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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

APPENDIX C
Epidemiologic Tables for Chapter 4

In Tables C-1, C-2, and C-3, respectively, studies are grouped according to whether their subjects had occupational exposures, had environmental exposures, or were specifically Vietnam veterans. The tables provide an overview of design aspects of those epidemiologic studies reviewed in this and earlier reports that presented results on more than one health outcome or that investigated populations that have been repeatedly studied. The summaries include the study’s design type, the numbers of subjects in the study and comparison populations, and a synopsis of how subjects were selected, how data were collected, what inclusion criteria were used, and how exposure was determined. Results were discussed in the appropriate health-outcome chapter of the Veterans and Agent Orange document in which the publication was reviewed. The citations for the articles in this appendix can be found in the reference list at the end of Chapter 4.

Contents of TABLE C-1 Epidemiologic Studies—Occupational Exposure

 

Page

PRODUCTION WORKERS

718

NIOSH Studies, 718

 

Monsanto Studies, 721

 

Dow Studies, 721

 

BASF Studies, 723

 

IARC Studies, 724

 

Studies from Other Chemical Plants, 728

 

AGRICULTURAL–FOREST PRODUCTS

729

Studies from the Agricultural Health Study, 729

 
Page
717

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Veterans and Agent Orange: Update 2006 APPENDIX C Epidemiologic Tables for Chapter 4 In Tables C-1, C-2, and C-3, respectively, studies are grouped according to whether their subjects had occupational exposures, had environmental exposures, or were specifically Vietnam veterans. The tables provide an overview of design aspects of those epidemiologic studies reviewed in this and earlier reports that presented results on more than one health outcome or that investigated populations that have been repeatedly studied. The summaries include the study’s design type, the numbers of subjects in the study and comparison populations, and a synopsis of how subjects were selected, how data were collected, what inclusion criteria were used, and how exposure was determined. Results were discussed in the appropriate health-outcome chapter of the Veterans and Agent Orange document in which the publication was reviewed. The citations for the articles in this appendix can be found in the reference list at the end of Chapter 4. Contents of TABLE C-1 Epidemiologic Studies—Occupational Exposure   Page PRODUCTION WORKERS 718 NIOSH Studies, 718   Monsanto Studies, 721   Dow Studies, 721   BASF Studies, 723   IARC Studies, 724   Studies from Other Chemical Plants, 728   AGRICULTURAL–FOREST PRODUCTS 729 Studies from the Agricultural Health Study, 729  

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Veterans and Agent Orange: Update 2006 Studies of Other Agricultural Workers, 731   United Farm Workers, 731   Upper Midwest Health Study, 731   Studies of Forestry Workers, 736   Studies of Herbicide–Pesticide Applicators, 736   PAPER AND PULP WORKERS 740 CASE–CONTROL STUDIES 741 TABLE C-1 Epidemiologic Studies—Occupational Exposure Reference Study Design Description Study Group (n) Comparison Group (n)a PRODUCTION WORKERS NIOSH Studies Reviewed in Update 2006 Lawson et al., 2004 Cohort Follow-on of NIOSH cross-sectional medical study (Sweeny et al., 1989, 1993); examined reproductive endpoints, in terms of exposure to TCDD at the time of conception estimated by pharmacokinetic model, in wives of chemical workers vs. referent neighbors 176 workers wives with 513 births 217 referent wives with 604 births NIOSH Studies Reviewed in Update 2002 Steenland et al., 2001 Cohort Reexamination and comparison of diabetes data from the NIOSH cohort and the AFHS; reconciled differences between study methods and protocols 267 NIOSH workers; 990 Ranch Hand subjects 227 NIOSH comparisons; 1,275 AFHS comparisons NIOSH Studies Reviewed in Update 2000 Calvert et al., 1999 Cohort Follow-up of workers employed more than 15 years at 2 plants that manufactured substances contaminated with TCDD; evaluated associations between serum TCDD and serum glucose (diabetes), TSH, total T4, T3 281 260

