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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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 popula- tions 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 docu- ment 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, 729 717

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718 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 Study Study Group Comparison Group (n)a Reference Design Description (n) PRODUCTION WORKERS NIOSH Studies Reviewed in Update 2006 Lawson Cohort Follow-on of NIOSH cross- 176 workers 217 referent wives et al., 2004 sectional medical study wives with 513 with 604 births (Sweeny et al., 1989, 1993); births 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 NIOSH Studies Reviewed in Update 2002 Steenland Cohort Reexamination and 267 NIOSH 227 NIOSH et al., 2001 comparison of diabetes data workers; comparisons; from the NIOSH cohort 990 Ranch 1,275 AFHS and the AFHS; reconciled Hand subjects comparisons differences between study methods and protocols NIOSH Studies Reviewed in Update 2000 Calvert Cohort Follow-up of workers 281 260 et al., 1999 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 continued

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719 APPENDIX C TABLE C-1 Continued Study Study Group Comparison Group (n)a Reference Design Description (n) Steenland Cohort Mortality of workers 5,132 (3,538 — et al., 1999 at 12 industrial plants subjects with that produced TCDD- exposure data contaminated materials, divided into using a job–exposure matrix septiles of to estimate TCDD exposure cumulative categories; endpoints were exposure; all cancers, lung cancer, 608 with ischemic heart disease, chloracne) diabetes, smoking-related cancer, and all other cancers Calvert Cohort Follow-up of workers 281 260 et al., 1998 employed more than 15 years before at 2 plants that manufactured TCDD- contaminated materials; to evaluate association between TCDD exposure and cardiovascular outcomes Halperin Cohort Follow-up of a cohort of 259 243 et al., 1998 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 NIOSH Studies Reviewed in Update 1998 Sweeney Cross- Non-cancer endpoints 281 260 et al., 1996, sectional for liver function, 1997/1998 gastrointestinal disorders, chloracne, serum glucose, hormone, lipid concentrations, diabetes in the group studied by Calvert et al. (1991) Halperin Cross- Surrogates for cytochrome 281 260 et al., 1995 sectional P-450 induction in group studied by Calvert et al. (1991) continued

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720 VETERANS AND AGENT ORANGE: UPDATE 2006 TABLE C-1 Continued Study Study Group Comparison Group (n)a Reference Design Description (n) NIOSH Studies Reviewed in Update 1996 Calvert Cross- PCT in group studied by 281 260 et al., 1994 sectional Calvert et al. (1991) Egeland Cohort Total serum testosterone and 248 231 et al., 1994 gondadotropin in chemical production workers exposed to dioxin, in group studied by Calvert et al. (1991) NIOSH Studies Reviewed in VAO Sweeney Cohort Peripheral neuropathy in 281 260 et al., 1993 group studied by Calvert et al. (1991) Alderfer Cohort Psychological assessment 281 260 et al., 1992 to determine depression in group studied by Calvert et al. (1991) Calvert Cohort Liver and gastrointestinal 281 260 et al., 1992 systems assessment in group studied by Calvert et al. (1991) Calvert Cohort Workers employed at 1 of 2 281 260 et al., 1991 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 Fingerhut Cohort Cancer mortality in 5,172 — et al., 1991 male workers from 12 plants producing TCDD- contaminated materials (1942–1984), compared with US population

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721 APPENDIX C TABLE C-1 Continued Study Study Group Comparison Group (n)a Reference Design Description (n) Monsanto Studies Reviewed in VAO Collins Cohort Mortality of workers 122 — et al., 1993 (through 1987) exposed (chloracne); and unexposed to dioxin 632 (without between March 8, 1949, and chloracne) Nov. 22, 1949, as indicated by presence of chloracne, compared with local population mortality rates Moses et al., Cohort Health outcomes in 117 109 1984 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 Suskind and Cohort Health outcomes (1979) at 204 163 Hertzberg, clinical examination among 1984 workers exposed to 2,4,5-T (1948–1969) compared with non-exposed workers at same Monsanto plant Zack and Cohort Mortality of all white 884 — Gaffey, male workers (1955–1977) 1983 employed at a Monsanto plant through Dec. 31, 1977, compared with mortality of standardized US population Zack and Cohort Mortality experience 121 — Suskind, among employees with 1980 chloracne exposed to TCP process accident in 1949 at Monsanto, compared with US male population standard Dow Studies in Update 2004 Bodner Cohort Additional 10-year follow- 2,187 — et al., 2003 up of cohort studied by Cook et al. (1986), through 1995; Dow cohort findings compared with IARC International Study and NIOSH Dioxin Registry continued

