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5 Epidemiologic Studies—New Citations and Background on Repeatedly Studied Populations The continuing effort to evaluate and integrate all results of human stud- ies 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 (dimethyl arsenic acid or DMA)—has involved the consideration of thousands of citations over the successive updates. Results of a study of a single population may be reported in connection with a multiplicity of health outcomes and more than one publication, particularly if a study is of the cohort design with repeated follow-ups. The major purpose of the chapters on epidemiology or epidemiologic studies in the original Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (VAO) report and its updates has always been to reduce repetition of design information in the health-outcomes chapters from outcome to outcome and from update to update. Deviating somewhat from the format of previous Veterans and Agent Orange (VAO) reports, this chapter first provides tables listing the epi- demiologic citations that are new, 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 October 1, 2006 (the closing date for inclusion in Veterans and Agent Orange: Update 2006 [Update 2006; IOM, 2007]) through September 30, 2008. For this chapter, for discussions of health outcomes, and for results tables in earlier reports in the VAO series, an organizational framework was used that categorized each publication containing primary epidemiologic findings as an occupational study, an environmental study, or a study of Vietnam veterans. 104

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10 EPIDEMIOLOGIC STUDIES Those categories were not intended to imply that any of the populations is intrin- sically more valuable for the committee’s purpose. Various study designs (most importantly, cohort, case–control, and cross-sectional) have strengths and weak- nesses (see Chapter 2) that influence their potential to contribute evidence of an association with the health outcomes considered in Chapters 6–9. This update retains the categorization scheme. The second part of this chapter discusses the design details of new reports on populations already under study and on multiple outcomes in new populations. The occupational-studies section covers studies of production workers, agriculture and forestry workers (including herbicide and pesticide applicators), and paper and pulp workers. The environmental-studies 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–veteran studies covers studies of US veterans conducted by the Air Force, the Centers for Disease Control and Prevention (CDC), the Depart- ment of Veterans Affairs (VA), the American Legion, and individual states; it also discusses studies of veterans from other nations (such as 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 piclo- ram), 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, hexachlorophene, and chloro- phenols, particularly 2,4,5-trichlorophenol. Some study investigators did not indi- cate 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. Available details of exposure assessment and use of the resulting data in analyses are discussed in Chapter 3, which follows the same sequence to categorize study populations. NEW CITATIONS To elucidate further the new epidemiologic data reviewed by the committee for this update, three tables that list new citations are included. Citations Reporting on a Single Health Outcome in New Populations New studies reporting on only a single health outcome in previously un- studied populations are listed in Table 5-1 with an indication of the outcome. Descriptions and critiques of the studies will appear only in the sections of the report that discuss the results on the particular health outcomes.

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106 VETERANS AND AGENT ORANGE: UPDATE 2008 TABLE 5-1 Citations on Study Populations New in Update 2008 with Results on a Single Health Outcome Health Exposure Measure(s) Outcome Author Study Design Having Results Reported Study Population Studies of Vietnam Veterans Chamie Case–control Self-reported exposure to Prostate cancer Vietnam veterans et al., 2008 Agent Orange who registered with Northern Califormia VA Health System and were followed in 1998–2006 Occupational Studies Monge et al., Population- Pesticides, including Childhood Costa Rican parents 2007 based picloram, 2,4-D leukemia of children with case–control childhood leukemia Samanic Case–control Herbicides (unspecified) Adult brain Patients with new et al., 2008 from JEM, self-reported tumors diagnosis of glioma occupational history or meningioma Solomon Cross- Pesticides; herbicide Neurologic Men born between et al., 2007 sectional users were 40% of “other symptoms 1933–1977 identified pesticides” users in 1991 census in rural areas of England and Wales Environmental Studies Abdelouahab Cross- Serum concentrations of Thyroid Men and women who et al., 2008 sectional POPs, including dl PCBs homeostasis consume freshwater 105, 118, 156 fish from Canadian lakes Brighina Case–control Herbicides, discussion PD PD patients from et al., 2008 of 2,4-D Wisconsin, Iowa, South Dakota, North Dakota Chao et al., Cross- Serum concentrations of Menstrual- Healthy Taiwanese 2007 sectional PCDDs, PCDFs, PCBs cycle mothers (18–40 years characteristics old) Chevrier et Birth cohort 34 PCBs, including dl Thyroid Pregnant women in al., 2008 PCBs 118, 156 levels during Salinas Valley, CA pregnancy Cok et al., Case–control Serum concentrations of Male infertility Surgical patients 2008 PCDDs, PCDFs, dl PCBs from Ankara University, School of Medicine, Turkey

