Veterans and Agent Orange Update 2002 (2003) / Chapter Skim
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4. Overview of Epidemiologic Studies
4. Overview of Epidemiologic Studies
Pages 103-214
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From page 103... ...
DVA also examined the morbidity and mortality experience of a subgroup of Vietnam veterans potentially exposed to high concentrations of herbicides Tom some US Army Chemical Corps units (Thomas and Kang, ~ 990~. In an extension of Thomas and Kang (]
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From page 104... ...
(2001) conducted a preliminary long-term health study of US Army Chemical Corps Vietnam veterans.
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From page 105... ...
and late adverse pregnancy outcomes in spouses of Vietnam veterans (Aschengrau and Monson, 1990) and PTSD among monozygotic twins who served dunng the Vietnam era (Goldberg et al., 1990~.
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From page 106... ...
a PRODUCTION WORKERS New NIOSH Studies Steenland et Cohort A study to reexamine and compare diabetes 267 NIOSH workers 227 NIOSH al., 2001 data from the NIOSH cohort and the 990 Ranch Hands Cornpansons United States Air Force Ranch in order to 1,275 Ranch Hand reconcile differences between the two Compansons study methods and protocals. NIOSH Studies Reviewed in Update 2000 Calvertet Cohort Continuing follow-up of workers employed 281 260 al., 1999 more than 15 years ago at 2 plants that manufactured substances contaminated with TCDD to evaluate associations between serum TCDD and serum glucose (diabetes)
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From page 107... ...
compared to non-exposed workers at same Monsanto plant Study of mortality experience of all white 884 male workers (1955-1977) employed at a Monsanto plant through Dec.
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From page 108... ...
population, 2001 chemical workers who manufactured or 40,600 unexposed formulated 2 4-D between 1945 and 1994. chemical workers Dow Studies Reviewed in Update 1998 Ramlow et Cohort Study of mortality in a cohort of workers 770 36,804 unexposed al., 1996 exposed topentachlorophenol(PCP)
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From page 109... ...
members of 1953 accident cohort 42 exposed (1988) extruder personnel No comparison group BASF Studies Reviewed in Update 1998 Ott and Cohort Zober, 1996 Cancer incidence and mortality experience 243 (through 1992)
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From page 110... ...
2,528 gas Hamburg, Germany exposed in varying workers degrees to herbicides contaminated with PCDD/F IARC Studies Reviewed in Update 1996 Kogevinas Case-control Two nested case-controlstudiesofthe STS:llcases S controls per case et al., 1995 relationship between STS and NHL and NHL: 32 cases occupational exposures in members of the L\RC cohort Kogevinas Cohort Cancer incidence and mortality experience 701 et al., 1993 of female workers in seven countries, potentially exposed to chlorophenoxy herbicides, chlorophenols, and dioxin compared to national death rates and cancer .
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From page 111... ...
L\RC Studies Reviewed in LAO Buenode Cohort Mortality experience of production workers 2,310 Mesquita et exposed to phenoxy herbicides and al., 1993 chlorophenols in We Netherlands compared to national rates Coggon et Cohort Mortality experience among four cohorts of 1,104 Factory A al., 1991 workers potentially exposed~l963-1985) 271 Factory B to phenoxy herbicides and chlorophenols 345 Factory C compared to national (England and Wales)
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From page 112... ...
a Studies from Other Chemical Plants Reviewed in Update 1998 Tonnet all, Cohort Study ofthelong-termimmune system 11 10 1996 effects of TCDD in industrial workers involved In production and maintenance operations at a German chemical factory producing 2,4,5-T between 1966 and 1976 Studies from Other Chemical Plants Reviewed in LAO Jennings et Cohort Assessment ofimrnunological 18 15 al., 1988 abnormalities among workers exposed to TCDD during accident manufacturing 2,4,5-T compared to matched controls l~hornas, Cohort Assessment of mortality experience as of 1,412 -- 1987 Jan. 1, 1981, for white men employed in fragrance and flavors plant with possible exposure to TCDD, compared to U.S.
