1 15 216 https://www.nal.usda.gov/exhibits/speccoll/files/original/bc54fa583efffdef8051d9f49a71404e.pdf 208c08c339cf33fd3b1a079fcdbc1162 PDF Text Text ItomDNunber °1861 Author Bangert, Joseph V. Corporate Author Commonwealth of Massachusetts Agent Orange Progra RdDOrt/ArtldO TltlO Health Survey of Massachusetts Vietnam Veterans, Summary Journal/Book Title Year 1986 Month/Day June Color 0 Number of Images 12 Descrlpton Notes Wednesday, July 11, 2001 Page 1862 of 1870 �COMMONWEALTH OF MASSACHUSETTS AGENT ORANGE PROGRAM Office of the Commissioner of Veteran's Services 100 Cambridge Street Boston, MA 02202 "Health Survey of Massachusetts Vietnam Veterans" SUMMARY June, 1986 �FOREWORD The Commonwealth of Massachusetts Agent Orange Program, a program of the Office of the Commissioner of Veterans' Services, was provided funding by the 1983 Massachusetts Legislature for the purpose of conducting, "medical and scientific testing related to the possible health effects of Agent Orange on Massachusetts Vietnam Veterans." In January, 1984, the Agent Orange Program, Office of the Commissioner of Veterans' Services (OCVS) was implemented to survey programmatic, medical and scientific options. The Agent Orange Program instituted the Agent Orange Medical /Scientific Advisory Board to provide technical recommendations, oversight and review of proposals and implemented medical and scientific programs and studies. In January, 1985, the Massachusetts Agent Orange Program, in cooperation with the Massachusetts Department of Public Health published the "Mortality Among Massachusetts Vietnam Veterans, 1972-1983" written by Michael Kogan, M.A., and Richard Clapp, M.P.H., as the first step in the Commonwealth's attempt to find some answers to the complex questions surrounding the issue of Agent Orange. This mortality study provides a stable foundation for our continued ongoing efforts to provide scientific, technical, verifiable data regarding the effects of Agent Orange where none had been previously available. The Massachusetts Agent Orange Program's "Health Survey of Massachusetts Vietnam Veterans, 1986" is the second step in our program's continuing efforts to determine the needs of Massachusetts Vietnam Veterans and their families. This survey utilized the "American Legion," or "Stellman questionnaire," with minor modifications. The survey results, contained within, are the result of over 2,000 Massachusetts Vietnam Veterans and their families, and dependents who took the time out to complete a rather detailed and complex form. Only 1,500 of the 2,000 questionnaires were included in the Massachusetts survey as they were chosen on the completedness of the questionnaire, and those filled out by Massachusetts veterans who had not been in the Vietnam theatre were excluded. The analysis of the data collected by the Massachsuetts Agent Orange Program was compiled and analyzed by Mr. Frank J. Bove, M.S., an epidemiologist and PhD candidate with Harvard University School of Public Health. We are indebted to the hard work of this young scientist. The Massachusetts Agent Orange Program also acknowledges the leadership role of Governor Michael S. Dukakis of Massachusetts as well as that of Commissioner of Veterans' Services, John Halachis in their ongoing committment to this program and its importance for the more than 50,000 Massachusetts Vietnam Veterans. We also acknowledge the General Court of the Commonwealth of Massachusetts, and in particular to Senator Fran Doris, Representative Thomas Vallely and former Representative Tom Lynch who took the leadership in bringing the Massachusetts Agent Orange Program into being. We would be remiss if we did not acknowledge the pioneering role of Mr. Christopher Gregory, the former Director of the Agent Orange Program in getting the program on line. We shall continue first and foremost to aggressively and independently survey and test Massachusetts Vietnam Veterans who bore the brunt of battle and will never be forgotten. Jsefob/V. Bangert, Director Massachusetts Agent Orange Program r �SUMMARY Fifteen hundred Vietnam veterans in Massachusetts completed health questionnaires in January 1985. The respondents were those who filed a claim against the $180 million proposed out of court settlement reached by attorneys' representing the seven chemical manufacturers of Agent Orange and Vietnam veterans. Although not a random sample of the more than 50,000 Massachusetts Vietnam veterans, the findings indicate a considerable amount of illness among the respondents including tumors, neurobehavioral problems, reproductive difficulties and birth defects among their offspring. These findings are consistent with the observed symptoms and disease found among those exposed to 2,4-D, 2,4,5-T and 2,3,7,8-TCDD (Dioxin) in the workplace or the environment. INTRODUCTION Concern about the long-term effects of exposure to Agent Orange is widespread among Vietnam veterans in the U.S. and Australia, as well as among the citizens of Vietnam. In southern Vietnam, recent studies report a variety of persistent clinical problems including recurring bouts of headaches, depression and anxiety, asthenia, loss of libido, GI disorders and adverse reproductive outcomes. Studies of workers exposed to dioxin contaminated substances have found elevated rates of lymphomas and soft tissue sarcomas. Neurologic and liver effects have also been reported. Table 1 lists the findings of some of these occupational studies. Table 2 lists the findings of a Massachusetts Departments of Public Health and Veterans Services study of mortality among Vietnam veterans. This study found elevated rates of soft tissue sarcomas, kidney cancer, motor vehicle accidents and suicides. Table 3 lists findings from other studies of Vietnam veterans. This survey of the health of Massachusetts Vietnam veterans is part of an on-going research program that was sparked by the findings of previous studies as well as the concerns raised by veterans. The results of this survey are consistent with those in the studies mentioned above. METHODS AND SUBJECTS In January, 1985, The Massachusetts Agent Orange Program instituted a large-scale media campaign to alert Vietnam veterans �of the court-imposed deadline for filing a claim against the proposed $180 million settlement reached by attorneys for the seven manufacturers of Agent Orange and Vietnam veterans. About 2,000 veterans filed claims during a two day period at the state's Office of Veterans Services. The American Legion health questionnaire was distributed to those filing claims. In addition, some 300 questionnaires were mailed to veterans who phoned the Agent Orange Program requesting to participate in the health survey. Approximately 1800 questionnaires were returned to the Agent Orange Program, fifteen hundred of these were selected based on the criteria of completedness and actual service in Vietnam. Staff of the Agent Orange Program as well as trained volunteers, all of whom were Vietnam veterans, assisted respondents with any questions or difficulties they encountered with the questionnaire. Concerning the birth outcome data requested by the questionnaire, if the veterans were not sure of the information being asked, they were provided with a self-addressed envelope and permitted to take the questionnaire home to consult with their spouses. RESULTS Analysis of the questionnaire data was performed using DBASE III. Over a quarter of the respondents stated that they were diagnosed with tumors (cancerous, benign, fatty or other). Nine were diagnosed with Hodgkins Disease. Nearly 22% of the respondents indicated that one or more of their children had birth defects. Out of 1907 live births reported in the questionnaires, 462 (24%) had at least one birth defect and 160 had more than one defect. Thirty-seven spina bifida, other brain or spine defects were reported. Table 4 presents the data on other congenital malformations. Nearly one-third of the respondents indicated a decrease in libido and 22% reported fertility difficulties (see Table 4). Nearly two-thirds of the respondents indicated persistent problems with tiredness, over half reported persistent headaches and difficulties with memory or concentration, and almost half reported nervous disorders (see Table 5). Seventy-three percent of the respondents answered yes to the question: "Have you or your family ever noticed a personality change?". Eighty-two percent of the respondents claimed they regularly had at least one of the following problems: depression, violent rage, anxiety and irritability. Most had more than one problem. Two hundred and seventy-five respondents reported suffering from mental Illness or a breakdown. Symptoms of peripheral neuropathy in the lower or upper extremities were reported in over two-thirds of the veterans. Indications of asthenia were found in over half of the questionnaires (see Table 5). �Many respondents reported GI disorders. Over a third stated they had repeated nausea without flu or other sickness. Over 25% reported repeated bouts with diarrhea. One-third indicated that they regularly experienced loss of appetite and 20% reported weight loss. CONCLUSION We reemphasize that the questionnaires were not randomly distributed and were completed on a volunteer basis by a selfselected group of MA veterans. This means that we cannot base a valid, scientific study on the information contained in these questionnaires. However, the questionnaires clearly indicate considerable disease and suffering among a relatively young group of people (93% under age 45, 80% under age 40). The symptoms and disease found are consistent with findings from other studies of people exposed to dioxin, 2,4-D and 2,4,5-T. REFERENCES Ashe WF, Suskind RR (1949,1950)tReports on chloracne cases, Monsanto Chemical Co., Nitro, W.VA. Baader EW, Bauer AJ (1951):Industrial intoxication due to pentachlorophenol. Indus Med Surg 20:289-290. Barr MM (1982) :letter to editor. ANZ J. Psych. 16: 88-89. » Barr MM (1983): Apparent progressive axonal dying back neuropathy in Vietnam veterans. Neuroscience Letters, Abstracts suppl. ll:s.29. Dugois P, et.al. (1956): Acne chlorlque au 2,4,5-T. Lyon Med 88:446-447. Erickson JD, et.al. (1984): Vietnam veterans1 risks for fathering babies with birth defects. JAMA 252:903-912. Goldman PJ (1973): Schwetst akute chlorakne, eine massenintoxikation durch 2,3,6,7-TCDD. Der Hautarzt 24:149-152. �Moses M, et.al. (1984): Health Status of workers with past exposure to 2,3,7,8-TCDD in the manufacture of 2,4,5-T: Comparison of findings with and without chloracne. Am J Ind Med 5:161-182. Pazderova-Vejlupkov J, et.al (1980): Chronic poisoning by 2,3,7,8-TCDD. Prac Lek 32::204-209. NIH Library Translation. Pazderova-Vejlupkov J, et.al (1981): The development and prognosis of chronic intoxication by TCDD in men. Arch Env Health 36:5-11. Poland AP, et.al. (1971): Health survey of workers in a 2,4-D and 2,4,5-T plant. Arch Env Health 22:316-327. Stellman S, Stellman J (1980): Health problems among 535 Vietnam veterans potentially exposed to toxic herbicides. Am J Epi 112:444 (abstract). Susklnd RR (1953): A clinical and environmental survey, Monsanto Chemical Co., Nitro, W.VA.. Report of the Kettering Laboratory, July. Suskind RR (1977): Chloracne and associated health problems in the manufacture of 2,4,5-T. Report to the NIEHS/IARC Joint Conference, Lyon, France. January. Telegina KA, Bikbulatova LJ (1970): Affection of the folllcular apparatus of the skin in workers employed in the production of the butyl ester of 2,4,5-T. Vestnik Derm Ven 44:35-39. �TABLE 1 REPORTED OCCUPATIONAL EXPOSURES TO DIOXIN-CONTAMINATED SUBSTANCES RESULTING IN HUMAN ILLNESS* Year,place & chemical(s) Type of exposure & number of cases Neurological effects Other effects References 1949 W.VA TCP, 2,4,5-T explosion 117 production 111 nervousness, irritability, insomnia, personality change,depression, headache,pain & weakness in lower extremities, per ipheral neuropathy fatigue, [Ashe & weight Suskind, loss, 1949, weakness, 1950; decreased Suskind, libido,im - 1953; Suskind, potence 1977] . 1949 Germany TCP production, industrial lab 17 pain & weakness,paresthesia,polyneuritis in lower extremities fatigue, decreased libido, impotence 1952 Germany TCP production 31 pain & weakness,paresthesia in lower extremities, memory & concentration deficits,sleep disturbances, apathy,dulled emotional response fatigue, [Susmyocardial kind, damage 1977] 1953 Germany TCP explosion 55 hearing impairment, peripheral neuropathy fatigue, [Golddrowsiness, man, myocardial 1973] damage 1956 France TCP production 17 peripheral neuropathy 1964 USSR TCP 2,4,5-T production 128 headache,memory loss, sleeplessness [Baader & Bauer, 1951] [Dugois, et.al., 1956] fatigue, [Telejoint pain gina & Bikbulatova, 1970] �TABLE 1 (continued) Year,place & chemical(s) Type of exposure & number of cases Neurological effects Other effects References 1965-68 Czechoslovakia TCP 2,4,5-T production 80 pain & weakfatigue, [Pazderoness in lower weight va-Vejlupkov, loss extremities/ somnolence, et.al., 1980; headache, insomnia,peri19811 pheral neuropathy, emotional & psychiatric disorders 1969 NJ TCP 2,4,5-T 2,4-D production 73 weakness in lower extremities,hypomania *adapted from Moses/et.al.,1984 [Poland, et.al. ' 1971] �TABLE 2 Standardized Proportional Mortality Ratios for Selected Causes of Death for Vietnam Veterans Compared with Either Non-Vietnam-Veterans or Non-Veteran Males ICO NO* CAUSE OF DcATH OBSERVES VIETNAM VETERAN DEATHS All Causes COMPARISON GROUP NON- VIETNAM VETERANS PMR 95% C.I. NON-VETERAN MALES PMR 95% C.I. 840 140-239 All Neoplasms 153-154 Colo-Rectal 162 Lung, Bronchus 171 Connective Tissue 9 880 189 Kidney 9 183 (96,348) 353 (191,651) 139 88 (75,103) 87 (74,102) 28 111 (77,160) 138 (96,199) • 129 95 (78,115) 112 (94,134) 8 113 (56,228) 85 (42,172) 98 (66,146) 102 (72,145) 25 (513,1510) 473 (262,855) 390-429 'Circulatory System 439-459 (except Cerebrovascular) 430-438 Cerebrovascular Disease 571 Cirrhosis of the Liver 29 94 (65,136) 90 (61,132) • E800-E999 All external causes 428 108 (98,119) H3 (103,124) E810-E825 Motor vehicle accidents 169 110 (95,127) 127 (106,152) E950-E958 Recorded suicides 102 93 (77,112) 118 (98,143) 799.9, Estimated suicides*1* E850-E869, E950-E958, 163 113 (96,132) 140 (120,163) 31 80 (56,114) 66 (46,94)' E980-E982 E960-E969 Homicides International Classification of Diseases, 9th Revision, code number. **See reference (6) for discussion of this category. Note that there were 13 deaths in the category 799.9. �TABLE 3 REPORTS ON THE HEALTH STATUS OF VIETNAM VETERANS Reference Exposed Health Effects Stellman & Vietnam Veterans 535 congenital malformations, GI disturbances,pain in joints,sleep and psychological disturbances Barr/1982; 1983 Vietnam Veterans Australia, 120 peripheral neuropathy, insomnia,depress ion, Irritability,lassitude, memory loss,headaches, attempted suicides Erickson, et.al. 1984 Vietnam Veterans 696 congenital malformations: spina bifida,cleft lip, impaired hearing,clubfoot Stellman, 1980 �TABLE 4 CONGENITAL MALFORMATIONS Total Number Birth Defect Prevalence * BDMP Incidence Rate * Spina Bifida,other brain or spine defects 37 195 18.4 clubfoot 24 126 24.5 cleft lip/palate 17 89 13.4 missing, deformed or extra toes/fingers 31 163 Down's Syndrome 11 58 7.9 hip abnormalities 21 111 27.0 heart defect 60 defect of the digestive system 35 hearing disorders 63 cerebral palsy 27.2** 6 other skeletal defects Condition requiring special education or care 46 122 * per 10,000 live births ** polydactyly and syndactyly OTHER REPRODUCTIVE PROBLEMS Problem Number % Loss of libido 487 32.4% Infertility 330 22.0% Infertility and saw physician 246 16.4% low birth weight children 162 8.1% (under 5.5 Ibs.) �10 TABLE 5 NEUROBEHAVIORAL DYSFUNCTION Problem Number % persistent tiredness (saw physician) 957 270 63.7% 18.0% persistent headaches (saw physician) 773 338 51.5% 22.5% nervous disorders (saw physician) 684 356 45.5% 23.7% difficulty with memory or concentration (saw physician) 786 165 52.3% 11.0% mental illness or breakdown (receiving some disability) 275 132 18.3% 8.8% 1233 1015 82.1% 67.6% 321 21.4% regularly depressed, get into a violent rage, anxious or irritable (more than one behavioral problem) Sensory symptoms of early stage peripheral neuropathy asthenia (need hands to rise from chair, can't climb stairs without holding onto railing, unable to do tasks requiring holding arms at shoulder level, difficulty grasping tools) 775 51.6% � 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 069 Folder The folder containing the original item. 1861 Series The series number of the original item. Series III Subseries III Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Bangert, Joseph V. Description An account of the resource <strong>Corporate Author: </strong>Commonwealth of Massachusetts Agent Orange Program Date A point or period of time associated with an event in the lifecycle of the resource 1986-06-01 Title A name given to the resource Health Survey of Massachusetts Vietnam Veterans, Summary Subject The topic of the resource state-funded Vietnam veterans study mortality trends congenital birth defects industrial exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/464c4ee717a0a2411a166973c82cc31d.pdf ab0da5137799558d60bc46d676ba46bf PDF Text Text Item ID Number 01848 Author Skinner, Katherine M. Corporate Author New England Research Institute, Inc., Watertown, Mass Report/Article HUB Women's Vietnam Veterans Health Study Protocol Development, Addendum, Literature Review and Bibliography, Deliverable A Journal/Book Title Year 000 ° Month/Day Color n Number of Images 9 DOSCTlptOn Notes Contract No. V101 (93)P-1138; Provides a brief review of occupational exposure of nurses to hexachlorophene. Wednesday, July 11, 2001 Page 1849 of 1870 �WOMEN'S VIETNAM VETERANS HEALTH STUDY PROTOCOL DEVELOPMENT CONTRACT NO. V101(93)P-1138 ADDENDUM LITERATURE REVIEW AND BIBLIOGRAPHY DELIVERABLE A SUBMITTED BY NEW ENGLAND RESEARCH INSTITUTE, INC. PRINCIPAL INVESTIGATOR SONJA M. MCKINLAY, Ph.D. NEW ENGLAND RESEARCH INSTITUTE, INC. 42 Pleasant Street Watertown, Massachusetts 02172 (617)923-7747 �This addendum provides a brief review of an important occupational exposure for nurses - hexachlorophene - not included in the original review. This review should be included as Sub-section 5.1 A Exposure; Hexachlorophene. in Section 5. Nursing: Occupational Risks. Author: Katherine M. Skinner, M.A. �5.1.A EXPOSURE; HEXACHLOROPHENE Fingerhut et al. (1985) in an update of an earlier article present a status report on the NIOSH Occupational Dioxin Registry. This report indicates, clearly, that 2,3,7,8-TCDD (abbreviated to TCDD) is a contaminant in the process of manufacturing hexachlorophene as well as 2,4,5-T. Figure 1, reproduced from this report, summarizes the chemical process which produces 2,4,5-T, hexachlorophene and TCDD as a contaminant. Hexachlorophene was used for many years as a cleansing and disinfecting agent, with nurses being a consistently exposed occupational