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Steenland et al., 1999 Cohort Mortality of workers at 12 industrial plants that produced TCDD-contaminated materials, using a job–exposure matrix to estimate TCDD exposure categories; endpoints were all cancers, lung cancer, ischemic heart disease, diabetes, smoking-related cancer, and all other cancers 5,132 (3,538 subjects with exposure data divided into septiles of cumulative exposure; 608 with chloracne) — Calvert et al., 1998 Cohort Follow-up of workers employed more than 15 years before at 2 plants that manufactured TCDD-contaminated materials; to evaluate association between TCDD exposure and cardiovascular outcomes 281 260 Halperin et al., 1998 Cohort Follow-up of a cohort of TCDD-exposed workers at 2 plants that manufactured TCDD-contaminated materials; to assess association between serum TCDD and immunologic outcome variables for eligible workers and matched neighborhood controls 259 243 NIOSH Studies Reviewed in Update 1998 Sweeney et al., 1996, 1997/1998 Cross-sectional Non-cancer endpoints for liver function, gastrointestinal disorders, chloracne, serum glucose, hormone, lipid concentrations, diabetes in the group studied by Calvert et al. (1991) 281 260 Halperin et al., 1995 Cross-sectional Surrogates for cytochrome P-450 induction in group studied by Calvert et al. (1991) 281 260

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a NIOSH Studies Reviewed in Update 1996 Calvert et al., 1994 Cross-sectional PCT in group studied by Calvert et al. (1991) 281 260 Egeland et al., 1994 Cohort Total serum testosterone and gondadotropin in chemical production workers exposed to dioxin, in group studied by Calvert et al. (1991) 248 231 NIOSH Studies Reviewed in VAO Sweeney et al., 1993 Cohort Peripheral neuropathy in group studied by Calvert et al. (1991) 281 260 Alderfer et al., 1992 Cohort Psychological assessment to determine depression in group studied by Calvert et al. (1991) 281 260 Calvert et al., 1992 Cohort Liver and gastrointestinal systems assessment in group studied by Calvert et al. (1991) 281 260 Calvert et al., 1991 Cohort Workers employed at 1 of 2 plants manufacturing TCDD-contaminated materials at least 15 years before; to assess chronic bronchitis, COPD, ventilatory function, thorax, lung abnormalities; compared with matched neighborhood controls 281 260 Fingerhut et al., 1991 Cohort Cancer mortality in male workers from 12 plants producing TCDD-contaminated materials (1942–1984), compared with US population 5,172 —

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Monsanto Studies Reviewed in VAO Collins et al., 1993 Cohort Mortality of workers (through 1987) exposed and unexposed to dioxin between March 8, 1949, and Nov. 22, 1949, as indicated by presence of chloracne, compared with local population mortality rates 122 (chloracne); 632 (without chloracne) — Moses et al., 1984 Cohort Health outcomes in Monsanto workers (1948–1969) with chloracne reported as a surrogate for 2,4,5-T exposure, compared with health outcomes in workers without chloracne as surrogate for no exposure 117 109 Suskind and Hertzberg, 1984 Cohort Health outcomes (1979) at clinical examination among workers exposed to 2,4,5-T (1948–1969) compared with non-exposed workers at same Monsanto plant 204 163 Zack and Gaffey, 1983 Cohort Mortality of all white male workers (1955–1977) employed at a Monsanto plant through Dec. 31, 1977, compared with mortality of standardized US population 884 — Zack and Suskind, 1980 Cohort Mortality experience among employees with chloracne exposed to TCP process accident in 1949 at Monsanto, compared with US male population standard 121 — Dow Studies in Update 2004 Bodner et al., 2003 Cohort Additional 10-year follow-up of cohort studied by Cook et al. (1986), through 1995; Dow cohort findings compared with IARC International Study and NIOSH Dioxin Registry 2,187 —

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Dow Studies Reviewed in Update 2002 Burns et al., 2001 Cohort Mortality in chemical workers who manufactured or formulated 2,4-D, 1945–1994 1,567 US population; 40,600 non-exposed chemical workers Dow Studies Reviewed in Update 1998 Ramlow et al., 1996 Cohort Mortality in PCP-exposed workers 770 US population 36,804 non-exposed workers Dow Studies Reviewed in Update 1996 Bloeman et al., 1993 Cohort Follow-up of cohort studied by Bond et al. (1988), through 1986 878 US population; 36,804 unexposed workers Dow Studies Reviewed in VAO Bond et al., 1989a Cohort Chloracne incidence among workers potentially exposed to TCDD; association with other risk factors 2,072 Internal comparison Bond et al., 1989b Cohort Extension of Ott et al. (1987), through 1984 2,187 — Bond et al., 1988 Cohort Mortality (through 1982) among workers potentially exposed to 2,4-D (1945– 1983) compared with US white men and all other male employees not exposed 878 US white male population; 36,804 non-exposed employees Bond et al., 1987 Cohort Extension of Cook et al. (1980); mortality through 1982 322 US white male population; 2,026 employees without chloracne Cook et al., 1987; Ott et al., 1987 Cohort Extension of Cook et al. (1986) through 1982 2,187 — Sobel et al., 1987 Case– control STS among Dow employees (1940–1979), compared with employees without STS, for possible association with several exposures 14 126

