3 15 46 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. 050 Folder The folder containing the original item. 1318 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/. Title A name given to the resource Abstract: Agricultural Exposure to 2, 4 -D Subject The topic of the resource agricultural exposure herbicide toxicology 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. 050 Folder The folder containing the original item. 1326 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 Lillie, Thomas H. James M. Livingston Mark A. Hamilton 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 1981 Title A name given to the resource Recommendations for Selecting and Decontaminating Pesticide Applicator Clothing Subject The topic of the resource agricultural exposure human testing protective clothing safety 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. 052 Folder The folder containing the original item. 1365 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 Kearney, Philip C. Source A related resource from which the described resource is derived Accidental Exposure to Dioxins: Human Health Aspects 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 Chapter 15: Problems in Agriculture with TCDD Subject The topic of the resource dioxin agricultural exposure health studies 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. 052 Folder The folder containing the original item. 1369 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 Miller, Stanton Source A related resource from which the described resource is derived Environmental Science and Technology 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 The PCB Imbroglio Subject The topic of the resource PCBs industrial exposure agricultural exposure EPA ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/da3caa0592b187a9fe0b379a6f96d658.pdf 17fd84e43bc32addceeabe6f690d31f0 PDF Text Text Item ID Number 01406 Author Corporate Author Report/Article TttlO Press Release: Arkansas Scientist Reports on Herbicide Exposure Studies, May 2,1985 Journal/Book Title Year Mouth/Day Color H Number of Images 2 Descripton Notes Tuesday, May 15, 2001 Page 1406 of 1514 �For release after 4 p.m., May 2, 1985. Arkansas Scientist Reports on Herbicide Exposure Studies MIAMI--Findings from studies that determined how much herbicide was absorbed into the bodies of forest workers applying herbicides were presented Thursday (May 2) by Dr. Terry L. Lavy, professor of agronomy at the University of Arkansas - Fayetteville, at the American Chemical Society's 189th national meeting here. Lavy, director of the Pesticide Residue Laboratory at the University of Arkansas, reported on applicator exposure to the commonly used forest herbicides 2,4-D, dichlorprop and picloram. The research was conducted with the cooperation of 80 forest pesticide applicators in nine locations in Arkansas, Mississippi and Oklahoma. The applicators provided the researchers with all of the urine they excreted during the 12 day study period. Research has shown that at least 90 percent of the amount of these compounds that is absorbed through the skin is excreted in the urine within five days, Lavy said. Therefore, analysis of the urine of the applicators provides a measure of the amount of chemical absorbed through the skin. Lavy also stated that the amount applicators absorb through the skin is much greater than the amount inhaled. The toxicological significance of the amounts of herbicides absorbed by the workers was determined using the "no observed effect levels" that are widely accepted by regulatory agencies, researchers and the industry. A margin of safety was determined by dividing the "no observed effect level" by the dose absorbed by workers. �The most exposed workers were those using backpack sprayers. The margin of safety for 2,4-D ranged from 245 for the backpack crew to 5,581 for the injection bar crew. If a worker has a margin of safety of 245, this means he could have absorbed 245 times more than he did before he would reach the "no observed effect level". Picloram margins of safety were as high as 943,400. The study was designed to compare exposure levels of workers applying the herbicides with ground application tools who took no special precautions to those who used a set of simple preventive measures, which included wearing new leather gloves and boots each day. The new gloves and boots significantly reduced exposure for all workers except those using backpack sprayers, apparently due to the high degree of spray contact with other parts of their bodies. Lavy has conducted nine worker exposure studies with eight different herbicides and insecticides. Workers involved with mixing or batching pesticide concentrates received a higher absorbed dose than those applying diluted sprays. In each case he has found that healththreatening levels of expoure did not occcur. He adds, however, that it is always wise to limit expoure to chemical products. Practices to reduce exposure include washing hands before eating, before using tobacco, and before using the bathroom; immediately washing with soap and water any skin on which pesticide is spilled; showering and changing clothing soon after exposure; and wearing clean clothing, including waterproof boots and gloves, during application. � 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. 053 Folder The folder containing the original item. 1406 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/. Title A name given to the resource Press Release: Arkansas Scientist Reports on Herbicide Exposure Studies, May 2, 1985 Subject The topic of the resource agricultural exposure protective clothing ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/58a1c94cabf0bf4422c8c83075ca0ab1.pdf 9114ea53e16e50431763db6705517d93 PDF Text Text Item ID Number 01425 AllthOT Doherty, Joyce Corporate Author United States Department of Health and Human Service Roport/Artldo TltlO Press Release Announcing Possible Link Between Herbicides and Non-Hodgkin's Lymphomas Journal/Book Title Year 1986 Month/Day Color Au ust 14 9 n Number of Imaoes f DOSOrlptOU NotOS A'so includes questions and answers to be used by OCC to respond to press inquiries on the agricultural use of herbicides study. Tuesday, May 15, 2001 Page 1425 of 1514 �HHS MHWi) D RAFT U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES EMBARGOED FOR RELEASE 4:30 p.m. EST Thursday, August 14, 1986 (tentative) National Cancer Institute Joyce Doherty (301) A National Cancer Institute (NCI) and University of Kansas study has found that Kansas farmworkers who used herbicides had a higher risk for developing non-Hodgkin's lymphomas than nonfarmers in the state. The farmers, however, did not have a higher than normal risk for soft-tissue sarcomas and Hodgkin's disease, as studies in Sweden had found. The Journal of the American Medical Association published the study results August 15,1986 (tentative). Farmers exposed to the herbicides for more than 20 days each year had six times the risk of developing non-Hodgkin's lymphoma compared to nonfarmers. Among these frequent users, those who mixed or applied the herbicides themselves had eight times the risk. These above-normal rates were associated with the use of phenoxy herbicides, especially 2,4-dichlorophenoxyacetic acid (2,4-D). Phenoxy herbicides are frequently used on pastureland and in growing wheat, corn, sorghum, and rice. Exposure to chemicals in herbicides is widespread in the United States. In addition to farming and forestry use, these chemicals are found in lawn and garden herbicides, blue stain retardants used in sawmills, slime control substances in paper and pulp manufacturing, cutting oils, wood preservatives, waterproofing agents for leathers and textiles, and medications. Phenoxy herbicides were also used in Agent Orange in Vietnam. Because of scientific and public concern about the chemicals, NCI conducted a population-based, case-control study of three cancers that earlier studies had linked to (more) �-2- herbicide exposures. The NCI scientists, led by Shelia K. Hoar, Ph.D., collaborated with scientists from the University of Kansas, led'by Frederick F. Holmes, M.D. NCI chose Kansas because the farmers frequently use herbicides on wheat, the state's major crop, and because Kansas has a statewide cancer reporting system. Dr. Hoar and her colleagues studied 424 male residents with soft-tissue sarcoma (133 cases), Hodgkin's disease (121), and non-Hodgkin's lymphoma (170) that had been newly diagnosed between 1976-1982. A panel of three pathologists confirmed the histology of each diagnosis. The scientists also studied 948 controls from the general white male population of Kansas. In telephone interviews, the subjects or close relatives of deceased subjects were asked detailed questions about farming practices, including herbicide and insecticide use. For a sample of the subjects, the scientists also located herbicide and insecticide suppliers to corroborate exposure information given in the interviews. The investigators