group. This substance was used routinely by nurses all through the period of the Vietnam conflict, until the late 1970's, when it was gradually withdrawn from use. Primarily used as a bacteriostatic agent, patients showered with hexachlorophene (marketed as pHisohex) for three consecutive days before elective operations. At time of surgery, the operative site would once again be scrubbed with pHisohex. All operating room personnel were required to scrub their fingers, hands and arms (up to the area just above the elbow) with brushes and pHisohex for fifteen minutes before participating in any operations. In the delivery room, the vaginal canal was usually cleansed with pHisohex before pelvic examinations were performed. Infants were bathed in pHisohex immediately after birth to remove meconeum, amniotic fluid and the vernix caseosa covering them. Hospital personnel were encouraged to wash their hands before touching another patient to prevent crosscontamination and thereby limit nosocomial infections. An editorial by Husaey in JAMA (1985), was the first to warn of adverse effects in the brain of newborns who developed staphylococcal infections after having been bathed in hexachlorophene. Bhargava et al (1976) reported that the effect on the blood coagulation process after dermal application of hexachlorophene was a reduction in coagulation time, an increase in the number of platelets and an enhancement of the ESR (esinophil sedimentation rate). Steinbeck (1977), who studied the local and systemic effects of commonly used cutaneous agents on mice and rabbits, reported that the mice showed no local toxic changes or tumor formation, and the systemic tumor incidence, i.e. tumors of the liver, lungs, lymphatic system, and other organs was similar to that of control animals. In rabbits, a number of proliferative benign and malignant ear tumors were observed in the positive controls, thereby demonstrating the efficacy of this model. Local toxic changes were seen in the benzalkonium and Al �hexachlorophene treated animals, but no skin tumors. Four animals had uterine tumors. In addition, one lung and one kidney tumor unrelated to the method of treatment were seen. An F.D.A. bulletin (1978) warned of drug induced abnormalities when hexachlorophene was used during pregnancy. A study by Siddicui et al. (1978) reports that an emulsion containing 0.25% hexachlorophene, 9.5% turpinal, 1.5% oil of turpentine, 13% ethanol, 6% castor oil distillate and 6% sodium salt, when given orally or instilled into conjunctival sacs of albino mice, produced lethal and insignificant toxic manifestations respectively, but a dose equivalent to 50 mg/kg given subcutaneously was found to produce a subacute lethal effect in guinea pigs. Fischer (1978) reported drug induced abnormalities in newborns exposed to hexachlorophene. Brandt et al. (1970) examined transplacental passage and embryonic fetal accumulation in mice. An experiment conducted by Maxwell and Le Quesne (1979) reported that in rats exposed to hexachlorophene for 3 weeks, maximum motor nerve conduction velocity in sciatic nerves was reduced by 7.5%. Histological examination showed intramyelin edema affecting some fibers and axonal degeneration of other fibers. In addition to intramyelin edema and axonal degeneration, segmental demyelination was present in animals who had been intoxicated with hexachlorophene for more than three months. However, there was no correlation between the degree of edema and reduction of conduction velocity. A letter published in Lancet. 1982, described hexachlorophene poisoning. Another letter by Martin-Bouyer and Stolley published the following week in Lancet described the toxicity of hexachlorophene. Myers et al (1982) adapted a non-invasive method for measurement of nerve blood flow to test the hypothesis that increased endoneural fluid pressure causes a reduction in nerve blood flow in the vasa nervosum. Their study supports the results that increased endoneural fluid pressure exacerbates the neuropathy by diminishing local blood flow. Winchell et al (1982) in studying toxic effects of hexachlorophene reported myelin-associated glycoprotein was localized immunocytochemically in periaxonal regions of oligodendraglia during hexachlorophene intoxication. Using a technique for microgravemetric analysis of nerve edema, Castello, Powell and Myers (1982) demonstrated A2 �increased water content in hexachlorophene neuropathy since there was a marked difference between hexachlorophene treated and control nerves. The water content of hexachlorophene intoxicated nerves was approximately 10% greater than control nerves. Schwetz (1985) reported adverse effects of environmental agents including hexachlorophene on the central nervous system caused by prenatal exposure. Rapoport, Menshikova and Bobkova (1985) reported an embryo toxicity associated with hexachlorophene after experimenting with dose induced pathology in guinea pigs. Using Falck-Hillarp fluorescence histochemistry, Henschenl and Olsen (1983) reported possible toxic effects of hexachlorophene or sympathetic adrenergic nerves. The experiment demonstrated a new aspect of hexachloropheneneurotoxicity degeneration of peripheral adrenergic nerve terminals and suggested that neurotoxic action on this unmyelinated fiber system should be looked for also in the central nervous system. Brandt, et al (1983) when studying the placental transfer of hexachlorophene in the Marmoset Monkey found the highest concentration in the liver and intestinal contents of the late fetus and newborn monkey. Bouin, Buentzet, Pradal (1983) in a study of resorption of drugs through the vaginal wall concluded that hexachlorophene is rapidly and largely absorbed through vaginal epithelium. Strickland et al (1983) reported that hexachlorophene from vaginal lubricants is variably absorbed from the vaginal mucosa and appreciable amounts can be detected in maternal and cord serum. Because of the potential for neonatal hexachlorophene toxicity, they recommended the use of alternative lubricants for pelvic examinations during labor. In a comparative study of chemically induced fetal death of mice, Dymin, et al (1984) reported the embryotoxic, gonadotoxic (oligosperma) and mutagenic effects of hexachlorophene. While studying the effects of reported hexachlorophene treatments on the mouse brain, Prosad et al (1984) concluded the catalytic efficiency of the mouse brain was significantly decreased during repeated hexachlorophene treatment. The fall in the activity potential of ACLE may account for the interference of hexachlorophene which may contribute to its neurotoxicity. A3 �After observing 5 infants with transcutaneous intoxication resulting from hexachlorophene contaminated talcum powder, Larregue et al (1984) described the dermatitis as characterized by its red pants shape, occurring suddenly/ its papyraceous aspect, and its association with severe encephalopathy. The neurologic signs with edematous degeneration of myelin characteristic of hexachlorophene toxicity, start with epileptic fits and progress rapidly to coma. The prognosis is serious leading either to death or to paraplegia. A recently published article by De Caprio et al (1987) examined the in vitro "dioxin-like activity of the environmental contaminant 1,2,4,5,7,8 hexachloro (9H)xanthene. After a number of sites in Missouri had been contaminated with polychlorinated dibenzodioxins and dibenzofurons from improper application of waste oil for dust control, 1,2,4,5,7,8-hexachloro(9H) xanthene, a byproduct of hexachlorophene manufacture was also detected. In view of the potential importance of this class of environmental contaminants, studies were then conducted to examine the acute oil toxicity in guinea pigs of in-vitro "dioxin-like" activity of 1,2,4,5,7,8 HCX. No compound or dose related mortality, body weight loss, or organ weight changes were noted at any dose level. Results using an in vitro bioassay for "dioxin-like" activity confirmed preliminary data suggesting 1,2,4,5,7,8- HCX, is about 10(6) times less potent than 2,3,7,8, tetrachlorodibenzo-p-dioxin (2,3,7,8, TCDD). These findings indicate that 1,2,4,5,7,8 HCX may represent a relatively low environmental hazard compared to 2,3,7,8 TCDD. A4 �Baurin, M; Guenzet J, Pradal, G.; Resorption of drugs through vaginal wall; J. Gynecol. Obstet. Biol. Reprod. 1983; 12(7):717-26. Bhargava, A.S.; Staben, P., Nienweboer, b; Giunzel, P; Effect of Hexachlorophene on the coagulation process in beagle dogs, Arzneimittedforshung, 1976;26(12):2183-5. Brandt, I; Dencker, L; Larson, Y., Transplacental passage and embryonic-fetal accumulation of hexachlorophene in mice, Toxicol Appl. Pharmacol; 1979, June 30; 49(2):393401. Brandt, I, Dencker L; Larson, K.S.; and Siddall R.A; Placental transfer of hexachlorophene in the marmoset monkey, Acta Pharmacol Toxicol. 1983 Apr;52(4)310-3. Carefully avoid hand disinfection, M.M.W.; 1978, Nov.lO;120(45):1973. Castellomi, Powell H.C; Myers R.R.; Microgravi-metric analyses of nerve edema, muscle Nerve, 1982, Apr 5; (4):261-4. DeCapro, A.P. Briggs, R., Gierthy, J.L., Kim, J.C., Dleepfer, R.D., "Acute Toxicity in the guinea pig and in vitro "dioxin-like" activity of environmental contaminant 1,2,4,5,7,8 hexachloro(9H)xanethese," J. Toxicol. Environ. Health 1987;20(3):241-8. Dymin, V.V., lushkov, G.G.; Minchenko, V.A.; Bogachut, G.P. Adropova, S.N.; Experimental studies on the embryotoxic, gonadotoxic and mutogenic effects of hexachlorophene; Gig Sanit 1984. Aug; (8):25-26. Fingerhut, M.A., Marlow, D.A., Haperim, W.E., and Honchar, P.A. The NIOSH Occupational Dioxin Registry; A Status Report. Presented at the 5th International Conf. on Dioxin, Bayreuth, Fed. Rep. of Germany, Sept. 16-19, 1985. Fischer W, Malformations caused by hexachlorophene, M.M.W. 1978 Novio; 120(45):1973. Hanig, J.P., Yoder, P.O., Krops, S., Protection with butylated hydroxytoluene (BHY+T) and other compounds against intoxication and mortality caused by hexachlorophene; Food Chem Toxicol; 1984 Mar 22(3):185-9 Henschen, A; Olson,L; Hexachlorophene induced degeneration of adrenergic nerves; a\application of quantitative image analysis to Falch-Hillarp flurescence histochemistry; Acta Neuropathol (1983)59(2):109-14. A5 �Hexachlorophene-interim caution regarding use in pregnancy. F.D.A. Bui. 1978, Aug-Sep;8 (4)26-7. Hopkins, J. Hexachlorophene: more bad new than good, Food Cosmet Toxicol, 1979, Aug; 17(4):410-2. Hussey, H.H., Editorial: Hexachlorophene bating of neonates, JAMA. 1975, Jul.14:233(2):172 Larreque, M., Laidet, B., Ramdene, P., Dyeridi A; Caustic diaper dermatitis and encephalitis secondary to the application of talcum contaminated with hexachlorophene; Ann Dermatol Venereal 1984; 111(9):789-97. Martin, Bouyer G, Stolley P.P., Hexachlorophene poisoning/Lancet 1982, May 15; 1 (8281):1121. Maxwell, I.e., Le Quesne, P.M., Conduction velocity in hexachlorophene neuropathy: correlation between electrophysiological and histological findings; J. Neurol .; 1979 Sep 43(1) 95-110. Myers, R.R; Mizisin A.P.; Powell, H.C.; Lampert P.W., Reduced nerve blood flow in hexachlorophene neuropathy; relationship to elevated endoneurial fluid pressure. J. Neuropathal EXP Neruo; 1982 Jul; 41(4) 391-9. Prasad, G.V., Rayendra, W., India K; Catalytic potential of field mouse Mus bllduga brain acetylcholinesterase during repeated hexachlorophene treatment, Toxicol Lett; 1984; Nov. 23(2):177-82. Rapoport, K.A.; Menshikova, T.A., Bobkova, E.A., Experimental data on the study of the embryotoxic acton of hexachlorophene, a component of antimicrobial textiles and household chemicals; Gig. Sanit; 1982 Oct; (10)26-9. Schwetz, B.A., Reproductive toxicity of environmental agents; Annu Rev. Public Health 1982;3:1-27. Siddigui, M.A. Mahmood I, Basit, N; Ahmed S., Bukhariao, Antimicrobial and toxicological studies on an antiseptic based on hexachlorophene and destructive destillate of castor oil. G. Batteriol Viol. Immunol. 1978, JulDec;71(7-12):191-9. Stenblack F; Local and systemic effects of commonly used cutaneous agents: Lifetime studies of 16 compounds in mice and rabbits Acta Pharmaciol Tociol. 1977 Nov; 41(5):41-31. Strickland, D.M.; Leonard R.G.; Staochonskey, S.; Benoit T; Wilson, R.T. Vaginal absorption of hexachlorophene A6 �during labor; Aroer J. Obstet. Gvnecol; 1983, Decl; 147(7):769-72. Winchell K.H., Sternberger N.H., Welister H.D., Myelinassociated glycoprotein localized immunocytochemically in periaxonal regions of abigodendroglia during hexachlorophene intoxication; Brain Res, 1982, May 13; 239(2) 679-84. A7 � 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 068 Folder The folder containing the original item. 1848 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 Skinner, Katherine M. Sonja M. McKinlay Description An account of the resource <strong>Corporate Author: </strong>New England Research Institute, Inc., Watertown, Massachusetts Title A name given to the resource Women's Vietnam Veterans Health Study Protocol Development, Addendum, Literature Review and Bibliography, Deliverable A Subject The topic of the resource Women Vietnam Veterans Health Study industrial exposure VA ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/623b4cbd8cd7ce67137660edb190fc1d.pdf 772408bd938746d030ed31e62d46c8bf PDF Text Text Item ID Number 01771 AllthOT Blair, Aaron Corporate Author Typescript: Research Protocol, a Case-Control Study of Lymphoma and Soft-Tissue Sarcoma: Association with Herbicide Exposures, [nd] Journal/Book Title Year 000 ° Month/Day Color Number of Imaoes : 16 Descrlpton Notes Monday, June 11, 2001 Page 1772 of 1793 �Research Protocol A CASE-CONTROL STUDY OF LYMPHOMA AND SOFT-TISSUE SARCOMA: ASSOCIATION WITH HERBICIDE EXPOSURES Aaron B l a i r S h e l i a K. Hoar E n v i r o n m e n t a l E p i d e m i o l o g y Branch N a t i o n a l Cancer Institute Landout 3C06 Bethesda, Maryland 20205 �A Case-Control Study of Lymphoma and Soft-Tissue Sarcoma: A s s o c i a t i o n w i t h H e r b i c i d e Exposures I. Introduction The E n v i r o n m e n t a l E p i d e m i o l o g y Branch of the National Cancer Institute is p l a n n i n g to conduct an e p i d e m i o l o g i c case-control i n v e s t i g a t i o n of soft-tissue sarcoma (STS), non- Hodgkin's lymphoma (NHL), and Hodgkin's disease (HD). The cases and controls, or t h e i r next-of-kin» w i l l be interv i e w e d by telephone to o b t a i n occupational h i s t o r i e s and other i n f o r m a t i o n p e r t i n e n t to the o r i g i n s of these cancers. P a r t i c u l a r attention w i l l be p a i d to h e r b i c i d e exposures. II. O b j e c t i v e The objective of t h i s study is to evaluate the effects of the f o l l o w i n g factors on the development of STS, NHL, and HD: 1) O c c u p a t i o n a l and non-occupational exposure to h e r b i c i d e s , in p a r t i c u l a r p h e n o x y a c e t i c a c i d s and c hloropheno1s. 2) Exposure to p h e n o x y a c e t i c a c i d - c o n t a i n i n g drugs, eg. c l o f i b r a t e . 3) Other factors such as g e n e t i c syndromes, f a m i l i a l c l u s t e r i n g , i m m u n o l o g i c d e f i c i e n c y , lymphedema, t r a u m a , and exposure to r a d i a t i o n , a r s e n i c , v i n y l c h l o r i d e , a n d r o g e n i c - a n a b o l i c steroids, a l l e r g e n i c extract i n j e c t i o n s , and a n i m a l s susceptible to �sarcoma-inducing viruses. III. L i t e r a t u r e R e v i e w Certain h e r b i c i d e s and h e r b i c i d e - c o n t a m i n a n t s been associated w i t h teratogenesis, have mutagenesis, and c a r e i n o g e n e s i s in a n i m a l and b a c t e r i a l e x p e r i m e n t s (Young AL et al., 1978). Recent e p i d e m i o l o g i c s t u d i e s from Sweden suggest that persons exposed to h e r b i c i d e s may at excess r i s k of cancer. be A retrospective cohort study of r a i l r o a d workers exposed to a m i t r o l e (3-am5no-1»2,4triazole) a n d p h e n o x y a c e t i c a c i d s ( 2 » 4 - d i c h l o r o p h e n o x y a c t i c a c i d and 2,4,5-trichlorophenoxyacetic a c i d ) showed of cancer L, i n c i d e n c e and m o r t a l i t y (Axelson 1974; Axelson 0 et a l . » 1980). and chlorophenols and (Hardell L and Sandstrom A, 1979; Hardell risks were whether L STS, 1979; et al., 1981). to were Sundell phenoxyacetic N H L , and Eriksson M HD et al., For all three cancers, increased f i v e - to s i x - fold, exposures 0 and Case-control studies revealed a s s o c i a t i o n s between exposure acids elevated rates regardless of c o n t a m i n a t e d by p o l y c h l o r i n a t e d d i b e n z o d i o x i n s (PCDDs) and dibenzofurans (PCDFs). There is w i d e s p r e a d p o t e n t i a l for exposure to phenoxy- a c e t i c a c i d s and chlorophenols. In a d d i t i o n to h e r b i c i d e f o r m u l a t i o n s these c h e m i c a l s appear retardants used in b l u e s t a i n i n s a w m i l l s , s l i m e control p r e p a r a t i o n s in paper and p u l p m a n u f a c t u r i n g , c u t t i n g o i l s and f l u i d s , wood p r e s e r v a t i v e s , waterproofing agents for leather and t e x t i l e s , and in m e d i c a t i o n s . Clofibrate, a plasma l i p i d - �l o w e r i n g d r u g * is a p h e n o x y a c e t i c a c i d - d e r i v a t i v e and has i n d u c e d h e p a t o c e l l u l a r c a r c i n o m a s and sarcomas boda and Azarnoff, 1979). If the reported in rats (Svo- epidemiologic associations are causal and as strong as suggested by the Swedish research, these agents could be r e s p o n s i b l e for a large p r o p o r t i o n of the cases of STS, NHL, and HD in the U n i t e d States. The e t i o l o g y of STS is largely unknown. A small propor- t i o n of cases are related to M e n d e l i a n syndromes and f a m i l i a l m u l t i p l e - c a n c e r syndromes (Tucker and F r a u m e n i , 1981; Li and F r a u m e n i , 1969; associated Blattner with et a l . » 1979). genetically Some cases are determined i m m u n o d e f i c i e n c y syndromes and i a t r o g e n i c immunosuppressed states (Hoover and F r a u m e n i , 1973; Spector et al., 1978). K i n l e n et al., 19797 C h r o n i c l y m p h e d e m a has been l i n k e d to sarcomas in case reports (Dubin et al., 1974). E x t e r n a l r a d i a t i o n therapy and r a d i o i s o t o p e s have also been associated w i t h the d e v e l o p m e n t of sarcomas ( K i m et al., 1978). Thorotrast, used for r a d i o g r a p h i c s t u d i e s of blood vessels in the l i v e r , resulted sarcomas in a n g i o s a r c o m a s of the l i v e r and at the s i t e of i n j e c t i o n (da Motta et al., Falk et al., 1979a). 