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Cook et al., 1986 Cohort Mortality experience (1940–1979) of men manufacturing chlorinated phenols, compared with US white men 2,189 — Bond et al., 1983 Cross-sectional Differences in potentially exposed and non-exposed workers for TCDD during chemical production, for (1) morbidity and (2) medical examination frequency, 1976–1978 (1) 183 (2) 114 (1) 732 (2) 456 Townsend et al., 1982 Cohort Adverse reproductive outcomes among wives of Dow employees potentially exposed to TCDD (1939– 1975), compared with wives whose husbands were not exposed 370 345 Cook et al., 1980 Cohort Mortality experience (through 1978) of male workers involved in a chloracne incident (1964) from TCDD exposure, compared with mortality experience of US white men 61 — Ott et al., 1980 Cohort Mortality experience among workers exposed to 2,4,5-T in manufacturing (1950–1971), compared with mortality experience of US white men 204 — BASF Studies Reviewed in Update 2000 Zober et al., 1997 Cohort (1953 accident) Cross-sectional (1988 cohort) Review and summary of previous BASF studies of morbidity and mortality in workers exposed to TCDD after BASF accidents in 1953 and 1988 154 surviving (as of 1989) members of 1953 accident cohort; 42 exposed (1988) extruder personnel None

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a BASF Studies Reviewed in Update 1998 Ott and Zober, 1996 Cohort Cancer incidence and mortality experience (through 1992) of workers exposed to TCDD after the BASF accident, during reactor cleanup, maintenance, or demolition (based on the cohort of Zober et al., 1990) 243 — BASF Studies Reviewed in Update 1996 Zober et al., 1994 Cohort Morbidity experience in the group studied Zober et al. (1990) 158 161 BASF Studies Reviewed in VAO Zober et al., 1990 Cohort Mortality experience of TCDD-exposed workers (1954–1987) at BASF plant, compared with population of FRG 247 — Thiess et al., 1982 Cohort Mortality experience among BASF employees potentially exposed to TCDD during Nov. 17, 1953, accident, compared with population and other workers not exposed 74 180,000 (Town); 1.8 million (district); 60.5 million (FRG); 2 groups of 74 each from other cohort studies IARC Studies Reviewed in Update 2006 ’t Mannetje et al., 2005 Cohort New Zealand phenoxy herbicide workers exposed TCDD and phenoxy herbicides 813 production workers; 699 sprayers   IARC Studies Reviewed in Update 2000 Neuberger et al., 1999 Austrian chloracne cohort Morbidity up to 1993 of exposed chemical workers assessed by health insurance data and health examination, laboratory measures, interviews with participating survivors and control subjects 159; 50 participated in examination Two control groups, comparable to 50 examination participants; numbers not given

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Hooiveld et al., 1998 Cohort Mortality (through 1991), using SMR, of Dutch factory workers assessed in relation to work and exposure history; SMR and relative risk analyses 562 (serum samples for 50); 140 men at accident 567 Jäger et al., 1998 Cohort Preliminary data from Neuberger et al., 1999 [English abstract only] 159, original cohort; 56 screened; 49 full data Matched non-exposed controls Neuberger et al., 1998 Cohort of exposed cases Preliminary data from Neuberger et al., 1999 50 Age and sex-matched controls; number not given Vena et al., 1998 Cohort 36 Worker cohorts from 12 countries, produced or sprayed phenoxyacid herbicides and chlorophenols, categorized in 1 of 3 TCDD or higher-chlorinated dioxin categories; non-cancer mortality (1939– 1992) analyzed by SMR comparison and Poisson multiple regression 21,863 None Flesch-Janys, 1997 Cohort Mortality (1952–1984) of German workers exposed to TCDD and other contaminants in herbicide and insecticide production; SMR and Cox regression model 1,189 — IARC Studies Reviewed in Update 1998 Kogevinas et al., 1997 Cohort Mortality (through 1992) of workers engaged in production or application of phenoxy herbicides and composed of (1) the Saracci et al. (1991) cohorts, (2) the German cohorts of Becher et al. (1996), and (3) the NIOSH cohorts of Fingerhut et al. (1991) 26,615 total (21,863 exposed; 4,160 probably exposed; 592 unknown exposure) —