found that, compared to nonfarmers, the farmers had about equal risk of developing soft-tissue sarcoma and a slightly lower than expected risk of Hodgkin's disease. Even after detailed analyses, they found no consistent patterns of excess risk for either of these cancers associated with length of time working or living on a farm, the crop or the acreage farmed, or the duration or frequency of herbicide use. For non-Hodgkin's lymphoma, the risk was slightly higher (about 30 percent) for all farmers compared to nonfarmers. The risk, however, increased significantly for farmers who used herbicides. Compared to nonusers, the risk increased to sixfold (600 percent) for farmers who were exposed to herbicides for more than 20 days per year. The level of risk was not related to the total years of herbicide use. Farmers who began using the herbicides before 1946 had a greater than 70 percent higher risk for non-Hodgkin's lymphoma compared to farmers who began use in the 1950s and 1960s. Use of insecticides did not increase the risk for non-Hodgkin's lymphoma. (more) �-3- The farmers who did not use protective equipment (gloves, masks, etc.) while using herbicides had a 40 percent higher risk fur non-Hodgkin's lymphoma than those who protected themselves. Similarly, farmerjs who used spray equipment that exposed them to more of the chemicals had an 80 percent higher risk than those who used safer application methods. The scientists also investigated possible causes for the above-normal non-Hodgkin's lymphomas other than the herbicides. They assessed the more established factors such as immune-altering conditions and drugs and the family history of cancer. They also assessed speculative factors such as cigarette smoking, coffee consumption, and ionizing radiation. None of these was found to change the herbicide association. The finding of excess non-Hodgkin's lymphoma associated with herbicide use in this study is consistent with earlier research done in Sweden and in some other U.S. states with heavy concentrations of agriculture. �The following Questions and Answers are to be used by OCC to repond to press inquiries on the agricultural use of herbicides study. They are not part of the .press release. �QUESTIONS AND ANSWERS 1. What types of herbicides were evaluated in this study? The scientists evaluated the use of phenoxyacetic acids, triazines, amides, benzoics, carbamates, trifluralin, and uracils. The farmers also reported nonspecific herbicide use such as liquids, sprays, and dusts. 2. Were insecticides also evaluated? Yes, the scientists asked detailed questions about use of insecticides. After they accounted for the herbicide use, they found no association between insecticide use and non-Hodgkin's lymphoma. 3. Dioxin contaminants are found in some herbicides. Did this study find any effects of dioxin in the herbicides? The study subjects reported most frequent use of 2,4-dichlorophenoxyacetic acid (2,4D), an herbicide that does not contain 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most carcinogenic dioxin isomer. The herbicide 2,4-D, however, may contain other, less toxic dioxin isomers. Very few subjects reported that they used 2,4,5trichlorophenoxyacetic acid (2,4,5-T), the herbicide known to be contaminated by the carcinogenic dioxin isomer, so the dioxin effects could not be effectively evaluated. �4. Are current herbicide and insecticide formulations safe if used as directed? Unknown. Until enough time has elapsed to allow for the latency period of nonHodgkin's lymphoma, the risks for use of current formulations will not be known. If the risks continue to drop, one can assume that current formulations, if applied according to directions, are safer than in the past. The farmers who began using the herbicides before 1946 had a higher risk than those who began their use later; however, even those who began to use the herbicides after 1965 had almost twice the expected number of lymphomas. 5. Do homeowners who use insecticides and herbicides on their property run a higher risk for cancer? This study did not show any excess risk associated with reported home or garden use of either insecticides or herbicides. NCI is currently collaborating with the University of Nebraska on a new study investigating this question. 6. What precautions can a farmer or homeowner use to protect against possible cancer risks? Although not designed to answer this question, the study did show that the risk for lymphoma decreased when the farmers used protective equipment to minimize their exposure to the herbicide. Homeowners should do the same. Most chemicals for home or garden use have warnings on labels about how the products should be used. �7. What about the danger to small children and pets who play on lavMhs that have been treated with herbicides or insecticides? - The population studied was adults only. It did not address risks for children. 8. Do Vietnam veterans who were exposed to Agent Orange have an increased risk for developing cancer? This study focused on agricultural use of herbicides. The methods of application, the amounts used, the climate, and the elimination of herbicides from the environment, might be very different in Kansas and Vietnam. Studies of Vietnam veterans to date do not report excess non-Hodgkin's lymphoma; however, these studies have been too small to detect moderate excesses, if they exist. � 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. 054 Folder The folder containing the original item. 1425 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 Doherty, Joyce Description An account of the resource Corporate Author: United States Department of Health and Human Services, National Cancer Institute Date A point or period of time associated with an event in the lifecycle of the resource August 14 1986 Title A name given to the resource Press Release Announcing Possible Link Between Herbicides and Non-Hodgkin's Lymphomas Subject The topic of the resource agricultural exposure case referent study ao_seriesIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 054 Folder The folder containing the original item. 1426 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/. Source A related resource from which the described resource is derived Chemical and Engineering News Date A point or period of time associated with an event in the lifecycle of the resource September 8 1986 Title A name given to the resource 2,4-D Herbicides Use Increases Risk of Rare Cancer Subject The topic of the resource agricultural exposure lymphomas case referent study ao_seriesIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 054 Folder The folder containing the original item. 1427 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 Colton, Theodore Source A related resource from which the described resource is derived Journal of the American Medical Association Date A point or period of time associated with an event in the lifecycle of the resource September 5 1986 Title A name given to the resource Herbicide Exposure and Cancer Subject The topic of the resource case referent study agricultural exposure 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. 054 Folder The folder containing the original item. 1434 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 Wiklund, Kerstin Lars-Erik Holm Source A related resource from which the described resource is derived Cancer Risks Among Agricultural Workers in Sweden Date A point or period of time associated with an event in the lifecycle of the resource 1986 Title A name given to the resource Soft Tissue Sarcoma Risk in Swedish Agricultural and Forestry Workers Subject The topic of the resource cancer risk assessment cohort study agricultural exposure 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. 054 Folder The folder containing the original item. 1440 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 Weisenburger, D.D. H. Schmidt S.J. Steele P.R. Babbitt J.O. Armitage Date A point or period of time associated with an event in the lifecycle of the resource 1987 Title A name given to the resource Abstract: Environmental Epidemiology of Non-Hodgkin's Lymphoma (NHL) in Eastern Nebraska Subject The topic of the resource lymphomas agricultural exposure herbicide application pesticide 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. 055 Folder The folder containing the original item. 1452 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/. Description An account of the resource Corporate Author: Industry Task Force II on 2,4-D Research Data Date A point or period of time associated with an event in the lifecycle of the resource 1990-01-01 Title A name given to the resource Public Concerns About 2,4-D Cancer Claims and the Facts Subject The topic of the resource health studies industrial exposure agricultural exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/f26aa9f9a3a38ce0705c563a39671522.pdf de0bf59326ee72507ba655dea437476f PDF Text Text °1465 Item ID Number MacMahon, Brian Corporate Author Report/Article TltlB Review °f Hoar et al and Related Literature Journal/Book Title Year 1986 Month/Day September 29 Color [J Number of Images 7 DOSCrlPton NOtBS "This review is prepared in response to EPA Purchase Order 6W-3948-NASA dated September 10,1986...