1979; Use of the r a d i o isotope, 1-125, for treatment of t h y r o t o x i c o s i s was followed e i g h t years later by the d e v e l o p m e n t of a sarcoma al., 1978). and suspected of the larynx ( M c K i l l o p et Other agents used m e d i c i n a l l y and o c c u p a t i o n a l l y of b e i n g associated w i t h d e v e l o p m e n t of STS i n c l u d e ! a r s e n i c , v i n y l c h l o r i d e , a n d r o g e n i c - a n a b o l i c steroids, i r o n - d e x t r a n i n j e c t i o n s , and a l u m i n u m compounds (Falk et al., �1979b, M c l l l m u r r a y and L a n g m a n , 1978; W e i n b r e n et al.,1978) V i r u s e s appear to be r e s p o n s i b l e for the i n d u c t i o n of sarcomas in c h i c k e n s * cats, and m i c e and may play a role in the causation of human sarcoma (Kufe et a l . » 1972)» a l t h o u g h there is no e p i d e m i o l o g i c e v i d e n c e to date. E p i d e m i o l o g i c studies have also suggested possible l i n k s between these diseases and selected occupations (Grufferman et al., 1976, Tucker and F r a u m e n i » 1981). Woodworkers* c l e r i c a l workers, accountants* engineers, lawyers, judges, p h y s i c i a n s , and t e x t i l e workers reportedly have an increased r i s k of HD, Several, but not a l l , cohort s t u d i e s of c h e m i s t s have demonstrated excess m o r t a l i t y from HD and NHL (Li et a l . » 1969; O l i n , 1976; O l i n , 1978; Searle et al., 1978; Hoar and Pell, 1981 ). Non-occupational factors associated w i t h HD and NHL i n c l u d e age, race, sex, g e o g r a p h i c a l l o c a t i o n (Cole and MacMahon, 1968), socioeconomic status, m a r i t a l status, e t h n i c i t y , r e l i g i o n , o b e s i t y , s m o k i n g h i s t o r y , coffee d r i n k i n g h a b i t s (Paffenbarger et al., 1977; Paffenbarger et al., 1978), f a m i l i a l cancer h i s t o r y , d i a b e t e s (Kalant and Seemayer, 1979), s y s t e m i c lupus erythematosus (Green et al., 1978), i n f e c t i o u s m o n o n u c l e o s i s (Carter et al., 1977), c e l i a c d i s e a s e (Douglas, 1977), i m m u n o d e f i c i e n c y syndromes ( F i l i p o v i c h et al., 1980), tonsi1lectomy (Gutensohn et al., 1975), i o n i z i n g r a d i a t i o n , c h e m o t h e r a p y (Krik o r i a n et al., 1979), i m m u n o s u p p r e s s i v e drugs (Hoover and F r a u m e n i , 1973), and other exposures. �Many factors h a v e been suggested as c o n t r i b u t i n g to the d e v e l o p m e n t of STS, NHL, and HD but need to be further e v a l u a t e d and q u a n t i f i e d . In p a r t i c u l a r , the heavy use of h e r b i c i d e s a n d t h e h i g h cancer r i s k p o s s i b l y associated w i t h t h e i r exposure underscores the urgent need to conduct an independent ep i detn i olog i c i n v e s t i g a t i o n of persons exposed to these p e s t i c i d e s . IV. Study Subjects 1) The case group w i l l consist of w h i t e men, aged 21 and older, d i a g n o s e d w i t h STS, NHL, or HD, from a r e g i o n where at least 10% of the w o r k i n g w h i t e p o p u l a t i o n has been engaged in o c c u p a t i o n a l a c t i v i t i e s that i n v o l v e contact w i t h h e r b i cides. Kansas has been selected since it is a w h e a t - p r o d u c i n g area where h e r b i c i d e use is great but use of i n s e c t i c i d e s and f u n g i c i d e s is c o n s i d e r a b l y less. The goal is to select 200 cases of each cancer, however because the study region is sparsely populated and these are rare tumors, a m i n i m u m of 100 cases of each cancer w i l l be acceptable. Cases from the last f i v e years w i l l be drawn from the U n i v e r s i t y of Kansas M e d i c a l Center Cancer Data S e r v i c e , a p o p u l a t i o n - b a s e d cancer r e g i s t r y . Next-of-kin w i l l serve as respondents for those cases who h a v e d i e d . 2) The controls w i l l be w h i t e men from the general p o p u l a t i o n of the g e o g r a p h i c area selected for study. Three controls w i l l be matched to each case on age (+/yearn), v i t a l status, and area of residence (probably a 2 �m u l t i - c o u n t y unit). For cases who are currently a l i v e , controls aged 65 years or older w i l l be selected from the Health Care F i n a n c i n g A d m i n i s t r a t i o n f i l e * to be p r o v i d e d by NCI; whereas, controls aged 64 years or younger could be selected by telephone t h r o u g h a random d i g i t d i a l i n g t e c h n i q u e . For cases who have d i e d before the i n i t i a t i o n of the study* the controls could be selected from Kansas state m o r t a l i t y files. In a d d i t i o n to age at death (+/- 2 years)» these controls would be matched to the cases on year of death. Persons whose cause of death is STS, NHL, HD, or a m a l i g n a n c y of an i l l - d e f i n e d s i t e (ICDA code 195) would be excluded. The next-of-kin w i l l be i n t e r v i e w e d . The same controls should be used for the three case series whenever p o s s i b l e . The goal is that each case h a v e three s u i t a b l y matched controls for c o m p a r i s o n . We anti- c i p a t e that 700 to 1000 controls w i l l be necessary to meet t h i s r e q u i r e m e n t . A s s u m i n g an level of .05 and 10% of the p o p u l a t i o n exposed to h e r b i c i d e s , a study of 100 cases w i t h a 3:1 m a t c h i n g r a t i o would be able to detect a m i n i m u m odds r a t i o of 2.7 w i t h 90% power. V. Pathology R e v i e w Pathology blocks, s l i d e s , and/or m e d i c a l records w i l l be o b t a i n e d for c o n f i r m a t i o n of the d i a g n o s i s of STS, or HD. NHL, S p e c i m e n s w i l l be r e v i e w e d by NCI p a t h o l o g i s t s . �VI. Interv i ew The cases and controls, or t h e i r next-of-kin, w i l l be i n t e r v i e w e d by telephone c o n c e r n i n g the f o l l o w i n g items: Date of b i r t h Place of b i r t h Mar i tal status Religion Ethnicity Height/Weight Education O c c u p a t i o n (emphasis on exposure to p h e n o x y a c e t i c acids, chlorophenolsi arsenic compounds, v i n y l c h l o r i d e , poultry, other b i r d s , and cats) N o n - o c c u p a t i o n a l use of h e r b i c i d e s Smok i ng Coffee d r i n k i n g Fam i 1 i a 1 cancer Trauma Present or past m e d i c a l c o n d i t i o n s (diabetes, eczema, a l l e r g i e s , chloracne, v a r i c e l l a [ c h i c k e n pox], s y s t e m i c lupus erythematosus, i n f e c t i o u s m o n o n u c l e o s i s , celiac disease, immunodeficiency syndromes) M e d i c a l treatments (phenoxyacetic a c i d - c o n t a i n i n g drugs, t o n s i l l e c t o m y , i o n i z i n g r a d i a t i o n , chemotherapy, immunos u p p r e s s i v e therapy, allergy shots, �vaccines, iron-dextran injections, a n d r o g e n i c - a n a b o 1 i c s t e r o i d s » Fowler's solution* amphetamines, diphenylhydanto i n, etc . ) VI. Proposed Study Steps 1. O b t a i n d e m o g r a p h i c , a g r i c u l t u r a l , and i n d u s t r i a l charact e r i s t i c s of the g e o g r a p h i c area from w h i c h the cases and controls w i l l be selected. 2. Develop an i n t e r v i e w schedule. Conduct a pretest and make necessary r e v i s i o n s . 3. O b t a i n necessary clearance for the i n t e r v i e w schedule and project protocol from the NCI E n v i r o n m e n t a l E p i d e m i o l o g y Branch T e c h n i c a l E v a l u a t i o n of Projects and Q u e s t i o n n a i r e s C o m m i t t e e , the Office of Management and Budget, state v i t a l records offices, and p a r t i c i p a t i n g hospitals. 4. Identify the w h i t e men, aged 21 years or older, who were d i a g n o s e d w i t h STS, NHL, or HD, and who r e s i d e d in the g e o g r a p h i c area selected for study. Select the cases from the f i v e most recent years. 5. Select three controls per case, m a t c h i n g on age (+/- 2 years), v i t a l status, year of d i a g n o s i s or d e a t h , and area of r e s i d e n c e (probably a m u l t i - c o u n t y u n i t ) . p o p u l a t i o n controls u s i n g HCFA f i l e s , random d i g i t d i a l i n g , and Kansas state m o r t a l i t y f i l e s . Use the Draw �same controls for the three case s e r i e s whenever possible. 6. O b t a i n c o p i e s of death c e r t i f i c a t e s for deceased cases and controls. 7. O b t a i n and r e v i e w pathology blocks, s l i d e s , and/or m e d i c a l records for c o n f i r m a t i o n of the d i a g n o s i s . 8. Develop t r a i n i n g and procedure manuals for s u p e r v i s o r s i i n t e r v i e w e r s * abstractors* and coders. 9. Locate cases and controls* or t h e i r next-of-kin. 10. Prepare i n t r o d u c t o r y and informed consent letters and o b t a i n consent of cases and controls* or t h e i r nexto f - k i n * p r i o r to c o n d u c t i n g i n t e r v i e w s * in accordance w i t h e x i s t i n g federal, state, and local r e g u l a t i o n s . 1 1 . H i r e a n d t r a i n s u p e r v i s o r s * i n t e r v i e w e r s , abstractors* and coders. 12. Conduct telephone i n t e r v i e w s of the cases and controls, or t h e i r next-of-kin. 13. O b t a i n c o r r o b o r a t i v e e v i d e n c e of h e r b i c i d e exposure from resources, such as employers, employees, or a g r i c u l t u r a l a g e n c i e s , for study subjects suspected of h a v i n g such exposure. T h i s i m p o r t a n t step w i l l reduce p o t e n t i a l observer b i a s i n t r o d u c e d by i n t e r v i e w e r s aware of the �study hypothes i s 14. R e v i e w , e d i t , and code all completed 15. Analyze the data. 16. W r i t e a f i n a l report 17. Document each step of the study interviews �REFERENCES Axelson 0 and Sundell L: H e r b i c i d e exposure* m o r t a l i t y and tumour incidence. workers. An e p i d e m i o l o g i e s ! i n v e s t i g a t i o n on Swedish r a i l r o a d Scand J Work E n v i r o n Health 11: 21-28, 1974. Axelson 0, Sundell L, Andersson K, et al.: H e r b i c i d e exposure and tumor m o r t a l i t y : An updated e p i d e m 5 o l o g i c i n v e s t i g a t i o n on Swedish r a i l r o a d workers. Scand J Work E n v i r o n Health 6: 73- 79, 1980. Blattner WA, M c G u i r e DB, M u l v i h i l l JJ, et al.: Geneology of cancer in a f a m i l y . J A M A 241: 259-261, 1979. Carter CD, Brown TM, Herbert JT, et al.: Cancer i n c i d e n c e f o l l o w i n g infectious mononucleosis. Am J E p i 106: 30-36, 1977. Cole P, M a c M a h o n B: M o r t a l i t y from H o d g k i n ' s disease in the U n i t e d States: E v i d e n c e for the m u l t i p l e e t i o l o g y hypothesis. Lancet: 1371-1376, 1968. da Motta LC, da S i l v a Horta J, Tavares MH: P r o s p e c t i v e e p i d e m i o l o g i c a l study of thorotrast-exposed p a t i e n t s in Portugal. Environ Res 18: 152-172, 1979. Douglas AP: C e l i a c d i s e a s e and l y m p h o m a of i n t e s t i n e s and b r a i n . N Engl J Med 296: 821, 1977. D u b i n HV, C r e e h a n EP, H e a d i n g t o n JT: L y m p h a n g i o s a r c o m a and c o n g e n i t a l l y m p h e d e m a of the e x t r e m i t y . A r c h Derm 1 1 0 : 608-614, 1974. �Eriksson M, H a r d e l l L> Berg NO, et al.: Soft-tissue sarcomas and exposure to c h e m i c a l substances: A case-referent study, Brit J Ind Med 38: 27-33, 1981. Falk H, Telles NC, Ishak KG, et al.: E p i d e m i o l o g y of thorotrastinduced h e p a t i c a n g i o s a r c o m a in the U n i t e d States. Environ Res 18: 65-73, 1979. Falk H, Thomas LB, Popper H, et al.: H e p a t i c angiosarcoma associated w i t h a n d r o g e n i c - a n a b o l i c steroids. Lancet 2' 1120-1123, 1979. F i l i p o v i c h AH, Spector BD, Kersey J: I m m u n o d e f i c i e n c y in humans as a r i s k factor in the development of m a l i g n a n c y . 259, Prev Med 9: 252- 1980. Green JA, Dauison AA, Walker W: lymphoma. Systemic lupus erythematosus and Lancet: 753-756, 1978. Grufferman S, Duong T, Cole P: O c c u p a t i o n and Hodgkin's disease. J Natl Cancer Inst 57: 1193-1195, 1976. Gutensohn N, Li FP, Johnson RE, et al.: Hodgkin's disease, t o n s i l lectomy and f a m i l y size. N Engl J Med 292: 22-25, 1975. H a r d e l l L, E r i k s s o n M, Lenner P, et al.: M a l i g n a n t lymphoma and exposure to c h e m i c a l s e x p e c i a l l y o r g a n i c solvents, chlorophenols and p h e n o x y a c i d s : A case-control 169-176, 1981. study. Br J Ca 43: �H a r d e l l L» Sandstrom A: Case-control study: Soft-tissue sarcomas and exposure to p h e n o x y a c e t i c a c i d s or chlorophenols. Br J Cancer 39: 711-717, 1979. Hoar SK and Pell S: A r e t r o s p e c t i v e cohort study of m o r t a l i t y and cancer i n c i d e n c e among chemists. J Occup Med 23: in press, 1981 Hoover R, F r a u m e n i JF, Jr.: R i s k of cancer in renal-transplant recipients. Lancet: 55-57, 1973. Kalant N, Seemayer T: M a l i g n a n t lymphoma in spontaneously d i a b e t i c rats. N Engl J Med 300: 737, 1979. Kim JH, Chu FC, Woodward HO, et al.: R a d i a t i o n - i n d u c e d soft-tissue bone sarcoma. R a d i o l 129: 501-508, 1978. K i n l e n LJ, S h e i l A G R , Peto J, et al.: C o l l a b o r a t i v e U n i t e d K i n g d o m A u s t r a l a s i a n study of cancer in p a t i e n t s treated w i t h i m m u n o s u p p r e s s i v e drugs. Br Med J 2: 1461-1466, 1979. K r i k o r i a n JG, Burke JS, Rosenberg SA, et al.: Occurrence of nonH o d g k i n ' s l y m p h o m a after therapy for H o d g k i n ' s disease. N Engl J Med 300: 452-458, 1979. Kufe D, H e h l m a n n R, S p i e g e l m a n S: Human sarcomas c o n t a i n i n g RNA related to the RNA of a mouse l e u k e m i a v i r u s . Science 175: 182-185, 1972. Li F P , F r a u m e n i J F , Jr.: R h a b d o m y o s a r c o m a i n c h i l d r e n : Epidemiologic study and i d e n t i f i c a t i o n of a f a m i l i a l cancer syndrome. J Natl �Cancer Inst 43: 1365-1373, 1969. Li FP, F r a u m e n i JF, J r . , Mantel N, et al.: Cancer m o r t a l i t y among chemists. J N a t l Cancer Inst 43: 1159-1164, 1969. M c l l l m u r r a y MB, Langman MJS: Soft-tissue sarcomas i n j e c t i o n s : An e p i d e m i o l o g i c a 1 survey. and i n t r a m u s c u l a r Br Med J 2: 864-865, 1978. M c K i l l o p JH, D o i g JA, Kennedy JS, et al.: Laryngeal m a l i g n a n c y f o l l o w i n g i o d i n e - 1 2 5 therapy for t h y r o t o x i c o s i s . Lancet 2' 1177-1179, 1978. O l i n G R : L e u k e m i a a n d H o d g k i n ' s disease among S w e d i s h c h e m i s t r y graduates. Lancet i i : 916, 1976. O l i n GR: The hazards of a c h e m i c a l laboratory e n v i r o n m e n t - A study of the m o r t a l i t y in two cohorts of Swedish c h e m i s t s . Am Ind Hyg Assoc J 39: 557-562, 1978. Paffenbarger R S , W i n g A L , Hyde Rf: C h a r a c t e r i s t i c s i n youth i n d i c a - t i v e of adult-onset H o d g k i n ' s disease. J Natl Cancer Inst 58: 1489-1491, 1977. Paffenbarger R S , W i n g A L , Hyde R T : C h a r a c t e r i s t i c s i n youth p r e d i c - t i v e o f adult-onset m a l i g n a n t l y m p h o m a s , m e l a n o m a s , a n d leukemias. J N a t l Cancer Inst 60: 89-92, 1978. j Searle CE, W a t e r h o u s e J A M , Henman BA, et al.: E p i d e m i o l o g i c a l study of the m o r t a l i t y of B r i t i s h c h e m i s t s . B r i t J Cancer 38: 192-193, �1978. Spector BD, Perry GS, Kersey JH: G e n e t i c a l l y d e t e r m i n e d i m m u n o d e f i c i e n c y diseases (GDID) and m a l i g n a n c y : R e p o r t from the immunodeficiency-cancer registry. 11: 12-29, C l i n Immu.nol Immunopath 1978. Svoboda DT and Azarnoff DL: Tumors in male rats fed ethylchlorop h e n o x y i s o b u t y r a t e , a h y p o l i p i d e m i c drug. Cancer Res 39: 3419-3428, 1979, Tucker MA and F r a u m e n i JF, Jr.: Soft tissue in Cancer E p i d e m i o l o g y and P r e v e n t i o n . D Schottenfeld and JF F r a u m e n i , Jr. (Eds). P h i l a d e l p h i a : WB Saunders Company, 1981 (in press). W e i n b r e n K » Salm R, Greenberg G: Intramuscular i n j e c t i o n s of iron compounds and o n c o g e n e s i s in man. Br Med J 1: 683-685, 1978. Young AL, C a l c a g n i JA, Thalken CE, et al.: The t o x i c o l o g y , e n v i r o n mental fate, and human r i s k of h e r b i c i d e Orange and its associated d i o x i n . USAF O c c u p a t i o n a l a n d E n v i r o n m e n t a l Health Laboratory T e c h n i c a l Report 78-92. � 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 1771 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 Blair, Aaron Sheila K. Hoar Title A name given to the resource Typescript: Research Protocol, a Case-Control Study of Lymphoma and Soft-Tissue Sarcoma: Association with Herbicide Exposures, [nd] Subject The topic of the resource case referent study lymphomas soft tissue sarcoma industrial exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/c7b4c2ff56c104ff469c33776b3e4eec.pdf 6842e2a58724a67bf7193de9c2e8fd57 PDF Text Text Item ID Number 01769 Author Woods, James S. Corporate Author Roport/Artldo TitlB Soft Tissue Sarcoma and Non-Hodgkin's Lymphoma in Relation to Phenoxyherbicide and Chlorinated Phenol Exposure in Western Washington JOIirnal/BOOk TltlB Journal of the National Cancer Institute Year 1987 Month/Day Ma Color NumbOT oflmaD.es v n 12 Descripton Notes Monday, June 11, 2001 Page 1770 of 1793 �Soft Tissue Sarcoma and Non-Hodgkin's Lymphoina In Relation to Phenoxyherbicide and Chlorinated Phenol Exposure In sg^a*!*! Vllaohtin/v$rtn 1-2 .•S'v/ s 8. Wood.-*, Ph.D., 3 Lincoln Pcilssar, P/j.D., * Richard K. Sewr,<m, P/7.D.,4 Linda S. Heuser, MA,4 and Bruce G., Kuiander, Af.D. 5>9 propionic acid (Silvex), which have been reported to be contaminated with TCDD as high as 30 ppm (16). Moreover, TCDD is the prototype of a larger series of halogenated aromatic hydrocarbons including other PCDDs, dibenzofurans, and biphenyls, all of which share similar biochemical properties and which may also contaminate phenoxyherbicide or chlorophenol products in commercial use. Hence concern exists regarding the possible health risks from exposure to chemical products in which any such contaminants may be present. The present study was conducted to investigate the relationship between the incidence of STSs and NHLs and past exposure to phenoxyhevbicides and chlorinated phenols with the use of population-based case-control approach. Subjects were drawn from the male population of western Washington State, where phenoxyacetic acid herbicides and chlorophenols have been widely utilized during the past 40 years by agricultural, forestry, and wood products industries. Specific emphasis was placed on identification of intervening factors or conditions that may influence human susceptibility to the risk of cancer in association with exposure to phenoxyacetic acids, chlorophenols, or PCDDs. ABSTRACT—A population-based case-control sfcudy was conducted in western Washington Stale io evaluais the relationship between occupations) exposure of men aged 20-79 to phenoxyacetic acid herbicides and chlorinated phenols and the risks of developing soft tissue sarcoma (STS) and non-Hodgkin's iymprioma (NHL). Occupational histories and other data were obtained by persona! interviews for 128 STS cases and 576 NHL cases, diagnosed between 1981 and 1984, and for 894 randomly selected controls without cancer. Among the study subjects with any past occupational exposure to phenoxyherbicides, ihe estimated relative risk ar.d 95% confidence intern! of developing STS was 0.80 (0,5-1.25, and of developing NHL, 1.07 (0.8-1.4). Risk estimates of developing STS and NHL associated with past crtlorophenoi exposure were 0.99 (0.7-1.5) and 0.99 (0.8-1.2), respectively. No increasing risk of eirfiar cancer was associated with overall duration or infensity of chemical exposure or with exposure to any specific pher.oxyherbicide per se. However, estimated <-isks of NHL were elevated among men who had been farmers, 1.33 {1.03-1.7), foresiry herbicide applicators, 4.80 (12-19.4), and for those potentially exposed to pr»enoxyherbicic!es in any occupation for 15 years or more ouring the period prior to 15 years before cancer diagnosis, 1.71 (1.04-2.8). increased risks of NHL were also observed among those with occupational exposure to organocriiorine insecticides, such as DOT [1,82 {1.04-3.2)} and organic solvents [1 35 (1.08-1.7)), and to other chemicals typically encountered in the agricultural, forestry, or wood products industries. These results demonstrate small but significantly increased risks of developing NHL in association with some occupational activities where phenoxyrterbicirjes have been used in combination with other types of chemicals, particularly for prolonged periods. They do not demonstrate a positive association between increased cancer risks and exposure to any specific phenoxyter&icide product alone. Moreover, these findings provide no evidence of increased risks of developing NHL associated with chlorinated phenol exposure or of developing STS associated with exposure to either class of chemicai.