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From page 113... ...
a Arbuckle et Cohort Spontaneous abortions in couples living on 2,110 women; 3,936 none al., 1999 full-time family-run farms in Ontario, pregnancies Canada Cohort Studies of Agricultural Workers Reviewed in Update 1998 Gambini et Cohort Cancer mortality (1957-1992) among a 958 al., 1997 cohort of rice growers in the Novara Province of northern Italy Kristensen Cohort Birth defects among the offspring of 192,417 births 61,351 births et al., 1997 Norwegian farmers born after 1924 Faustiniet Cohort Study ofimmune system components and 10 Internal al., 1996 functions among farmers who mixed and comparison applied commercial formulations containing the chlorophenoxy herbicides 2,4-D and MCPA Cohort Studies of Agricultural Workers Reviewed in Update 1996 Dean, 1994 Cohort Study of mortality from brain and (population size hematopoietic cancers of agricultural unclear)
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From page 114... ...
among agricultural workers in Sweden compared to rates expected from the 1960 population census Burmeister, Cohort Study ofmortalityoffarmers compared to 6,402 13,809 1981 nonfarmers in Iowa (1971-1978) New Cohort Studies of Forestry Workers Thorn et al., Cohort Study of mortality and cancer incidence in 261 243 2000 a cohort of Swedish lumberjacks exposed to phenoxy herbicides Cohort Studies of Forestry Workers Reviewed in LAO Green, 1991 Cohort Green, 1987 Cohort Mortality experience of male forestry 1,222 workers (195~1982)
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From page 115... ...
in Finland (1955-1971) , through 1989, compared to general population rates for morbidity and mortality Garry et al., Cross- Evaluation of health outcomes resulting 719 No comparison 1994 sectional from exposure to pesticides by male group pesticide appliers in Minnesota Cohort Studies of Herbicide/Pesticide Sprayers Reviewed in LAO Swaen et al., Cohort 1992 Cancer mortality experience (through 1,341 1987)
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From page 116... ...
(1987) 20,245 -- al., 1988b cohort through 1984 Wild et Cohort Risk of HD and NHL among Swedish 20,245 -- al., 1987 pesticide appliers from date of license through 1982, compared to expected number of cases in the total population Blair et al., Cohort Mortality experience of white male Florida 3,827 -- 1983 pesticide appliers compared to U.S.
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From page 117... ...
and NHL lymphomas (1987-1990) PMR Study of neurodegenerative diseases and analysis win occupational risk factors from 27 states nested case control Case-control Study of Parkinson's disease and various 380 rural factors, including exposure to herbicides and wood preservatives in Germany Liou et al., 1997 Tatham et al., 1997 Schulte et al., 1996 Seidler et al., 1996 based on 130,420 death certificates 764 240 1,659 977 379 neighborhood controls; 376 regional controls Case-Control Studies Reviewed in Update 1996 Hardell et Case-control al., 1994 Mellemgaar Case-control d et al., 1994 Study of the association between 105 occupational exposures and parameters related to NHL in white males in Sweden Study of cases of renal-cell carcinoma (2~ 365 79 years)
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From page 118... ...
75 men 55 women Comparison Group (N) 150men 1 10 women 824 187 Case-Control Studies Reviewed in MAO Cantor et al., Case-control Population-based case-control study of 1992 NHL in Iowa and Minnesota men for association with farmmg exposures Smith and Case-control Study of STS and malignant lymphomas in 82 Christophers men diagnosedl982-1988inAustralia, , 1992 compared to other cancers for association with exposure to phenoxy herbicides and chlorophenols Brown et al., Case-control Population-based case-control study of 578 1990 leukemia in Iowa and Minnesota men for association with farming exposures Eriksson et Case-control Study of male cases of STS (25-80 years)
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From page 119... ...
study for association with phenoxy herbicides in farm workers Woods and Polissar, 1989 Alavanja et PMR Mortality experience of USDA extension 1 495 al., 1988 analysis with agents (1970-1979) evaluated for specific nested case- cancer excess; case-control study of control specific cancers identified from PMR analysis Dubrow et Case-control Death certificate study (1958-1983)
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From page 120... ...
for association with herbicide use, compared to women without ovarian cancer Hardell et Case-control Study of primary liver cancer diagnosed 98 al., 1984 2,168 2,936 1,961 197~1981 in men 25-80 years, residing in northern Sweden compared to populationbased controls for association with occupational exposure to phenoxyacetic acids and chlorophenols 120 1,961 127 200
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From page 121... ...