[and was] prompted by the publication of Hoar et al in the September 5, 1986 issue of JAMA." Tuesday, May 15, 2001 Page 1465 of 1514 �Review of Hoar et al ' and related literature This review is prepared in response to EPA Purchase Order 6W-3948-NASA dated September 10, 1986. According to Jerome Blondell's letter accompanying the purchase order: "The key question is: What does the 'weight of evidence' say about the risk of lymphoma for agricultural workers exposed to 2,4-D? Is 2,4-D a likely cause of lymphoma?" This question was prompted by the referenced publication of Hoar et al in the September 5, 1986 issue of JAMA. Hoar et al This Is a population-based case-control study of all male cases of soft-tissue sarcoma (STS), Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) identified in the State of Kansas over a 7-year period. 3 controls, matched for age and living-or-dead status, were selected - either by random digit telephone dialing (for living cases under 65 years of age), from Medicare files (for living cases 65 or older) or from Kansas state mortality files (for dead cases). Information on occupation and exposure to herbicides was obtained by telephone interview - with the case or control for half of the subjects with STS or NHL (and corresponding controls) and one-third of the HD cases and controls, and with the next of kin for the remaining, deceased subjects. This' study shows every indication of having been carefully and competently carried out. I see no methodologic problems that are likely to have produced the reported positive association between use of herbicides (predominantly uracil and phenoxyacetic acids) and NHL. The strong and statistically Hoar SK, Blair A, Holmes FF et al. Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 1986; 256:1141-7. �-2- significant increasing risk of NHL with increasing frequency of herbicide use (days per year) supports the idea that the association is real, but the weak, and barely significant association with years of use argues somewhat against it. There are some points of detail which should be noted, although none jeopardize the principal findings, so far as I can judge: - presumably to have series of the three tumors of approximately equal size (200, 173 and 200), the investigators selected a sample of 200 cases of NHL from the 29$ available. The relevance of this sampling is that, if the investigators had had any inkling of what their results would be, they would probably not have discarded 93 cases of NHL, and it must be presumed that it was not an a priori hypothesis that an association would be found only for NHL. - there is an unexplained, but statistically highly significant, difference between the three groups of cases in the proportion of identified cases which were interviewed. This is primarily due to the low proportion of.NHL cases which were excluded, either because they were not confirmed histologically (i.e. were not eligible) or because, if eligible, they were not interviewed. The differential loss occurs at several levels. Thus, the percentages of SDS, HD and NHL cases not histologically confirmed were 19, 15 and 10 percent, respectively. Of the eligible cases, the percentages not interviewed were 4, 8 and 1, respectively. It is difficult to see any relevance of these differences to the study conclusions, but it is curious that determination of eligibility and success in interviewing were both more complete in the group of cases for which an association is found. - for a high proportion of subjects (50% of cases of STS and NHL and �-3- their controls), the exposure information was obtained from surrogates since the subjects themselves were dead. One would suspect that surrogate-supplied information on occupation would be reasonably accurate, but one must question surrogates' knowledge of what specific herbicides were used and on how many days of the year. Since any inaccuracy involved would presumably apply to both cases and controls this cannot be regarded as a possible explanation of the association noted. In fact, it would tend to reduce any true association that exists. One might even wonder, in fact, whether it could explain the lack of association found for STS and HD - tumors for which others / have reported associations with phenoxyacetic acid exposures. - although both years of herbicide use and days of use per year show statistically significant trends for NHL risk, it is useful to note the small numbers on which these trends rest. Only two individual categories show significant differences between NHL cases and controls - use for 16 years or more (based on 16 cases, RR 2.0 and of marginal statistical significance), and use for 21 or more days per year (based on 7 cases, RR 6.0 and more clearly significant). It is not stated to what extent these categories overlap - i.e. contain the same individuals - but it is noteworthy that, in the most persuasive category (use for 21 or more days per year), where there are 7 cases, the expected number based on the controls would be about 2.3. It would take only 2 or 3 cases misclassified to this category (or controls misclassified out of it) to render the difference not statistically (or biologically) significant. - the authors' Table 1 shows that farmers for whom no use of herbicides were reported had RR higher than non-farmers (RR = 1.3) and while this �-4- is not formally significant (at p.less than 0.05) it is approaching significance (the lower 95% confidence limit is 0.8) and is not much different from that for all farmers (1.4). The latter similarity results, of course, from the small size of the group of herbicide users that does show substantially increased risk. - the paper's Table 2 shows risk ratios associated with ever-use of specific herbicides. Among 8 groups of herbicides (including a category "nonspecified"), the RR associated with phenoxyacetic acid is lower than that for any other group except the uracils. The RRs range from 1.3 to 12.5, that for the phenoxyacetic acids being 2.2. Besides the phenoxyacetic acids, RRs significantly above 1.0 are seen for triazines (2.5), amides (2.9), trifluralin (12.5) and nonspecified" (5.8). The focus on the phenoxyacetic acids seems to stem from their frequency of use (second only to the uracils), rather than from the level of risk associated with their use. In summary there are some questions and uncertainty in the data from this study - as there are in all epidemiologic studies - but, if there were no other evidence available, this study would stand as a good basis for the hypothesis that the risk of non-Hodgkin's lymphoma is increased by agricultural exposure to the phenoxyacetic acids - principally 2,4-D - and perhaps other herbicides. I would not accept this study as grounds for concluding that such associations clo exist - only as a basis for hypotheses which must be tested in other data. �-5- Other studies Paradoxically, it is unfortunate that this study is not the only one to provide evidence on this topic. In fact this study was prompted by previous studies suggesting that STS, HD and NHL were all increased in persons exposed to phenoxyacetic acid and other herbicides. It is when one tries to fit the results of the Kansas study into the context of previous work that matters become difficult. I do not believe that the authors' conclusion that "the study confirms the reports from Sweden and several US states that NHL is associated with farm pesticide use, especially phenoxyacetic acids" is justified. The Swedish studies of Hardell et al 2 showed elevated risks of 5- 6-fold for all three cancers investigated by Hoar et al. Exposure in the Swedish study was defined as "ever exposed" - principally on the basis of occupational history - and it is not possible to compare levels of exposure in the two studies to determine whether lower exposures could account for the lower RRs found in the US study (among all exposed). However, the important discrepancy is that the Swedish study found significant associations for all three tumors and the US study only for one. Before concluding that the US study is confirmatory of the Swedish one with respect to NHL one must understand the reason for the discrepancy with respect to STS and HD. The reasons for these discrepancies whether in the exposures studied, the method of study, or simply chance - are as cogent as is the agreement with respect to NHL. Until there is an adequate explanation for the discrepancies one can have little confidence that the agreement represents reality. 