—JNC! 1987; 78:399-910. ABBREVIATIONS USED: CSS=Cancer Surveillance System; 2,4-0=2.4(dichlorophenoxy;acetkacid; DDT= l,l'-(2,2.2-trichloroethylidcoe;bis [•1-chIorobenz.enel; !CD-O = International Classification of Diseases for Oncology, First Revision; NHI. = non-Hodgkin's lymphoma; PCDD— poll/chlorinated dibenzo-p-dioxin; STS—soft tissue sarcoma; 2,4,5-T= (2,4.5-mchlorophcnoxy(acetic acid; TCOD=2,3,7,8-tetrachlorodibenzop-dioxin. 1 Recent studies from Sweden (7-5) and elsewhere (6-10} have reported an increased risk of STSs or NHLs in association with occupational exposures to phenoxyacetic acid herbicides and/ or chlorinated phenols. Negative studies of this association have also appeared (11-15). Implicated as the putative carcinogen in most of these studies is TCDD (CAS: 1746-01-6), a trace contaminant formed during the manufacture of chemicals that are derived from alkaline hydrolysis of 1,2,4,5tetrachlorobenzene. Of particular concern in this respect are 2.4,5-trichlorophenol and the phenoxyherbicides 2,4,5-T (CAS: 93-76-5) and 2-<2,<t,5-trichlorophenoxy)- Received June 30, 1986: accepted October 2!, 1986. ^Supported by Public Health Service grant CA-29900 from the Division ot Extramural Activities, National Cancer Institute. 'Batielle Human Affairs Research Centers, 4000 N.E. -Hst St., Scattie, WA 98105. 'The Fred Hutchinson Cancer Research Center, 1124 Columbia St., Seattle. WA 98 KM. Swedish Hospital Medical Center. Seattle. WA 98104. 6 We are indebted to the staff of the Epidemioiostic Research Unit of the Fred Hutchinson Cancer Research Center for their assistance in the conduct of this study. Also, we gratefully thank Frans M. Enzinger, M.D.. Chairman, Department of Soft Tissue Pathology, Armed Forces Institute of Pathology, Washington, DC, for assisting in the confirmation and histologic classification of soft tissue sarcoma case materials in this study. 899 JNCI. VOL. 78, NO. 5, MAY 1987 �900 Woods, Polissar, Severson, et ai. SUBJECTS AND METHODS Acquisition oj cases and controls.—From 1983 through 1985 men with either STS or NHL were identified through the CSS, a population-based turner registry that has covered 13 counties of western Washington State since 1974. Men eligible to participate in the study were between the ages of 20 and 79 at diagnosis and had been diagnosed during the years 1981-84 as having either STS or NHL, as classified hisiologically by the World Health Organization ICD-O (17). Case definitions of eligibility for STS by OCD-O codes are 8800-8804, 8810-8813, 8830-8832, 8840, 8850-8860, 8890-8920, 8990-8991, 904090-14, 9120, 9130, 9150, 9170, 9251, 9260, 9503, 9540-9560, and 9580-9581. Case definitions of eligibility for NHL by ICD-O codes are 9590-9642, 9690-9701, and 9750. The CSS obtains data, from all hospitals throughout a 13-county region, and essentially complete population coverage is attained. During 1983-85 a control group without STS or NHL was also selected. Live control subjects aged 20-64 were chosen by means of a random-digit-dialing procedure as described by Waksberg (18). Because the elderly are relatively sparse in the general population, it was not economical to locate all older controls by random digit dialing. Thus additional live coutrol subjects aged 65-79 were chosen at random from data supplied by the Health Care Financing Administration covering Social Security recipients in the study area. Controls were group matched to NHL cases by vital status and 5-year age group with a ratio of 1.2 controls per case. Deceased controls exclusive of homicides and suicides were identified from noncancer death certificates for persons aged 20-79 with a date of death occurring during the study period and with a residence within the 13-county study area. The disposition of case and control subjects according to vital status, interview outcome, and pathologic review of STS is presented in table 1. Interview procedure.—All study subjects, including proxies, were interviewed in person by experienced interviewers at a time and location of their choice. The interview lasted approximately 1 hour and covered the participant's residential, military, and medical histories with a detailed section on occupational exposures to herbicides, chlorophenois, and other chemicals prior to diagnosis or interview. Detailed information on known or suspected risk factors for STS and NHL, including past history of iraraunosuppressive disorders, use of immunosuppressant medication, or family history of cancer or immune disease, was also obtained. Additional information, including pathology, stage, extent of dasease, and date of diagnosis, was collected for each case from data supplied by the CSS, "Exposure" for all variables refers to that occurring prior to the date of diagnosis for the cases and prior to the date of interview for controls. The effect of recall differences on cancer risk owing to the difference in lapse time between diagnosis and interview for the cases {^1 yr) versus initial contact and interview for controls (•=*! mo) was evaluated and found to be negligible. Risk estimates among living and deceased cohorts were comparable for essentially al! associations; hence living and deceased groups were combined in all analyses. The questionnaire utilized in the interview was designed after identifying the principal occupations and activities undertaken within the study area that have involved the manufacture or use of phenoxyherbicides and/or chlorophenois. Such occupations and activities were identified in consultation with local industrial and university representatives who had had long-term experience with forestry, wood products, and agricultural industries in the Pacific Northwest. This consultation resulted in identification of 34 specific job titles (e.g., wood products worker; herbicide applicator) and 37 specific job activities (e.g., spray weeds with phenoxyherbicides; manufacture chlorophenois) involving potential exposure to either phenoxyherbicides or chlorophenois. In addition, 14 specific phenoxyherbicide or chloropheriol preparations in common commercial use in the study area were identified. Each job title or activity was then assigned to a "high," "medium," "low," or "no" exposure category for both phenoxyherbicides and chiorophenols, reflecting the consensus of the consultant group of the likely intensity of exposure to each TABLE 1.—A ease-control study of STS and NHL in relation to phetioxyherkicide a>id cM&ro-phmol Subject Total identified as eligible Physician refusal Respondent refusal Other reasons for noninterview Total interviewed Excluded by pathologic review Excluded as noneligihle post interview 4 Total subjects for analysis Dead Living No. Percent 150 20 -1 6 120 21 2 13 3 4 80 18" _ 97 _ JNCI. VOL. 78. NO. 5, MAY 1987 Dead Living Dead Living No. Percent No. Percent No. Percent No. Percent 527 80 15 24 408 15 3 o 77 219 23 8 10 178 — 11 4 5 81 622 — 95 51 476 — —4 — —1 288 — 29 40 219 — 0 10 14 76 12 0 Percent _-. 13 -I 7 77 28" — 31 — 402 174 — 475 219 — No. 56 7 2 4 43 " Percent of total interviewed. Based on diagnosis, age, residence, or date of diagnosis. 6 Controls NHL STS Subject disposition e m western Washington State: —6 ._. __ 15 8 77 — — — �STS and NHL and Chemical Exposure in WA 901 chemical received in that occupation. Examples oC occupational activities in- each exposure category are : given in the tables. In the interview, cue questions refeiring to each specific job tide, activity, or chemical preparation were asked to determine whether a subject had worked in an occupation involving probable exposure to phenoxyherbicides or chlorophenols. If an affirmative response to any cue question was elicited, a series of additional inquiries was made to acquire detailed information regarding the extent of exposure to specific chemicals of interest and the precise lime intervals during which each exposure episode had occurred. Among the additional questions asked was an inquiry regarding the name and address of the supervisor or a close co-worker in eacli job episode where possible chemical exposure had occurred. This information was used with subject's permission to corroborate self-reported exposure to specific chemicals and to verify exposure histories in instances where the subject or his proxy was uncertain regarding the actual exposure circumstances in that job. Additional measures taken to reduce the likelihood of recall bias with respect to the reporting of pherioxyherbicide or chlorophenol exposure included avoiding a deliberate focus on these specific chemicals in the interview and conducting the interview during a period (1983-85) of relatively low local or national media attention to die herbicide-cancer issue, The .-study was not advertised locally, and subjects were not made aware of the focus of the investigation except that it had broad implications with respect to environmental factors related to cancer etiology. In coding occupational exposure to phenoxyherbicides or chlorophenols based on job descriptions, the inclusive dates during which a person was employed in any specific occupation or activity were recorded in the questionnaire. In the analysis, however, occupational exposure to phenoxyherbicides and chlorophenols was considered to have begun no earlier than 1945 and 1937, respectively, the years when these chemicals first came into widespread commercial use in the study area. The coding of each job episode held by a study subject according to intensity and duration of exposure permitted evaluation of the exposure history of each subject in terms of duration of continuous or cumulative exposure at each dose level. Thus a complete exposure profile on each subject for each class of chemical under evaluation was obtained. Quality control procedures.—Several quality control procedures were employed 10 verify the accuracy of the data collected by interview. First, 145 respondents from a total of 1,444 who completed interviews were randomly selected and were recontacted by telephone approximately 1 month after the interview date. Interview and reinterview responses to seven questions were compared. Five of the seven questions reflected an 88% or higher agreement with the original interview, and one item had an 81* agreement rate. The remaining item, cups of coffee consumed per week, had a 34% agreement rate, although 55% of the discrepancies involved minor disagreements regarding the precise number of cups consumed. A second quality control procedure consisted of independent receding of a random sample of 238 coded interviews. The overall agreement rate between codes and recedes was 99%. The agreement rate was 98.9% for codes pertaining to phenoxyherbicides and 98.3% for codes pertaining to chlorophenols. Pathologic review of soft tissue sarcoma case materials,—Pathologic review of histologic slides and/or sections prepared from tissue blocks of STS cases was conducted to verify die initial diagnosis of STS. Reviews v/ere performed by a pathologist (B.K.) with expertise in soft tissue tumors. For the review of STS, specimen materials were acquired from each participating hospital where the initial diagnosis of STS was made and were then coded and sent "blind" to the project pathologist. In all, histologic material from 155 cases was obtained for review. Twenty percent of the slides or sections were resubmitted to the pathologist as an internal check of his first diagnosis. In a few circumstances the project pathologist disagreed with either the CSS or himself regarding the diagnosis of either STS per se or the specific histologic classification of STS. In these instances a sample of the disparate slides was sent to the Armed Forces Institute of Pathology in Washington, DC, for resolution of STS and/or histologic-type classification. This three-tier STS evaluation procedure resulted in retention of 45% of the STS cases in the study with histologic diagnosis as originally determined, and an additional 34% of cases retained with STS were confirmed although they were at a different histologic classification than originally made. Of the original cases 21% were determined either not likely to be STS, or of indeterminate pathology, and, consequently, were excluded from the study. Many of these were primary bone tumors. In light of the widely accepted high level of reliability associated with the accurate identification of NHL according to broad histologic classifications, pathologic materials from NHL cases were not reviewed for verification in this study. Statistical methods.—The data analysis includes estimates of relative risks as odds ratios and their 95% confidence intervals for a number of variables of interest. The most common confounding variable was age; thus all relationships were age adjusted by 5- or 10-year age groups, where possible. Pooled odds ratios were calculated by means of the Mantel-Haenszel method (19). Test-based confidence intervals were calculated by means of the method of Miettinen (20). In addition, logistic regression analysis (21) was used to evaluate the joint effect of several variables and possible interactions between chemical exposure and other potential risk factors on cancer risks. The total number of subjects represented in each analysis varies according to the rate of unknown responses: for occupational assessments unknowns were omitted from the analyses. In all other analyses unknowns were included in the "none" or "no exposure" category. The percentage of the total study population responding affirmatively with respect to specific job titles, exposures, or other characteristic is presented in the tables. "Significance" in all analyses was determined at the 5% level. JNCI, VOL. 78, NO. S, MAY 1987 �902 Woods, PoSlssar, Scverson, et at. - - , •• -."•< .£!,*'&4:$^': • • " ' ' "'' "•' TABLE 2.~Seteeted eharaeteriatics of 128 STS cose men, 576 NHL cose me-it {diagnosed 1981-84),. and 604 interviewed population control men (1933-85) Specification- •.•"'- ;• •• • -&;$••V.STS; % ' * NHL, % . - - - - : VU,, T'-' • Controls, % — -vw High school graduate:," ^g.78.6.v54,:,72.0 " U n k n o w n •-'»'..• '•'. -'-i/ :'5^'-V^ 1.7 ! Race .---. 4;;';^-'-: |,^*&.'•; "' • . -.White , ;.V X89.8s^'^'•.94.4"Black ife, 2.3 ;':*iV'i'2.1 Other , • • ; • ' •ff;.7.0. '^'.^•."•'^•o 4 Unknown , • -., . o.;i ^v'0.8. • • '•' Annual income level >'.•>*;-•• •'• .'•n, ' <$15,000/yr ::!25.8 • '-''••:' 28.0' $I5,000-$30,000/yr . . •V 32,8 ' -':!' 37.3 >$30,000/yr ••-33.6 "" 33.5 Refused '.:. 3.9 O.S Unkown •' 3.9 ' ""' "0.7 :;^-.ii;ao. 26.4 70.6 3.0 95.1 2.3 2.6 39.2 34-3 0.7 ' 1.7 w ' V RESULTS Characteristics of the Study Population Table 2 presents a comparison of NHL and STS cases and controls for selected demographic attributes. The 3 groups were similar in most respects. Notable differences included a higher proportion of STS cases than controls among subjects in the 20-39 age group and a higher percentage of STS cases in the "other" race category. Asians account principally for this difference. Risks Related to Intensity of Chemical Exposure When estimates of relative risks of both SI'S and NHL were determined for various levels of phenoxyherbicide or chlorophenol exposure among the entire study population, no increasing trend or risk estimates significantly different from unity for any exposure level were seen (table 3). However, elevations in risk were observed for several specific occupations involving chemical exposure. Estimates of relative risks of STS and NHL for various occupations involving exposure principally to phenoxyherbicides are shown in table 4. When viewed across job categories involving increasing levels of exposure, no clear indication of increasing risk is observed. No significantly increased risks of either cancer were seen among those in occupations involving low exposure to phenoxyherbicides, although a nearly significant 1.70 (0.9-3.1) odds ratio for NHL was observed among landscapers. Among those in medium-exposure occupations, no significantly elevated risks of STS were seen. A small but significantly increased risk of NHL [1.33 (1.03-1.7)] was observed among farmers, an occupation traditionally associated with regular use of weed killers. This observation is consistent with reports from other studies that have identified agricultural occupational groups at increased NHL risk (22-25). Further evaluation of this JNCf. VOL. 78. NO. 5, MAY 1987 observation with regard to duration of exposure and to use of specific substances indicated that the risk of NHL increased from 1.02 (0,7-1.5) among those working as farmers from 1'to-9 years to 1.62 (0.9-2.9) among farmers^ with, 10-19 years in that occupation. However,' no" increased risks of developing NHL were observed among those with more than 20 years as farmers, 0.92(0.5-1.6).. Additionally, there were no increased risks of NHL among farmers who reported having "regularly worked with" 2,4-D [0.68 (0.3-1.4); CAS: 94-75-7], 2,4,5-T [0.74 (0.3-2.1)], or phenoxyherbicides per se [0.71 (0.3-1.5)] when compared with study subjects reporting no phenoxyherbicide exposure. The estimated risk of developing NHL among fanners who reported having regularly ; sprayed weed killers by backpack, tractor, or aircraft was H.13 (0.7-1.9). A risk of developing NHL equal to 1.46 (0.8-2.8) was observed among farmers who reported having worked with the specific organochlorine insecticides DDT and chlordane. In occupations associated with high herbicide exposure, none was associated with a statistically significant increased risk of developing STS. A substantially increased risk of developing NHL [4.80 (1.2-19.4)] was noted for persons who claimed to have worked regularly in jobs involving the spraying of weed killers in national, state, or commercial forests. However, increased risks of tins magnitude were not observed among those engaged in other herbicide spraying activities or among those who worked as herbicide formulators or applicators per se. Further evaluation of the risk of NHL observed among forestry herbicide sprayers with respect to specific chemicals used and duration of exposures indicated that all forestry sprayers reported the combined use of 2,4-D and 2,4,5-T as well as various -commercial herbicide preparations containing these and other chemicals. An infinite risk estimate was attained for developing NHL among forestry herbicide applicators specifically in association with phenoxyherbicide TABLE 3. —Risk (pooled odd-s ratio) of developing STS or NHL in men aged 20--79 by estimated intensity of past occupational exposure to phenoxyherbicides or chloro-phenols: 128 STS cases and 576 NHL cases (diagnosed 1981-84) and 694. papulatwn control men (interviewed 1983-85) in western Washington State" Exposure category STS NHL OR (95% CD OR (95% CD Percent study population Phenoxyherbicides None Low Medium High 1.0 0.56(0.3-1.1) 0.99(0,6-1.7) 0.89(0.4-1.9) 1.0 0.90(0.6-1.3) 0.95(0.7-1.3) 1.24(0.8-1.9) 63.3 12.0 16.5 8.2 Chlorophenols None Low Medium High 1.0 0.90 (0.5-1,.6) 0.93 (0.6-1..5) 0.93 (0.5-1..8) 1.0 0.97 (0.7- i .3) 0.92 (0.7-1.2) 0.92 (0.9-1.4) 41.5 16.5 31.8 10.2 "The percentage of the total study population in each exposure category is also presented. �SYS and NHL and Chemical Exposure in WA TABLE 4.