Burmeister Case-control Study of multiple myeloma, NHL, prostate 550 multiple myeloma 1,100 et al., 1983 and stomach cancer mortality (1964 1978) 1,101 NHL in white men 30 years or older compared to 4,827 prostate 2,202 mortality from other causes for association 1,812 stomach 9,654 with farming practices including herbicide 3,624 use in Iowa Hardell and Case-control Study of HD diagnosed in men 25-85, Bengtsson, between 1974 and 1978 in northern 1983 Sweden, compared to population-based sample without cancer for association with occupational exposure to phenoxyacetic acid and chlorophenols Smith et al., Case-control Preliminary report of men with STS 80 1983 reported 197~1980 in New Zealand, compared to controls with other cancers for association with phenoxyacetic acid exposure Burmeister Case-control Study of leukemia deaths (1964-1978)
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From page 122... ...
Mailed exposure questionnaire on lifetime occupational history, oral cancer risk factors, pesticide use, smoking, SES, and place of residence Rix et al., Cohort Cancer incidence rates of blue collar 14,788 (14,362 were 1998 workers at three Danish paper mills were identified for follow compared to population rates from national up) population and mortality registers Paper/Pulp Studies Reviewed in LAO Jappinen Cohort Cancer incidence (through 1987)
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From page 123... ...
R) after 15 years of follow-up through 1991 232,747 Seveso Studies Reviewed in Update 1996 Bertazzi et al., Cohort Study of cancer incidence in Seveso residents 724 zone A 181,579 1993 (aged 20 to 74 years)
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From page 124... ...
15 Stockbauer et al., Cohort Study of adverse reproductive outcomes (1972- 402 births 804 births 1988 1982) among mothers potentially exposed to TCDD-contaminated areas of Missouri (1971)
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From page 125... ...
Chapaevsk, Russia Russia Other Environmental Studies Reviewed in Update 2000 Schreinemachers Cross 2000 sectional Study of cancer mortality rates in 4 northern wheat-producing states using wheat acreage per county as surrogate for exposure. Other Environmental Studies Reviewed in Update 1998 Gallagher et al., Case- Community-based study of primary basal cell BCC: 226 406 1996 control carcinoma(BCC)
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From page 126... ...
a Waterhouse et PMR Study of NHL, HD, and CLL in a rural 42 males 4 controls per al., 1996 analysis Michigan community 32 females case with nested case control Cohort Svensson et al. 1995 We is glasKuperus et al., 1995 Wolf and Karmaus, 1995 Cohort Crosssectional Mortality and cancer incidence experience in two cohorts of Swedish fishermen Study of the immunological effects of pre- and postnatal PCB or TODD exposure in 207 Dutch infants from birth to 18 months Study of the effects of inl~alative exposure to 221 TODD and related compounds in wood preservatives on cell-mediated immunity in _ day care center employees East coast: 2,896 West coast: 8,477 105 breast-fed 102 bottle-fed 189 Other Environmental Studies Reviewed in Update 1996 Butterfield et al., Case- Study of possible environmental risk factors 63 1993 control associated with young-onset Parkinson's disease Peper et al., 1993 Descriptive Study of environmental exposure to dioxins and 19 furans and potential association with adverse neuropsychological effects in Germany 68 None Other Environmental Studies Reviewed in LAO Lampi et al., Nested Study of cancer incidence among a community 56 colon cancer; 688 1992 case- in Finland exposed to water and food 40 bladder control/ contaminated with chlorophenols (1987)
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From page 127... ...
Comparison Group (N) a UNITED STATES STUDIES New Ranch Hand Studies Michaleket Cohort Based onphysicalexamination~roughl992 and 931 1,199 al., 2001a medical record reviewed through March of 1993, analyzed association between serum dioxin levels and hepatic abnormalities 127
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From page 128... ...