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10 EPIDEMIOLOGIC STUDIES TABLE 5-1 Continued Health Exposure Measure(s) Outcome Author Study Design Having Results Reported Study Population Cooney Case–control Pesticides, herbicides Wilm’s tumor 523 case mothers and et al., 2007 (childhood 517 controls from US cancer) and Canada Dhooge Cross- Serum concentrations Reproductive 101 Flemish men et al., 2006 sectional of TCDD (5 months parameters 20–40 years old after PCB, dioxin food- contamination episode in Belgium) Eriksson Population- Herbicides; specific NHL Swedish patients et al., 2008 based phenoxy herbicides, with diagnosis of case–control including 2,4,5-T; 2,4-D; NHL December 1, MCPA 1999–April 30, 2002 Hancock Family-based Self-reported herbicide PD PD patients, family et al., 2008 case–control or chlorophenoxy acid or members (with, ester use without PD) Heilier et al., Cross- Serum concentrations of PE, DEN 47 patients with 2006 sectional dl compounds endometriosis, DEN Heilier et al., Matched Serum concentrations of PE, DEN 88 matched triads: 2007 case–control PCDDs, PCDFs, PCBs women with DEN, women with PE, controls Hertz- Cohort Serum concentrations of Sex ratio Cord blood extracted Picciotto PCBs, including dl PCBs from pregnant et al., 2008 105, 118, 170, 180 women in San Francisco Bay area Meyer et al., Case–control Agricultural pesticides Hypospadias Cases and controls 2006 including 2,4-D and born 1998–2002 in dicamba. Pounds of eastern Arkansas pesticides applied or persisting within 600 m of subject’s home during gestational weeks 6–16 Nishijo Cross- Serum TEQs, seven Birth weight Japanese women, et al., 2008 sectional pesticides their newborn infants Polsky et al., Case–control Serum concentrations of Erectile Ontario men 2007 PCBs, including dl PCBs dysfunction 118, 156; total PCBs, chlorinated pesticides continued

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108 VETERANS AND AGENT ORANGE: UPDATE 2008 TABLE 5-1 Continued Health Exposure Measure(s) Outcome Author Study Design Having Results Reported Study Population Rudant Case–control Maternal household Childhood Residents of France et al., 2007 herbicide use during hematopoietic pregnancy malignancies Sagiv et al., Cohort Serum concentrations of Infant size at Four towns near 2007 PCBs, including dl PCBs birth (weight, PCB-contaminated 118, 180; non-dl PCBs length, head harbor in 138, 153 circumference) Massachusetts Spinelli Population- Serum concentrations of NHL Residents of British et al., 2007 based dl PCBs 105, 118, 156; Columbia, Canada case–control non-dl PCBs Teitelbaum Population- Self-reported lifetime Breast cancer Women living on et al., 2007 based residential use of lawn Long Island, New case–control and garden pesticides York (unspecified) Toft et al., Cross- Endocrine-disrupting Semen quality Inuits, three 2007 sectional compounds; dl activity European populations by CALUX, AHR competitive activity Tsuchiya Case–control Serum TEQ of dioxin Endometriosis, Infertile Japanese et al., 2007 (sum of dl compounds); polymorphisms women TEQ of PCBs (sum of mono-ortho PCBs) Tsukimori Retrospective Serum concentrations of Pregnancy Yusho subjects 36 et al., 2008 survey PeCDF; dl PCBs 126, outcomes years after 1968 169 (loss, preterm) incident Xu et al., Case–control Herbicides (unspecified) Nasal NK/T- Patients in East Asia 2007 cell lymphoma Zambon Population- Residential duration Sarcoma Residents of Province et al., 2007 based, and distance from 33 of Venice, Italy case–control industrial sources ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; AHR, aryl hydrocarbon receptor; CALUX, chemically activated luciferase gene expres- sion; DEN, deep endometriotic nodules; dl, dioxin-like; JEM, job–exposure matrix; MCPA, 2-methyl-4-chlorophenoxyacetic acid; NK/T-cell, natural killer T-cell; NHL, non-Hodgkin’s lymphoma; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDF, polychlorinated dibenzofuran; PD, Parkinson’s disease; PE, peritoneal endometriosis; PeCDF, 2,3,4,7,8-pentachlorodibenzofuran; POP, persistent organic pollutants; TCDD, 2,3,7,8-tetrachlorod- ibenzo-p-dioxin; TEQ, toxicity equivalent quotient; TSH, thyroid-stimulating hormone; VA, Depart- ment of Veterans Affairs.