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Becher et al., 1996 Cohort Cancer mortality (through 1989) among German workers in 4 chemical factories exposed to 2,4,5-T and/or trichlorophenol (subcohorts I and II), and phenoxy herbicides and chlorophenols (subcohorts III and IV) 2,479 — Flesch-Janys et al., 1995 Cohort Cancer and circulatory system mortality among chemical plant workers in Hamburg, Germany, exposed to herbicides contaminated with PCDD/F 1,189 2,528 gas workers IARC Studies Reviewed in Update 1996 Kogevinas et al., 1995 Case– control Nested studies of the relationship between STS and NHL and occupational exposures in the IARC cohort 11 cases, STS; 32 cases, NHL 5 controls per case Kogevinas et al., 1993 Cohort Cancer incidence and mortality experience of female workers in 7 countries, potentially exposed to chlorophenoxy herbicides, chlorophenols, and dioxin, compared with national death rates and cancer incidence rates 701 — Lynge, 1993 Cohort Cancer incidence in the group studied by Lynge (1985); follow-up extended through 1987 3,390 men; 1,071 women — Kogevinas et al., 1992 Cohort STS and malignant lymphoma mortality in an international cohort of production workers and herbicide sprayers (group studied by Saracci et al., 1991) 14,439 (13,482 exposed, 416 probably exposed, 541 unknown exposure) 3,951 non-exposed employees

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a IARC Studies Reviewed in VAO Bueno de Mesquita et al., 1993 Cohort Mortality experience of production workers exposed to phenoxy herbicides and chlorophenols in the Netherlands, compared with national rates 2,310 — Coggon et al., 1991 Cohort Mortality experience among 4 cohorts of workers potentially exposed (1963– 1985) to phenoxy herbicides and chlorophenols, compared with national (England and Wales) and local population expected numbers 1,104, Factory A; 271, Factory B; 345, Factory C; 519, Factory D — Manz et al., 1991 Cohort Mortality experience of workers (1952–1984) at Hamburg, Germany, Boehringer plant exposed to TCDD, compared with national mortality and workers from another company 1,184 men 399 women (a) population (b) 3,120 gas workers Saracci et al., 1991 Cohort Mortality experience of 20 international cohorts of herbicide sprayers and production workers, compared with national expected mortality experience 16,863 men; 1,527 women — Coggon et al., 1986 Cohort Mortality experience (through 1983) among workers manufacturing and spraying MCPA (1947–1975), compared with expected number of deaths among men of England and Wales and for rural areas 5,754 — Lynge, 1985 Cohort Cancer incidence among Danish workers exposed to phenoxy herbicides compared with expected results from the general population 3,390 men; 1,069 women —

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Wolfe et al., 1995 Cohort Paternal serum dioxin and reproductive outcomes of Ranch Hand veterans, compared with Air Force veterans from Southeast Asia who did not spray herbicides 932 1,202 Reports from AFHS Reviewed in VAO AFHS, 1992 Cohort Reproductive outcomes of AFHS participants 791 942 AFHS, 1984a, 1987, 1990, 1991b Cohort Baseline morbidity, follow-up examination results 1,208 baseline 1,668 baseline AFHS, 1983, 1984b, 1985, 1986, 1989, 1991a Cohort Mortality updates, Ranch Hands who sprayed herbicides in Vietnam, compared with Air Force C-130 air and ground crew veterans in Southeast Asia who did not spray herbicides 1,261 (original cohort) 19,101 (original cohort) Michalek et al., 1990 Cohort Mortality of Ranch Hands, compared with Air Force C-130 air and ground crew veterans in Southeast Asia 1,261 19,101 Wolfe et al., 1990 Cohort Health status of Ranch Hands at second follow-up, compared with Air Force C-130 air and ground crew veterans in Southeast Asia 995 1,299 CDC Studies Reviewed in Update 2006 Boehmer et al., 2004 Cohort Vietnam Experience Study—post-service mortality 18,313   CDC Studies Reviewed in VAO Decoufle et al., 1992 Cohort Association between self-reported health outcomes and perception of exposure to herbicides based on Vietnam Experience Study 7,924 7,364 O’Brien et al., 1991 Cohort Interview report and mortality for NHL based on Vietnam Experience Study 8,170 7,564

