallel manner, offspring of identical twin brothers genetically relate to their twin uncle as closely as they do to their own father but offspring in a maternal half-sibship share neither common gents nor a common environment with their spouse uncle. 0036-8075/79/0914-1153$00.50/0 Copyright © 1979 AAAS 1153 �Table 1. Regression and correlation analyses of Block Design Test scores and fingerprint ridge counts.* Block design scores Relationship Coefficient Son or daughter on father or mother Nephew or niece on twin uncle or aunt Nephew or niece on spouse uncle or aunt Offspring on midparent Monozygotic twins Full siblings Half-siblings Father-mother Regressions 0.28 ± 0.04 0.23 ± 0.06 -0.01 ± 0.06 0.54 ± 0.07 Correlations 0.68 ± 0.06 0.24 ± 0.08 0.10 ± 0.12 0.06 ± 0.10 N Ridge count N Coefficient 572 318 241 254 0.42 0.37 -0.06 0.82 ± ± ± ± 0.05 0.05 0.07 0.07 564 310 247 254 65 297 318 102 0.96 0.36 0.17 0.05 ± ± ± ± 0.03 0.08 0.12 0.10 60 296 310 98 The regressions and correlations for all genetic relationships differ significantly from zero; those for the two nongenetic relationships, the spouse correlation and the regression of nephew or niece on spo'use uncle or aunt, do not. Sample sizes for most of the estimates are modest, however, and confidence intervals are quite large. measure of cognitive ability except vocabulary has lower error variance (8). Block design correlates highly with the vocabulary and information subtests, yet in contrast to these verbal tests is but weakly correlated with education (9) and, perhaps as a consequence, is not influenced by assortative mating (10), again in contrast to the verbal scales. To serve as a genetic guide for the analysis of block test scores, we have analyzed the fingerprint ridge counts of the study population. Total ridge count is a well-documented example of polygenic inheritance (11) that is largely unaffected by postnatal environmental influences, the number of ridges being fixed about the 12th week after conception. The block test was administered to 550 members of 65 MZ twin kinships (12). The regression and correlation results for block design and total ridge count are summarized in Table 1 (13). For both traits, familial resemblance appears to be a direct function of shared genes. The parent-offspring regression is comparable in magnitude to that between twin uncle or aunt and nephew or niece (14) but in the absence of shared genes neither trait exhibits significant familial aggregation. There is no resemblance between spouse uncle or aunt and nephew or niece nor between husband and wife. Neither environmental covariance nor assortative mating appears to influence either trait. The parallel pattern of results for block design and for ridge count provides evidence of significant genetic Variation in nonverbal intelligence. We emphasize that the evidence is obtained from normal children reared in their natural homes by their biological parents, children who differ in no known way from the larger population to which we wish to draw inferences (75). Table 2 presents heritability estimates for both 1154 traits that can be derived from the data. The estimates show remarkably close agreement across the multiple genetic relationships contained within each kinship, but the reader is cautioned that they are not statistically independent. Our analyses suggest that substantial variance in Block Design Test scores is genetic in origin (16). An equivalent conclusion, of course, is that substantial variance in those scores is attributable to nongenetic influences, and the twin-family methods which establish genetic variance can also identify systematic sources of environmental influence on nonverbal IQ. 0ur methodology enables us to assess uniquely one potential source of environmental variation, that of maternal effects. A nested analysis of variance of the offspring data permits a direct comparison of the relative similarity of maternal and paternal half-siblings. In this preliminary sample, we find no evidence of maternal effects in block design data, although such influences are present in verbal IQ scores (17). Independently, Table 2. Heritability estimates for Block Design Test scores and total ridge counts.* Estimated h2 Relationship Block design scores Total ridge count Midparent-offspring Parent-offspring Twin uncle or auntnephew or niece Full siblings Half-siblings .54 .56 .82 .84 .46 .48 .40 .74 .72 .68 The ratio of additive genetic variance to total phenotypic variation defines the heritability, li'2. From the composition of phenotypic covariances, the regression or correlation of relatives can be expressed as estimates of A 2 (19). Interpretation of the estimates should take into account the imprecision of the coefficients on which they are based, the restricted range of variation in our sample, and the fact that possible effects of common environment and dominance variation have been ignored. however, a prenatal environmental influence has been demonstrated by contrasting MZ twins classified into mono- and dichorionic placenta! types (18). RICHARD J. ROSE Department of Psychology, Indiana University, Bloomington 47405 E. L. HARRISJ. C. CHRISTIAN Department of Medical Genetics, Indiana University School of Medicine, Indianapolis 46202 W. E. NANCE Department of Human Genetics, Medical College of Virginia, Richmond 23298 References and Notes 1. S. V. S. Theis, How Foster Children Turn Out (State Charities Aid Association, New York, 1924). 