2 Hardell L, Eriksson M, Lenner P, et al. Malignant lymphoma and exposure to chemicals, especially organic solvents, chlorophenols and phenoxy adds: a case-control study. Br J Cancer 1981; 43:169-76. �-6- It is beyond the scope of this contract to review all the published relevant literature but perusal of the articles accompanying the review request does not lead to any clear impression of support for or evidence against the conclusion of Hoar et al. Pearce et al report a case-control study of 83 cases of NHL and conclude that there was no significant difference between cases and controls with regard to potential exposure to phenoxy herbicides. However, in this relatively small study, the results (RR 1.4, 90% CL 0.7-2.5) are not statistically incompatible with the RR (2.2) reported by Hoar et al for ever-use of phenoxyacetic acids; 4 Lynge reports a cohort study of persons exposed in the manufacture of various pesticides. The numbers are very small but are more suggestive of an association for STS (obs. 5, exp. 1.84) than for lymphoma (HN and NHL not distinguished) (obs. 7, exp. 5.37) among all employees, and there was no case of NHL among the 41 cancer deaths among persons^employed in the manufacture and packing of phenoxy herbicides specifically. The total number of cancer deaths expected in this group was 41.46. Lung cancer showed a significant excess (obs. 12, exp. 6.11). Other studies, because of small numbers, lack of specificity of exposure and/or other reasons, carry little evidential weight. The key question The key question in Mr. Blondell's letter quoted earlier is in fact two questions - what does the 'weight of evidence* say about the risk of lymphoma 3 Pearce NH, Smith AH, Howard JK, Sheppard, RA, Giles HJ, Teague CA. NonNon-Hodgkin's lymphoma and exposure to phenoxyherbicides, chlorophenols, fencing work, and meat works employment: a case-control study. Br J Ind Med 1986; 43:75-83. 4 Lynge E. A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. Br J Cancer 1985; 52:259-70. �-7- for agricultural workers exposed to 2,4-D,- and is 2,4-D a likely cause of lymphoma? The second question cannot be answered (except perhaps by animal experiment) until the first is answered, since without an association there is no causation. In my opinion the weight of evidence does not support the conclusion that there is an association between exposure to 2,4-D and NHL. It is axiomatic that, except when relative risks are very high - and sometimes even then - no single study will establish an association between an exposure and an outcome. The acceptance of an association depends on a number of studies showing consistent results across populations and across different epidemiologic methods. The study of Hoar et al is a strong study - strong enough on its own to establish a hypothesis of relationship of exposure to 2,4-D with some small proportion of cases of NHL - a hypothesis that clearly deserves attempts at refutation or support in other populations. When one attempts to place the results of this study among the results of those published previously, the picture becomes very confusing - much more so than if Hoar et al had been the only study published. Taken as a whole, I believe that the weight of evidence indicates that an association between 2,4-D and NHL remains a hypothesis that is still to be tested. I am unwilling to speculate as to whether 2,4-D causes NHL (or some'cases of NHL) until the evidence is clear that there is an association between them. Brian MacMahon, M.D., Ph.D. September 29, 1986 � 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. 1465 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 MacMahon, Brian Date A point or period of time associated with an event in the lifecycle of the resource September 29 1986 Title A name given to the resource Review of Hoar et al and Related Literature Subject The topic of the resource soft tissue sarcoma lymphomas cancer risk assessment agricultural exposure 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 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. 1471 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 Newton, Michael Logan A. Norris 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 https://www.nal.usda.gov/exhibits/speccoll/files/original/cc003259921469b55098670d20129bfd.pdf 8bd0632d88c32faeffadf3da676f2c69 PDF Text Text Item ID Number 01766 Hoar Author > Sheila K. Corporate Author ROpOTt/ArtiClO TitlO Agricultural Herbicide Use and Risk of Lymphoma and Soft-Tissue Sarcoma Journal/Book Title Year JAMA 1986 Month/Day Color September 5 D Number of Imaoas 1 DOSCrlptOII NfltBS See Item 1465 for a review. Monday, June 11, 2001 Page 1767 of 1793 �Original Contributions Agricultural Herbicide Use and Risk of Lymphoma and Soft-Tissue Sarcoma Shelia K. Hoar, ScD; Aaron Blair, PhD; Frederick F. Holmes, MD; Cathy D. Boysen; Robert J. Robel, PhD; Robert Hoover, MD; Joseph F. Fraumeni, Jr, MD A population-based case-control study of soft-tissue sarcoma (STS), Hodgkin's disease (HD), and non-Hodgkin's lymphoma (NHL) in Kansas found farm herbicide use to be associated with NHL (odds ratio [OR], 1.6; 95% confidence interval [Cl], 0.9, 2.6). Relative risk of NHL increased significantly with number of days of herbicide exposure per year and latency. Men exposed to herbicides more than 20 days per year had a sixfold increased risk of NHL (OR, 6.0; 95% Cl, 1.9, 19.5) relative to nonfarmers. Frequent users who mixed or applied the herbicides themselves had an OR of 8.0 (95% Cl, 2.3, 27.9) for NHL. Excesses were associated with use of phenoxyacetic acid herbicides, specifically 2,4-dichlorophenoxyacetic acid. Neither STS nor HD was associated with pesticide exposure. This study confirms the reports from Sweden and several US states that NHL is associated with farm herbicide use, especially phenoxyacetic acids. It does not confirm the case-control studies or the cohort studies of pesticide manufacturers and Vietnam veterans linking herbicides to STS or HD. (JAMA 1986;256:1141-1147) EPIDEMIOLOGIC studies from Sweden have suggested that workers exposed to phenoxyacetic acid herbicides and chlorophenols are at excess risk of soft-tissue sarcoma (STS), Hodgkin's disease (HD), and nonHodgkin's lymphoma (NHL).1'3 For all three cancers, risks were increased fivefold to sixfold, regardless of whether exposures were contaminated by polychlorinated dibenzodioxins or diFrom the Epidemiology and Biostatistics Program, National Cancer Institute, Bethesda, Md (Drs Hoar, Blair, Hoover, and Fraumeni); the Cancer Data Sen/ice, University ot Kansas Medical Center, Kansas City (Dr Holmes and Ms Boysen); and the Division of Biology, Kansas State University, Manhattan (Dr Robel). Reprint requests to Epidemiology and Biostatistics Program, National Cancer Institute, Landow 4C16. Bethesda, MD 20892 (Dr Hoar). JAMA, Sept 5, 1986—Vol 256, No. 9 benzofurans. There have also been several reports of increased STS and NHL among workers producing phenoxyacetic acid herbicides'1'7 and among farmers.8"10 See also p 1176. Concern over possible carcinogenic risks from phenoxyacetic acids and chlorophenols is heightened by the potential for widespread exposure. In addition to herbicide formulations used in agriculture and in the Vietnam war, these chemicals occur in blue stain retardants used in sawmills, slime control preparations in paper and pulp manufacturing, cutting oils and fluids, wood preservatives, waterproofing agents for leather and textiles, and medications.1 For these reasons, a population-based case-control study was conducted to clarify whether agricultural use of herbicides and insecticides affects risk of STS, HD, and NHL in the United States. METHODS Kansas, a major wheat-producing state, was chosen as the location for the study, since herbicides have been used more frequently than other pesticides on wheat. 2,4-Dichlorophenoxyacetic acid (2,4-D) has been the most commonly used herbicide in Kansas; substantial amounts of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) have also been used, along with myriad other chemicals." Cases All newly diagnosed cases of STS, HD, and NHL among white male Kansas residents, aged 21 years or older, from 1976 through 1982, were identified through the University of Kansas (Kansas City) Cancer Data Service, a population-based registry covering the state of Kansas. Cancer reporting, mandated by Kansas law, is considered complete, as evidenced by a higher annual incidence rate for STS (4.1/ 100 000) than reported by the nearby Iowa National Cancer Institute-sponsored Surveillance, Epidemiology, and End Results registry (3.4/100 000). There were 200 men diagnosed with Herbicide Use—Hoar et al 1141 �Table 1.—Soft-Tissue Sarcoma, Hodgkin's Disease, and Non-Hodgkin's Lymphoma in Relation to Duration and Frequency of Herbicide Use Soft-Tissue Sarcoma No. of Controls No. of Cases Odds Ratio (95% Confidence Interval) Nonfarmers 286 38 1.0 Farmers Duration of herbicide use, y 0 662 95 1.0 (0.7, 470 Hodgkin's Disease No. of Cases Non-Hodgkln's Lymphoma Odds Ratio (95% Confidence Interval) Odds Ratio (95% Confidence Interval) No. of Cases 50 1.0 ) 1.6) 71 0.8 (0.5, 1.2) 133 93 1.3 (0.8, 2.1) 37 1.0 ; 1.4 (0.9, 2.1) \ '. .. 73 1.1 (0.7, 1.8) 43 0.7 (0.5. 