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a CDC, 1990a Case– control Selected Cancers Study: population-based case–control study of all men born 1921–1953; cases diagnosed area covered by 8 cancer registries, controls selected by random-digit dialing 1,157 NHL; 342 STS; 310 HD; 48 nasal carcinoma; 80 nasopharyngeal carcinoma; 130 primary liver cancer 1,776 CDC, 1990b Case– control Selected Cancers Study: population-based case–control study of all men born 1921–1953; cases diagnosed in area covered by 8 cancer registries, controls selected by random-digit dialing for NHL 1,157 1,776 CDC, 1990c Case– control Selected Cancers Study: STS 342 1,776 CDC, 1990d Case– control Selected Cancers Study: HD, nasal cancer, nasopharyngeal cancer, primary liver cancer 310 HD; 48 nasal carcinoma; 80 nasopharyngeal carcinoma; 130 primary liver cancer 1,776 CDC, 1989b Cohort Vietnam Experience Study: random sample, US Army enlisted men, 1965–1971 2,490 1,972 CDC, 1988a Cohort Vietnam Experience Study: random sample, US Army enlisted men, 1965–1971, psychosocial outcomes 2,490 1,972 CDC, 1988b Cohort Vietnam Experience Study: physical health outcomes 2,490 1,972 CDC, 1988c Cohort Vietnam Experience Study: reproductive outcomes 12,788 children 11,910 children CDC, 1987; Boyle et al., 1987 Cohort Vietnam Experience Study: mortality 9,324 8,989 Erickson et al., 1984 a,b Case– control CDC birth defects study, children born in the Atlanta, Georgia, area 1968–1980, comparing paternal Vietnam experience and potential Agent Orange exposure for birth defects cases and normal controls 7,133 4,246

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Department of Veterans Affairs Studies Reviewed in Update 2006 Kang et al., 2006 Cohort Army Chemical Corp; serum TCDD, Vietnam veterans {sprayers vs. not sprayers} vs not Vietnam vet 1,499 1,428 Department of Veterans Affairs Studies Reviewed in Update 2002 Kang et al., 2001 Cohort Health of Army Chemical Corps Vietnam veterans, compared with Army Chemical Corps veterans who did not serve in Vietnam 2,872 2,737 Kang et al., 2000a Cohort Self-report pregnancy outcomes for female Vietnam veterans, compared with contemporary veterans not deployed to Vietnam; odds ratios calculated for reproductive history and various birth defects 3,392 women; 1,665 women with indexed pregnancy 3,038 women; 1,912 women with indexed pregnancy Kang et al., 2000b Cohort Gynecologic cancers among female Vietnam veterans, compared with veteran controls 484 5,946 Department of Veterans Affairs Studies Reviewed in Update 1998 Dalager and Kang, 1997 Cohort Morbidity and mortality experience (1968–1987), Army Chemical Corps Vietnam veterans, compared with US men; extension of Thomas and Kang (1990) 2,872 2,737 Mahan et al., 1997 Case– control Lung cancer among Vietnam veterans (1983–1990) 329 269 111 McKinney et al., 1997 Cross-sectional Tobacco use in veterans and non-veterans by 1987 NMES 15,000 — Bullman and Kang, 1996 Cohort Mortality of veterans with non-lethal (combat and noncombat) wounds sustained during the Vietnam war 34,534 — Watanabe and Kang, 1996 Cohort Mortality experience (1965–1988) of Army and Marine Corps Vietnam veterans; extension of Breslin et al. (1988) and Watanabe et al. (1991) 33,833 36,797 Dalager et al., 1995b Case– control HD Cases diagnosed 1969–1985 among Vietnam-era veterans 283 404

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Watanabe and Kang, 1995 Cohort Post-service mortality among Marine Vietnam veterans 10,716 9,346 Department of Veterans Affairs Studies Reviewed in Update 1996 Dalager et al., 1995a Cohort Update of Thomas et al. (1991) through Dec. 31, 1995 4,586 5,325 Bullman et al., 1994 Case– control Association between testicular cancer and surrogate measures of exposure to Agent Orange in male Vietnam veterans 97 311 Department of Veterans Affairs Studies Reviewed in VAO Bullman et al., 1991 Case– control PTSD cases in Vietnam veterans, compared with Vietnam veterans without PTSD, for association with traumatic combat experience 374 373 Dalager et al., 1991 Case– control NHL cases diagnosed 1969–1985 among Vietnam-era veterans, compared with cases of other malignancies among Vietnam-era veterans, for association with Vietnam service 201 358 Eisen et al., 1991 Cohort Health effects in male monozygotic twins serving in the armed forces during Vietnam era (1965–1975) 2,260 2,260 Thomas et al., 1991 Cohort Mortality experience (1973–1987) among female Vietnam veterans, compared with female non-Vietnam veterans and for each cohort compared with US women 4,582 5,324 Watanabe et al., 1991 Cohort Mortality experience (1965–1984) in Army and Marine Corps Vietnam veterans, compared with: (1) branch-specific (Army and Marine) Vietnam-era veterans, (2) all Vietnam-era veterans combined, (3) the US male population 24,145 Army 5,501 Marines (1) 27,145 Army 4,505 Marines (2) 32,422 combined Vietnam era (3) US male population