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109 EPIDEMIOLOGIC STUDIES Citations Reporting on Multiple Health Outcomes in New Populations Newly accessed citations reporting on multiple health outcomes in popula- tions that have not been studied before are listed in Table 5-2, which indicates which outcomes were investigated. Single comprehensive discussions of the studies are 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 of Chapters 6–9. TABLE 5-2 Citations on Study Populations New in Update 2008 with Results on Multiple Health Outcomes Health Study Exposure Measures(s) Having Outcome(s) Author Design Results Reported Study Population Occupational Studies Richardson Population- Exposure estimates derived NHL, CLL German nationals, et al., 2008 based from JEM for chlorophenols, 15–75 years of age, case– herbicides, others newly diagnosed control NHL cases that occurred between 1986 and 1998 Environmental Studies Karouna- Cross- Serum concentrations of 17 Hypertension, Former employees, Renier sectional PCDD and PCDF congeners diabetes, liver their families, et al., 2007 function residents living near Pensacola, Florida, wood treatment plant Read et al., Ecologic 2,4,5-T All cancers, Residence 2007 STS, HD, near 2,4,5-T NHL, CLL manufacturing plant in New Zealand Ueruma Cross- Serum concentrations of Diabetes, lipid Stratified sample of et al., sectional PCDD/Fs, dl PCBs, total TEQ levels Japanese men and 2008a,b women aged 15–73 years old The remainder of these citations report on a variety of individual outcomes addressed in the NHANES surveys conducted in 1999–2002 and 2003–2004. Everett Cross- Serum concentrations of Diabetes NHANES-IV et al., 2007 sectional HxCDD, dl PCB-126, DDT continued

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110 VETERANS AND AGENT ORANGE: UPDATE 2008 TABLE 5-2 Continued Health Study Exposure Measures(s) Having Outcome(s) Author Design Results Reported Study Population Everett Cross- Serum concentrations of Hypertension NHANES (1999– et al., sectional PCBs, including dl PCBs 118 2002, 1999–2004) 2008a,b and 126 Ha et al., Cross- Serum concentrations of Cardiovascular NHANES 2007 sectional PCDDs, PCDFs, dl and non-dl disease (1999–2002) (1/3 PCBs, including dl PCBs 118, subsample) 126, 156, 169, 170, 180 Lee DH Cross- Serum concentrations of 6 Diabetes NHANES et al., 2006 sectional POPs, including HpCDD, (1999–2002) OCDD Lee DH Cross- Serum concentrations of 19 Arthritis, NHANES et al., sectional POPs, including PCDDs; rheumatoid (1999–2002) 2007a PCDFs; dl PCBs 118, 126, 169 arthritis Lee DH Cross- Serum concentrations of 19 Insulin NHANES et al., sectional POPs, including PCDDs; resistance in (1999–2002) 2007b PCDFs; dl PCBs 118, 126, 169 nondiabetic adults Lee DH Cross- Serum concentrations of 19 Lipid levels, NHANES et al., sectional POPs, including PCDDs; hypertension (1999–2002) 2007c PCDFs; dl PCBs 118, 126, 169 Turyk Cross- Serum concentrations of total Thyroid NHANES (1999– et al., 2007 sectional PCBs, total TEQs (dioxin, hormones 2000, 2001–2002) furans, coplanar mono-ortho- substituted PCBs) ABBREVIATIONS: 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; CLL, chronic lymphocytic leu- kemia; DDT, dichlorodiphenyltrichloroethane; dl, dioxin-like; HD, Hodgkin’s disease; HpCDD, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin; HxCDD, 1,2,3,6,7,8-hexachlorodibenzo-p-furan; JEM, job–exposure matrix; NHANES, National Health and Nutritional Examination Survey; NHL, non- Hodgkin’s lymphoma; OCDD, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDD/Fs, dioxins and furans combined; PCDF, polychlorinated dibenzofuran; POP, persistent organic pollutants; STS, soft-tissue sarcoma; TEQ, toxicity equivalent quotient. 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. Placing each new publication in historical context helps the com- mittee to avoid factoring into its deliberations repeatedly what is actually a single