—Risk (pooled odds ratio) of developing STS or NHL in men aged. 20-79 for specific occupations and activities involving potential pkenoxyherbicide exposure: ISS men toith STS and-576 men with, NHL in western Washington State (diagnosed 1981-84) ' ' ' -population control men (interviewed 1983-85)" Phenoxy herbicides Occupation or activity ^ __ OR (95% CI) _ _NHL Percent study population OR (95% CD - Low exposure Landscaper Railway worker Telephone lineman Medium exposure Gardener-groundskeeper Fanner Working in sprayed area High exposure Herbicide formulator-mixer Herbicide applicator Spraying herbicides from backpack Spraying herbicides from tractor or aircraft Spraying farmlands with herbicides Spraying forests with herbicides Spraying near utility lines or railroad tracks 3.6 0.92 (0.3-2.8) 1.14 (0.6-2.2) 0.73 (0.1-3.6) 1.70 (0.9-3.1) 1.06 (0.7-1.5) 1.28 (0.6-2.6) 10.7 1.07 (0.5-2.2) 1.25 (0.8-1.9) 1.34 (0.7-2.6) 0.83 (0.5-1.4) 1.33* (1.03-1.7) 1.33 (0.9-2.0) 30.0 1.24 1.77 0.80 1.27 1.35 1.53 (0.7-3.3) 1.33 (0.8-3.9) 0.82 (0.4-1.5) 1.51 (0.9-2.5) 1.35 (0.8-2.4) 4.80* (1.2-19.4) 1.03 (0.3-3.1) 2.1 2.2 3.3 4.9 4.3 1.0 0.9 (0.3-5.3) (0.5-6.6) (0.3-2.4) (0.5-3.1) (0.5-3.3) — — 2.4 6.1 8.4 "The percentage of the total study population in each occupation or activity is also presented. exposure, inasmuch as there were no control subjects who served as forestry herbicide sprayers and did not use phenoxyherbicides. This association was statistically significant with P=.OQ4. However, only a very small number of exposed subjects (7) were involved. The risks of STS and NHL associated with all occupations involving potential exposure to phenoxyherbicides considered together were 0.80 (0.5-1.2) and 1.07 (0.8-1.4), respectively. The risks of developing NHL associated with exposure specifically to 2,4-D and 2,4,5-T and to phenoxyherbicides in general among the entire study population were 0.73 (0.4-1.3), 0.98 (0.5-2.0), and 0.87 (0.51.5), respectively. Table 5 presents risk estimates of SI'S and NHL for various occupations and activities involving chlorophenol exposure. As in the case of phenoxyherbicides, no clear indication of increasing risks of either STS or NHL is apparent when viewed across job categories in. volving increasing levels of exposure to chlorophenols. Somewhat elevated risks of developing STS are suggested for lumber graders [2.66 (1.1-6.4)] and log-lumber inspectors [4.83 (0.6-38.2)], although other jobs involving comparable chlorophenol exposure offer no suggestion of substantially increased STS risks. No specific jobs involving chiorophenol exposure were associated with increased risks of developing NHL. When all TABLE 5.—Risk (pooled odds ratio) of developing STS or NHL in men aged £0-79 for specific occupations and activities involving potential chlorophenol exposure: ISS men ivith STS and 576 mm with NHL in western Washington State (diagnosed 1981-84) and «'&4 population control men (interviewed Chlorophenol Occupation or activity OR (95% CI) Low exposure Planer mill worker Feeder man Bander man Medium exposure: Log-lumber inspector Sawmill worker Wood products worker Fork lift driver in mill High exposure Lumber grader Wood preserver Manufacturer of chlorophenols Percent study population STS OR (95% CI) 1.55 (0.5-4.7) 1.31 (0.4-4.7) 0.90 (0.2-4.4) 1.39 (0.7-2.7) 1.44 (0.7-2.81) 1.45 (0.6-3.4) 3.1 2.9 1.8 4.83 0.97 1.27 1.52 0.40 (0.0-3.6) 1.03(0.7-1.4) 0.88 (0.6-1.3) 1.44 (0.8-2.6) 0.4 15.0 13.0 4.2 0.94(0.5-1.9) 1.64 (0.6-4.2) 1.72 (0.9-3.4) 3.1 (0.6-38,2) (0.5-1.8) (0.7-2.3) (0.6-3.6) 2.66* (1.1-6.4) 0.79 (0.1-5.9) 1.37 (0.4-4.3) 1.4 3.0 "The percentage of the total study population in each occupation or activity is also presented. P<.05. 6 JNCI. VOL 78. NO. 5. MAY 1987 903 �904 Woods, Poilssar, Severson, et al. occupations involving potential exposure to chlorophenois were considered together, the risks of developing STS and NHL were 0.99 (0.7-1.5) and 0.99 (0.8-1.2), respectively. Results of Supervisor-Co-worker Survey Corroboration of self-reported occupational exposure to pherioxyherbicides, chlorophenols, and other chemicals was sought through telephone contact with employer supervisors or co-workers of subjects who had been employed in jobs involving potential exposure to such substances. Confirmation of subjects' responses regarding exposure was provided in essentially all instances where employers or co-workers could be reached. There were no significant differences between agreement rates for cases or controls. The ability to acquire corroborative evidence of exposure (==80% of contacts attempted) was greatest for most recent occupations held. Risks Related to Duration of Chemical Exposure Inasmuch as cancer risks may vary with length of exposure to specific carcinogens or tumor-promoting agents, it was of interest to estimate the relative risks of STS and NHL for various lengths of cumulative exposure to either phenoxyherbicides or chlorophenols. Hence risk estimates of both cancer types for 10-year durations (1-10, 11-20, >20) of exposure to phenoxyherbicides or chlorophenols were calculated. In this context, exposure refers to any level of occupational phenoxyherbicide or chloropbeaol exposure during any portion of the time period since 1946 or 1937, respectively, up to the date of diagnosis (cases) or interview (controls). "Duration" refers to the total length of cumulative exposure during this time period. From these calculations, it was determined that the risk of neither STS nor NHL increased with the duration of phenoxyherbicide or chlorophenol exposure for periods of 20 years or more when all levels of exposure are considered concomitantly. Moreover, no increased risks of either cancer were seen when increasing lengths of exposure to only high levels of phenoxyherbicides or chlorophenols were considered. Evaluation of a Latent Period tor Cancer Development The average latent period for a carcinogenic effect of aromatic hydrocarbons in humans has been postulated to be on the order of 15-30 years (26). It was, therefore, of interest to determine if exposure to either phenoxyherbicides or chlorophenols prior to an assumed latent period of 15 years before cancer diagnosis was associated with an increased risk of STS or NHL. For these determinations, the risk of each cancer type were calculated for two durations of cumulative exposure (1-14 and >15 yr) during the period between 1946 or 1937 for phenoxyherbicides and chlorophenols, respectively, and 15 years prior to diagnosis or interview. The results revealed a significant increase in the risk of NHL [3.71 (1.04-2.8)] among those with cumulative exposures to phenoxyherbicides of more than 15 years during the period preceding 15 years before diagnosis. When a 5-year latent period for cancer development was assumed, the risk of NHL among those with 15 years or more of prelatency phenoxyherbicide exposure dropped to 1.29 (0.9-2.0). In contrast, the risk of developing NHL was 2.51 (0.5-13.0) among subjects with more than 15 years of herbicide exposure prior to a 25-year assumed latent period. No increased risks of STS for either chemical or of NHL for chlorophenols were observed in relation to chemical exposure for any latent period or cumulative exposure assumption. Evaluation of Other Risk Factors for STS and NHL Since autoimmune diseases, primary immunodeficiency syndromes, and other conditions that compromise immune competence may act as independent risk factors of STS or NHL, it was of interest to determine the risks of either type of cancer associated with such conditions existing prior to the year of cancer diagnosis (or interview). Table 6 presents risk estimates of STS TABLE fj.—Risk {pooled odds ratio) of developing STS or NHL among men aged 20-70 with/actors or conditions associated with compromise of Immune competence: 128 men with STS and 576 men with NHL (diagnosed 1981-84) and 69l> population controls (interviewed 1983-85) in western Washington, State" Risk factor Malaria Preexisting cancer Nonskin Skin Corticosteroids Rheumatoid arthritis Low gamma or imrnunoglobulin Irnrnunosuppressant drug therapy 6 Immune deficiency in a blood relative STS NHL OR (95% CD OR (95% CD 1.14(0.4-3.1) 1.47 (0.9-2.5) 4.7 0,88 (0.3-2.5) 1.47 (0,7-3.1) 0.70 (0.4-1.1) 1.24 (0.7-2.1) 1.57r( 1.03-2.4) 0.91 (0.7-1.2) 1.38 (0.9-2.2) 1.59 (0.5-4.ti) 10.97r (2.1-57.3) 1.51 (0.4-o.ti) 4.8 7.5 27.5 5.9 1.0 0.7 0.6 "The percentage of the total study population with each risk factor is also presented. *Azathioprine, cyclophosphamide, chlorarnbucil, and/or mercaptopurine. ' P<.05. JNCI. VOL, 78, NO. 5, MAV 1987 Percent study population �STS and NHL and Chemical Exposure in WA 905 TABLE 7. —Risk (pooled odds ratio) of developing STS or NHL among men aged 20-79 associated with miscellaneous occupational factors or conditions among 128 men with STS and 576 men vrilh NHL (diayaosed 1981-84) and 694 population controls (intervieujed 1983-85) in western Washington State" Condition Insecticides Chlordane DDT Industrial chemicals Organic solvents Lead-lead arsenate Welding-metal fumes Chloracne Skin blisters from chemicals Cigarette smoking Coffee drinking J!TS NHL OR (95% CI) OR (95% CI) 0.96 (0.2-4.8) 1.10 (0.4-3.2) 1.61 (0.7-3.8) 1.82* (1.04-3.2) 1.6 4.0 1.10 1.51 1.30 3.32 1.72 0.93 0.49 1.35* (1.06-1.7) 1.60* (1.1-2.3) 1.31* (1.03-1.7) 2.12 (0.6-7.0) 1.06 (0.7-1.6) 0.85 (0.8-1.1) 1.28 (0.9-1.9) 29.8 12.0 31.1 1.0 7.8 73.5 89,8 (0.7-1.7) (0.9-2.6) (0.9-2.0) (0.8-14.0) (0.9-3.2) (0.6-1.4) (0.4-1.2) Percent study population " The percentage of the total study population with each condition or factor is also presented. * P<-.ftfi and NHL for a number of such conditions or factors. All assessments were made from subject interviews, not from medical records, Immunosuppressant drug therapy received for any reason prior to the year of diagnosis of NHL was the greatest risk factor for either cancer. Immune deficiency in a blood relative was also associated with an increased (although nonsignificant) risk of NHL. In contrast, the use of cordcosteroids for observed periods of use up to 29 years was not associated with an increased risk of either cancer type. Of specific note is the 1.38-fold increased risk of NHL observed in relation to a history of rheumatoid arthritis. Although not statistically significant, this observation is interesting in light of the current controversy surrounding the question of increased risks of NHL among persons afflicted with autoimmune diseases (27). Preexisting skin cancer was also associated with a slightly increased risk of both STS and NHL. Although the type of skin cancer was not ascertained in this study, several histologic types of STS and NHL can have dermal manifestations that could have been misreponed as "skin cancer." Among these are the soft tissue tumors, dermatofibrosarcoma (8832/3) and Kaposi's sarcoma (9140/3), and the non-Hodgkin's lymphorna, mycosis fungoides (9700-9701/3). Kaposi's sarcoma was excluded from evaluation in this study, and none of those reporting skin cancer was found to have this form of STS. Among those 12 STS cases reporting a prior history of skin cancer, none was found to have dermatofibrosarcorna; among 53 NHL. cases, none had confirmed mycosis fungoides. Malaria was evaluated as a potential risk factor for STS and NHL in light of studies suggesting an etiologic association between malarial infection and the risks of developing sarcomas or lymphomas through mechanisms involving piasmodial suppression of immune defenses against malignant diseases (28, 29). The risk of developing neither STS nor NHL was significantly elevated in association with a self-reported prior history of malaria alone. Finally, table 7 presents risk estimates associated with various occupational and/or lifestyle factors that were observed in the present study to independently alter the risk of STS or NHL and that might, therefore, be considered as potential modifiers of the effect of chemical exposure on cancer risks. Of particular note is the significantly increased risk of NHL seen among men with previous exposure to organic solvents, lead or lead arsenate pesticides, and welding and metal fumes. The risk of NHL was also elevated among men reporting previous exposure to the organochiorine insecticides chlordane and DDT. Also of note is the increased risk of both STS and NHL observed among those reporting a prior incidence of chioracne. Although this condition was not clinically confirmed in this study, this observation is of considerable interest inasmuch as chioracne is an important clinical manifestation of exposure to high levels of chlorinated dibenzodioxins and furans in humans (30). The statistical association of reported chioracne with phenoxyherbicide exposure was of borderline significance (P<.075) in this study. Neither cigarette smoking nor coffee drinking was a risk factor for either cancer. Not shown in table 7 are a number of other factors or conditions that were also evaluated as potential risks factors, but for which no significant or suggestive associations with either STS or NHL were found. These include: exposure to radiation, x-rays, or radioactive materials; exhaust fumes from motorized equipment; home use of phenoxyherbicides; residency near areas sprayed with weed killers; tuberculosis vaccination; consumption of multiple vitamins; eating fish caught in Puget Sound; and use of alcohol. Logistic regression analysis was used to estimate the potential interaction between phenoxyherbicides or chlorophenois and various other single variables appearing in table 6 or 7 as well as others of interest. Intervening variables for which the interaction with phenoxyherbicides or chlorophenois were determined included: organochiorine pesticides (DDT+chlordane), lead-lead arsenate, welding or metal fumes, inherited or acquired diseases of the immune system, any prior cancer, prior skin cancer, home use of phenoxyherbicides, family hisJNCI. VOL. 78. NO. 5, MAY 1987 �903 Woods, Polissar, Severson, et ai. lory of cancer, and family history of diseases of the immune system. A1J analyses were controlled for age. Results of the logistic regression analysis for these variables confirmed the magnitude of the risks shown in tables 6 and 7. None of the interactions between chlorinated phenol or phenoxyherbicide exposure and these variables was statistically significant, with the exception of that between phenoxyherbicides and organic solvents as a. risk factor for NHL. The odds ratio for joint exposure compared with exposure to neither substance was 1.50 with a 95% confidence interval of 1.03-2.18. The odds ratio estimates from the model for exposure solely to organic solvents or phenoxyherbicides were nonsignificandy 1.12 and 0.85, respectively. The significance of the joint exposure in this case may be a result of the large number of comparisons made in this study or, possibly, due to a genuine synergistic effect. Positive although nonsignificant interactions were also observed between exposure to either phenoxyherbicides or chlorophcnols and coexisting or preexisting autoimmune diseases or immune deficiency syndromes when those listed on table 6 and others (mononucleosis, celiac sprue, and Sjogren's syndrome) were considered jointly. T'his interaction was most notable with chlorophenols where the odds ratio for joint exposure (compared with neither) was 1.40 (0.95-2.07) as compared with 0.91 (0.72-1.14) and 1.32 (0.99-1.78), respectively, for chlorophenol or immune deficiency alone. These observations are worthy of note in light of the widely held theory (31) that the etiology of malignant lyniphomas involves failure of immunoregulation in the face of a persistent stimulus for lymphocyte proliferation. In autoimmune diseases, chronic amigenic stimulation is provided by the constant exposure to self-antigens, whereas in primary immunodeficiency syndromes, recurrent infections are the likely source for antigenic stimulation. In contrast, TCDD is well recognized as a suppressant of both humoral and cell-mediated immunity in animals (32-34) and has been recently characterized as a depressant of cell-mediated immunity in humans during prolonged, low-level exposure (35). Immunosuppression by other PCDDs has also been described (36). Therefore, further consideration should be given to the possibility that the statistical interactions, however slight, observed in this study between phenoxyherbicides or chlorophenols and immunosuppressive disorders have biologic relevance with respect to the etiology of NHL in humans. DJSCUSSJON The results of the present study demonstrate significantly increased risks of developing NHL among men in occupations involving farming and forestry herbicide spraying and for occupations involving prolonged phenoxyacedc acid herbicide exposure when a latent period of 15 or more years before cancer diagnosis is considered. However, neither phenoxyherbicides nor chlorophenols alone appear to constitute a sufficient cause of either NHL or STS when evaluated within a populaJNCI, VOL. 78, NO. 5, MAY 1987 tion residing in western Washington State, since increased cancer risks were not observed for numerous other occupations or activities involving