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Bullman et al., 1990 Cohort Mortality experience in Army I Corps Vietnam veterans, compared with Army Vietnam-era veterans 6,668 deaths 27,917 deaths Farberow et al., 1990 Case– control Psychological profiles, military factors associated with suicide and MVA fatalities in Los Angeles County Vietnam-era veterans (1977–1982) 22 Vietnam suicides; 19 Vietnam-era suicides 21 Vietnam MVA; 20 Vietnam-era MVA Thomas and Kang, 1990 Cohort Morbidity and mortality experience (1968–1987) in Army Chemical Corps Vietnam veterans compared with US men 894 — True et al., 1988 Cross-sectional PTSD and Vietnam combat experience among Vietnam-era veterans 775 1,012 Breslin et al., 1988 Burt et al., 1987 Cohort Mortality experience (1965–1982) in Army and Marine Corps Vietnam veterans, compared with Vietnam-era veterans who did not serve in Southeast Asia, standardized by age and race; nested NHL case–control study 24,235 26,685 Kang et al., 1987 Case– control STS cases (1975–1980) diagnosed at the Armed Forces Institute of Pathology, compared with controls identified from patient logs of referring pathologists or their departments, for association with Vietnam service and likelihood of Agent Orange exposure 217 599 Kang et al., 1986 Case– control STS (1969–1983) in Vietnam-era veterans, for association with branch of Vietnam service as a surrogate for Agent Orange exposure 234 13,496 American Legion Studies Reviewed in VAO Snow et al., 1988 Cohort PTSD in association with traumatic combat experience among American Legion members serving in Southeast Asia (1961–1975) 2,858 Study group subdivided for internal comparison

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Stellman et al., 1988b Cohort Physical health, reproductive outcomes among American Legion members who served in Southeast Asia (1961–1975), for association with combat and herbicide exposure 2,858 3,933 Stellman et al., 1988c Cohort Social, behavioral outcomes among American Legion members who served in Southeast Asia (1961– 1975), association with combat and herbicide exposure 2,858 3,933 State Studies Reviewed in Update 2006 Engel et al., 2005 Cohort AHS examine phenoxy herbicides and breast cancer incidence among farmer wives in Iowa and North Carolina 309 30,145 Kirrane et al., 2005 Cross-sectional AHS in Iowa and North Carolina; phenoxy herbicide exposure and retinal degeneration in wives of farmers 31,173   Lee et al., 2004 Population based /case-control Continues Ward et al., 1997 study on diet. Evaluate risk of the stomach and oesophageal adenocarcinomas associated with farming and agricultural pesticide use in eastern Nebraska 170 (adenocarcinoma of stomach) 137 (oesophagus) 502 State Studies Reviewed in Update 1998 Clapp, 1997 Case– control Selected cancers identified (1988–1993) among Massachusetts Vietnam veterans, compared with Massachusetts Vietnam-era veterans with cancers of other sites; update of Clapp et al., 1991 245 999 State Studies Reviewed in Update 1996 Visintainer et al., 1995 Cohort Mortality experience (1965–1971) in male Michigan Vietnam veterans, compared with non-Vietnam veterans from Michigan 3,364 deaths 5,229 deaths