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111 EPIDEMIOLOGIC STUDIES observation. Such clusters of studies are useful in describing the course of a population’s response to an exposure, and joint consideration of an entire body of research on a population may yield insight into relationships with potential confounding factors. Many of the cohorts that have contributed to the cumula- tive findings of the VAO committees are no longer being followed; however, the cohorts’ histories are briefly recapitulated in the body of this report. 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 Oc- cupational Safety and Health (NIOSH), the International Agency for Research on Cancer (IARC), and the National Cancer Institute (NCI); residents of Seveso; and Ranch Hand personnel. For the sake of thoroughness, the discussions of specific health outcomes and the associated cumulative-results tables in Chapters 6–9 include references to studies discussed in previous VAO reports and to new studies. However, in drawing its conclusions, the committee focused on the most recent update (Update 2006) when multiple reports on the same cohorts and health outcomes were available. Individual researchers who belong to research consortia evaluating cohorts in large multicenter studies (such as the IARC and NCI cohort studies) sometimes publish reports based solely on the subset of subjects they themselves are monitoring. All the studies are noted in the present report, but in drawing its conclusions the committee focused on the studies of the larger, multicenter cohorts. The new citations on previously studied populations are listed in Table 5-3. For citations listed there, the current citation is discussed in the context of the history of publications on the population with an explanation of how the new work meshes with earlier efforts. TABLE 5-3 Citations on Previously Studied Populationsa Exposure Measure(s) Health Outcome(s) Author Study Design Having Results Reported Study Population Studies of Vietnam Veterans Cypel and Retrospective Service in Mortality from all causes; VA Environmental Kang, 2008 cohort Vietnam during all cancers; cancers of Epidemiology Vietnam War large intestine, pancreas, Service cohort of lung, breast, uterus, CNS, female Vietnam, lymphopoietic system; Vietnam-era circulatory system veterans diseases continued

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112 VETERANS AND AGENT ORANGE: UPDATE 2008 TABLE 5-3 Continued Exposure Measure(s) Health Outcome(s) Author Study Design Having Results Reported Study Population Gupta et al., Longitudinal Serum Serum testosterone, AFHS (sprayers 2006 prospective concentrations of benign prostatic vs nonsprayers) cohort TCDD hyperplasia Michalek Prospective Serum Diabetes, cancer AFHS (calendar and Pavuk, cohort concentrations of period of service, 2008 TCDD days spraying, years in SEA) Occupational Studies Hansen Cohort Pesticides, Cancer: buccal cavity Danish male et al., 2007 including 2,4-D; and pharynx, digestive gardeners 2,4,5-T organs and peritoneum, respiratory system, male genital organs, urinary system, skin, STS, lymphatic and hematopoietic tissue Hoppin Cohort Pesticides, Respiratory outcomes AHS et al., 2006c including 2,4-D; (wheeze) 2,4,5-T Hoppin Cohort (cross- Pesticides, Farmer’s lung AHS et al., 2007a sectional including 2,4-D; analysis) 2,4,5-T Hoppin Cohort Pesticides, Chronic bronchitis AHS et al., 2007b including 2,4-D; 2,4,5-T Hoppin Cohort (cross- Pesticides, Atopic and nonatopic AHS (women et al., 2008c sectional including 2,4-D asthma only) analysis) Kamel et al., Cross- Pesticides, Neurologic symptoms AHS 2007a sectional including 2,4-D; 2,4,5-T Kamel et al., Case–control Pesticides, PD AHS 2007b including 2,4-D; 2,4,5-T Lee WJ Cohort Pesticides, Colorectal cancer AHS et al., 2007 including 2,4-D; 2,4,5-T