comparable opportunity for exposure to these substances. In this regard, the present findings are not consistent with results of studies conducted in Swedish and other populations, which report consistent and substantially increased risks of both types of cancer in association with occupational exposure to specific chlorophenols or phenoxyacetic acids or to combinations of these chemicals. In consideration of possible reasons underlying the apparent lack of consistency between the results of Swedish studies and those conducted here and elsewhere, three issues that have not received major attention with regard to this question include: a) differences in the intensities or dosages of chemicals received by workers in comparable occupational activities, b) differences in the extent of environmental (nonoccupational) exposure to the chemicals received by the respective study populations, and c) differences between study populations with respect to the proportional distribution of other risk factors that in combination with phenoxyherbicides or chlorophenols contribute causally to the cancers putatively associated with chemical exposure alone. In addressing the question of differences in dosages of chemicals received by workers engaged in comparable job activities, it is likely that, should the chemicals under investigation independently increase cancer risks in humans, this effect should be more apparent among persons receiving higher dosages. In considering this possibility as it pertains specifically to application of phenoxyherbicides, it is known that spraying activities, as well as work in sprayed areas, extend over substantially shorter periods of the year in Sweden than occur in western Washington State, owing largely to climatic differences in the length of the growing season. Thus Swedish workers participate in activities in which phenoxyherbicide exposure is typically consolidated within a 2- to 3-month period annually, during which spraying activities involving intensive herbicide exposures that extend over several consecutive weeks at a time are not uncommon (/, 37). In contrast, the annual spraying season in the Pacific Northwest extends over 6-7 months, during which individual spraying episodes usually span only a few days at a time and may be separated by weeks or even months during which no spraying is performed. Such differences in herbicide use patterns could conceivably lead to Swedish applicators receiving appreciably higher cumulative exposures to biologically active substances than occurs among workers engaged in less intensive use patterns, as supported by several studies of this question (38, 39). To analyze this possibility quantitatively, we have employed the phannacokinetic model developed by Gehring et al. (40) from the oral study of 2,4,5-T in humans to calculate maximum absorbed daily dosages of herbicide received by Swedish and American workers. The workers in question engaged in activities with comparable job description, namely, herbicide applica- �STS and NHL and Chemical Exposure in WA 907 tor with the use of tractor-drawn equipment. Calculations, based on urinary herbicide concentrations with the use of data derived from studies of applicators under actual field conditions (37, 41), indicate that the maximum daily dose of 2,4,5-T absorbed by American workers in an application operation involving two sprayings, 2 weeks apart, is in the range of 12-86 /ug/kgbody weight, with a mean maximum daily dose of 45 MS^kg-In contrast, calculated maximum daily dosages received by Swedish workers, doing the same type of work but involving spraying for 3-4 hours/day over a consecutive 2-week period, ranged from 11 to 315 ftg/kg, with a mean maximum daily dosage of 90 /*g/kg. Maximum daily dosages received by American workers involved in other modes of herbicide application were backpack crew, 19-104 Mg/kg; helicopter crew, 17-23 Mg/kg; and mixers, 12-138 pg/kg. These results suggest that maximum daily dosages of herbicides received by Swedish applicators could substantially exceed those received by American counterparts as well as those engaged in other modes of spraying operations. From the pharmacokinetic studies in humans {•/#), it is known that 2,4,5-T is absorbed and excreted in the urine with a half-life of about 1 day following a single oral exposure. Moreover, from measurements of urinary 2,4,5-T, the maximum dose that can be absorbed on repeated exposures is estimated to be about 100 jug/kg/day, with the expected maximum concentration in plasma of individuals receiving repeated daily doses reaching a plateau after 3 days of such exposure. Based on these considerations, the calculated mean maximum daily dose of 2,4,5-T received by Swedish workers under the occupational circumstances described above (90 ng/kg) would approximate that required to produce the maximum plasma concentration of 2,4,5-T that could be sustained during spraying operations. Thus Swedish applicators would experience higher sustained tissue levels during repeated frequent exposure episodes, as well as higher tissue concentrations of any PCDDs or other contaminants that would be concomitantly absorbed than would be experienced by American counterparts, who receive lower exposures on a more sporadic basis. Although the implications of these calculations with respect to human cancer risks are difficult to estimate, they are nevertheless of interest in light of findings from recent studies of Swedish subjects (42) involving analysis of PCDDs in abdominal fat from both cases of STS and NHL as well as control subjects. These studies reported that cancer cases exposed to phenoxyherbicides 16-31 years previously had levels of highly chlorinated PCDDs significantly higher than control subjects unexposed to phenoxyherbicides. Interestingly, no differences in case or control TCDD levels were seen. These findings are consistent with the observations from both Swedish (2) and Danish (7) studies of increased cancer risks among persons exposed to phenoxyherbicides and chlorophenols that do not contain detectable levels of TCDD per se but that are most likely contaminated with a variety of other chlorinated dibenzodioxins and furans (43, 44), some of which have been shown to have carcinogenic potential (45, 46). Moreover, the capacity of TCDD, and presumably its approximate isostereoisomers, to act as a cocarcinogen (47) and a tumor promoter (48, 49) have been well characterized. These properties are highly dose dependent. Thus the exposure of Swedish workers to potentially higher concentrations of biologically active substances associated with the use or manufacture of phenoxyherbicides or chlorinated phenols is a consideration possibly consistent with the higher cancer risks observed in studies on such subjects. A recent study by Hoar et al. (25) showing that the relative risk of NHL dramatically increased with the number of days of phenoxyherbicide use per year among agricultural workers in the United States supports this view. Differences in risk estimates observed between this and the Swedish studies might also be accounted for on the basis of variation in the extent of nonoccupational exposure received by the general populations in areas where the studies were conducted. Several investigators (50, 51) have recently reported widespread contamination of the general population in the United States and Canada with PCDDs and PCDFs, based on analysis of human fat samples. The findings indicate that, although higher levels of total dioxins and other contaminants may be seen in some exposed persons, there is considerable overlap in actual tissue concentrations of such substances between some persons with confirmed occupational exposures and others who are not previously known to have been exposed through job-related activities. These observations suggest dial epidemiologic studies conducted in areas where the extensive use of phenoxyherbicides and chlorophenols has occurred may have inadvertently included subjects who have experienced significant exposure to the chemicals of concern outside of the occupational setting. Should this be the case, it is possible that estimates of actual risk based on recall of occupational exposures alone may be underestimated, owing to nondifferential misciassification of subjects according to exposure status (52). To estimate the extent to which nonoccupational exposure to phenoxyherbicides may have occurred in the present investigation, we have evaluated data from several air-monitoring studies (53, 54) conducted during the spraying season in the Pacific Northwest. These data indicate that phenoxyacetic acids as well as PCDDs can be transported in the atmosphere, either as vapor or adsorbed on particles, for distances ranging from several hundred feet up to a mile from die application area (54), depending on weather conditions and mode of dispersion. The maximum concentration of 2,4,5-T, for example, found in 24-hour collections from sampling stations in one study (55) was 3.4 MS/m3- Concentrations of up to 10 /ig/rn3 of other phenoxyherbicides have been detected at sampling sites in agricultural regions of Washington State (56). If it is assumed that a 70-kg person inhales 30 m3 of air per day, a person residing in the proximity of a sprayed area could conceivably receive a dose of 2,4,5-T equal to 1.5 /ig/kg/day during the spraying operation solely from atmospheric sources. These levels are on the order of 10-50 times less than those JNQ. VOL. 78, NO. 5. MAY 1987 �908 Woods, Poiissar, Severson, et ai. received from occupational sources, as described above, and moreover are received via a different route of exposure (inhalation versus dermal), which could alter absorption rales appreciably. However, 24% of STS cases, 23% of NHL cases, and 21% of control subjects in the present study responded positively to the question "Have you ever lived in an area where weed spraying was routinely done by truck or airplane?" This response suggests that considerable population exposure to phenoxyherbicides and their contaminants from environmental sources could have occurred over the 40-year exposure-assessment period. Eliminating subjects who reported residential or home use exposures to phenoxyherbicides or chlorophenols in the present study did not alter the estimated risks of developing STS or NHL. Hence it is unlikely that bias due to such exposures could account for the large differences in risk estimates observed between these and the Swedish studies. Nevertheless, should phenoxyherbicides and/or their contaminants increase the risk of cancer at environmental exposure levels, or, as recently suggested, produce subclinical immune system alterations that may predispose to sucli risks (35), it is possible that risk estimates based solely on assessment of occupational exposures could be attenuated as a result of exposure misclassification. Confirmation of this possibility awaits further investigations based on direct analysis of tissue chemical content or the development of a reliable surrogate measure of past chemical exposure. A third possible reason for a lack of consistency between the results of this and the Swedish studies may be differences between the study populations with respect to the proportional distribution of factors or conditions other than chemical exposure that contribute to the cancers under evaluation. If, for example, a specific inherited, lifestyle, or environmental condition that independently predisposes to increased risks of the cancer(s) associated widi chemical exposure is more prevalent among Scandinavians than among other populations, increased cancer risks could be observed in the former group, even if the prevalence of phenoxyherbicide or chlorophenol exposure were the same or even less than that occurring elsewhere. In this regard it is interesting to note in the present study that exposure to the insecticides DDT and lead arsenate as well as to agricultural and industrial chemicals, such as organic solvents and welding-rnetal furnes, are associated with significantly increased risks of developing NHL (table 7). Compromise of the immune system (31), exposure to zoonotic viruses (24, 57), and chronic mitogenic stimuli (2-f, 31) have also been suggested as etiologic factors for NHL. The extent to which differences in the proportional distribution of such factors between Swedish and the local study populations might account for the inconsistencies observed between the results of this and the Swedish studies cannot be currently estimated, since neither the specific conditions that modify the effects of chemical exposure on cancer risks nor their prevalence among the respective populations have as yet been idenJNCI. VOL. 78, NO. 5. MAY 1987 tified. However, information based on interview responses from existing studies (4) indicates that Swedish populations may have had as much as twice the frequency of exposure to DDT (5.8-7.8 vs. 3.8% locally) as well as to total insecticides (14.6 vs. 7.9%), and this higher exposure may underlie some increased risk of developing cancer, particularly NHL, independently of or in combination with the chemicals currently under study. On the other hand, the frequency of exposure to organic solvents, for which a small but significant interaction with phenoxyherbicides was observed in this study, was approximately equal (28.2 vs. 29.9%) between Swedish and local study populations. Similarly, the frequency of cigarette smoking, now or ever, among Swedish and local study populations was comparable (71 vs. 73%). Little or no data are available regarding population differences in nutritional, medical, or other lifestyle factors that might serve as component causes of STS or NHL or that modify the effect of chemical exposures on cancer risks. The prospect that inherited factors or conditions among Scandinavians might contribute to increased risks of developing cancer in that population when exposed to the chemicals under investigation is another possibility that might account for differences in risk estimates observed. Although specific studies of this question have as yet to be accomplished, laboratory investigations have shown that the binding affinity of the TCDD receptor in biological tissues, as well as subsequent receptor-mediated events, are genetically determined and may vary considerably even among different strains of the same animal species (58). That such variations are also a characteristic of human genealogy is suggested by recent studies (59) that demonstrate both the presence of the Ah (TCDD) receptor in human lung as well as considerable heterogeneity in the human population in regard to lung Ah receptor concentrations. . Moreover, evidence of heritable differences in aryl hydrocarbon hydroxylase induction among humans (60) has been presented. Recently, a hereditary predisposition for the development of STS has been described in the study of Danish phenoxyherbicide manufacturers (7). However, no attempt has been made to determine the frequency of this condition among Scandinavian or other populations or to investigate the extent to which the presence of such a condition could modify the effect of chemical exposure on cancer risks. In the present investigation, we have taken advantage of the fact that approximately 6% of the population of the study area is of Scandinavian heritage (61) to make a crude evaluation as to the extent to which this factor (Scandinavian heritage) might constitute an increased risk of STS or NHL in association with phenoxyherbicide or chlorophenol exposure. For this assessment, the surnames ot all study subjects were segregated into Scandinavian or "other" categories by a member of the University of Washington Department of Scandinavian Languages and Literature who had expertise in Scandinavian genealogy. Through this effort 169 subjects with Scandinavian surnames were identified including �STS and NHL and Chemical Exposure In WA 909 15 STS cases, 66 NHL cases, and 88 controls. No increased cancer risks were associated with having Scandinavian as compared with non-Scandinavian names. However, when the analysis was restricted to Scandinavians only, the risk estimates for STS in relation to past occupational chemical exposures were substantially greater than those observed among the study population as a whole both for high-level phenoxyherbicide [2.8 (0.5-15.6)] and high-level chlorophenol [7.2 (2.1-24.7)] exposures. These estimates are comparable in magnitude to those reported among subjects in Swedish (1-5) and Danish (7) studies. Moreover, the distribution of predominant histologic types of STS was comparable to that reported from the Swedish studies (2). No increased risks of NHL in relation to chemical exposures were observed among persons with Scandinavian surnames. Although the assignment of Scandinavian ancestry in these studies remains unconfirmed, the results are interesting inasmuch as they suggest that factors specific to Scandinavian descent, as opposed to residency or occupation in Scandinavian countries, may contribute to increased risks of STS when exposed to the chemicals under evaluation in this study. Further investigation of this issue may be warranted to help resolve the inconsistency between Swedish studies and those conducted elsewhere. In conclusion, the results of the present investigation demonstrate increased risks of NHL in several specific occupations in which phenoxyacetic acid herbicides are used, as well as for prolonged occupational exposure to these substances. However, they are not consistent with results from Swedish and other studies reporting substantially increased risks of either STS or NHL associated with phenoxyherbicides or chlorophenols as sole or major component causes of these diseases. 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Health status of workers with past exposure to 2,3,7,8-<eirachlorodit>enzo-p-dioxin in the manufacture of 2,4,5-tetrachiorophenoxy acetic acid: Comparison of findings with and without chloracne. Am J Ind Med 1984; 5:161-182. (31) ROBBINS SL, COTRAN RS, KUMAR V. Diseases of white cells, lymph nodes, and spleen. In: Pathologic basis of disease. 