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Veterans and Agent Orange: Update 2006 (2007)
Board on Population Health and Public Health Practice (BPH)

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Veterans and Agent Orange: Update 2006

4
Epidemiologic Studies—New Citations for Update 2006 and Background on Repeatedly Studied Populations

The continuing effort to evaluate and integrate all results from human studies pertinent to possible health effects of exposure to any of the chemicals of interest (2,4-dichlorophenoxyacetic acid [2,4-D]; 2,4,5-trichlorophenoxyacetic acid [2,4,5-T] and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]; 4-amino-3,5,6-trichloropicolinic acid [picloram]; and cacodylic acid [dimethylarsinic acid or DMA]) has involved the consideration of thousands of citations over the successive updates. Results on a single population may be reported concerning a multiplicity of health outcomes and in more than one publication, particularly when a study is of the cohort design with repeated follow-ups.

The major purpose of the chapters on “epidemiology” or “epidemiologic studies” in Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (VAO; IOM, 1994) and its updates has always been to reduce repetition of design information in the health outcomes chapters from endpoint to endpoint and from update to update. Deviating somewhat from the format of previous VAO reports, this chapter first provides tables listing the epidemiologic citations new to this update, which represent a compendium of the sources of new information on health outcomes in humans considered by this committee. The citations correspond to publications that appeared from June 1, 2004 (the closing date for inclusion in the previous update), through September 30, 2006.

Earlier reports in the VAO series used an organizational framework for this chapter, for discussions of health outcomes, and for results tables, which categorized each publication containing primary epidemiologic findings as an occupational study, an environmental study, or a study of Vietnam veterans. These categories were not intended to imply that any of these populations is intrinsically more valuable for the committee’s purpose. Various study designs

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Veterans and Agent Orange: Update 2006 4 Epidemiologic Studies—New Citations for Update 2006 and Background on Repeatedly Studied Populations The continuing effort to evaluate and integrate all results from human studies pertinent to possible health effects of exposure to any of the chemicals of interest (2,4-dichlorophenoxyacetic acid [2,4-D]; 2,4,5-trichlorophenoxyacetic acid [2,4,5-T] and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]; 4-amino-3,5,6-trichloropicolinic acid [picloram]; and cacodylic acid [dimethylarsinic acid or DMA]) has involved the consideration of thousands of citations over the successive updates. Results on a single population may be reported concerning a multiplicity of health outcomes and in more than one publication, particularly when a study is of the cohort design with repeated follow-ups. The major purpose of the chapters on “epidemiology” or “epidemiologic studies” in Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (VAO; IOM, 1994) and its updates has always been to reduce repetition of design information in the health outcomes chapters from endpoint to endpoint and from update to update. Deviating somewhat from the format of previous VAO reports, this chapter first provides tables listing the epidemiologic citations new to this update, which represent a compendium of the sources of new information on health outcomes in humans considered by this committee. The citations correspond to publications that appeared from June 1, 2004 (the closing date for inclusion in the previous update), through September 30, 2006. Earlier reports in the VAO series used an organizational framework for this chapter, for discussions of health outcomes, and for results tables, which categorized each publication containing primary epidemiologic findings as an occupational study, an environmental study, or a study of Vietnam veterans. These categories were not intended to imply that any of these populations is intrinsically more valuable for the committee’s purpose. Various study designs