a Michalek et Cohort Based on physical examination in 1982, 1985, 926 1,067 al., 2001b 1987,1992, and 1997 and medical records through 1997, analyzed association between serum dioxin 918 1,144 levels and peripheral neuropathy 872 1,131 834 1,110 761 1,086 Michaleket Cohort Based onphysicalexaminationin 1982, 1985, 1,046 1,223 al., 2001c 1987, and 1992 and medical record through 1997, analyzed association between serum dioxinlevels 1,017 1,292 and hematological function 996 1,298 953 1,280 Barrett et all, Cohort Based on tests ofcognitive functioning m1982, 937 1,052 2001 and dioxin levels measured in 1987 and 1992, analyzed association between serum dioxin levels and cognitive functioning Steenland et Cohort A study to reexamine and compare diabetes data 267 NIOSH 227 NIOSH al., 2001 from the NIOSH cohort and the United States Air workers Compansons Force Ranch in order to reconcile differences 990 Ranch Hands 1,275 Ranch between the two study methods and protocals. Hand Chansons Ranch Hand Studies Reviewed in Update 2000 AFHS, 2000 Cohort Evaluation of 266 health-related end points, 995 1,299 including assessments often clinical areas: general health, neoplasia, neurological, psychological, gastrointestinal, cardiovascular, hematologic, endocrine, immunologic, and pulmonary Longnecker Cohort Based on physical examination and medical 1,281 and record review through 1992, analyzed association 1,197 Michalek, between serum dioxin levels and diabetes mellitus 2000 among the comparison group (no Ranch Hands)
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From page 129... ...
cohort) conflict, compared with Air Force C-130 air and ground crew veterans in Southeast Asia who did not participate in herbicide spraying missions Wolfe et al., Cohort Paternal serum dioxin levels and reproductive 932 1,202 1995 outcomes of Ranch Hand veterans compared with Air Force veterans from Southeast Asia who did not participate in herbicide spraying missions Ranch Hands Studies Reviewed in MAO AFHS, 1992 Cohort Reproductive outcomes of participantsin~e Air 791 942 Force Health Study AFHS, Cohort Baseline morbidity and follow-up exam results of 1,208 (baseline)
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From page 130... ...
a Wolfe et al., Cohort Heal status of Ranch Hands at second follow- 995 1,299 1990 up, compared with Air Force C-130 air and ground crew veterans in Southeast Asia Centers for Disease Control (CDC) Studies Renewed in MAO Decoufle et Cohort Association between self-reported health 7,924 7,364 aL, 1992 outcomes and perception of exposure to herbicides based on Vietnam Expenence Study Owned et Cohort Interview report and mortality for NHL based on al., 1991 - Vietnam Experience Study CDC, 1990a Case-control Selected Cancers Study -- population-based casecontrol study of all men born between 1921 and 1953; cases diagnosed area covered by eight cancer registries and controls selected by random- 80 digit dialing CDC, 1990b Case-control Selected Cancers Study -- population-based casecontrol study of all men born between 1921 and 1953; cases diagnosed area covered by eight cancer registries and controls selected by randomdigit dialing: NHL CDC, 1990c Case-control Selected Cancers Study: soft tissue sarcomas CDC, 1990d Case-control Selected Cancers Study: HD, nasal cancer, nasopharyngeal cancer, and primary liver cancer CDC, 1989b Cohort Vietnam Experience Study -- random sample of U.S.
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From page 131... ...
a Kang et al., Cohort Study of gynecologic cancers among female 484 5,946 2000b Vietnam veterans compared to veteran controls Kang et al., Cohort A study evaluating the health of Anny Chemical 2,872 2,737 2001 Corps Vietnam veterans compared to Army Chemical Corps veterans who did not serve in Vietnam DVA Studies Reviewed in Update 1998 Dalager and Cohort Morbidity and mortality experience (1968-1987) 2,872 2,737 Kang, 1997 of Army Chemical Corps Vietnam veterans compared to U.S.