1.2) 1-5 53 5 0.7 (0.2, 2.0) 9 0.9 (0.4, 2.2) 9 1.3 (0.6, 3.1) 6-15 58 5 0.7 (0.2, 1.9) 8 0.8 (0.3, 1.9) 12 1.6 (0.7. 3.4) >16 57 11 1.4 (0.6, 3.1) 10 1.2 (0.5. 2.6) 16 2.0 (1.0, 4.0) Unknown 24 1 X for trend 3 0.13 0.11 2.06 .45 P (one-tailed) Frequency of herbicide use, d/y 0 1 .46 .02 497 74 1.1 (0.7, 1.7) 45 0.7 (0.4, 1.1) 94 1.3 (0.8, 2.0) 1-5 102 9 0.6 (0.3. 1.5) 16 1.0 (0.5, 1.9) 19 1.4 (0.7, 2.6) 6-10 29 2 0.5 (0.1, 2.3) 2 0.4 (0.1. 1.7) 6 1.6 (0.5, 4.3) 11-20 13 5 2.9 (0.8, 9.5) 2 1.3 (0.2. 6.8) 5 2.6 (0.8, 8.8) >21 12 1 0.8 (0.04, 6.5) 3 1.0 (0.2. 4.1) 7 6.0 (1.9, 19.5) 9 4 Unknown X for trend P (one-tailed) STS and 173 men with HD. A random sample of 200 men was drawn from the 297 men diagnosed with NHL from 1979 through 1981. Pathology specimens for 87% of the cases were reviewed by a panel of three pathologists to confirm the diagnoses and to standardize the subgroup terminology.12113 Specimens for the remaining cases either could not be obtained (11%) or were of poor or insufficient quantity to allow review (2%). For STS, HD, and NHL cases, the confirmation rates were 81%, 85%, and 90%, respectively. Among the eligible histologically confirmed cases, 139 were STS, 132 HD, and 172 NHL. Controls The controls were white men from the general population of Kansas. Three controls (N=1005) were matched to each patient on age (± 2 years) and vital status. For living patients, controls aged 65 years or older were selected from the Health Care Financing Administration file (Medicare), whereas controls aged 64 years or younger were selected by telephone, using a two-staged random digit-dialing technique.14 Control selection was not biased by differences in telephone coverage for urban (91%) and rural (90%) white Kansan households.15 For 1142 JAMA, Sept 5. 1986-vol 256, No 9 2 3 0.002 .50 -0.56 .29 3.33 .0004 farm locations and sizes, herbicides 92.3% of the working residential teleand insecticides used, years and acres phone numbers called, a person antreated, names and locations of compaswered who was willing to provide the nies where pesticides were purchased, names and ages of household members method of application, days per year aged 21 to 64 years and, if someone in exposed, and use of protective equipthe household was selected as a control, ment. Information on other crops was the household address. For deceased not obtained; however, in 1978, these patients, the controls were selected four crops constituted 94% of Kansas from Kansas state mortality files, with farm acreage and 87% of acres treated the additional matching factor of year with herbicides.11'16 All but four subof death. Persons with a cause of death jects who lived or worked on farmland of STS, HD, NHL, a malignancy of an as adults grew at least one of the four ill-defined site (International Classification of Diseases code 195), homicide, specified crops. Interviews were obtained from 133 or suicide were excluded. One half of patients with STS, 121 with HD, 170 the patients with STS and NHL died with NHL, and 948 controls, which before the initiation of the study, while represented 95% of the eligible subonly one third of the patients with HD had died. The next of kin were inter- jects (patients, 96%; controls, 94%). The overall response rate, a weighted viewed for deceased subjects. The same controls were used for comparisons average accounting for the initial with the three different cancer series refusals in the random digit-dialing control selection process, was 93%. when of comparable age. Interview The patients and controls, or their next of kin, were interviewed by telephone between December 1982 and January 1984. The questions on farming practices covered the calendar years working or living on farmland during which any of four specific crops (wheat, corn, sorghum, or pasture) were grown or livestock was raised, the Pesticide Suppliers' Survey To evaluate potential observation bias, corroborative evidence of the selfreported pesticide exposures was sought for a sample of 130 subjects with farming experience. Suppliers for 110 subjects were.located and provided information on the subject's crops and herbicide and insecticide purchases. Herbicide Use—Hoar et al �Table 2.—Non-Hodgkin's Lymphoma in Relation to Herbicide Group No. of Cases No. of Controls Never farmed 37 286 Ever use* Phenoxyacetic acids 24 78 Herbicide Group Odds Ratio (95% Confidence Interval) 1.0 2.2 (1.2, 4.1) 14 43 2.5 (1.2, 5.4) Amides 8 22 2.9 (1.1, 7.6) Triazines Benzoles 1 2 4.0 (0.1, 62.6) Carbamates 2 3 5.6 (0.6, 45.9) Trifluralin 3 2 12.5 (1.6, 116.1) 19 114 8 11 5.8 (1.9, 17.2) 24 78 2.2 (1.2, 4.1) 13 101 1.0 (0.5, 2.1) 3 11 2.2 (0.4, 9.1) ' 0 1 Uracils Nonspecified Hierarchical usef Phenoxyacetic acids Uracils; no phenoxyacetic acids Triazines; no phenoxyacetic acids or uracils Amides; no phenoxyacetic acids, uracils, or triazines 1.3 (0.7, 2.5) 'Farmers could report more than one group. tFarmers were assigned to only one group. Risk Measurements The measure of association between pesticide exposures and risk of cancer was the odds ratio (OR). All estimates were adjusted for the effects of age by stratification. Maximum likelihood estimates of the overall risk and the 95% confidence interval (CI) were computed by Cart's method.17 Matched analyses yielded results similar to those provided by the unmatched approach. The unmatched analyses are presented since they allowed control of additional factors that were not matching factors and increased power by pooling controls for each case series. For durationresponse relationships, significance was assessed by means of Mantel's one-tailed linear trend test.18 Logistic regression was also performed to evaluate simultaneously several components of pesticide exposure.19 RESULTS Ninety-five patients with STS, 71 with HD, and 133 with NHL reported having worked or lived on farmland, compared with 662 controls, yielding ORs of 1.0 (95% CI, 0.7, 1.6), 0.8 (95% CI, 0.5, 1.2), and 1.4 (95% CI, 0.9, 2.1), respectively (Table 1). No trend with years spent working or living on a farm was observed. Risks did not vary by v crop or farm acreage. Herbicides Farm herbicide use on any of the four specific crops (wheat, corn, sorJAMA, Sept 5, 1986—Vol 256, No. 9 ghum, or pasture) was reported by 22 patients with STS, 28 with HD, and 40 with NHL, compared with 192 controls, yielding ORs of 0.9 (95% CI, 0.5, 1.6), 0.9 (95% CI, 0.5, 1.5), and 1.6 (95% CI, 0.9, 2.6), respectively. There was a significant trend (P=.02) in risk of NHL with increasing years of herbicide use and with number of days of herbicide exposure per year (j°=.0004) (Table 1). Persons exposed to herbicides more than 20 days per year had an OR of 6.0 (95% CI, 1.9,19.5). There was no association with years of herbicide use after adjustment for annual days. On the other hand, adjustment for years of herbicide use changed the OR for the five patients and six controls exposed more than 20 days per year from 6.0 to 7.4 (95% CI, 1.6, 38.9), relative to the least exposed users. The risk of NHL associated with herbicide use did not change significantly when restricted to exposures incurred before 1976, the earliest possible date of death for the pooled control series. The NHL risk also rose with increasing time since first exposure. Farmers who started using herbicides after 1965, from 1956 through 1965, 1946 through 1955, and before 1946 had ORs of 1.3,1.7,1.7, and 3.3, respectively. This trend was diminished by controlling for frequency of herbicide use, but farmers who began use before 1946 still had an excess risk (OR, 2.2). No association was seen with number of acres treated with herbicides. No consistent patterns of excess risk of STS or HD were seen with either duration or frequency of herbicide use. More detailed analyses showed no association between agricultural factors and the occurrence of STS or HD, so the remainder of this report will describe only the NHL results. Subjects who reported usually mixing or applying the herbicides themselves (OR, 1.9; 95% CI, 1.1, 3.3) had higher risks for NHL than those who reported that someone else performed these functions (OR, 1.1). Indeed, the trends in the OR with increasing frequency and duration of use derived mainly from the workers who mixed or applied the herbicides themselves. For example, men who mixed or applied the herbicides and who were exposed for one to five, six to ten, 11 to 20, and more than 20 days per year had ORs of 1.4 (95% CI, 0.7, 3.0), 1.5 (95% CI, 0.5, 4.6), 1.8 (95% CI, 0.4, 7.4), and 8.0 (95% CI, 2.3, 27.9; seven patients, nine controls). Farmers who did not use protective equipment, such as rubber gloves or masks, had a higher OR associated with herbicide use (OR, 2.1; 95% CI, 1.0, 4.2) than those who protected themselves (OR), 1.5; 95% CI, 0.7, 3.1). Higher risks for herbicide use were also seen among farmers who used backpack or hand sprayers (OR, 2.3; 95% CI, 1.0,5.2), an application method with greater potential for personal exposure than other methods.20 After excluding persons who used backpack or hand sprayers, the ORs for tractormounted or mist-blower spraying and aerial application of herbicides were both 1.5. Too few subjects remained for evaluation of the group that applied herbicides only in the soil. A logistic regression analysis was performed to examine risk accounting for all pesticide exposure variables simultaneously. The results showed that age and annual days of herbicide exposure were significantly related to NHL risk. Restricting the analysis to persons exposed to herbicides and using categorical variables yielded ORs of 1.1 (95% CI, 0.3,4.0), 1.3 (95% CI, 0.3, 6.0), and 10.3 (95% CI, 2.1, 49.5) for persons exposed to herbicides six to ten, 11 to 20, and more than 20 days per year, respectively, relative to persons exposed one to five days per year. Increased risk was also associated with use of a backpack or hand sprayer (OR, 1.3; 95% CI, 0.5, 3.7) and failure to use protective equipment (OR, 2.0; 95% CI, 0.8, 5.1). Total period of herbicide use was not associated with NHL when the other pesticide exposure variables were controlled. The effect of personally mixing or applying herbicides could not be evaluated; the overwhelming majorHerbicide Use—Hoar et al 1143 �Table 3.