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Veterans and Agent Orange: Update 2006 (most importantly cohort, case–control, and cross-sectional) have strengths and weaknesses (see Chapter 2) that influence their potential to contribute evidence of an association with the health outcomes considered in Chapters 6–9 of this report. Update 2006 has retained the categorization scheme; cycling through these categories, the second part of this chapter discusses the design details of new reports on populations already under study and of studies on new populations reporting multiple endpoints. The occupational section covers studies of production workers, agriculture and forestry workers (including herbicide and pesticide applicators), and paper and pulp workers. The environmental section covers studies of populations unintentionally exposed to unusually high concentrations of herbicides or dioxins as a result of where they lived, such as Seveso, Italy; Times Beach, Missouri; and the southern portion of Vietnam. The section on Vietnam veterans covers studies of US veterans conducted by the Air Force, the Centers for Disease Control and Prevention (CDC), the Department of Veterans Affairs (VA), the American Legion, and individual states; it also discusses studies of veterans from other nations (e.g., Australia and Korea) that fought in Vietnam. In addition to reviewing studies involving exposures to the chemicals of interest (2,4-D; 2,4,5-T and its contaminant TCDD; cacodylic acid; and picloram), this and earlier VAO committees have examined any available studies that address compounds chemically related to the herbicides used in Vietnam, such as 2-(2-methyl-4-chlorophenoxy) propionic acid (MCPP), hexachlorophene, and chlorophenols, particularly 2,4,5-trichlorophenol (2,4,5-TCP). Some study investigators do not indicate in their published reports the specific herbicides to which study participants were exposed or the magnitude of exposure; those complicating factors were considered when the committee weighed the relevance of a study, as detailed in Chapter 2 of this report. Available details of exposure assessment and use of the resulting data in analyses are discussed in Chapter 5, which follows the same sequence to categorize study populations. NEW CITATIONS REVIEWED IN UPDATE 2006 To elucidate further the new epidemiologic data reviewed by the committee for Update 2006, three tables have been added to this chapter that list new citations. Tables 4-1 and 4-2 both list citations for studies of populations that have not been reviewed in previous updates; studies listed in Table 4-1 address single health outcomes, and studies in Table 4-2 address multiple health outcomes. Studies listed in Table 4-1 are discussed and critiqued in the health-outcome section for the outcome investigated. To reduce repetition in the report, studies in Table 4-2 are described in detail in this chapter and only briefly in the health-outcome sections; this avoids recapitulation of the information every time a new health outcome from the same study is discussed. Finally, new studies that report on populations that have been discussed in previous updates are listed in Table 4-3; these are described in detail in this chapter in the context of associated studies

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Veterans and Agent Orange: Update 2006 TABLE 4-1 Citations on Study Populations New in Update 2006 with Results on a Single Health Outcome Author Year Study Design Exposure(s) Having Results Health Outcome Reported Study Population Occupational Studies Merletti et al. 2006 Case– control Pesticides (collinear results for herbicides, insecticides, and fungicides) Bone sarcomas Studies of rare cancers in seven European countries Morahan and Pamphlett 2006 Case– control Herbicides/ pesticides ALS Contributors to Australian Motor Neuron Disease DNA Bank Fritschi et al. 2005 Case– control Phenoxy herbicides NHL (B-cell, diffuse large B-cell, follicular) Cases diagnosed 2000–2001 in New South Wales Nordby et al. 2004 Record linkage Purchase proxies for general pesticide use Lip cancer Norwegian farmers Hardell and Eriksson 1999 Case– control Phenoxy herbicides, MCPA NHL Population from northern and middle Sweden Nordstrom et al. 1998 Case– control Herbicides Hairy-cell leukemia Population-based study of patients Hallquist et al. 1993 Case– control Phenoxy herbicides; chlorophenols Thyroid cancer Cases from Swedish Cancer Registry Environmental Studies Ascherio et al. 2006 Prospective cohort Pesticides/herbicides Parkinson’s disease Cancer Prevention Study II Nutrition Cohort Bloom et al. 2006 Cross-sectional Serum dioxins, serum TEQs Thyroid function New York State Angler Cohort Study Lee CC et al. 2006 Cross-sectional Serum TEQ PCDD/Fs Liver disease (fatty liver, hepatic function) Residents around incinerators in Taiwan Lin et al. 2006 Ecologic cross-sectional Residence in areas defined by ambient TEQ levels after incinerator operation Reproduction (gestational age, birth weight, and sex ratio) Births before and after incinerator in operation for three residential cohorts

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Veterans and Agent Orange: Update 2006 Author Year Study Design Exposure(s) Having Results Health Outcome Reported Study Population Mills and Yang 2006 Cross-sectional Organochlorines and triazine herbicides Breast cancer Latina women in California Porpora et al. 2006 Case– control Blood levels of PCBs (dioxin-like compounds) Endometriosis Italian women undergoing laparoscopy Foster et al. 2005 Cross-sectional 2nd trimester serum dioxin TEQ (CALUX) Thyroid function (TSH and thyroxine) in mother Pregnancies at McMaster University (2002–2003) Heilier et al. 2005 Case– control Dioxin TEQs in blood Endometriosis Belgian surgical patients vs healthy gynecologic patients Reynolds et al.   2005a Case– control Tissue levels (TCDD, TEQs) in breast biopsies Breast cancer Patients with breast cancer or benign breast condition Reynolds et al. 2005b Case– control Gestational proximity to use of pesticides listed as “probable human carcinogen” (including cacodylic acid) Childhood cancers (all, leukemias, CNS) California Childhood Cancer Study Sterling and Hanke 2005 Case reports Dioxin Chloracne Individual poisonings Wang et al. 2005 Cross-sectional PCDD, PCDF, and PCB congeners Thyroid function and growth hormone status Measurements from cord blood, one minute after delivery Cohen et al. 2004 Case histories No specific exposures AL amyloidosis Six case histories of people with AL amyloidosis and NHL Kato et al. 2004 Case– control “Herbicides/lawn pesticides” NHL Women diagnosed 10/1995–9/1998 in upstate New York