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From page 132... ...
in Vietnam era veterans 234 1986 for association with branch of Vietnam service as a surrogate for Agent Orange exposure 599 13,496 American Legion Studies Reviewed in LAO Snow et al., Cohort Assessment of PTSD in association with 2,858 Study group 1988 traumatic combat experience among American subdivided for Legionnaires serving in Southeast Asia (1961- internal 1975) comparison Stellman et Cohort Assessment of physical health and reproductive 2,858 3,933 al., 1988b outcomes among American Legionnaires who served in Southeast Asia (1961-1975)
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From page 133... ...
among 214 1991 Massachusetts Vietnam veterans, compared to Massachusetts Vietnam era veterans with cancers of other sites Study of Maine Vietnam veterans compared to 249 atomic test veterans and general population for health status and reproductive outcomes Study of PTSD in chloracne as indicator of 6 exposure to TCDD and control Vietnam veterans in Massachusetts Mortality experience of Wisconsin veterans compared to nonveterans (Phase 1~; mortality experience of Wisconsin Vietnam veterans and Vietnam era veterans compared to nonveterans and other veterans (Phase 2) Deprez et Descriptive al., 1991 Levy, 1988 Crosssectional Anderson et Cohort al., 1986a Anderson et Cohort al., 1986b Mortality experience of Wisconsin Vietnam era veterans and Vietnam veterans compared to U.S.
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From page 134... ...
and mental health, and that of their partners and children Australian Studies Reviewed in Update 1998 Crane et al., Cohort 1997a Crane et al., Cohort 1997b O'Toole et Crossal., sectional 1996a,b,c Mortality experience (through 1994) of Australian 59,036 males veterans who served in Vietnam 484 females Mortality experience (through 1994)
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From page 135... ...
Australian Studies Reviewed in LAO Field and Cohort Study of Tasmanian Vietnam veterans compared 357 281 Kerr, 1988 to neighborhood controls for adverse reproductive and childhood health outcomes Fett et al., Cohort Australian study of mortality experience of 19,205 25,677 1987a Vietnam veterans compared to Vietnam era veterans through 1981 Felt et al., Cohort Australian study of cause-specific mortality 19,205 25,677 1987b experience of Vietnam veterans compared to Vietnam era veterans through 1981 Forcieret Cohort Australian study ofmortalityin Vietnam veterans 19,205 Internal al., 1987 by job classification, location, and time of service comparison Donovan et Case-control Australian study ofcasesofcongenitalanomalies 8,517 8,517 al., 1983, in children born ~ 1969-1979) , compared to 1984 infants born without anomalies for association with paternal Vietnam service Other Vietnam Veterans Studies Reviewed in Update 1998 Chinh et al., Cohort Study of antinuclear antibodies and sperm 25 63 1996 autoantibodies among Vietnamese veterans who 36 served 5-10 years in a "dioxin-sprayed zone" a The dash ( -- )
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From page 136... ...
American Journal of Industrial Medicine 26:243-253. Assennato G
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From page 137... ...
1996. Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.
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From page 138... ...
workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. American Journal of Industrial Medicine 25:559571.
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From page 139... ...
workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Environmental Health Perspectives 106(Suppl 2~:635643.
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From page 140... ...
1986. Evaluation of the mortality experience of workers exposed to the chlorinated dioxins.
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From page 141... ...
American Journal o f Industrial Medicine 22:305-312. Evans RG, Webb KB, Knutsen AP, Roodman ST, Roberts DW, Bagby JR, Garrett WA Jr, Andrews IS Jr.
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From page 142... ...
1991. A cohort mortality study of forestry workers exposed to phenoxy acid herbicides.
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From page 143... ...
1997. Mortality and cancer incidence among sawmill workers exposed to chlorophenate wood preservatives.
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From page 144... ...
women Vietnam veterans. American Journal Industrial Medicine 38~4~:447~54.
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From page 145... ...
1992. Cancer mortality from soft-tissue sarcoma and malignant lymphomas in an international cohort of workers exposed to chlorophenoxy herbicides and chlorophenols.
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From page 146... ...
2001b. Serum dioxin and peripheral neuropathy in veterans of Operation Ranch Hand.
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From page 147... ...
American Journal of Industrial Medicine 5:161-182. Musicco M, SantM, Molinari S
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From page 148... ...
1991. Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols.
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From page 149... ...
1992. Phenoxy herbicides and chlorophenols: a case-control study on soft tissue sarcoma and malignant lymphoma.
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From page 150... ...
American Journal of Industrial Medicine 3:179-189. Thomas TL.
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From page 151... ...
1995. Paternal serum dioxin and reproductive outcomes among veterans of Operation Ranch Hand.
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From page 152... ...