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

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

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724 VETERANS AND AGENT ORANGE: UPDATE 2006 TABLE C-1 Continued Study Study Group Comparison Group (n)a Reference Design Description (n) BASF Studies Reviewed in Update 1998 Ott and Cohort Cancer incidence and 243 — Zober, 1996 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) BASF Studies Reviewed in Update 1996 Zober et al., Cohort Morbidity experience in the 158 161 1994 group studied Zober et al. (1990) BASF Studies Reviewed in VAO Zober et al., Cohort Mortality experience of 247 — 1990 TCDD-exposed workers (1954–1987) at BASF plant, compared with population of FRG Thiess et al., Cohort Mortality experience among 74 180,000 (Town); 1.8 1982 BASF employees potentially million (district); exposed to TCDD during 60.5 million (FRG); Nov. 17, 1953, accident, 2 groups of 74 each compared with population from other cohort and other workers not studies exposed IARC Studies Reviewed in Update 2006 ’t Mannetje Cohort New Zealand phenoxy 813 production et al., 2005 herbicide workers exposed workers; 699 TCDD and phenoxy sprayers herbicides IARC Studies Reviewed in Update 2000 Neuberger Austrian Morbidity up to 1993 of 159; 50 Two control groups, et al., 1999 chloracne exposed chemical workers participated in comparable to cohort assessed by health insurance examination 50 examination data and health examination, participants; laboratory measures, numbers not given interviews with participating survivors and control subjects

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

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726 VETERANS AND AGENT ORANGE: UPDATE 2006 TABLE C-1 Continued Study Study Group Comparison Group (n)a Reference Design Description (n) Becher Cohort Cancer mortality (through 2,479 — et al., 1996 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) Flesch- Cohort Cancer and circulatory 1,189 2,528 gas workers Janys et al., system mortality among 1995 chemical plant workers in Hamburg, Germany, exposed to herbicides contaminated with PCDD/F IARC Studies Reviewed in Update 1996 Kogevinas Case– Nested studies of the 11 cases, STS; 5 controls per case et al., 1995 control relationship between STS 32 cases, NHL and NHL and occupational exposures in the IARC cohort Kogevinas Cohort Cancer incidence and 701 — et al., 1993 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 Lynge, 1993 Cohort Cancer incidence in the 3,390 men; — group studied by Lynge 1,071 women (1985); follow-up extended through 1987 Kogevinas Cohort STS and malignant 14,439 (13,482 3,951 non-exposed et al., 1992 lymphoma mortality in exposed, employees an international cohort of 416 probably production workers and exposed, 541 herbicide sprayers (group unknown studied by Saracci et al., exposure) 1991)

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

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767 APPENDIX C TABLE C-3 Continued Study Comparison Group (n)a Reference Design Description Study Group (n) Wolfe Cohort Paternal serum dioxin and 932 1,202 et al., 1995 reproductive outcomes of Ranch Hand veterans, compared with Air Force veterans from Southeast Asia who did not spray herbicides Reports from AFHS Reviewed in VAO AFHS, Cohort Reproductive outcomes of AFHS 791 942 1992 participants AFHS, Cohort Baseline morbidity, follow-up 1,208 baseline 1,668 1984a, examination results baseline 1987, 1990, 1991b AFHS, Cohort Mortality updates, Ranch Hands 1,261 (original 19,101 1983, who sprayed herbicides in Vietnam, cohort) (original 1984b, compared with Air Force C-130 cohort) 1985, 1986, air and ground crew veterans in 1989, Southeast Asia who did not spray 1991a herbicides Michalek Cohort Mortality of Ranch Hands, 1,261 19,101 et al., 1990 compared with Air Force C-130 air and ground crew veterans in Southeast Asia Wolfe Cohort Health status of Ranch Hands at 995 1,299 et al., 1990 second follow-up, compared with Air Force C-130 air and ground crew veterans in Southeast Asia CDC Studies Reviewed in Update 2006 Boehmer Cohort Vietnam Experience Study—post- 18,313 et al., 2004 service mortality CDC Studies Reviewed in VAO Decoufle Cohort Association between self-reported 7,924 7,364 et al., 1992 health outcomes and perception of exposure to herbicides based on Vietnam Experience Study O’Brien Cohort Interview report and mortality for 8,170 7,564 et al., 1991 NHL based on Vietnam Experience Study continued

