1 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. 034 Folder The folder containing the original item. 0669 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 Gehring, P.J. C.G. Kramer B.A. Schwetz J.Q. Rose V.K. Rowe Source A related resource from which the described resource is derived Toxicology and Applied Pharmacology Date A point or period of time associated with an event in the lifecycle of the resource 1973 Title A name given to the resource The Fate of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) Following Oral Administration to Man Subject The topic of the resource human testing human metabolism clinical trials 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. 037 Folder The folder containing the original item. 0803 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 Khanna, R. N. J. D. Kohli Description An account of the resource Corporate Author: International Symposium on Industrial Toxicology, 1st, Lucknow, 1975. Industrial Toxicology Research Centre. 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 Metabolism of Chlorophenoxy Herbicides in Man Subject The topic of the resource herbicide toxicology human testing dioxin 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. 037 Folder The folder containing the original item. 0812 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 Kimbrough, Renate D. Source A related resource from which the described resource is derived Environmental Health Perspectives 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 Determining Exposure and Biochemical Effects in Human Population Studies Subject The topic of the resource health studies human testing study protocol 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. 038 Folder The folder containing the original item. 0828 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 Kohli, J.D. R. N. Khanna B. N. Gupta Source A related resource from which the described resource is derived Xenobiotica Date A point or period of time associated with an event in the lifecycle of the resource 1974 Title A name given to the resource Absorption and Excretion of 2,4,-Dichlorophenoxyacetic Acid in 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. 038 Folder The folder containing the original item. 0829 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 Kohli, J.D. R. N. Khanna B. N. Gupta Source A related resource from which the described resource is derived Archives Internationales de Pharmacodynamie Date A point or period of time associated with an event in the lifecycle of the resource 1974 Title A name given to the resource Absorption and Excretion of 2,4,5-Trichlorophenoxy Acetic Acid in 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. 038 Folder The folder containing the original item. 0864 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 Leng, M. L. T. L. Lavy J. C. Ramsey W. H. Braun Date A point or period of time associated with an event in the lifecycle of the resource 1981-09-01 Title A name given to the resource Typescript: Review of Studies with 2,4,5 - T in Humans Including Applicators Under Field Conditions Subject The topic of the resource agricultural exposure herbicide application herbicide 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. 038 Folder The folder containing the original item. 0865 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 Leng, M. L. J. C. Ramsey W. H. Braun T. L. Lavy Source A related resource from which the described resource is derived Pesticide Residues and Exposure : Based on a Symposium Sponsored by the Division of Pesticide Chemistry at the Second Chemical Congress of the North American Continent (180th ACS National Meeting), Las Vegas, Nevada, August 26-27, 1980. 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 Review of Studies with 2,4,5 - Trichlorophenoxyacetic Acid in Humans Including Applicators Under Field Conditions Subject The topic of the resource agricultural exposure herbicide application herbicide 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. 040 Folder The folder containing the original item. 0903 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 Meyer, Channing R. Source A related resource from which the described resource is derived Environmental Health Perspectives 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 Liver Dysfunction in Residents Exposed to Leachate from a Toxic Waste Dump Subject The topic of the resource EPA environmental hygiene 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. 040 Folder The folder containing the original item. 0927 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 Newton, Michael Logan A. Norris Source A related resource from which the described resource is derived Fundamental and Applied Toxicology Date A point or period of time associated with an event in the lifecycle of the resource July/August 1981 Title A name given to the resource Potential Exposure of Humans to 2, 4, 5 -T and TCDD in the Oregon Coast Ranges Subject The topic of the resource agricultural exposure dioxin human testing herbicide application 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. 042 Folder The folder containing the original item. 1010 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 Riihimaki, V. S. Asp A. M. Seppalainen S. Hernberg 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 Symptomatology, Morbidity and Mortality Experience of Chlorinated Phenoxyacid Herbicide (2, 4 - D; 2, 4, 5 -T) Sprayers in Finland: A Clinical and Epidemiological Study Subject The topic of the resource industrial exposure dioxin human testing herbicide application 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. 1037 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. W. H. Braun G. E. Blau P. J. Gehring Source A related resource from which the described resource is derived Toxicology 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 The Fate of 2,4-Dichlorophenoxyacetic Acid (2,4-D) Following Oral Administration to 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. 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