1980. The mortality experience of workers exposed to tehachlorodibenzodioxin in a trichlorophenol process accident.
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From page 153... ...
and in Chapter 5 of Veterans and Agent Orange: Updlate 1996 (IOM, 1996) , Update 1998 (IOM, 1999)
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From page 154... ...
Biomarkers of exposure can provide crucial information for both occupational and environmental studies, in that a quantitative exposure estimate can be assigned to each incliviclual in the study. The most important biomarker in the context of Vietnam veterans' exposure to Agent Orange is the measurement of TCDD in serum.
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From page 155... ...
Studies of occupational exposure to dioxins focus primarily on chemical-plant workers who produce phenoxy herbicides or chiorophenols. Other occupationally exposed groups include workers in agriculture and forestry who spray herbicides, sawmill workers exposed to chlorinated dioxins from contaminated wood preservatives, and pulp and paper workers exposed to dioxins through the puIp-bleaching process.
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From page 156... ...
The full cohort was established by using the International Register of Workers Exposed to Phenoxy Herbicides and Their Contaminants. Twenty cohorts were combined for this analysis: one each from Canada, Finland, and Sweden; two each from Australia, Denmark, Italy, the Netherlands, and New Zealand; and seven from the United Kingdom.
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From page 157... ...
Exposure was reconstructed by using individual job records, company e xposure q uestionnaires d eveloped s pacifically for t he s tudy, and, in some cohorts, measurements of TCDD and other dioxin and Bran congeners in serum and adipose tissue and in the workplace. The 21,863 workers exposed to phenoxy herbicides or chIorophenols were classified in three categories: those exposed to TCDD or higher-chIonnated dioxins (N= 13,831)
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From page 158... ...
and most recently in 2001 (Burns et al., 2001~; neither of these studies modified the exposure-assessment procedures of the ong~nal study. A cohort study of manufacturing workers exposed to pentachloropheno} was also conducted by Dow (Ramlow et al., 1996~.
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From page 159... ...
The Ontario Farm Family Health Study has produced several studies relevant to phenoxyacetic acid herbicide exposures, including 2,4-D. A study of male pesticide exposure and pregnancy o utcome ~ Savitz et al., ~ 997)
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From page 160... ...
Herbicide and Pesticide Spraying Studies of herbicide sprayers are relevant because it can be presumed that appliers had more sustained exposure to herbicides; however, they were also likely to be exposed to a multiplicity of chemicals, and this would complicate the assessment of any individual or group exposure to specific phenoxy herbicides or TCDD. Some studies have attempted to measure exposure of appliers on the basis of information Dom work records on acreage sprayed or number of days of spraying.
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From page 161... ...
A recent study of Canadian farmers examined pesticide exposures of men (McDuffie et al., 2001~. D ala o n p esticide e xposure w ere c ollected b y q uestionnaires, including information on specific chemicals (including 2,4-D)
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From page 162... ...
Those findings demonstrate a significant association between zone of residence and serum TCDD, but much of the variability in TCDD concentrations is still unexplained by these models.
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From page 163... ...
(2000) reported on an investigation of apparent clusters of cases of soft-tissue sarcoma and non-Hodgkin's lymphoma in the vicinity of a municipal solid-waste incinerator in Doubs, France.
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From page 164... ...
No attempt was made to create exposure categories based on residential location within the city, nor with occupational or lifestyle factors that might have influenced TCDD exposure. Other Studies Two other epidemiologic studies have been conducted in association with industrial-facility emissions.
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From page 165... ...
The herbicides were used by the US Air Force's Operation Ranch Hand to defoliate inland hardwood forests, coastal mangrove forests, and to a lesser extent cultivated land by spraying from aircraft and helicopters. According to military records of Operation Ranch Hand, from August 1965 to February 1971 a total of 17.6 million gallons of herbicide was sprayed over about 3.6 million acres in Vietnam (NAS, 1974~.
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From page 166... ...
Ground Spraying of Herbicides The number of US military personnel exposed to herbicides is impossible to determine precisely, but most of those assigned to Operation Ranch Hand can be presumed to have been exposed to Agent Orange and other herbicides. In addition, the US Army Chemical Corps, using hand equipment and helicopters, conducted smaller spray operations, such as defoliation around special forces c amps; c learance of perimeters of airfields, depots, and other bases; and smallscale crop destruction (Thomas and Kang, 1990; Warren, 1968~.