3d ed. Philadelphia: Saunders, 1984:653-704. (32) ZINKL J, Vos JG, MOORE JA. el al. Hematologic and clinical JNCI. VOL. 78. NO. 5, MAY 1987 �910 Woods, Polissar, Severson, et al. (33) (34) (35) (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) chemistry effects of 2,3,7,8-tetrachloiodibcn/o-p-dioxin in laboratory animals. Environ Health Perspect 1973; 5:111-118. CLARKE DA, GAUI.DIE J, SZKWCZUK MR, ei al. Enhanced suppressor cell activity as a mechanism of immunosuppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Soc Expt Biol Med 1981; 168:290-299. VF.CCHI A, SIRONI M, CANEGRATI MA, et al. Immunosuppressive effects of 2,3(7,8-tetrachlorodibenzo-£-dioxin in strains of mice with different susceptibility to induction of aryl hydrocarbon hydroxyiase. Toxicol Appl Pharmacol 1983; 68:434-441. HOFFMAN RE, STEHR-GREEN PA, WEBB RB, et al. Health effecis of long-term exposure to 2,3,7,8-ietrachlorodibenzo-p-dioxin. JAMA 1986; 255:2031-2038. HOLSAPPLE MP, McC'AY JA, BARNES DN. Immunosuppression without liver induction by subchronic exposure to 2,7-dichIorodibenzo-]t>-dioxin in adult female B6C3F] mice. Toxicol Appl Pharmacol 1986; 83:445-455. KOLMODIN-HEDMAN B, ERNE K, ENGQVisT A. Testing of professional exposure to phenoxyacids (2,4-D and 2,4,5-T). Arbete och Halsa, Vetenskaplig Skriftserie 1979; 17 (in Swedish). NEWTON N, NORRIS LA. Potential exposure of humans to 2,4,5-T and TCDD in the Oregon coastal ranges. Fund Appl Toxicol 1981; 1:339-346. TASKAR PK, DAS YT, TROUT JR, et al. Measurement of 2,4dichlorophenoxyacetic acid (2,4-D) after occupational exposure. Bull Environ Contam Toxicol 1982; 29:586-591. GEHRING PJ, KRAMER CG, SCHWETZ BA, et al. The fate of 2,4,5trichlorophenoxyacetic acid (2,4,5-T) following oral administration to man. Toxicol Appl Pharmacol 1973; 26:352-361. LENG ML, RAMSEY JC, BRAUN WH. Review of studies with 2,4,5trichlorophenoxyacetic acid in humans including applicators under field conditions. ACS Symp Ser Vol 182. Washington, DC: Am Chem Soc, 1982:135-156. HARDELL L, AXEI.SON O. Phenoxyherbicides and other pesticides in the etiology of cancer. Some comments on the Swedish experiences in cancer prevention. Strategies in the workplace. San Francisco: University of California, J984. NORSTROM A, RAPPE C, LINDALL R, et al. Analysis of some older Scandinavian formulations of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid for contents of chlorinated dibenzo-p-dioxins and dibenzofurans. Scand J Work Environ Health 1979; 5:375-378. DICKSON D. PCP dioxins found to pose health risks. Nature 1980; 283:418. National Toxicology Program. NIH bioassay of 2,7-dichlorodibenzo-p-dioxin for possible carcinogenicity. Technical Report Series No. 123, 1979. . NIH bioassay of a mixture of 1,2,3,6,7,8- and 1,2,3,7,8,9hexachlorodibenzo-£-dioxins for possible carcinogenicity (gavage study). Technical Report Series No. 198, 1980. JNCI. VOL. 78, NO. 5, MAY 1987 (47) Koi!Rl RE, Rw>£ TH, JOGLEKAR R, et al. 2,3,7,8-Tetrachlorodiben/o-/>dioxin as carcinogen causing 3-methylcholanthreneinilinted subcutaneous tumors in mice genetically "nonresponsive" at Ah locus. Cancer Res 1978; 38:2777-2783. (48) PITOT HC, GOLDSWORTHY T, CAMPBELL HA, et al. Quantitative evaluation of the promotion by 2,3,7,8-letrachlorodibenzo-pdioxin of hepatocarcinogenesis from diethylniirosaminc. Cancer Res 1980; 40:3616-3620. (49) ABERNATHY DJ, GREENLEE WF, HUBAND JC, et al. 2,3,7,8-Tetrachlorodibenzo-jt>-dioxin (TCDD) promotes the transformation of C3H/10T1/2 cells. Carcinogenesis 1985; 6:651-653. (50) RYAN JJ, WILLIAMS DT, LAU BP, et al. In: Keith LH, Choudhary G, Rappc C, cds. Chlorinated dioxins and dibenzofurans in the total environment. II. Boston: Butterworth 1984:205-214. (51) GROSS ML, LAY JO, LYON PA, et al. 2,3,7,8-Tetrachlorodibenzo/>-dioxin levels in adipose tissues of Vietnam veterans. Environ Res 1984; 33:261-268. (52) COPELAND KT, QlECKOWAY H, HOLBROOK RM, et al. Bias due to misclassificatiori in the estimate of relative risk. Am J Epidemiol 1977; 105:488-495. (53) ADAMS DF, JACKSON CM, BAMESBERGER WL. Quantitative studies of 2,4-D esters in the air. Weeds 1974; 12:180-283. (54) RENNE DS, WOLF MA. Experimental studies of 2,4-D herbicide drift characteristics. Ag Meterol 1979; 20:7-24. (55) BAMESBERGER WL, ADAMS DF. An atmospheric survey for aerosol and gaseous 2,4-D compounds. In: Gould RF, ed. Organic pesticides in the environment. Chapt 18. Adv Chem Ser. Washington, DC: Am Chem Soc, 1966:219-227. (56) BOVEY RW. Uses of phenoxyherbicides and iheir methods of application. Chapt 3. In: Bovey RW, Young AL, eds. The science of 2,4,5-T and associated phenojcyherbicides. New YorkWiley, 1980:49-69. (57) BLAIR A, HAYES HM. Mortality patterns among US veterinarians. 1947-77: An expanded study. Int J Epidemiol 1982; 11:391-397 (55) GASIEWICZ TA. Evidence for a homologous nature of Ah receptor among various mammalian species. In: Poland A, Kimbroug:. RD, eds. Biological mechanisms of dioxin action. Banbur report No. 18. Cold Spring Harbor, NY: Cold Spring Harbi.; Laboratory, 1984:161-175. (59) ROBERTS EA, GOLAS CL, OKF.Y AB. Ah receptor mediating indu' lion of aryl hydrocarbon hydroxyiase: Detection in huma . lung by binding of [2,3,7,8-3H]tetrachlorodibenzo-j!J-dioxi-'. Cancer Res 1986; 46:3739-3743. (60) NEBERT DW, JENSEN NM. The Ah locus: Genetic regulation :,' the metabolism of carcinogens, drugs and other environment, chemicals by cytochrome P-450-mediated monooxygenasc • CRC Grit Rev Biochem 1979; 6:401-437. (61) 1980 Census of population. Vol 1. Characteristics of the popui. tion. Chapt C. General social and economics characterisn*. Part 49. Washington, DC: U.S. Dept of Commerce, 1983. � 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 1769 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 Woods, James S. Lincoln Polissar Richard K. Severson Linda S. Heuser Bruce G. Kulander Source A related resource from which the described resource is derived Journal of the National Cancer Institute Date A point or period of time associated with an event in the lifecycle of the resource 1987-05-01 Title A name given to the resource Soft Tissue Sarcoma and Non-Hodgkin's Lymphoma in Relation to Phenoxyherbicide and Chlorinated Phenol Exposure in Western Washington Subject The topic of the resource cancer risk assessment lymphomas dioxin industrial exposure ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/7b982586fc4da1dc4c6be53fcac84b2c.pdf 304d1826437992bbdc8e1342914d875f PDF Text Text Itom ID Number 01764 Author Fingerhut, Marilyn A. Corporate Author ROpOrt/ArtiOlO TltlO Review of Exposure and Pathology Data for Seven Cases Reported as Soft Tissue Sarcoma Among Persons Occupational^ Exposed to DioxinContaminated Herbicides Journal/Book Title 1984 Year Month/Day Color ' Number of Images 17 Descpipton Notes Monday, June 11, 2001 Page 1765 of 1793 �187 REVIEW OF EXPOSURE AND PATHOLOGY DATA FOR SEVEN CASES REPORTED AS SOFT TISSUE SARCOMA AMONG PERSONS OCCUPATIONALLY EXPOSED TO DIOXIN-CONTAMINATED HERBICIDES Marilyn, A. Fingerhut, Ph.D* William E. Halperin, M.D., M.P.H.* Patricia A. Honchar, Ph.D* Alexander B. Smith, M.D., M.S.* David H. Groth, M.D.* William 0. Russell, M.D.** *National Institute for Occupational Safety and Health Cincinnati, Ohio 45226 **North Ridge General Hospital and Cancer Foundation, Fort Lauderdale, Florida 33334 This paper is a work of the U.S. Government; therefore copyright does not apply. From Public Health Risks of the Dioxins, proceedings of a symposium held on . October 19-20, 1983 at The Rockefeller University, New York City. Edited by William W. Lowrance. Published by William Kaufmann, Los Altos, California, 1984. �188 Fingerhutetal. Data from two Swedish studies (1,2) and a review of four U.S. studies (3) of dioxin-exposed workers have suggested that occupational exposure to dioxin-contaminated products is associated with an increased risk of soft tissue sarcoma (STS). Soft tissue sarcomas are malignant neoplasms arising throughout the body from mesenchymal supporting tissue other than bone (4). The principal types of histopathologic subtypes and their frequencies 'are listed in Table 1. : Table 1. Histopathologic varieties of sarcoma of soft tissue.* r > tPercentage of Histopathological Variety Total Cases r Rhabdomyosarcoma 19.2 "' Fibrosarcoma 19.0 Liposarcoma 18.2 Malignant fibrohistiocytoma 10.5 Sarcoma of Soft Tissue, type unspecified 10.0 Synovial sarcoma 6.9 Leiomyosarcoma 6.5 Malignant schwannoma 4.9 Angiosarcoma 2.7 Other types 1.9 * Table presented in Suit, H.D., Sarcoma of soft tissue, CA-A Cancer Journal for Clinicians 1978; 28:284-295. The percentages were derived from a study of 1,215 sarcomas by the Task Force for Sarcoma of Soft Tissue of the American joint Committee on Cancer (5). Dioxins are generated as unintended contaminants during the chemical manufacture of chlorinated phenoxy acetic acids and chlorinated phenols. The most toxic of the 75 dioxin isomers, 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD), is generated during �Review of Reported Soft, Tissue Sarcoma Cases 189 the production of trichlorophenol (TCP) and its derivative, the herbicide 2/4,5-trichlorophenoxyacetic acid (2,4,5-T). Industrial workers who produce chlorinated phenoxy acetic acids and chlorophenols, and herbicide applicators who spray these products, potentially have been exposed to the products and their dioxin contaminants. In 1977, several cases of soft tissue sarcoma were reported among Swedish lumberjacks who had had prior exposure to phenoxy herbicides. This clinical observation led researchers in Sweden to conduct two separate case control studies (1,2). Both studies found that persons with occupational exposure to phenoxy acids or chlorophenols had a fivefold increased risk of developing a soft tissue sarcoma. At" about the same time, four studies (6-9) were conducted in~j> U.S. manufacturing plants of workers exposed to the herbicide 2,4,5-T and its chemical precursor, trichlorophenol. The dioxin isomer contaminating these products is the most toxic form, 2,3,7,8-TCDD. None of the four studies found any statistically significant excess in total mortality or in death from cancer which was attributed to dioxin exposure. However, each cohort was small and of insufficient statistical power to allow adequate evaluation of rare causes of death. Honchar (3) reviewed the deaths in the four cohorts, and found that three (2.9%) of the total 105 deaths in the merged cohorts were reported to be from soft tissue sarcoma. Based on national statistics, only 0.07% of deaths was expected to be due to this cause. Table 2 lists these three deaths as Cases 1 to 3. Subsequently, Dr. Ralph Cook of Dow Chemical Company reported a fourth, living person in one of these cohorts as having a soft tissue sarcoma (10). This individual, Case 4, is now deceased. Dr. Marion Moses of Mt. Sinai reported an additional case of soft tissue sarcoma in an individual (Case 5) employed at one of the same four chemical manufacturing sites (11). Subsequently, two additional persons, Cases 6 and 7, were reported to have soft tissue sarcomas (12). They worked at a chemical manufacturing site which produced 2,4,5-T, but which had not been previously studied, and their exposures had not been confirmed at the time of the reports. �190 Fingerhutetal. Table 2. Exposure data from original publications for the seven U.S. workers. Case Number Type of Exposure Type of Report Reference TCP Mortality Study Zack, J. and Suskind, R.S, Journal of Occupational Medicine 1980; 22;11-14. 2,4,5-T Mortality Study Zack, J. and Gaffey, W.R. Environmental Science Research 1983; 26;575-591. TCP Mortality Study Cook, R.R. et al. Journal of Occupational Medicine T980; 22:530-32. TCP Case Report Cook, R.R. Lancet 1981,; i:618-619. ^ TCP, 2,4,5-T Case Report Moses, M. and Selikoff, I.J. Lancet 1981; i: 1370. 6 Chlorophenols Case Report Johnson, F.E. et al. Lancet 1981; i:40. 7 Chlorophenols Case Report Johnson, F.E. et al. Lancet 1981; i:40. We have obtained detailed employment records, medical and pathological reports, tissue specimens and death certificates for these seven individuals and present here detailed descriptions of our occupational and pathologic reviews. We hope, through this report, to focus attention on the problems associated with the study of soft tissue sarcomas in dioxin-exposed populations. In addition to our work at the National Institute for Occupational Safety and Health (NIOSH), studies of the health effects of dioxin are underway at the Centers for Disease Control (CDC), the Veterans Administration (VA), the National Institutes of Health (NIH), and various state agencies in this country. Other organizations, both here and abroad, are also conducting studies of soft tissue sarcoma, and the International Agency for Research on Cancer (IARC) of the World Health Organization is considering an International Dioxin Registry. �Review of Reported Soft Tissue Sarcoma Cases 191 EXPOSURE DATA FOR THE SEVEN CASES Table 3 presents the exposure history of each individual. We used a rigorous criterion of exposure. An individual was considered exposed to products contaminated with 2,3,7,8-TCDD if he had a company record of assignment to a department producing trichlorophenol or 2,4,5-T. Table 3. Work history information for the seven U.S. workers. 'Duration of Exposure (Years) Case Number Facility Years of Employment 1 A 1946-1978 TCP Operator 1.9 •" 2 A 1946-1972 2,4,5-T Operator 2.0 3 B 1950-1975 Maintenance 3.5 4 B 1951-1982 TCP Operator Plant Mechanic (TCP Department) 19.0 job Title 5 A 1943-1975 Maintenance Service 6 C 1978-1980 Production Worker 7 C 1951-1980 Production Worker 11 days The work histories confirmed the original reports that Cases 1, 2, and 4 were production workers assigned to the trichlorophenol or 2,4,5-T departments. Case 3 was a maintenance worker identified by the company as assigned to a building where trichlorophenol was produced. Case 5 was a maintenance and service worker for 32 years in a chemical manufacturing site which produced trichlorophenol, 2,4,5-T, and many other chemicals, but he had no record of specific assignment to a trichlorophenol or 2,4,5-T department. Case 6 worked two and one-half years in a plant which made 2,4,5-T. He was a production worker but had no record of assignment to the 2,4,5-T area. Case 7 is the father of Case 6 and was a production worker at the same facility for 29 years. His work history showed no record of assignment to the 2,4,5-T area, although he did work for 11 days �192 Fingerbut etal. following hire in 1951 in a pentachlorophenol area. Pentachlorophenol is contaminated with hexa-, hepta- and octachlorinated isomers of dioxin, but does not contain 2,3,7,8-TCDD. These last three individuals illustrate some of the difficulties encountered in attempting to verify exposure in chemical workers. In general, production workers qlo have records of regular assignment to specific departments within <|:omplex chemical manufacturing plants, although their records do not show temporary changes in assignments. However, maintenance workers such as Case 5 often work throughout an entire facility and never have recorded assignments in specific departments From our examination of their work histories we concluded that these three workers did not meet our stringent criterion of exposure, they had no recordsjof assignment to a 2,4,5-T or trichlorophenol process. However, absence of such documentation does not eliminate i ' the possibility than they were exposed to dioxin contaminated products during their routine activities. PATHOLOGY DATA FOR THE SEVEN CASES Table 4 summarizes clinical observations obtained from company medical records, hospital records, and pathology reports for the seven individuals. All cases were reported to have soft tissue sarcomas. Table 4. Medical information for the seven U.S. Case Number Tumor 1 Malignant fibrous histiocytoma Onset of Tumor workers. Age at Onset Chloracne 1978 58 yes yes Adenocarcinoma, bladder Liposarcoma, rectum 1958 34 1972 49 3 Fibrosarcoma 1973 52 dermatitis 4 Malignant fibrous histiocytoma 1979 58 yes Neurogenic sarcoma 1980 57 no 2 �Review of Reported Soft Tissue Sarcoma Cases 193 Table 4. Continued. Case Number Tumor 6 Fibrosarcomatous mesothelioma 1980 33 no Liposarcoma 1980 53 no 7 Onset of Tumor Age at Onset Chloracne Cases 1, 2, and 4 had records of diagnosed chloracne. Case 3 had dermatitis of the face and neck while assigned to the trichlorophenol building during a period when 49 trichlorophenol workers developed chloracne (8). But no chloracne was found in the records of Cases 5, 6, and .7. V Table 5 presents data on the latency of the tumors (time from first exposure to diagnosis of the tumor) for each individual. Table 5. Latency of tumors for seven U.S. workers. Case Number First Assignment to 2,4,5-T or TCP Department STS Tumor Onset Latency* (Years) Age at Onset 1 1949 1978 29 58 2 1950 1971 21 49 3 1964 1973 9 52 4 1951 1979 28 58 5 never 1980 N.A.** 57 6 never 1980 N.A. 33 7 never 1980 N.A. 53 * Time from first exposure to onset of tumor. ** Not applicable. Adequate latency for development of cancer was experienced by the four individuals with records of assignment to trichlorophenol or 2,4,5-T departments (Cases 1 to 4). Since no records of specific departmental assignment to TCP or 2,4,5-T departments exist for the �194 Fingertmt et al. remaining three individuals, latency cannot be assigned for exposure to 2,3,7,8-TCDD, DEATH CERTIFICATE DATA VS. PATHOLOGIC DIAGNOSES AND ICD CODING CATEGORIES Table 6 compares the diagnoses made by the attending pathologists with the information on the death certificates. Table 6. Comparison of death certificate data with original pathologic diagnoses for the seven U.S. workers. 1 Case Number Death Certificate 1 Malignant fibrous histiocytoma Malignant fibrous histiocytoma 2 Liposarcoma Liposarcoma 3 Pibrosarcoma Fibrosarcoma 4 Malignant fibrous histiocytoma Malignant fibrous histiocytoma 5 Carcinomatosis Myxoid neurogenic sarcoma Metastatic mesothelioma Fibrosarcoma consistent with fibrosarcomatous mesothelioma N.A.