2. H. ). Muller,/. Hercd. 16, 433 (1925). 3. L. J. Cronbach,/lm. Psychol. 30, 1 (1975); L. J. Kamin, The Science and Politics of IQ (Erlbaum, Potomac, Md., 1974); H. Munsinger, Psychol. Bull. 82, 623 (1975); L. J. Kamin, ibid. 85, 194 (1978); J. Shields, in Progress in Clinical and Biological Research: Twin Research, W. E. Nance, G. Allen, P. Parisi, Eds. (Liss, New York, 1978), p. 79. 4. W. E. Nance and L. A. Corey, Genetics 83, 811 (1976); R. J. Rose, J. Z. Miller, M. DumontDriscoll, M. Evans,Behav. Genet. 9,71 (1979). 5. A serious problem with all published adoption studies is that no data on biological fathers of the adopted children are available. Consequently, the extent of assortative mating by the biological mothers is unknown. Significant assortative mating is likely present [R. Plomin, J. C. DeFries, M. K. Roberts, Science 1%, 449 (1977)], and estimates of genetic influence based on present adoption data may be inflated. 6. S. C. Kohs, Intelligence Measurement: A Psychological and Statistical Study Based upon the Blocks-Design Tests (Macmillan, New York, 1923). 7. U. Gault, Aust. J. Psychol. 6, 85 (1954); J. Cohen, J. Consult. Psychol. 21, 451 (1957); ibid. 23, 285 (1959); A. J. Kaufman,/. Consult. Clin. Psychol. 43, 135 (1973). 8. D. Wechsler, Manual for the Wechsler Adult Intelligence Scale (Psychological Corp., New York, 1955); Manual for the Wechsler. Intelligence Scale for Children—Revised (Psychological Corp., New York, 1974); National Center for Health Statistics, Intellectual Development of Youth as Measured by a Short Form of the Wechsler Intelligence Scale (PHS Publ. 1000-Series 11-No. 129, Government Printing Office, Washington, D.C., 1973). 9. J. E. Birren, K. F. Riegcl, D. E. Morrison, J. Gerontol. 16,363 (1961); D. Wechsler, The Measurement and Appraisal of Adult Intelligence (Williams & Wilkins, Baltimore, cd. 4, 1958). 10. T. Williams, Behav. Genet. S, 405 (1975). 11. S. B. Holt, Br. Med. Bull. 17, 247 (1961). 12. There were 278 males and 272 females, of whom 130 were twin parents, 102 nontwin parents, and 318 offspring. The 232 parents ranged in age from 31 to 64 years [mean = 43; standard deviation (S.D.) = 8.9], their 318 offspring from 6 to 38 years (mean = 15.8; S.D. = 7.1). This is a volunteer, Caucasian sample. Some self-selection, expected in voluntary research, is evident in socioeconomic and educational characteristics of the participants. The IQ data exhibit elevated means and restricted variances: Wechsler scales are standardized on representative national samples with mean = 10 and S.D. = 3; Block Design Test scores of this sample have mean = 11.98 and S.D. = 2.78. Means and variances are homogenous for the twin and nontwin parents, for the children and adults, and for males and females. As part of a half-day protocol of medical and behavioral research, the subjects were tested individually by trained examiners, the same team . of examiners being assigned to all members of each MZ kinship. Subjects aged 6 through 15 (189 offspring) were given the 1974 revision of the Wechsler Intelligence Scale for Children (WISC); subjects age 16 and over (129 offspring and all parents) were tested with the WcchsSCIENCE. VOL. 205 �ler Adult Intelligence Scale (WAIS). The block design subtests of the WISC and WAIS are quite comparable. In samples of 16- to 17-year-old youth, the intertest correlation of block design is as high as its rctest reliability on either test alone and exceeds that of any other performance subtest [R. T. Ross and J. Morledge, J. Consult. Psychol. 31, 331 (1967); M. Y. Quereshi and J. M. Miller,/. Educ. Meas. 7, 105 (1970)]. Raw scores from the block design subtest were standardized according to norms in appendices in the Wechsler manuals (8) for 30 agebands from ages 6 to 16 and 7 age-bands from ages 16 to 64. Usable ridge count data were obtained from 522 members of 60 MZ kinships in the sample. All family members were genotyped with multiple blood markers to confirm monozygosity, for paternity exclusion, and for future linkage analyses. 13. The analysis employed here is identical with that previously reported for plasma cholesterol [J. C. Christian and K. W. Rang, Am. J. Hum. Genet. 20, 462 (1977)]. Regression coefficients are used for their predictive value between generations, and correlation coefficients are used to measure relationships within the same generation. Regression coefficients are the preferred measure of parent-offspring resemblance, because they are less affected by range restriction, assortativc mating, and variable sibship size [J. C. DeFries, R. C. Johnson, A. R. Kuse, G. E. McClearn, J. Polovina, S.'G. Vandenberg, J. R. Wilson, Behav. Genet. 