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From page 167... ...
(1995) developed several indexes of herbicide exposure for members of the Ranch Hand cohort and tried to relate them to the measurements of serum TCDD from 1987 to ~ 992.
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From page 168... ...
Other Vietnam Veterans Surveys of Vietnam veterans who were not part of the Ranch Hand or Army Chemical Corps groups indicate that 25-55% believe that they were exposed to herbicides (CDC, 1989; Erickson et al., 1984a,b; Stellman and Stellman, 1986~. A few attempts have been made to estimate exposure of the Vietnam veterans who were not part of the Ranch Hand or Army Chemical Corps groups.
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From page 169... ...
The CDC Birth Defects Study developed an exposure opportunity index to score Agent Orange exposure (Erickson et al., ~ 984a,b)
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From page 170... ...
1996. Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.
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From page 171... ...
1986. Evaluation of the mortality experience of workers exposed to the chlorinated dioxins.
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From page 172... ...
2001b. Serum dioxin and peripheral neuropathy in veterans of Operation Ranch Hand.
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From page 173... ...
1991. Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols.
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From page 174... ...
American Journal of Industrial Medicine 18:665-673.
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From page 175... ...
In assessing a possible relation between herbicide exposure and risk of cancer, one key issue is the magnitude of exposure of those included in a study. A s noted in Chapter 5, the detail and accuracy of exposure assessment vary widely among the studies reviewed by the committee.
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From page 176... ...
Great uncertainties remain about the magnitude of potential risk posed by exposure to herbicides and TODD in the occupational, environmental, and veteran studies reviewed by the committee. Many of those studies have inadequate controls for important confounders, and the information needed to extrapolate from the exposure in the studies to that of individual Vietnam veterans is lacking.
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From page 177... ...
Their mortality experience is compared with national rates and with that in more than 40,000 other company employees who worked at the same location. There were 330 deaths in the 1,517 male employees who have an average follow-up of 26.2 years.
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From page 178... ...
On the basis of its evaluation of the epidemiologic evidence reviewed in this and previous Veterans and Agent Orange reports, the present committee finds that there is still limiter! or suggestive ~78
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From page 179... ...
a OCCUPATIONAL New Studies Burns et al., 2001 Dow 2,4-D production workers cancer of the digestive organs Studies Reviewed in Update 2000 Steenland et al., 1999 Hooiveld et al., 1998 Rixetal.,1998 Male Female Studies Reviewed in Update 1998 Gambini et al., 1997 Kogevinas et al., 1997 Becher et al., 1996 Ott and Zober, 1996 Ramlow et al., 1996 US chemical production workers Dutch chemical production workers Danish paper mill workers Italian rice growers IARC cohort Workers exposed to TCDD (or higher-chlorinated .
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From page 180... ...
Studies Reviewed in Update 1996 Blair et al., 1993 US farmers in 23 states White males 657 1.0 (1.0-1.1) Nonwhite females 23 1.9 (1.2-2.8)
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From page 181... ...
Studies Reviewed in MAO Breslin et all, 1988 Army Vietnam veterans 88 1.1 (0.9-1.5) Marine Vietnam veterans 17 0.8 (0.~1.6)
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From page 182... ...
Studies Reviewed in Update 1998 Gambini et al., 1997 Italian rice growers Kogevinas et al., 1997 IARC cohort Workers exposed to TCDD (or higher-chlorinated dioxins) Becher et al., 1996 Ott and Zober, 1996b Ramlow et al., 1996 Studies Reviewed in Undate 1996 workers not exposed to TCDD (or higherchlorinated dioxins)
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From page 183... ...
R females 12 0.7 (0.4-2.2) VIETNAM VETERANS Studies Reviewed in Update 2000 AFHS, 2000b Air Force Ranch Hand veterans 183 7 1.5 (0.4-s.s'
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From page 184... ...
a OCCUPATIONAL Studies Reviewed in Update 2000 Steenland et al., 1999 US chemical production workers Hooiveld et al., 1998 Dutch chemical production workers Rix et al., 1998 Danish paper mill workers Studies Reviewed in Update 1998 Kogevinas et al., 1997 IARC cohort Becher et al., 1996 Workers exposed to TODD (or higher-chlorinated dioxins) Workers not exposed to TCDD (or higher-chlorinated Cot)
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From page 185... ...