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11 EPIDEMIOLOGIC STUDIES TABLE 5-3 Continued Exposure Measure(s) Health Outcome(s) Author Study Design Having Results Reported Study Population Mills and Nested Pesticides, Gastric cancer California Cancer Yang, 2007 case–control including 2,4-D Registry; United Farm Workers roster (1973– 1996), California Department of Pesticide Regulation Montgomery Cohort Pesticides, Diabetes AHS (5-year et al., 2008 including 2,4-D; follow-up of 2,4,5-T; 2,4,5-TP; licensed pesticide dicamba applicators) Pelclová Case–control Serum Endothelial dysfunction, Poisoned Czech et al., 2007 concentrations of impaired microvascular production TCDD reactivity workers Saldana Cohort Pesticides, Gestational diabetes AHS et al., 2007 including 2,4-D; 2,4,5-T; 2,4,5-TP; dicamba Samanic Cohort Dicamba Cancer incidence AHS et al., 2006 Urban et al., Case series Serum Polyneuropathy, other Poisoned Czech 2007 concentrations of neurologic effects production TCDD workers Valcin et al., Cohort Herbicides Chronic bronchitis AHS (nonsmoking 2007 women) Weselak Cohort In utero exposure Cough, asthma, allergy Ontario Farm et al., 2007 to phenoxy Family Health herbicides, Study including 2,4-D; 2,4-DB; MCPA; dicamba Environmental Studies Baccarelli Cohort Serum Neonatal thyroid function Seveso births et al., 2008 (residential- concentrations of (TSH), birth weight, sex 1994–2005 based TCDD; maternal ratio population) exposure to TCDD continued

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114 VETERANS AND AGENT ORANGE: UPDATE 2008 TABLE 5-3 Continued Exposure Measure(s) Health Outcome(s) Author Study Design Having Results Reported Study Population Consonni Cohort Serum Mortality—all cancers; Seveso population et al., 2008 concentrations of specific cancers: diabetes, by zone TCDD circulatory, respiratory, digestive disease Eskenazi Cohort Serum Fibroids Seveso Women’s et al., 2007 concentrations of Health Study TCDD Miligi et al., Case–control Herbicides Cancers of Italian multicenter 2006 including hematolymphopoietic case–control study phenoxy system (NHL, CLL, herbicides, 2,4-D, HD, leukemia, multiple MCPA myeloma) Mocarelli Cohort Serum Male fertility Seveso Zone A et al., 2008 concentrations of men vs age- TCDD matched men residing outside contamination zone Viel et al., Population- Residential Breast cancer Residents of 2008 based proximity to Besancon, France case–control municipal solid- waste incinerator (GIS-derived dioxin exposure) Warner Cohort Serum Ovarian function Seveso Women’s et al., 2007 concentrations of Health Study TCDD ABBREVIATIONS: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4-DB, 2-(2,4-diichlorophenoxy) bu- tyric acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; 2,4,5-TP, 2-(2,4,5-trichlorophenoxy) propionic acid; AFHS, Air Force Health Study; AHS, Agricultural Health Study; ALL, acute lymphocytic leuke- mia; CLL, chronic lymphocytic leukemia; CNS, central nervous system; GIS, geographic information system; HD, Hodgkin’s disease; MCPA, 2-methyl-4-chlorophenoxyacetic acid; NHL, non-Hodgkin’s lymphoma; PCB, polychlorinated biphenyl; PD, Parkinson’s disease; SEA, Southeast Asia; STS, soft- tissue sarcoma; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; THS, thyroid-stimulating hormone; VA, Department of Veterans Affairs. aThroughout the report the same alphabetic indicator following year of publication is used con- sistently for the same article when there were multiple citations by the same first author in a given year. The convention of assigning the alphabetic indicator in order of citation in a given chapter is not followed.