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a State Studies Reviewed in VAO Fiedler and Gochfeld, 1992 Kahn et al., 1992a,b,c Cohort New Jersey: outcomes in select group of herbicide-exposed Army, Marine, and Navy Vietnam veterans, compared with veterans self-reported as unexposed 10 Pointman I 55 Pointman II 17 Pointman I 15 Pointman II Clapp et al., 1991 Case– control Massachusetts: selected cancers identified (1982–1988) among Vietnam veterans, compared with Massachusetts Vietnam-era veterans with cancers of other sites 214 727 Deprez et al., 1991 Descriptiv e Maine: Vietnam veterans, compared with atomic test veterans and general population, for health status and reproductive outcomes 249 113 Atomic test veterans Levy, 1988 Cross-sectional Massachusetts: PTSD in chloracne as indicator of exposure to TCDD; control Vietnam veterans   625 Anderson et al., 1986a Cohort Wisconsin: mortality experience, veterans compared with non-veterans (Phase 1); mortality experience of Vietnam veterans and Vietnam-era veterans, compared with non-veterans and other veterans (Phase 2) (superseded by Anderson et al., 1986b) 110,815 white male veteran deaths; 2,494 white male Vietnam-era veteran deaths; 923 white male Vietnam veteran deaths 342,654 white male non-veteran deaths; 109,225 white male other veteran deaths Anderson et al., 1986b Cohort Wisconsin: mortality experience in Vietnam-era veterans and Vietnam veterans, compared with US men, Wisconsin men, Wisconsin non-veterans, and Wisconsin other veterans 122,238 Vietnam-era veterans; 43,398 Vietnam veterans — Goun and Kuller, 1986 Case– control Pennsylvania: STS, NHL, selected rare cancer cases, compared with controls without cancer for Vietnam experience in men (1968–1983) 349 349 Deceased Holmes et al., 1986 Cohort West Virginia: mortality experience (1968–1983) of veterans, Vietnam veterans, Vietnam-era veterans, compared with non-veterans; Vietnam veterans compared with Vietnam-era veterans 615 Vietnam veterans 610 Vietnam era veterans —

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Pollei et al., 1986 Cohort New Mexico: chest radiographs of Agent Orange Registry Vietnam veterans, compared with radiographs of control Air Force servicemen, for pulmonary and cardiovascular pathology 422 105 Kogan and Clapp, 1985, 1988 Cohort Massachusetts: mortality experience (1972–1983) among white male Vietnam veterans, compared with non-Vietnam veterans and all other non-veteran white men in Massachusetts 840 Deaths 2,515 deaths in Vietnam-era veterans Lawrence et al., 1985 Cohort New York: mortality experience in (1) Vietnam-era veterans, compared with non-veterans and (2) Vietnam veterans, compared with Vietnam-era veterans (1) 4,558 (2) 555 17,936 941 Rellahan, 1985 Cohort Hawaii: health outcomes in Vietnam-era (1962–1972) veterans residing in Hawaii, associated with Vietnam experience 232 186 Wendt, 1985 Descriptiv e Iowa: health effects and potential exposure to Agent Orange among veterans who served in Southeast Asia 10,846 None Greenwald et al., 1984 Case– control New York: STS cases, compared with controls without cancer for Vietnam service and herbicide exposure including Agent Orange, dioxin, or 2,4,5-T 281 281 live controls; 130 deceased controls Newell, 1984 Cross-sectional Texas: preliminary (1) cytogenetic, (2) sperm, (3) immune response tests in Vietnam veterans, compared with controls (1) 30; (2) 32; (3) 66 (1) 30; (2) 32; (3) 66 Other Studies American Vietnam Veterans Reviewed in VAO Tarone et al., 1991 Case– control Testicular cancer (18–42 years old) cases, January 1976–June 1981, compared with hospital controls, for association with Vietnam service 137 130

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Aschengrau and Monson, 1990 Case– control Cases with late adverse pregnancy outcomes compared with normal control births, for association with paternal Vietnam service (1977–1980) 857 congenital anomalies 61 stillbirths; 48 neonatal deaths 998 Goldberg et al., 1990 Cohort Male twin pairs who served in Vietnam era (1965–1975), for association between Vietnam service and PTSD 2,092 2,092 Aschengrau and Monson, 1989 Case– control Association between husband’s military service and spontaneous abortion at or by 27 weeks, compared with women delivering at 37 weeks 201 1,119 STUDIES OF AUSTRALIAN VIETNAM VETERANS Studies of Australian Vietnam Veterans Reviewed in Update 2006 ADVA, 2005a Cohort Cancer incidence from 1982 to 2000 among Australian male Army, Navy, and Air Force veterans who served in Vietnam between May 1962 and July 1973 59,179 total; 41,084 (Army); 13,538 (Navy); 4,570 (Air Force)   ADVA, 2005b Cohort Retrospective mortality study of male Australian personnel who served between May 1962 and July 1973 vs. Australian men in general community 59,179   ADVA, 2005c Cohort Retrospective cohort study of male National Service personnel who served in the Vietnam era between 1966 and July 1973. Examined all deaths identified from the end of service to 31 December 2001 and all cancers diagnosed from 1982 to 31 December 2000 43,969 total; 19,240 veterans; 24,729 non-veterans   Leavy et al., 2006 Case– control Cancer registry of Western Australia and prostate cancer; deployment to Vietnam 606 471