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Veterans and Agent Orange: Update 2006 Author Year Study Design Exposure(s) Having Results Health Outcome Reported Study Population Reynolds et al. 2004 Cohort Residential distance from application of “probable human carcinogens” (including cacodylic acid), “endocrine disruptors” (including 2,4-D; cacodylic acid) Breast cancer California Teachers Study cohort Matsuura et al. 2001 Prospective cohort PCDDs; PCDFs; PCBs Thyroid function Breast-fed vs bottle-fed infants Nagayama et al. 2001 Cross-sectional Serum TEQs Thyroid hormone levels Yusho patients Studies of Vietnam Veterans Leavy et al. 2006 Case– control Service in Vietnam Prostate cancer Cancer registry of Western Australia ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; ALS, amyotrophic lateral sclerosis; CALUX, Chemically Activated Luciferase Gene Expression; DNA, deoxyribonucleic acid; MCPA, 2-methyl, 4-chlorophenoxyacetic acid; NHL, non-Hodgkin’s lymphoma; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDF, polychlorinated dibenzofuran; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TEQ, total toxicity equivalency; TSH, thyroid-stimulating hormone. reviewed by earlier VAO committees and are addressed briefly thereafter in the relevant health-outcome sections. Citations Reporting on a Single Endpoint in New Populations New studies reporting on only a single health outcome in previously unstudied populations are listed in Table 4-1 with an indication of the outcome. A description and critique of each study will appear only in the section of the report where the results on health outcomes are discussed. Citations Reporting on Multiple Endpoints in New Populations Newly accessed citations reporting on multiple health outcomes in populations that have not been studied before are listed in Table 4-2, which indicates which endpoints were investigated. A single comprehensive discussion of each

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Veterans and Agent Orange: Update 2006 TABLE 4-2 Citations on Study Populations New in Update 2006 with Results on Multiple Health Outcomes Author Year Study Design Exposure(s) Having esults Health Outcome(s) Reported Study Population Occupational Studies Chen Z et al. 2006 Case–control Maternal exposure to herbicides Childhood cancers Children’s Oncology Group, US study of germ-cell carcinomas Chiu et al. 2006 Case–control Occupational exposure to herbicides NHL Upper Midwest Health Study McLean et al. 2006 Cohort Nonvolatile organochlorine compounds Cancer mortality by type International collaborative study of pulp and paper industry Carreon et al. 2005 Case–control Arsenicals, phenoxy herbicides; 2,4-D Gliomas in women Upper Midwest Health Study Chen et al. 2005 Case–control Parental occupational exposures to pesticides and chemicals Childhood cancers Children’s Oncology Group, US study of germ-cell carcinomas Lee et al. 2005 Case–control 2,4,5-T; 2,4-D Brain cancer Residents of eastern Nebraska Mills and Yang 2005 Nested case–control 2,4-D Breast cancer United Farm Workers members (1987–2001) Mills et al. 2005 Nested case–control 2,4-D Leukemias, NHL United Farm Workers members (1987–2001) Oh et al. 2005 Cross-sectional Dioxin Immunotoxicity, effects on sperm Waste incerator workers Park et al. 2005 Cross-sectional “Pesticides” in farming (based on usual occupation on death certificate) Neuro-degenerative diseases: PD, presenile dementia, Alzheimers, motor neuron disease All deaths in 22 states from 1992–1998 Chiu et al. 2004 Pooled analysis Occupational exposure to herbicides NHL Upper Midwest Health Study