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191 EPIDEMIOLOGIC STUDIES Montgomery MP, Kamel F, Saldana TM, Alavanja MC, Sandler DP. 2008. Incident diabetes and pesticide exposure among licensed pesticide applicators: Agricultural Health Study, 1993–2003. American Journal of Epidemiology 167(10):1235–1246. Morris PD, Koepsell TD, Daling JR, Taylor JW, Lyon JL, Swanson GM, Child M, Weiss NS. 1986. Toxic substance exposure and multiple myeloma: A case–control study. Journal of the National Cancer Institute 76:987–994. Morrison H, Semenciw RM, Morison D, Magwood S, Mao Y. 1992. Brain cancer and farming in western Canada. Neuroepidemiology 11:267–276. Morrison H, Savitz D, Semenciw RM, Hulka B, Mao Y, Morison D, Wigle D. 1993. Farming and prostate cancer mortality. American Journal of Epidemiology 137:270–280. Morrison HI, Semenciw RM, Wilkins K, Mao Y, Wigle DT. 1994. Non-Hodgkin’s lymphoma and agricultural practices in the prairie provinces of Canada. Scandinaian Journal of Work, Eni- ronment and Health 20:42–47. Moses M, Lilis R, Crow KD, Thornton J, Fischbein A, Anderson HA, Selikoff IJ. 1984. Health status of workers with past exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the manufacture of 2,4,5-trichlorophenoxyacetic acid: Comparison of findings with and without chloracne. Ameri- can Journal of Industrial Medicine 5:161–182. Musicco M, Sant M, Molinari S, Filippini G, Gatta G, Berrino F. 1988. A case–control study of brain gliomas and occupational exposure to chemical carcinogens: The risks to farmers. American Journal of Epidemiology 128:778–785. Nanni O, Amadori D, Lugaresi C, Falcini F, Scarpi E, Saragoni A, Buiatti E. 1996. Chronic lympho- cytic leukæmias and non-Hodgkin’s lymphomas by histological type in farming-animal breeding workers: A population case–control study based on a priori exposure matrices. Occupational and Enironmental Medicine 53(10):652–657. Nelson CJ, Holson JF, Green HG, Gaylor DW. 1979. Retrospective study of the relationship between agricultural use of 2,4,5-T and cleft palate occurrence in Arkansas. Teratology 19:377–383. Neuberger M, Kundi M, Jäger R. 1998. Chloracne and morbidity after dioxin exposure (preliminary results). Toxicology Letters 96/97:347–350. Neuberger M, Rappe C, Bergek S, Cai H, Hansson M, Jager R, Kundi M, Lim CK, Wingfors H, Smith AG. 1999. Persistent health effects of dioxin contamination in herbicide production. Enironmental Research 81(3):206–214. Newell GR. 1984. Deelopment and Preliminary Results of Pilot Clinical Studies. Report of the Agent Orange Adisory Committee to the Texas Department of Health. University of Texas System Cancer Center. Ngo AD, Taylor R, Roberts CL, Nguyen TV. 2006. Association between Agent Orange and birth defects: Systematic review and meta-analysis. International Journal of Epidemiology 35: 1220–1230. Nguyen HD. 1983. Pregnancies at the Polyclinic of Tay Ninh Province. Summarized in: Constable JD, Hatch MC. Reproductie effects of herbicide exposure in Vietnam: Recent studies by the Vietnamese and others. As cited in Constable and Hatch, 1985. Nishijo M, Tawara K, Nakagawa H, Honda R, Kido T, Nishijo H, Saito S. 2008. 2,3,7,8-tetrachloro- dibenzo-p-dioxin in maternal breast milk and newborn head circumference. Journal of Exposure Science and Enironmental Epidemiology 18(3):246–251. Norström A, Rappe C, Lindahl R, Buser HR. 1979. Analysis of some older Scandinavioan formula- tions of 2,4-dichlorophenoxy acetic acid for contents of chlorinated dibenzo- p-dioxins and dibenzofurans. Scandanaian Journal of Work, Enironment and Health 5:375–378. Nurminen T, Rantala K, Kurppa K, Holmberg PC. 1994. Agricultural work during pregnancy and selected structural malformations in Finland. Epidemiology 1:23–30. O’Brien TR, Decoufle P, Boyle CA. 1991. Non-Hodgkin’s lymphoma in a cohort of Vietnam veterans. American Journal of Public Health 81:758–760.

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