—Non-Hodgkin's Lymphoma in Relation to Duration. 2,4-Dichlorophenoxyacetic Acid Use No. of Cases Duration of use, ' y 1-5 No. of Controls 37 Never farmed Frequency, and Latency of 286 Odds Ratio (95% Confidence Interval) 1.0 3 16 1.3 (0.3.5.1) 7 6-15 22 2.5 (0.9, 6.8) 16-25 8 15 3.9 (1.4, 10.9) >26 6 17 2.3 (0.7, 6.8) X for trend 3.560 P (one-tailed) .0002 Frequency of use.t d/y 1-2 17 2.7 (0.9.8.1) 3-5 4 16 1.6 (0.4. 5.7) 6-10 4 16 1.9 (0.5, 6.7) 11-20 4 9 3.0 (0.7. 11.8) 2:21 5 6 7.6 (1.8. 32.3) X for trend 3.733 .0001 P (one-tailed) First year of uset 1966 or later 5 21 1.9 (0.6. 6.0) 1956-1965 9 23 2.9 (1.1. 7.2) 1946-1955 8 24 2.1 (0.8. 5.6) Before 1946 2 2 6.2 (0.6. 65.3) 3.561 X for trend P (one-tailed) .0002 •five controls had missing data. tOne patient and ten controls had unknown frequency of exposure. {First available for use in 1942. ity of subjects involved in the logistic analysis either mixed or applied the herbicides themselves. Significant excesses were associated with ever use of phenoxyacetic acids, triazines (eg, atrazine, cyanazine, metribuzin, prometone, propazine, terbutryn), amides (eg, alachlor, propachlor), trifluralin, and nonspccified herbicides, such as "liquids," "sprays," and "dusts" (Table 2). Most farmers reported use of chemicals in several of the herbicide subgroups. Since the a priori hypotheses dealt with phenoxyacetic acids, we assessed risks associated with herbicides ranked in a hierarchical manner (Table 2). In the absence of phenoxyacetic acid exposure, the NHL risk associated with triazine exposure was reduced to 1.9 (95% CI, 0.4, 8.0) and the risk with uracil herbicides (eg, bromacil, terbacil) was reduced to 1.0 (95% CI, 0.5, 2.1). In this study, phenoxyacetic acid herbicide use was essentially synonymous with use of 2,4-D (OR, 2.3; 95% CI, 1.3, 4.3), since only three patients and 18 controls had used 2,4,5-T, and all but two of these controls had also used 2,4-D. Use of 2,4-D only, ie, eliminating 2,4,5-T users, was associated with an OR of 2.6 (95% CI, 1.4, 5.0). There were significant, although inconsistent, increases in NHL risk in relation to the duration, frequency, and latency of 2,4-D use (Table 3). The 2,4-D users exposed to herbicides more Table 4.—Non-Hodgkin's Lymphoma in Farmers in Relation to Use of Herbicides and Insecticides Annual Days of Use Herbicides 0 No. of Cases No. of Controls 90 474 Odds Ratio* (95% Confidence Interval) 1.0 1-5 11 57 1.1 (0.5, 2.3) >6 6 18 2.1 (0.7.5.9) No. of Cases 4 Odds Ratio (95% Confidence Interval) No. of Controls Odds Ratio (95% Confidence Interval) No. of Cases No. of Controls 21 1.1 (0.3.3.5) 94 495 1.0 100 1.1 (0.6, 2.1) 53 2.1 (0.9. 4.9) 8 43 1.2 (0.5. 2.9) 19 12 35 2.3 (1.0. 4.9) 18 Insecticide use, adjusted for herbicide use 1.1 (0.6, 2.2) No. of Cases No. of Controls 90 474 1-2 2 12 2:3 2 9 Odds Ratio* (95% Confidence Interval) Odds Ratio* (95% Confidence Interval) No. of Controls 1.3 (0.7, 2.4) 107 549 30 1.7 (0.7, 4.1) 10 42 1.2 (0.5. 2.8) 48 1.7 (0.8, 3.5) 14 57 1.4 (0.6, 3.1) No. of Controls 17 75 0.9 (0.1. 4.2) 8 1.5 (0.2. 8.1) 12 Herbicide use, adjusted lor insecticide use Odds Ratio* (95% Confidence Interval) No. of Cases No. of Cases 1.0 Adjusted for Herbicide Use Ever Used Herbicides Never Used Herbicides Insecticides 0 Adjusted for Insecticide Use Ever Used Insecticides Never Used Insecticides 1.0 1.4 (0.8. 2.4) •Odds ratio relative to farmers, no herbicide or insecticide use. 1144 JAMA. Si-nt 5. 1986—Vol 256. No 9 Herbicide Use—Hoar et al �than 20 days per year had an OR of 7.6 (95% CI, 1.8, 32.3). However, these variables cannot be determined with complete accuracy because the questionnaire elicited dates and frequency of use of any herbicide on each farm instead of dates and frequency for each specific herbicide. Therefore, the actual years or days of 2,4-D use may be less than that reported for all herbicides on a farm. Risk associated with herbicide exposure was also examined by subgroups of NHL. There were no differences in the ORs associated with herbicide use when cases were categorized by histologic types (follicular, diffuse, and not specified) and by grade (prognostic groupings of low, intermediate, and high), as classified by the National Cancer Institute Working Formulation.13 In addition, no significant differences in risk for any tumor were associated with either age at diagnosis or-vital status at interview. Deceased subjects had just slightly lower risks of NHL associated with overall herbicide exposure (OR, 1.5; 95% CI, 0.7, 3.3) or long-term exposure (OR, 5.5; 95% CI, 0.7, 41.3) than did living subjects (OR, 1.7; 95% CI, 0.8, 3.7; and OR, 5.6; 95% CI, 1.1, 28.9; respectively). Insecticides Insecticide use on crops or animals was reported by 54 patients with NHL and 275 controls, yielding an OR of 1.5 (95% CI, 0.9,2.4). There was no association with increasing years of insecticide use. Risk increased significantly but inconsistently with days of exposure per year. Men exposed to insecticides more than six days per year had a 2.8-fold increased NHL risk (95% CI, 1.2, 6.5). Farmers who started using insecticides after 1965, from 1956 through 1965, 1946 through 1955, and before 1946 had ORs of 1.5,0.7,1.5, and 1.7, respectively. No association was seen with number of acres treated with insecticides. Other exposure variables, such as mixing and applying insecticides, application method, and insecticide type, showed little or no association with NHL risk. Herbicides vs Insecticides Table 4 shows that NHL risk increased with annual days of herbicide exposure, but was not further increased by simultaneous use of insecticides. Adjustment for insecticide exposure did not alter the ORs for herbicide use. On the' other hand, risk increased only slightly with annual days of insecticide exposure within strata of herbicide use. Adjustment for herbicide use decreased the OR for JAMA, Sept 5, 1986-Vol 256, No. 9 insecticide use from 1.5 to 1.1 (95% CI, 0.6, 2.2). Similar analyses based on years of exposure also suggested that risk was more strongly associated with exposure to herbicides than to insecticides. The number of subjects was too small for a more detailed stratified analysis of herbicide or insecticide use. In a logistic analysis of all pesticide variables, insecticide exposure was not found to be significantly related to risk. The important variables remained age and annual days of herbicide exposure. The elevation in NHL risk (OR, 1.3) seen among farmers who did not report herbicide use may be due to other exposures encountered in farming activities or to biased misclassification of exposure status. However, it is not likely that more patients than controls underreported herbicide exposure. Slightly fewer "nonexposed" farming patients with NHL (52%) than controls (55%) were deceased, with interviews supplied by next of kin who might underreport exposures. Approximately the same percentage of "nonexposed" farming patients (4%) and controls (5%) were usually employed in agriculture. Fungicides Thirty-two patients with NHL and 105 controls treated seeds with fungicides (OR, 2.1; 95% CI, 1.2, 3.7). Risk was elevated among both herbicide users (22 patients, 68 controls; OR, 2.3; 95% CI, 1.2, 4.3) and farmers who had never used herbicides (ten patients, 37 controls; OR, 1.9; 95% CI, 0.8, 4.4). No other information on fungicide use was collected to allow further evaluation of this association. Pesticide Suppliers' Data Suppliers usually reported less pesticide use than subjects. Agreement on specific years of exposure was better for insecticide use than herbicide use. There were no consistent differences between agreement rates for patients and controls. Multiplying the number of patients and controls who reported any herbicide use by the percentage of verified herbicide use yielded a recalculated OR