* Myxoid liposarcoma 7 * Not applicable. Original Pathology " Individual is alive, Of the six deceased cases, all of whom had hospital diagnoses of soft tissue sarcoma, only four had soft tissue sarcoma noted on their death certificates (Cases 1 to 4). A similar finding was noted in a study of the accuracy of death certificates conducted by Percy et al. in 1981 (13). They reviewed almost 50,000 hospital diagnoses and death certificates and found that of 252 soft tissue sarcomas diagnosed in hospital records, only 142 death certificates for those individuals (55%) reported the soft tissue sarcomas. Hence using �Review of Reported Soft Tissue Sarcoma Cases 195 death certificates as the primary source of cases may lead to underascertainment of cases. We found in our review that all four death certificates with notations of soft tissue sarcoma (Cases 1 to 4) belonged to persons who had diagnoses of soft tissue sarcoma made by the attending pathologists. In contrast, Percy (13) found in her large study that only 56% of death certificates with notation of soft tissue sarcoma were supported by hospital records with the diagnoses of soft tissue sarcoma. Hence using death certificates as the primary source of cases and not confirming hospital or pathologic information may lead to overascertainment. Researchers conducting epidemiologic studies should be fully aware of possible underascertainment or overascertainment. Table 7 illustrates another issue in the use of death certificate data: consistency in classification by nosologists, the experts who code cause of death from death certificates according to the rules of the International Classification of Disease System (14). Table 7. Comparison of death certificate information and nosologic coding of the information. Case Number 1 ICD Category* Original Honchar Publication** Review*** Death Certificate Malignant fibrous histiocytoma 173.9 171 * World Health Organization, Manual of the International Statistical Classification Diseases, injuries and Causes of Death, Geneva. Ninth Revision, 1975. ** Zack, J.A. and Suskind, R.S. 1980; 22:11-14. Journal of Occupational Medicine *** Honchar, P.A. and Halperin, W.E. Lancet 1981; i:26S-269. Case 1 was reported in the original publication as having a malignant fibrous histiocytoma, which was coded in ICD Category 173.9, "Other malignant neoplasm of skin, site unspecified". Honchar indicated in �196 Rngerhutfital. her review (3) that the choice of her nosologist was ICD 171, "Malignant neoplasm of connective and other soft tissue". Misclassification in ICD categories could introduce significant error. The data in Table 7 suggest that coding by more than one trained nosologist may be desirable. Another important issue of classification not addressed by this review has serious implications for studies of soft tissue sarcoma. The international Classification of Disease System is a site-oriented classification scheme. Therefore, sarcomas that develop in the parenchymatoas organs such as the uterus or stomach are coded into the ICD categories for the organ site. Only soft tissue sarcomas of the supporting tissue of the body not specified as arising in organs are coded in the ICD Category 171. It is possible, therefore, to select soft tissue sarcoma cases for case control studies in two ways. For the early Swedish studies (1,2) cases were selected by their histopathologic characteristics; approximately 60% of these cases are coded in categories other than ICD 171 (15). A current case control study in New Zealand (16) includes only soft tissue sarcoma cases coded as ICD 171. Such differences in study design must be recognized when evaluating results. The problem presented by the ICD dual classification scheme is slightly different for cohort mortality studies. It is possible to compare sarcomas coded as ICD 171 with those arising in the national population; however, we are not aware of population rates for soft tissue sarcoma coded into other ICD categories. ORIGINAL REPORT DATA VS. NEW REVIEW DATA Table 8 compares the original pathologic diagnoses for the seven individuals with the diagnoses selected in two independent pathologic reviews of tissue specimens. �Review of Reported Soft Tissue Sarcoma Cases 197 Table 8. Comparison of the original pathology reports with reports of two reviewers.* Original Pathology Case Number Review #1 Review #2 Malignant fibrous histiocytoma Malignant fibrous histiocytoma Malignant fibrous histiocytoma Invasive pleomorphic liposarcoma Poorly differentiated carcinoma Carcinoma, poorly differentiated Fibrosarcoma Clear cell carcinoma spindle cell with spindling, renal renal carcinoma 4 Malignant fibrous histiocytoma Malignant fibrous histiocytoma Malignant ' schwannoma 5 Myxoid neurogenic sarcoma Leiomyosarcoma Malignant fibroh ist iocy tomcux Malignant schwannoma Malignant schwannoma 6 Fibrosarcoma Liposarcoma Myxoid liposarcoma Myxoid . liposarcoma * The tissue specimens were reviewed by one of the authors (W.O.R.) and also by Franz M. Enzinger, M.D. and Sharon M. Weiss, M.D. of the Armed Forces Institute of Pathology, Washington, DC. Although all seven individuals received diagnoses of soft tissue sarcoma by the original pathologists, only five of the cases were diagnosed as soft tissue sarcoma in each of the two reviews. In both reviews Cases 2 and 3 were identified as carcinomas rather than sarcomas. These results indicate that review of tissue specimens by pathologists with expertise in diagnosing soft tissue sarcomas is necessary for epidemiologic studies. A difficult problem arises for cohort mortality studies because there is no comparison group for cases ascertained by expert pathologists. Rates of disease commonly used for comparison are those taken from compilations of population rates based on information from death certificates. The adequacy of diagnosis of histological subtypes of soft tissue sarcoma is another issue raised by the data in Table 8. Although the original pathologists and the reviewers all agreed that five individuals had soft tissue sarcomas, they agreed on the histological subtype for only two individuals, Cases 1 and 7. Even the expert �198 Ftagerhutetal. reviewers disagreed on subtype diagnoses for Cases 4 and 5. Because of the difficulties involved in diagnosing the histological subtypes, particularly when only a limited amount of tissue is available for review, we recommend that epidemiologic studies continue to focus on the outcome soft tissue sarcoma, and assess the distribution of subtypes only cautiously and with a recognition of the limitations involved. The next two tables summarize the exposure histories and the pathologic findings and compare them to the information published in the original reports. Table 9 presents data for the four production workers identified in company studies (6-10) as, 2,4,5-T/ or >• trichlorophenol-exposed workers. r •X Table 9. Comparison of original reports with results from this review for production workers identified by companies as TCP* or 2,4,5-T workers. Case Number Reported Exposure This Original Review Reoort Cause of death Original This Report Review 1 TCP TCP STS STS 2 2,4,5-T 2,4,5-T STS Carcinoma 3 TCP TCP STS Carcinoma 4 TCP TCP STS STS * Terms: TCP, trichlorophenol; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; STS, soft tissue sarcoma. The reported exposures were confirmed by documentation that the four individuals had been assigned to 2,4,5-T or TCP processes. All had been reported as having soft tissue sarcomas, but we report that the two expert pathologists confirm that only two individuals (Cases 1 and 4) had soft tissue sarcomas. Both of these individuals worked in trichlorophenol processes, had diagnosed chloracne, and were present during incidents of unusual operating conditions with probable exposure to 2,3,7,8-TCDD. The histological subtype of malignant fibrous histiocytona was selected by all three pathologists for Case 1. Case 4 also received a diagnosis of malignant fibrous �Bevlew of Reported Soft Tissue Sarcoma Cases 199 histiocytoma from the original pathologist and one reviewer. The second reviewer identified the subtype as a neurogenic schwannoma. Table 10 presents the same comparison for the three individuals originally described in case reports by physicians (11,12). Table 10. Comparison of original reports with results from this review for production workers originally described as case reports by physicians. Case Number Reported Exposure Original This Report Review Pathologic Diagnosis Original This / Report Review 5 Possibly 2,4,5-T,* TCP None STS STS 6 Possibly chlorophenols None STS STS 7 Possibly chlorophenols PCP STS STS * Terms: 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; TCP, trichlorophenol; PCP, pentachlorophenol; STS, soft tissue sarcoma. Review of the tissue specimens for all three workers were confirmed that they had soft tissue sarcomas. Examination of the work history records of the individuals did not document assignment to 2,4,5-T or trichlorophenol departments. However, Case 7 worked briefly upon hire in a pentachlorophenol department. CONCLUSION Swedish research (1,2) has drawn attention to the issue of soft tissue sarcoma and dioxin exposure. While each of the original four U.S. studies (6-9) reported non-positive findings, a reanalysis (3) and further reports (10,11) strengthened the suspicion that an association might exist. Honchar (3) and Cook (10) called for detailed examination of the data. We present the detailed assessment of exposure history and pathologic diagnosis and report that of the four soft tissue sarcoma cases identified by death certificates among �200 Fingerhut et al. the TCP and 2,4,5-T workers, two are confirmed following pathologic review of tissues as soft tissue sarcoma. It Is not possible to use our data to draw a definitive conclusion regarding the suspected association because we are not aware of any population rates for soft tissue sarcoma based upon pathologic review of tissue specimens. Cases 5, 6 and 7 were originally described in.the literature as individual case reports. All three are confirmed as cases of soft tissue sarcoma. Our review of their work histories did not find any record of assignment to 2,4,5-T or trichlorophenol departments, although Case 7 worked briefly in a pentachlorogfhenol department/ a product contaminated with isomers of dioxin considered to be less toxic than 2,3,7,8-TCDD. Although these workers do not meet our , stringent criterion of exposure by virtue of assignment 'to a 2,4,5-T or TCP department, we cannot exclude the possibility that they had undocumented contact with 2,4,5-T or TCP. This review examines the complexities in evaluating the dioxin exposure of individuals and the pathologic diagnoses of soft tissue sarcoma. It emphasizes the need for carefully-designed large epidemiologic studies to adequately assess whether there is an association of soft tissue sarcoma with exposure to dioxincontaminated products. We have shown that the use of the death certificate, even with the original pathologic diagnosis may lead to overascertainment or underascertainment of cases of soft tissue sarcoma. Finally, we reassert that further research, particularly the completion of National Institute for Occupational Safety and Health studies based upon approximately 6,000 U.S. workers, is necessary to confirm or refute the association first suggested in the Swedish studies. ABSTRACT We have reviewed medical and exposure records and pathology specimens of seven U.S. chemical workers reported in the.literature to be cases of soft tissue sarcoma (STS) and to have had dioxin exposure. The cases were of interest because two Swedish studies demonstrated a strong association between STS and dioxin exposure. �Review of Reported Soft Tissue Sarcoma Cases 201 Four U.S. workers from four small mortality cohorts had been reported to have died of soft tissue sarcoma. We found that these individuals had employment records of assignment to production of TCP and 2,4,5-T which are contaminated with the most toxic dioxin isomer, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3 ,1,8-TCDD), but pathologic review of their tissue indicates that only two are cases of soft tissue sarcoma. Three additional individuals had been described by physicians as case reports. They are confirmed as cases of soft tissue sarcoma, but we did not find any record of assignment to these production departments. One person worked briefly in the production of pentachlorophenol, which is contaminated with other isomers of. i ' dioxin. We suggest that identification of cases of STS through either .death certificates alone or through pathology records can lead to errors of ascertainment. We reassert that further research, particularly the completion of studies by the National Institute for Occupational Safety and Health based upon approximately 6,000 U.S. workers, is necessary to confirm or refute the association first suggested in the Swedish studies. �202 Fingerhut et al. REFERENCES 1. Hardell, L. and Sandstrom, A. Case-Control Study: Soft-Tissue Sarcomas and Exposure to Phenoxyacetic Acids or Chlorophenols. British Journal of Cancer 1979; 39:711-717. 2. Eriksson, FT., Berg, N., Hardell, L., Moller, T. and Alexson, o. Soft-Tissue Sarcomas and Exposure to Chemical Substances: A Case-Referent Study. British Journal of Industrial Medicine 1981; 38:27-33. 3. Honchar, P.A., and Halperin, W.E. 2,4 ,5-Trichloropl^enol and £oft Tissue Sarcoma. Lancet 1981; i:268-269. 4. Suit, H.D. Sarcoma of Soft Tissue. Clinicians 1978; 28:284-295. 5. Russell, W.o. et al. CA-A Cancer Journal for- A Clinical and Pathological Staging System for Soft Tissue Sarcomas. Cancer 1977; 40:1562-1570. 6. Zack, J.A. and Suskind, R.S. The Mortality Experience of Workers Exposed to Tetrachlorodibenzodioxin in a Trichlorophenol Process, journal of Occupational Medicine 1980; 22:11-14. 7. ott, M.G., Holder, B.B. and Olson, R.D. A Mortality Analysis of Employees Engaged in the Manufacture of 2,4,5-Trichlorophenoxyacetic Acid. Journal of Occupational Medicine 1980; 22:47-50. 8. Cook, R.R., Townsend, J.C. and Ott, M.G. Mortality Experience of Employees Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Journal of Occupational Medicine 1980; 22:530-532. 9. Zack., J.A. and Gaffey, W.R. A Mortality Study of Workers Employed at The Monsanto Company plant in Nitro, West Virginia. Environmental Science Research 1983; 26:575-591. �Review of Reported Soft Tissue Sarcoma Cases 10. Cook, R.R. Dioxin, Chloracne and Soft Tissue Sarcoma. 203 Lancet 1981; 1:618-619. 11. Moses, M. and Selikoff, I.J. Soft Tissue Sarcomas, Phenoxy Herbicides and Chlorinated Phenols. Lancet 1981; i:1370. 12. Johnson, P.E., Kugler, N.A. and Brown, s.M. and Chlorinated Phenols. Soft Tissue Sarcomas Lancet 1981; i:40. 13. Percy, C., Stanek, E. and Gloeckler, L. Accuracy of Cancer Death Certificates and Its Effect on Cancer Mortality Statistics. American Journal of Public Health 1981; 71:242-250'. 14. World Health Organization, Manual of the International Statistical _ . „ __ _ B ^ « _ ^ « _ ~ w ^ _ B v w ^ _ ^ ___ —.^^—^^^ff^—i- Classification of Diseases, Injuries and Causes of Death (1975) Ninth Revision. Geneva, 1977. 15. Summarized from Exhibit 1299, prepared by L. Hardell for the U.S. Environmental Protection Agency, October 24, 1979. 16. Smith, A.H. et al. Do Agricultural Chemicals Cause Soft Tissue Sarcoma? initial Findings of a Case Control Study in New Zealand. Community Health Studies 1982; 6:114-119. � 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 1764 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 Fingerhut, Marilyn A. William E. Halperin Patricia A. Honchar Alexander B. Smith David H. Groth William O. Russell Date A point or period of time associated with an event in the lifecycle of the resource 1984 Title A name given to the resource Review of Exposure and Pathology Data for Seven Cases Reported as Soft Tissue Sarcoma Among Persons Occupationally Exposed to Dioxin-Contaminated Herbicides Subject The topic of the resource Sweden industrial exposure cancer risk assessment 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 079 Folder The folder containing the original item. 2028 Series The series number of the original item. Series III Subseries IV Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource June 13 1984 Title A name given to the resource Transcript of Proceedings: Royal Commission on the Use and Effects of Chemical Agents on Australian Personnel in Vietnam, 13 June 1984 Subject The topic of the resource Australian Royal Commission Hearings congenital birth defects Seveso 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 079 Folder The folder containing the original item. 2027 Series The series number of the original item. Series III Subseries IV Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource June 12 1984 Title A name given to the resource Transcript of Proceedings: Royal Commission on the Use and Effects of Chemical Agents on Australian Personnel in Vietnam, 12 June 1984 Subject The topic of the resource Australian Royal Commission Hearings dioxin Seveso 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 072 Folder The folder containing the original item. 1908 Series The series number of the original item. Series III Subseries IV Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Jessop Description An account of the resource <strong>Corporate Author: </strong>Commonwealth of Australia, Senate, Standing Committee on Science and the Environment Date A point or period of time associated with an event in the lifecycle of the resource April 1 1982 Title A name given to the resource Reference: Pesticides Inquiry (Official Hansard Report), Sydney, Thursday, 1 April 1982. Subject The topic of the resource Australian Parliamentary hearings industrial exposure herbicide toxicology ecological impact 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 070 Folder The folder containing the original item. 1882 Series The series number of the original item. Series III Subseries IV Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource <strong>Corporate Author: </strong>Department of Health, Canberra, Australia Date A point or period of time associated with an event in the lifecycle of the resource 1981-01-01 Title A name given to the resource Comment on the Use of Cacodylic Acid in Vietnam Subject The topic of the resource herbicide blue health effects 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 1481 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 Kimbrough, Renate D. Vernon N. Houk Description An account of the resource <strong>Corporate Author: </strong>Center for Environmental Health, Centers for Disease Control, Public Health Service, U.S. Department of Health and Human Service Title A name given to the resource The Effects of Chlorinated Dibenzodioxins on Human Health Subject The topic of the resource dioxin industrial exposure health effects chloracne 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 1456 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 Cook, R. R. G. G. Bond R. A. Olson M. G. Ott M.R. Gondek Title A name given to the resource Typescript: Evaluation of the Mortality Experience of Workers Exposed to the Chlorinated Dioxins and Executive Summary: Update of Mortality Experience of Workers Exposed to Chlorinated Dioxins Subject The topic of the resource mortality trends industrial exposure Michigan Dow 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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 <strong>Corporate Author: </strong>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 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 1445 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 Lavy, T. L. L. A. Norris J. D. Mattice D. B. Marx Source A related resource from which the described resource is derived Environmental Toxicology and Chemistry 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 Exposure of Forestry Ground Workers to 2,4-D, Picloram, and Dichlorprop Subject The topic of the resource 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 <p style="margin-top: -1em; line-height: 1.2em;">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.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> 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. 1422 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 Schecter, Arnold N. C. A. Weerasinghe Michael Gorss Thomas Gasiewicz John D. Constable John Jacob Ryan Date A point or period of time associated with an event in the lifecycle of the resource April 15 1986 Title A name given to the resource Typescript: Human Tissue Levels of Dioxin and Furan Isomers in Potentially Exposed and Control Patients Up to 15 Years After Cessation of 2,3,7,8-TCDD Environmental Contamination Subject The topic of the resource breast milk testing industrial exposure adipose tissue testing ao_seriesIII