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Veterans and Agent Orange: Update 2006 Author Year Study Design Exposure(s) Having esults Health Outcome(s) Reported Study Population Lee et al.   2004a Case–control 2,4,5-T; 2,4-D Cancer (esophageal, stomach) Residents of eastern Nebraska Lee et al. 2004b Pooled analysis Occupational exposure to herbicides NHL Upper Midwest Health Study Ruder et al. 2004 Case–control Arsenicals, phenoxy herbicides, 2,4-D Gliomas in men Upper Midwest Health Study Torchio et al. 1994 Cohort Farm work Cancer mortality Men licensed to use agricultural pesticides in Piedmont area of Italy Reif et al. 1989 Mixed Forestry worker Cancer incidence Men entered in New Zealand Cancer Registry from 1980–1984 Magnani et al. 1987 Case–control Herbicides, chlororphenol Cancers of brain, kidney, esophagus, pancreas, and melanoma Male residents of three English counties Environmental Studies Chen et al. 2006 Cross-sectional PCDD/Fs Hypertension, diabetes, glucose modulation, liver function Tiawanese residents living near an incinerator Lee et al. 2006 Repeat 2,4-D in carpet dust NHL Same study as Colt et al., 2005 and Hartge et al., 2005 Colt et al. 2005 Repeat 2,4-D in carpet dust NHL Same study as Hartge et al., 2005 and Lee WJ et al., 2006 De Roos et al. 2005a Case–control Dioxin, PCBs, furans, TEQs in plasma NHL NCI SEER Case– control of NHL

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Veterans and Agent Orange: Update 2006 Author Year Study Design Exposure(s) Having esults Health Outcome(s) Reported Study Population Hartge et al. 2005 Case–control 2,4-D in carpet dust NHL NCI SEER Case– control of NHL (same study as Colt et al., 2005 and Lee WJ et al., 2006) Tango et al. 2004 Environmental   Dioxin Spontaneous abortion or infant death (with or without congenital malformations), low birth weight Residential proximity to incinerators ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; CNS, central nervous system; HD, Hodgkin’s disease; NCI, National Cancer Institute; NHL, non-Hodgkin’s lymphoma; NIOSH, National Institute of Occupational Safety and Health; PCB, polychlorinated biphenyl; PD, Parkinson’s disease; SEER, Surveillance Epidemiology and End Results; TEQ, total toxicity equivalency. study is presented in this chapter, organized according to the type of study population. The results, with comments related to their reliability or limitations, appear in the appropriate outcome-specific sections. Their design information is presented in the cumulative tables in Appendix C. New Citations on Previously Studied Populations A number of long-term studies of populations exposed to the herbicides sprayed in Vietnam or to their components are of particular importance to the VAO project. It is essential that laboriously amassed information on a single population be recognized as such. Placing each new publication in historical context helps the committee to avoid factoring what is actually a single observation into its deliberations repeatedly. Such clusters of studies are useful in describing the timecourse of a population’s response to an exposure, and joint consideration of an entire body of research on a population may permit more insightful evaluation of relationships with potential confounding factors. Many of the cohorts that have contributed to the cumulative findings of the VAO committees have become dormant; the cohorts’ histories are briefly recapitulated in the body of this report, and the design properties of publications on them are tabled in Appendix C. Additional background information can be found in earlier reports in this series. Many cohorts potentially exposed to any of the chemicals of interest are monitored periodically, including the cohorts of the National Institute for Occupational

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Veterans and Agent Orange: Update 2006 TABLE 4-3 Citations on Previously Studied Populations Author Year Study Design Exposure(s) Having Results Health Outcome(s) Reported Study Population Occupational Studies Farr et al. 2006 Cohort VAO chemicals not specifically addressed Reproduction—fertility (timing of menopause) AHS Hoppin et al. 2006 Cohort Commercial pesticide applicators; 2,4-D Respiratory effects (wheeze) AHS Alavanja et al. 2005 Cohort Farmers, spouses of farmers, commercial applicators Cancer incidence (full spectrum) (1993–2002) AHS Blair et al. 2005a Cohort Farmers (years used pesticides ≤10 or >10), spouses of farmers Mortality (cancers—all and specific, diabetes, COPD, cardiovascular, renal) AHS De Roos et al. 2005b Nested case– control “Herbicides,” 2,4-D Rheumatoid arthritis Women in AHS Engel et al. 2005 Cohort Ever/never use of phenoxy herbicides; 2,4-D; 2,4,5-T; 2,4,5-TP Breast cancer incidence AHS Kamel et al. 2005 Cohort Days exposed to herbicides Neurologic symptoms AHS ’t Mannetje et al. 2005 Cohort Phenoxy herbicide production worker or sprayer (also exposed to TCDD) Cancer mortality (full spectrum) Subcohort of IARC cohort (New Zealand) Alavanja et al. 2004 Cohort Farmers, spouses of farmers, commercial applicators Lung cancer incidence AHS Farr et al. 2004 Cohort VAO chemicals not specifically addressed Reproduction—fertility (timing of menstrual cycle) AHS Lawson et al. 2004 Cross-sectional Paternal serum lipid TCDD levels at conception based on PBPK exposure reconstruction Reproduction—birth weight, preterm delivery, birth defects NIOSH cohort