9, 23 (1979)]. Regression and intraclass correlation coefficients were estimated by the pairwise method [B. Rosner, A. Donner, C. H. Hennekens, Appl. Stat. 26, 179 (1977)]. The regression of offspring on midparent value is included in Table 1, since in the absence of common environmental variance it is a direct estimate of heritability [A. Vetta, Soc. Biol. 24, 166 (1977); J. C. DeFries, G. C. Ashton, R. C. Johnson, A. R. Kuse, G. E. McClearn, M. P. Mi, M. N. Rashad, S. G. Vandenberg, J. R. Wilson, Be. hav. Genet. 8, 281 (1978)]. 14. Normative age-banding may not fully correct for the substantial age differences intrinsic to our measurement of adult-child resemblance. Inadequacies of age standardization and nonequivalence of the two tests would reduce adult-child resemblance relative to that of sibs and half-sibs who are more closely matched in age. 15. We assume that there exist no unique biases in the parental behavior or family structure of MZ twins or the experiences of their children. The assumption is untested, but plausible: personality characteristics of MZ twins cannot be distinguished from those of singletons [J. C. Loehlin and R. C. Nichols, Heredity, Environment and Personality (Univ. of Texas Press, Austin, (1976)], and the same is probably true of their parental behavior. The frequency of MZ twinning is equivalent across social and ethnic groups and is not known to be associated with any systematic factors. 16. This analysis is consistent with evidence from a recent adoption study in Minnesota [S. Scarr and R. A. Weinberg, in Readings About Individual and Group Differences, L. Willerman and R. G. Turner, Eds. (Freeman, San Francisco, 1979)]. 17. R. J. Rose, paper presented at the Second International Congress on Twin Studies, Washington, D.C., 1977. 18. Chorion type is reported to influence similarity of full-scale IQ's in MZ twin children [M. Melnick, N. C. Myrianthopoulos, J. C. Christian, Am. J. Hum. Genet. 30, 425 (1978)], and we are now studying block design performance in a sample of adult MZ co-twins whose placentation was documented at birth; preliminary results (R. J. Rose et at., in preparation) suggest a significant effect of chorion type on within-pair variation. 19. The expected value of parent-offspring regression is fcz/2. To estimate hcritability, the regression of offspring on single parent is doubled. Since the variance of midparent values is half the variance of individual parent values, the regression of offspring on midparent provides a direct estimate of A 2 . If effects of dominance variation and common environments are ignored, z the correlation of full siblings also estimates /i /2, that of half siblings A2/4. For details, see references cited in (13). The correlations of MZ twins provide upper limit estimates of heritability confounded by their closely shared environments; the estimates arc .68 for blocks and .96 for ridge counts. 20. This is publication number 78-41 from the Indiana University Human Genetics Center. It was supported by PHS grant GM 21054. 21 August 1978; revised 5 July 1979 SCIENCE, VOL. 205, 14 SEPTEMBER 1979 The Cheetah: Native American Abstract. Two North American fossil species of large felids, hitherto regarded as Late Cenozoic pumas (mountain lion), are in fact closely related to the living cheetah, Acinonyx, of Africa and Eurasia .Anew subgenus (Miracinonyx) is proposed for the American species. Cheetahs and pumas may have had a common ancestor in the Miocene of North America. Fossils of Puma-like cats are relatively common in the Late Cenozoic of North America (/). One species of supposed Puma, "Felis" studeri, from the Pliocene of the Texas panhandle, has long been recognized as distinct from Puma concolor because of morphological similarities with Old World cheetahs, but previous work has attributed the similarities to parallel evolution (/, 2). Excavations at the Late Pleistocene deposits of Natural Trap Cave, Wyoming (3), indicated that another species previously referred to Puma, "Felis" trumani (4), also possesses several characters of dentition, skull, and limb architecture that are remarkably "cheetah-like." Again, the similarities were attributed to parallelism, and "F." trumani was styled as the "cheetah-like cat" (3). Continued excavations at the Wyoming site have yielded hundreds of bones of this felid (5), and more recent work (6) has revealed numerous shared derived characters that link "F." studeri and "F." trumani to Old World Acinonyx. Other work (7) has utilized multivariate comparison of upper and lower tooth rows to group the two American species; evolutionary affinities with Old World cheetahs were also suggested. Except for size differences and several features which are interpreted as retained primitive characters, the fossils of "F." studeri and "F." trumani are almost identical with Old World Acinonyx species (6). The points of similarity are so extensive and of such a complex nature that a hypothesis attributing their origin to other than common genetic descent would require pushing the concept of parallel evolution to an unprecedented extreme. The systematic paleontology follows: Family: Felidae Genus: Acinonyx Miracinonyx subgen. nov. Derivation of name. From Latin "mirus": surprising, amazing; and Acinonyx: Old World cheetah. Diagnosis. Distinguished from Puma and other medium-sized felids by elongation of distal limbs (radius-ulna, tibia-fibula, calcaneum, metapodials); braincase short and expanded; postorbital constriction wide; frontals broad and flat; internal nares enlarged; orbital shelf (zygo- matic process of maxilla) short; skull highly arched; coronoid process of ramus weak, slopes noticeably posterior; canines weak; short mandibular diastema; protocone reduced or absent; auditory bulla elongate and flattened anteriorly. The latter character distinguishes Miracinonyx from Old World cheetahs (8). Acinonyx studeri may be distinguished from A. trumani by greater overall skull size and elongate, widely spaced occipital condyles (2). Old World cheetahs (subgenus Acinonyx) are distinguished from the subgenus Miracinonyx by a prominent anterior or anterolingual cusp on P3, inflation of frontal sinus and auditory bullae, and greater development of the medial anteroposterior ridge of the basioccipital. Geographic distribution. Western United States: Texas (2), Nevada (4), Wyoming (3). Temporal distribution. Middle Blancan to Late Pleistocene. Type species. Acinonyx (Miracinonyx) trumani (Orr, 1969) (4). Included species. Type species and Acinonyx (Miracinonyx) studeri (Savage, 1960) (2). Description. The skull of Miracinonyx is highly arched, with the facial and cranial regions sloping anteriorly and posteriorly from the interorbital area of the frontals. Shortening of the facial region and enlargement of the P3 have reduced the upper diastema and crowded the P2 tightly between the P3 and canine. Both upper and lower canines are reduced, the lower prcmolars are relatively narrow, and the protocone of the upper carnassial is greatly reduced or absent. The zygomatic process of the maxilla, which in Puma forms a distinct shelf in the orbit floor, is reduced. Shortening of the cranial region of the skull gives a bulging appearance to the braincase; the anterior portion of the zygomatic arch is shortened, and the postorbital constriction is widened. The frontals are greatly widened and flat, with the orbits set far apart and high on the face. The postorbital process of the frontals is distinct and of a sharp angular shape; because of frontal sinus inflation the postorbital processes of Old World Acinonyx appear more rounded. Dorsally, the skull of Acinonyx is readily distinguishable from Puma, which has a prominent postorbital con- 0036-8075/79/0914-1155S00.50/0 Copyright © 1979 AAAS 1155 � 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. 049 Folder The folder containing the original item. 1291 Series The series number of the original item. Series III Subseries II Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Rose, Richard J. E. L. Harris J. C. Christian W. E. Nance Source A related resource from which the described resource is derived Science Date A point or period of time associated with an event in the lifecycle of the resource September 14 1979 Title A name given to the resource Genetic Variance in Nonverbal Intelligence: Data From the Kinships of Identical Twins Subject The topic of the resource human testing 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. 044 Folder The folder containing the original item. 1068 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Spector, Beatice D. Guy S. Perry III John H. Kersey Source A related resource from which the described resource is derived Clinical Immunology and Immunopathology Date A point or period of time associated with an event in the lifecycle of the resource 1978 Title A name given to the resource Genetically Determined Immunodeficiency Diseases (GDID) and Malignancy: Report from the Immunodeficiency - Cancer Registry Subject The topic of the resource health studies human testing 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. 047 Folder The folder containing the original item. 1192 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Carlson, Lars A. Birgitta Kolmodin-Hedman Source A related resource from which the described resource is derived Acta Medica Scandinavica Date A point or period of time associated with an event in the lifecycle of the resource 1972 Title A name given to the resource Hyper - [alpha] - Lipoproteinemia in Men Exposed to Chlorinated Hydrocarbon Pesticides Subject The topic of the resource industrial exposure pesticide toxicology human testing health effects 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. 048 Folder The folder containing the original item. 1198 Series The series number of the original item. Series III Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource D'Ercole, A. Joseph Robert D. Arthur Jimmie D. Cain Ben F. Barrentine Source A related resource from which the described resource is derived Pediatrics Date A point or period of time associated with an event in the lifecycle of the resource 1976-06-01 Title A name given to the resource Insecticide Exposure of Mothers and Newborns in a Rural Agricultural Area Subject The topic of the resource DDT pesticide toxicology human testing ao_seriesIII