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768 VETERANS AND AGENT ORANGE: UPDATE 2006 TABLE C-3 Continued Study Comparison Group (n)a Reference Design Description Study Group (n) CDC, Case– Selected Cancers Study: population- 1,157 NHL; 1,776 1990a control based case–control study of all men 342 STS; 310 born 1921–1953; cases diagnosed HD; 48 nasal area covered by 8 cancer registries, carcinoma; 80 controls selected by random-digit nasopharyngeal dialing carcinoma; 130 primary liver cancer CDC, Case– Selected Cancers Study: population- 1,157 1,776 1990b control 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 CDC, Case– Selected Cancers Study: STS 342 1,776 1990c control CDC, Case– Selected Cancers Study: HD, nasal 310 HD; 48 nasal 1,776 1990d control cancer, nasopharyngeal cancer, carcinoma; 80 primary liver cancer nasopharyngeal carcinoma; 130 primary liver cancer CDC, Cohort Vietnam Experience Study: random 2,490 1,972 1989b sample, US Army enlisted men, 1965–1971 CDC, Cohort Vietnam Experience Study: random 2,490 1,972 1988a sample, US Army enlisted men, 1965–1971, psychosocial outcomes CDC, Cohort Vietnam Experience Study: physical 2,490 1,972 1988b health outcomes CDC, Cohort Vietnam Experience Study: 12,788 children 11,910 1988c reproductive outcomes children CDC, 1987; Cohort Vietnam Experience Study: 9,324 8,989 Boyle mortality et al., 1987 Erickson Case– CDC birth defects study, children 7,133 4,246 et al., 1984 control born in the Atlanta, Georgia, area a,b 1968–1980, comparing paternal Vietnam experience and potential Agent Orange exposure for birth defects cases and normal controls

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

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

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771 APPENDIX C TABLE C-3 Continued Study Comparison Group (n)a Reference Design Description Study Group (n) Bullman Cohort Mortality experience in Army I 6,668 deaths 27,917 et al., 1990 Corps Vietnam veterans, compared deaths with Army Vietnam-era veterans Farberow Case– Psychological profiles, military 22 Vietnam 21 Vietnam et al., 1990 control factors associated with suicide suicides; 19 MVA; 20 and MVA fatalities in Los Angeles Vietnam-era Vietnam-era County Vietnam-era veterans suicides MVA (1977–1982) Thomas Cohort Morbidity and mortality experience 894 — and Kang, (1968–1987) in Army Chemical 1990 Corps Vietnam veterans compared with US men True et al., Cross- PTSD and Vietnam combat 775 1,012 1988 sectional experience among Vietnam-era veterans Breslin Cohort Mortality experience (1965–1982) 24,235 26,685 et al., 1988 in Army and Marine Corps Vietnam Burt et al., veterans, compared with Vietnam- 1987 era veterans who did not serve in Southeast Asia, standardized by age and race; nested NHL case–control study Kang et al., Case– STS cases (1975–1980) diagnosed 217 599 1987 control 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 Kang et al., Case– STS (1969–1983) in Vietnam- 234 13,496 1986 control era veterans, for association with branch of Vietnam service as a surrogate for Agent Orange exposure American Legion Studies Reviewed in VAO Snow et al., Cohort PTSD in association with traumatic 2,858 Study group 1988 combat experience among subdivided American Legion members serving for internal in Southeast Asia (1961–1975) comparison continued

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

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773 APPENDIX C TABLE C-3 Continued Study Comparison Group (n)a Reference Design Description Study Group (n) State Studies Reviewed in VAO Fiedler and Cohort New Jersey: outcomes in select 10 Pointman I 17 Pointman Gochfeld, group of herbicide-exposed 55 Pointman II I 1992 Army, Marine, and Navy Vietnam 15 Pointman Kahn et al., veterans, compared with veterans II 1992a,b,c self-reported as unexposed Clapp Case– Massachusetts: selected cancers 214 727 et al., 1991 control identified (1982–1988) among Vietnam veterans, compared with Massachusetts Vietnam-era veterans with cancers of other sites Deprez Descriptive Maine: Vietnam veterans, compared 249 113 Atomic et al., 1991 with atomic test veterans and test veterans general population, for health status and reproductive outcomes Levy, 1988 Cross- Massachusetts: PTSD in chloracne 6 25 sectional as indicator of exposure to TCDD; control Vietnam veterans Anderson Cohort Wisconsin: mortality experience, 110,815 white 342,654 et al., veterans compared with non- male veteran white male 1986a veterans (Phase 1); mortality deaths; 2,494 non-veteran experience of Vietnam veterans and white male deaths; Vietnam-era veterans, compared Vietnam-era 109,225 with non-veterans and other veteran deaths; white veterans (Phase 2) 923 white male male other (superseded by Anderson et al., Vietnam veteran veteran 1986b) deaths deaths Anderson Cohort Wisconsin: mortality experience in 122,238 — et al., Vietnam-era veterans and Vietnam Vietnam-era 1986b veterans, compared with US veterans; 43,398 men, Wisconsin men, Wisconsin Vietnam veterans non-veterans, and Wisconsin other veterans Goun and Case– Pennsylvania: STS, NHL, selected 349 349 Kuller, control rare cancer cases, compared with Deceased 1986 controls without cancer for Vietnam experience in men (1968–1983) Holmes Cohort West Virginia: mortality experience 615 Vietnam — et al., 1986 (1968–1983) of veterans, Vietnam veterans veterans, Vietnam-era veterans, 610 Vietnam era compared with non-veterans; veterans Vietnam veterans compared with Vietnam-era veterans continued