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Veterans and Agent Orange: Update 2006 Author Year Study Design Exposure(s) Having Results Health Outcome(s) Reported Study Population Environmental Studies Pahwa et al. 2006 Case– control Any phenoxy herbicide, 2,4-D HD, multiple myeloma, STS Cross-Canada Study of Pesticides and Health Baccarelli et al. 2005b Cohort Serum TCDD Health status (GI disease, endocrine, respiratory, allergy, infectious disease, misc), current dioxin levels Chloracne cases vs unexposed & exposed controls from Seveso Eskenazi et al. 2005 Cross-sectional Serum TCDD Age at menopause Seveso Women’s Health Study McDuffie et al. 2005 Case– control Any phenoxy herbicide, 2,4-D NHL Cross-Canada Study of Pesticides and Health Warner et al. 2004 Cross-sectional Serum TCDD Age at menarche Seveso Women’s Health Study Studies of Vietnam Veterans Kang et al. 2006 Cross-sectional Serum TCDD, deployed {sprayers vs non-sprayers} vs non-deployed Diabetes, GI/digestive disease (liver disorders = hepatitis), circulatory disorders (heart conditions, hypertension), respiratory disorders, all cancer Army Chemical Corps Vietnam-era veterans Pavuk et al. 2006 Cohort Serum TCDD level (low or high group) Prostate cancer AFHS ADVA 2005a Cohort Deployed veterans vs. Australian population Cancer incidence (full spectrum) (1982–2000) Male Australian Vietnam veterans (all, Army, Navy, Air Force)

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Veterans and Agent Orange: Update 2006 Author Year Study Design Exposure(s) Having Results Health Outcome(s) Reported Study Population ADVA 2005b Cohort Deployed veterans vs. Australian population Mortality through 2001 (endocrine, nervous, circulatory, respiratory, digestive, external causes, cancer) Male Australian Vietnam veterans ADVA 2005c Cohort Deployed vs. non-deployed National Service veterans Mortality, cancer incidence (as in ADVA, 2005a,b) Australian male Army National Service Vietnam veterans   AFHS 2005 Cross-sectional Ranch Hand vs Comparison subjects, serum TCDD Lipid levels, liver enzymes, cardiovascular findings AFHS subjects participating in 2002 exam cycle Ketchum and Michalek 2005 Cohort Cohort grouping Mortality (cancer, endocrine, nervous system, circulatory, respiratory, or digestive diseases) AFHS Pavuk et al. 2005 Cohort Serum TCDD level (4 groups), years in SEA Cancer (melanoma, other skin, prostate) AFHS (Comparison subjects only) Boehmer et al. 2004 Cohort Deployed vs. non-deployed men Mortality through 2000 (endocrine, metabolic, immune, nervous system, respiratory, circulatory, and digestive diseases; cancer) CDC’s Vietnam Experience Study Kern et al. 2004 Cohort Serum TCDD Diabetes (insulin sensitivity) AFHS ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; 2,4,5-TP, 2 (2,4,5-trichlorophenoxy) propionic acid; ADVA, Australian Department of Veterans Affairs; AFHS, Air Force Health Study; AHS, Agricultural Health Study; ALL, acute lymphocytic leukemia; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; GI, gastrointestinal; HD, Hodgkin’s disease; IARC, International Agency for Research on Cancer; NCI, National Cancer Institute; NHL, non-Hodgkin’s lymphoma; NIOSH, National Institute for Occupational Safety and Health; PBPK, physiologically-based pharmacokinetic; PCB, polychlorinated biphenyl; SEA, Southeast Asia; SEER, Surveillance Epidemiology and End Results; STS, soft-tissue sarcoma; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; VAO, Veterans and Agent Orange.