of 1.8 for NHL, which was slightly higher than the OR based on interview data only (1.6). Agreement between suppliers and subjects improved when pesticide use during the last ten years was considered. Nonfarming Exposures Nonfarming exposures did not confound the association between NHL and agricultural use of herbicides. Nonfarming pesticide use in home gardens and yards was not associated with NIIL. The OR associated with ever smoking at least 100 cigarettes was slightly below 1 (OR, 0.7; 95% CI, 0.5, 1.0), as it was for lifetime consumption of at least 100 cups of coffee (OR, 0.8; 95% CI, 0.5, 1.4). Consumption of raw, unpasteurized milk products had no effect on NHL risk (OR, 1.1; 95% CI, 0.8, 1.6). Eight patients with NHL had diabetes, half the expected number (OR, 0.5; 95% CI, 0.2, 1.2). No subjects had systemic lupus erythematosus, celiac disease, or immunodeficiency syndromes or had received immunosuppressive drugs. Seven patients with NHL reported previous radiation treatment (OR, 0.9; 95% CI, 0.4, 2.2). Subjects reporting a family history of cancer had a significant risk of NHL (OR, 2.3; 95% CI, 1.6, 3.2). Three patients and four controls reported a relative with lymphoma (OR, 4.0; 95% CI, 0.7, 22.2). COMMENT This investigation confirms the results of the case-control study by Hardell et al3 that initially suggested an association between herbicide use and NHL. Our finding of a sixfold increase of NHL among farmers exposed to herbicides more than 20 days per year is consistent with the sixfold excess risk associated with exposure to either phenoxyacetic acids or chlorophenols in the Swedish study. In both Sweden and Kansas, risk was elevated among persons exposed to phenoxyacetic acids, eg, 2,4-D, not likely to be contaminated by dioxins.21'22 These findings are consistent also with a number of descriptive studies suggesting increased lymphoma risk among agricultural workers, particularly in regions where herbicide use is common.8"10-23^ Cohort studies of pesticide manufacturing workers and applicators have in general been too small to examine adequately the risk of NHL. Danish workers manufacturing 2 methyl-4 chlorophenoxyacetic acid had seven NHL deaths with 5.4 expected, a nonsignificant 30% excess.25 No NHL cases have been observed in five other cohort studies of exposed workers, but the total number of workers involved was only 2705.26-29 Also, the Vietnam veteran experience offers little evidence to date for an-.association between NHL and herbicide exposure. The mortality study of 1247 men who applied herbicides in Project Ranch Hand reported no deaths due to lymphoma, as of December 1982,30 but less than one such death was expected in this small cohort. An unusual presentation of NHL of Herbicide Use—Hoar et al 1145 �the scalp was reported in two men of 158 who developed chloracne while employed in a British plant manufacturing pentachlorophenol.31 The expected number of cases of cutaneous NHL was far less. A similar association of cutaneous NHL with occupations involving spraying phenoxyacetic acid herbicides was found in Sweden.32 In our study, only one patient had cutaneous NHL, but he reported no herbicide exposure. An association between phenoxyacetic acid herbicides and NHL may have biologic plausibility through the relationships between dioxin contaminants and the immune system, as postulated by Hardell et al.3 Dioxin suppresses cell-mediated immunity33 and causes thymic involution in laboratory animals,34 while NHL occurs excessively in various immunodeficiency states of humans.35"37 Dioxin is also a potent animal carcinogen, with the risk seen for squamous cell carcinomas of the lung, hard palate/nasal turbinates/ tongue, hepatocellular carcinomas, follicular cell thyroid adenomas, and skin fibrosarcomas.38"43 However, it should be noted that 2,4-D, the herbicide most frequently used by subjects in this study, has not been shown to be carcinogenic in animals44 or immunosuppressive21'45 (S. Wong, PhD, written communication, Dec 12, 1985). 2,4-Dichlorophenoxyacetic acid does not contain 2,3,7,8-tetrachIorodibenzo-p-dioxin, the most carcinogenic dioxin isomer, although other less toxic isomers may occur.21122 The increased risk for farmers first using 2,4-D before 1946 may indicate the presence of carcinogenic impurities in the early formulations, with subsequent improvements jn the manufacturing process. Alternatively, the high risk of NHL among persons exposed 40 years ago may reflect a long latency period. The technology necessary to identify the isom- ers of the contaminants was not available in the early time period.21 The Swedish case-control studies and several of the industrial cohort studies have been criticized on a variety of grounds, including possible inaccurate diagnoses, observation and/or recall bias, and lack of control for confounding variables.5'48 The current study was designed to address a number of these concerns. The cases were drawn from all incident cases in a defined population. Included for analysis were only cases histologically confirmed as NHL by an expert review panel. The response rate for both cases and controls was high. The relationship between NHL and herbicide use was specific: there was no relationship between such use and the two other cancer sites studied, and the association was with herbicide and not insecticide use. Indeed, the association was limited to two subcategories of herbicides, phenoxyacetic acids and triazines. This degree of specificity argues against a significant role for either observation or recall bias in the association. In addition, independent assessments of herbicide exposure (as reported by self or next of kin, and by pesticide supplier) yielded similar estimates of risk. Finally, while the origins of NHL in the general population are largely unknown, some known risk factors (eg, immune-altering conditions and drugs, family history)35137'47-54 as well as several speculative factors (eg, cigarette smoking, coffee consumption, ionizing radiation)W2>5W7 were assessed and found not to confound the herbicide association. Several circumstances offered opportunities for inaccuracies in the assessment of pesticide exposures. These include the memories of subjects, the knowledge of relevant practices by next of kin, the vagueness of some questions concerning exposure, and the opportu- The study was supported in part by contract N01-CP-ES-11027 from National Cancer Institute. We thank Ariel B. Baker and Naomi E. Washburn for assisting the study manager; Rita Kingma, Lois I. Murphy, and Jeanine M. Peterson for interviewing; Vesta Gee and Claudia J. Oblak for coding; Shelley Hobbs and Melanie Wall for secretarial assistance; Joan L. Van Nice, Pros Bunag, and Dolores Wiesmann for identifying and locating study subjects; Fritz Lin, MD, and H. Clarke. Anderson, MD, for reviewing pathology samples; Edward Brown, Ila Dave, and Ko Jam Liu for computer programming; and Richard H. Adamson, PhD, Susan M. Sieber, PhD, and Elizabeth K. Weisburger, PhD, for reviewing the manuscript. cet 1981;1:1370. 7. Johnson FE, Kugler MA, Brown SM: Soft-tissue sarcomas and chlorinated phenols. Lancet 1981; 2:40. 8. Cantor KP: Farming and mortality from nonHodgkin's lymphoma: A case-control study. Int J Cancer 1982^9:239-247. 9. Burmeister LF, Everett GD, Van Lier SF, et al: Selected cancer mortality and farm practices in Iowa. Am J Epidemic! 1983:118:72-77. 10. Buesching DP, Wollstadt L: Cancer mortality among farmers. JNCI 1984;72:503. 11. Waldron AC, Park EL: Pesticide Use on Major Crops in the North Central Region , . . 1978, research bulletin 1132, Wooster, Ohio, Ohio Agricultural Research and Development Center, 1981. 12. International Classification of Disease for Oncology. Geneva, World Health Organization, 1976. 13. Non-Hodgkin's Lymphoma Pathologic Classi- fication Project: NCI sponsored study of classification of non-Hodgkin's lymphomas: Summary and description of a working formulation for clinical usage. Cancer 1982;49:2112-2135. 14. Waksberg J: Sampling methods for random digit dialing. J Am Slot Assoc 1978;73:40-46. 15. Census of the Population: 1970, vol 1, General Housing Characteristics, pt 18, Kansas. US Bureau of the Census, 1973. 16. Kansas Crop and Livestock Reporting Service: Pesticides: 1978 Pesticide Usage. Topcka, Kan, US Dept of Agriculture, Economics, Statistics, and Cooperatives Service. 17. Gart JJ: Point and interval estimation of the common odds ratio in the combination of 2X2 tables with fixed marginals. Biometrika 1970; 57:471-475. 