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

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775 APPENDIX C TABLE C-3 Continued Study Comparison Group (n)a Reference Design Description Study Group (n) Aschengrau Case– Cases with late adverse pregnancy 857 congenital 998 and control outcomes compared with normal anomalies Monson, control births, for association 61 stillbirths; 48 1990 with paternal Vietnam service neonatal deaths (1977–1980) Goldberg Cohort Male twin pairs who served in 2,092 2,092 et al., 1990 Vietnam era (1965–1975), for association between Vietnam service and PTSD Aschengrau Case– Association between husband’s 201 1,119 and control military service and spontaneous Monson, abortion at or by 27 weeks, 1989 compared with women delivering at 37 weeks STUDIES OF AUSTRALIAN VIETNAM VETERANS Studies of Australian Vietnam Veterans Reviewed in Update 2006 ADVA, Cohort Cancer incidence from 1982 to 59,179 total; 2005a 2000 among Australian male Army, 41,084 (Army); Navy, and Air Force veterans who 13,538 (Navy); served in Vietnam between May 4,570 (Air Force) 1962 and July 1973 ADVA, Cohort Retrospective mortality study of 59,179 2005b male Australian personnel who served between May 1962 and July 1973 vs. Australian men in general community ADVA, Cohort Retrospective cohort study of male 43,969 total; 2005c National Service personnel who 19,240 veterans; served in the Vietnam era between 24,729 1966 and July 1973. Examined all non-veterans deaths identified from the end of service to 31 December 2001 and all cancers diagnosed from 1982 to 31 December 2000 Leavy Case– Cancer registry of Western Australia 606 471 et al., 2006 control and prostate cancer; deployment to Vietnam continued

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776 VETERANS AND AGENT ORANGE: UPDATE 2006 TABLE C-3 Continued Study Comparison Group (n)a Reference Design Description Study Group (n) Studies of Australian Vietnam Veterans Reviewed in Update 2000 AIHW, Cohort Validation of the male veterans’ 6,842 — 1999 study (CDVA, 1998a) by medical documents, doctors’ certification, records on a disease or death registry CDVA, Cohort Self-reported data on male members 49,944 mailed; — 1998a of the Australian Defence Force 39,955 and the Citizen Military Force responded 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 CDVA, Cohort Self-reported data on female 278 mailed — 1998b members of the Australian Defence 225 responded 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 Studies of Australian Vietnam Veterans Reviewed in Update 1998 Crane Cohort Mortality experience (through 59,036 men — et al., 1994) of Australian veterans who 484 women 1997a served in Vietnam Crane Cohort Mortality experience (through 1994) 18,949 24,646 et al., of Australian national servicemen 1997b who served in Vietnam O’Toole Cross- Survey of self-reported health status 641 — et al., sectional (1989–1990) of Australian Army 1996a,b,c Vietnam veterans Studies of Australian Vietnam Veterans Reviewed in VAO Field and Cohort Tasmanian Vietnam veterans, 357 281 Kerr, 1988 compared with neighborhood controls for adverse reproductive and childhood health outcomes Fett et al., Cohort Mortality experience in Vietnam 19,205 25,677 1987a veterans, compared with Vietnam- era veterans through 1981

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777 APPENDIX C TABLE C-3 Continued Study Comparison Group (n)a Reference Design Description Study Group (n) Fett et al., Cohort Cause-specific mortality experience 19,205 25,677 1987b in Vietnam veterans, compared with Vietnam-era veterans through 1981 Forcier Cohort Mortality in Vietnam veterans by 19,205 Internal et al., 1987 job classification, location, time of comparison service Donovan Case– Congenital anomalies in children 8,517 8,517 et al., 1983, control (1969–1979), compared with 1984 infants born without anomalies, for association with paternal Vietnam service STUDIES OF VIETNAM VETERANS FROM OTHER COUNTRIES Other Vietnam-Veteran studies Reviewed in Update 2004 Kim H-A Cohort Immunotoxicologic effects of 51 (24 veterans– 36 et al., 2003 Agent Orange exposure on Korean patient; 27 Vietnam veterans veterans–normal) Kim J-S Cross- Agent Orange exposure and Korean 1,224 154 et al., 2003 sectional Vietnam veterans Mo et al., Cohort Skin and general disease patterns 332 None 2002 among Korean Vietnam veterans Other Vietnam-Veteran studies Reviewed in Update 1998 Chinh Cohort Antinuclear antibodies and sperm 25 63; 36 et al., 1996 autoantibodies among Vietnamese veterans who served 5–10 years in a “dioxin-sprayed zone” 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.