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Studies of Australian Vietnam Veterans Reviewed in Update 2000 AIHW, 1999 Cohort Validation of the male veterans’ study (CDVA, 1998a) by medical documents, doctors’ certification, records on a disease or death registry 6,842 — CDVA, 1998a Cohort Self-reported data on male members of the Australian Defence Force and the Citizen Military Force who landed in Vietnam or entered Vietnamese water. Questions on physical (including reproductive history) and mental health, and that of their partner(s) and children 49,944 mailed; 39,955 responded — CDVA, 1998b Cohort Self-reported data on female members of the Australian Defence Force and the Citizen Military Force who landed in Vietnam or entered Vietnamese water. Questions on physical (including reproductive history) and mental health, and that of their partner(s) and children 278 mailed 225 responded — Studies of Australian Vietnam Veterans Reviewed in Update 1998 Crane et al., 1997a Cohort Mortality experience (through 1994) of Australian veterans who served in Vietnam 59,036 men 484 women — Crane et al., 1997b Cohort Mortality experience (through 1994) of Australian national servicemen who served in Vietnam 18,949 24,646 O’Toole et al., 1996a,b,c Cross-sectional Survey of self-reported health status (1989–1990) of Australian Army Vietnam veterans 641 — Studies of Australian Vietnam Veterans Reviewed in VAO Field and Kerr, 1988 Cohort Tasmanian Vietnam veterans, compared with neighborhood controls for adverse reproductive and childhood health outcomes 357 281 Fett et al., 1987a Cohort Mortality experience in Vietnam veterans, compared with Vietnam-era veterans through 1981 19,205 25,677

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Veterans and Agent Orange: Update 2006 Reference Study Design Description Study Group (n) Comparison Group (n)a Fett et al., 1987b Cohort Cause-specific mortality experience in Vietnam veterans, compared with Vietnam-era veterans through 1981 19,205 25,677 Forcier et al., 1987 Cohort Mortality in Vietnam veterans by job classification, location, time of service 19,205 Internal comparison Donovan et al., 1983, 1984 Case– control Congenital anomalies in children (1969–1979), compared with infants born without anomalies, for association with paternal Vietnam service 8,517 8,517 STUDIES OF VIETNAM VETERANS FROM OTHER COUNTRIES Other Vietnam-Veteran studies Reviewed in Update 2004 Kim H-A et al., 2003 Cohort Immunotoxicologic effects of Agent Orange exposure on Korean Vietnam veterans 51 (24 veterans– patient; 27 veterans–normal) 36 Kim J-S et al., 2003 Cross-sectional Agent Orange exposure and Korean Vietnam veterans 1,224 154 Mo et al., 2002 Cohort Skin and general disease patterns among Korean Vietnam veterans 332 None Other Vietnam-Veteran studies Reviewed in Update 1998 Chinh et al., 1996 Cohort Antinuclear antibodies and sperm autoantibodies among Vietnamese veterans who served 5–10 years in a “dioxin-sprayed zone” 25 63; 36 ABBREVIATIONS: 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; AFHS, Air Force Health Study; CDC, Centers for Disease Control and Prevention; CDVA, Commonwealth Department of Veterans’ Affairs; HD, Hodgkin’s disease; MVA, motor vehicle accidents; NIOSH, National Institute for Occupational Safety and Health; NHL, non-Hodgkin’s lymphoma; NMES; National Medical Expenditure Survey; PTSD, posttraumatic stress disorder; SMR, standardized mortality ratio; STS, soft-tissue sarcoma; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; Update 2006, Veterans and Agent Orange: Update 2006 (IOM, 2007); Update 2004, Veterans and Agent Orange: Update 2004 (IOM, 2005); Update 2002, Veterans and Agent Orange: Update 2002 (IOM, 2003); Update 2000, Veterans and Agent Orange: Update 2000 (IOM, 2001); Update 1998, Veterans and Agent Orange: Update 1998 (IOM, 1999); Update 1996, Veterans and Agent Orange: Update 1996 (IOM, 1996); and VAO, Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam (IOM, 1994). a Comparison group based on a population (e.g., US white men, country rates); details are given in the text for population specifics.