18. Mantel N: x2 test with 1 degree of freedom, extension of the Mantel-Haenzel procedure. Am Stat Assoc J 1963;58:690-700. nities for more than one pesticide supplier per subject. The evidence suggests that the errors introduced by these factors are likely to be similar for cases and controls. This random misclassification of exposure would tend to dilute risk estimates, rather than produce spurious associations. While this may have led us to miss an association between pesticide use and STS or HD, it is unlikely to have created the association with NHL. If inaccurate exposure assessment occurred, we would have underestimated the magnitude of the risks involved. If the risks reported are accurate, and if they reflect a true causal relationship, then the amount of NHL in the current study attributable to herbicide exposure would be 11%.M Despite the limitations of the exposure information, the sixfold excess risk of NHL among high-intensity users of herbicides is cause for concern, particularly since the association was mainly for phenoxyacetic acids and was apparent using several different measures of exposure. Since over 42 million pounds of phenoxyacetic acid herbicides were applied to US farmlands in 1976,59 the carcinogenic effects suggested by this study and others have important public health implications. References / 1. Hardell L, Sandstrom A: Case-control study: Soft-tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols. Br J Cancer 1979; 39:711-717. 2. Eriksson M, Hardell L, Berg NO, et al: Softtissue sarcomas and exposure to chemical substances: A case-referent study. Br J Ind Med 1981;38:27-33. 3. Hardell L, Eriksson M, Lenner P, ct al: Malignant lymphoma and exposure to chemicals especially organic solvents, chlorophenols and phenoxy acids: A case-control study. Br J Cancer 1981; 43:169-176. 4. Honchar PA, Halperin WA: 2,4,5-T,trichlorophenol, and soft-tissue sarcoma. Lancet 1981; 1:268-269. 5. Cook RR: Dioxin, chloracne, and soft-tissue sarcoma. lancet 1981:1:618-619. 6. Moses M, Selikoff IJ: Soft-tissue sarcomas, phenoxy herbicides, and chlorinated phenols. Lan1146 JAMA. Sept 5. 1986-Vd 256. No. 9 Herbicide Use—Hoar et al �19. Engelman L: Stepwise Logistic Regression in BMDP STATISTICAL SOFTWARE, Dixon WJ (cd). Berkeley, University of California Press, 1983, pp 330-344. 20. Libich S, To JC, Frank R, ct al: Occupational exposure of herbicide applicators to herbicides used along electric power transmission line rightof-way. Am Ind Hyg Assoc J 1984;45:56-62. 21. International Programme on Chemical Safety: Environmental Health Criteria 29: 2,4-Dichlarophtfnoxyacetic Acid (2J-D). Geneva, World Health Organization, 1984. 22. Cochranc WP, Singh J, Miles W, ct al: Determination of chlorinated dibcnzo-p-dioxin contaminants in 2,4-D products by gas chromatographymass spectromctric techniques. J Chromatoyr 1981;217:289-299. 23. Stubbs HA, Harris J, Spear RC: A proportionate mortality analysis of California agricultural workers, 1978-1979. Am J Ind Mcd 1984;6:305320. 24. Pearcc NE, Smith AH, Fisher DO: Malignant lymphoma and multiple myeloma linked with agricultural occupations in a New Zealand cancer registry-based study. Am J Epidemiol 1985; 121:225-237. 25. Lynge E A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. Br J Cancer 1985;52259270. 26. Zack JA, Suskind RR: The mortality experience of workers exposed to tetrachlorodibenzodioxin in a trichlorophenol process accident J Occup Med 1980^2:11-14. 27. Ott MG, Holder BB, Olson Rft A mortality analysis of employees engaged in the manufacture of 2,4,5-trichlorophcnoxyacetic acid. J Occup Med 1980-^2:47-50. 28. Cook RR, Townscnd JC, Ott MG, ct al: Mortality experience of employees exposed to 2,3,7,8tetrachlorodibcnzo-p-dioxin (TCDD). J Occup Med 1980;22:530-532. 29. Riihimaki V, Asp S, Hernberg S: Mortality of 2,4-dichlorophcnoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid herbicide applicators in Finland: First report of an ongoing prospective cohort study. Scand J Work Environ Health 1982;8:3742. 30. Project Ranch Hand II: An EpidemMogic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides, Baseline Mortality Study Results. Brooks Air Force Base, Tex, Epidemiology Division, Data Sciences Division, US Air Force School of Aerospace Medicine, 1983. 31. Bishop CM, Jones AH: Non-Hodgkin's lym- JAMA, Sept 5, 1986—Vol 256, No. 9 phoma of the scalp in workers exposed to dioxins. Lancet 1981:2:369. 32. Olsson H, Brandt I.; Non-Hodgkin's lymphoma of the skin and occupational exposure to herbicides. iMnci-t 1981 £579. 33. Vos JG, Moore JA, Zinkl JG: Effect of 2,3,7,8tetrachlorodiI>enzo-/>-dioxin on the immune system of laboratory animals. Environ Health Persptxt 1973;5:149-162. 34. Harris MW, Moore JA, Vos JG, ct al: General biological effects of TCDD in laboratory animals. Environ Health Perspect 1973;5:101-109. 35. I loovcr R, Fraumeni JF Jr: Risk of cancer in renal transplant recipients. Lancet 1973;2:55-57. 3G. Kinlcn LJ, Sheil AGR, Peto J, et al: Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosupprcssive drugs. Br Med J 1979;1461-1466. 37. Filipovich AH, Spector I5D, Kersey J: Immunodeficiency in humans as a risk factor in the development of malignancy. Prev Med 1980;9:252259. 38. Crow KD: Soft tissue sarcomas and chlorinated phenols. Lancet 1981^:369. 39. Kociba RJ, Keycs DG, Bcyes JE, et al: Results of a two-year chronic toxicity and oncogcnicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats. Toxicol Appl Pharmacol 1978; 46:279-303. 40. Kociba RJ, Keycs DG, Beyer JE, ct al: Longterm toxicologic studies of 2,3,7,8-tctrachlorodibenzo-p-dioxin (TCDD) in laboratory animals. Ann NYAcad Set 1979;320:397-404. 41. Van Miller JP, Lalich JJ, Allen JR- Increased incidence of neoplasms in rats exposed to low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Chemospkere 1977;10:625-632. 42. National Toxicology Program (Report 80-31): Carcinoyenesis Bioassay of 2,3,7,8-Tctrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in OsborneMendel rats and BeCSFl mice (Gavage Study), technical report scries 209, National Institutes of Health publication 82-1765. Research Triangle Park, NC, Ucpt of Health and Human Services, 1982. 43. National Toxicology Program (Report 80-32): Carcinogenesis Bioassay of 2,3,7,K-Tetrachlorodibenzo-p-dioxin (CAS No. 1746-01-6) in SurissWebster Mice (Dermal Study), technical report scries 209, National Institutes of Health publication 82-1757. Research Triangle Park, NC, Dept of Health and Human Services, 1982. 44. Young AL, Calcagni JA, Thalken CE, et at The Toxicology, Environmental Fate, and Human Risk of Herbicide Orange and Its Associated Dioxin, US Air Force technical report 78-92. Brooks AFB, Tex, US Air Force Occupational and Environmental Health Lalmralory, 1978. 45. Blakely BR, Schicfcr BH: The effect of topically applied n-butylestcr of 2,4-dichlorophenoxyacctic acid on the immune response in mice. J Appl Toxicol, in press. 46. Cole P: Direct testimony before the Administrator of the Environmental Protection Agency of the United States of America in re. The Dow Chemical Company, ct al. KIFRA Docket No. 415, ct al, Washington, DC, Oct 23,1980. 47. Li FP, Fraumeni JF Jr, Mantel N, ct al: Cancer mortality among chemists. JNCI 1969;43:11591164. 48. Olin Git The hazards of a chemical laboratory environment- A study of the mortality in two cohorts of Swedish chemists. Am Ind Hyg Assoc J 1978;39:557-562. 49. Searle CE: Epidcmiologic study of the mortality of British chemists. Br J Cancer 1978^8:192193. 50. Monson RR, Fine LJ: Cancer mortality and morbidity among rubber workers. JNCI 1978; 61:1047-1053. 51. Cantor KP, Fraumeni JF Jr Distribution of non-Hodgkin's lymphoma in the United States between 1950 and 1975. Cancer Res 1980;40:26452652. 52. Kalant N, Sccmaycr T: Malignant lymphoma in spontaneously diabetic rats. N Engl J Med 1979;30ft737. 53. Green JA, Dawson AA, Walker W: Systemic lupus crythcmatosus and lymphoma. Lancet 1978; 2:753-756. 54. Douglas AP: Ccliac disease and lymphoma of intestines and brain. N Engl J Med 1977;296:821. 55. Vianna NJ, Polan A: Lymphomas and occupational benzene exposure. Lancet 1979;21394-1395. 56. Paffenbarger RS, Wing AL, Hyde RT: Characteristics in youth predictive of adult-onset malignant lymphomas, melanomas, and leukemias. JNCI 1978:60:89-92. 57. Krikorian JG, Burke JS, Rosenberg SA, et al: Occurrence of non-Hodgkin's lymphoma after therapy for Hodgkin's disease. N Engl J Med 1979:300:452-458. 58. Cole P, MacMahon R Attributable risk percent in case-control studies. Br J Prev Soc Med 1971;25:242-244. 59. Eichcrs TR, Andrilcnas PA, Anderson TW: Fanners' Use of Pesticides in 1976, agricultural economic report 418. National Economic Analysis Division, Economics, Statistics, and Cooperatives Service, US Dept of Agriculture, 1978. Herbicide Use—Hoar et al 1147 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 066 Folder The folder containing the original item. 1766 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Hoar, Sheila K. Aaron Blair Frederick F. Holmes Cathy D. Boysen Robert J. Robel Robert Hoover Joseph F. Fraumeni, Jr. Source A related resource from which the described resource is derived JAMA Date A point or period of time associated with an event in the lifecycle of the resource September 5 1986 Title A name given to the resource Agricultural Herbicide Use and Risk of Lymphoma and Soft-Tissue Sarcoma Subject The topic of the resource soft tissue sarcoma agricultural exposure cancer risk assessment lymphomas ao_seriesIII