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Veterans and Agent Orange: Update 2006 Lee WJ, Purdue MP, Stewart P, Schenk M, De Roos AJ, Cerhan JR, Severson RK, Cozen W, Hartge P, Blair A. 2006. Asthma history, occupational exposure to pesticides and the risk of non-Hodgkin’s lymphoma. International Journal of Cancer 118(12):3174–3176. Lerda D, Rizzi R. 1991. Study of reproductive function in persons occupationally exposed to 2,4-dichlorophenoxyacetic acid (2,4-D). Mutation Research 262:47–50. Levy CJ. 1988. Agent Orange exposure and posttraumatic stress disorder. Journal of Nervous and Mental Disorders 176:242–245. Lin C-M, Li C-Y, Mao I-F. 2006. Birth outcomes of infants born in areas with elevated ambient exposure to incinerator generated PCDD/Fs. Environment International 32(5):624–629. Liou HH, Tsai MC, Chen CJ, Jeng JS, Chang YC, Chen SY, Chen RC. 1997. Environmental risk factors and Parkinson’s disease: A case–control study in Taiwan. Neurology 48(6):1583–1588. Longnecker MP, Michalek JE. 2000. Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure. Epidemiology 11(1):44–48. Lovik M, Johansen HR, Gaarder PI, Becher G, Aaberge IS, Gdynia W, Alexander J. 1996. Halogenated organic compounds and the human immune system: Preliminary report on a study in hobby fishermen. Archives of Toxicology Supplement 18:15–20. Lynge E. 1985. A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark. British Journal of Cancer 52:259–270. Lynge E. 1993. Cancer in phenoxy herbicide manufacturing workers in Denmark, 1947–87—An update. Cancer Causes and Control 4:261–272. Magnani C, Coggon D, Osmond C, Acheson ED. 1987. Occupation and five cancers: A case–control study using death certificates. British Journal of Industrial Medicine 44(11):769–776. Mahan CM, Bullman TA, Kang HK, Selvin S. 1997. A case–control study of lung cancer among Vietnam veterans. Journal of Occupational and Environmental Medicine 39(8):740–747. Manz A, Berger J, Dwyer JH, Flesch-Janys D, Nagel S, Waltsgott H. 1991. Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet 338:959–964. Masala G, Di Lollo S, Picoco C, Crosignani P, Demicheli V, Fontana A, Funto I, Miligi L, Nanni O, Papucci A, Ramazzotti V, Rodella S, Stagnaro E, Tumino R, Vigano C, Vindigni C, Seniori Costantini A, Vineis P. 1996. Incidence rates of leukemias, lymphomas and myelomas in Italy: Geographic distribution and NHL histotypes. International Journal of Cancer 68(2):156–159. Mastroiacovo P, Spagnolo A, Marni E, Meazza L, Bertollini R, Segni G, Borgna-Pignatti C. 1988. Birth defects in the Seveso area after TCDD contamination. Journal of the American Medical Association 259:1668–1672 [published erratum appears in the Journal of the American Medical Association 1988, 260:792]. Matsuura N, Uchiyama T, Tada H, Nakamura Y, Kondo N, Morita M, Fukushi M. 2001. Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan: Report from research on environmental health. Clinical Pediatric Endocrinology 10(1):1–6. May G. 1982. Tetrachlorodibenzodioxin: A survey of subjects ten years after exposure. British Journal of Industrial Medicine 39:128–135. May G. 1983. TCDD: A study of subjects 10 and 14 years after exposure. Chemosphere 12: 771–778. McDuffie HH, Klaassen DJ, Dosman JA. 1990. Is pesticide use related to the risk of primary lung cancer in Saskatchewan? Journal of Occupational Medicine 32(10):996–1002. McDuffie HH, Pahwa P, McLaughlin JR, Spinelli JJ, Fincham S, Dosman JA, Robson D, Skinnider LF, Choi NW. 2001. Non-Hodgkin’s lymphoma and specific pesticide exposures in men: Cross-Canada study of pesticides and health. Cancer Epidemiology, Biomarkers and Prevention 10(11):1155–1163. McDuffie HH, Pahwa P, Robson D, Dosman JA, Fincham S, Spinelli JJ, McLaughlin JR. 2005. Insect repellents, phenoxyherbicide exposure, and non-Hodgkin’s lymphoma. Journal of Occupational and Environmental Medicine 47(8):806–816.

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