1997 Seveso residents 15-year follow-up Zone B males Zone B females Svensson et al., 1995 Zone R males Zone R females Swedish fishermen—mortality East coast West coast Swedish fishermen incidence East coast West coast Studies Reviewed in Update 1996 Bertazzi et al., 1993 Seveso residents—10-year follow-u~morbidity Zone B males 185 309 s 24 9 6 8 14 2 21 24 10 3 7 2 2 19 12 3 9 59 o o 367 o 1.0 (0.9-~.1)
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From page 186... ...
VIETNAM VETERANS Studies Reviewed in Update 2000 AFHS, 2000~ Air Force Ranch Hand veterans 7 1.5 (0.~5.5) AIHW, 19993 Australian Vietnam veterans male 188 221 expected (191-251)
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From page 187... ...
Studies Reviewed in LAO Ronco et al., 1992 Danish self-employed male farm workers 137 0.6 ~ < .05) Swaen et al., 1992 Dutch herbicide appliers 3 2.2 (0.4-6.4)
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From page 188... ...
Bertazzi et al., 1989b Seveso residents 10-year follow-up Zone B males 2 1.1 (0.3~.5) VIETNAM VETERANS Studies Reviewed in Update 1998 Crane et al., 1997a Australian military Vietnam veterans Crane et al., 1997b Australian national service Vietnam veterans 6 Studies Reviewed in Update 1996 38 1.4 (1.~1.9)
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From page 189... ...
No relevant occupational or Vietnam-veteran studies have been published since Update 2000 (TOM, 2001~. Synthesis The evidence from epidemiologic studies is inadequate to link herbicide exposure to hepatobiliary cancer; no new published information was found to change this opinion.
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From page 190... ...
a OCCUPATIONAL Studies Reviewed in Update 2000 Steenland et al., 1999 US chemical production workers Rix et al.. 1998 Danish paper-mill workers Males Females Studies Reviewed in Update 1998 Gambini et al., 1997 Italian rice growers Kogevinas et al., 1997 IARC cohort Workers exposed to TCDD (or higher-chlorinated dioxins)
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From page 191... ...
Collins et al., 1993 Monsanto 2,4-D production workers 2 1.4 (0.2-5.2) Studies Reviewed in TAO Ronco et al., 1992 Danish and Italian fang workers Danish male self-e~loyed farmers 23 0.4 (*
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From page 192... ...
Hoffman etal., 1986 Residents ofQuailRun Mobile Home Park O * VIETNAM VETERAN S Studies Reviewed in Update 2000 AFHS, 2000 Air Force Ranch Hand veterans 2 1.6 (0.2-11.4)
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From page 193... ...
Reported risk factors for nasal cancer include occupational exposure to nickel and chromium compounds (Hayes' 1997) ' wood dust (Demers et al.' 1995)
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From page 194... ...
TABLE 6-9 Selected Epidemiologic Studies Nasal and Nasopharyngeal Cancer Reference Study Population Exposed Estimated Relative Risk Casesa (95% CI) a OCCUPATIONAL Studies Reviewed in Update 2000 194
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From page 195... ...
VIETNAM VETERANS Studies Reviewed in Update 2000 AFHS, 2000 Air Force Ranch Hand veterans Studies Reviewed in Update 1998 Crane et al. 1997a Australian military Vietnam veterans Nasal cancer Nasopharyngeal cancer Australian national service Vietnam veterans Nasal cancer Nasopharyugeal cancer Crane et al.
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From page 196... ...
Research suggests that gastroesophageal reflex, human papillomavirus, a weakened immune system, and occupational exposure to asbestos and some chemicals and dusts may also increase incidence (ACS, 1998~. —~ ——A — TABLE 6-10 Average Annual Cancer Incidence (per 100,000)
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From page 197... ...
Strength of Evidence In Epidemiologic Studies Conclusions On the basis of its evaluation of the epidemiologic evidence reviewed in this and previous Veterans and Agent Orange reports, the committee finds that there is limited or suggestive evidence of an association between exposure to at least one of the chemicals of interest (2 4-D 2,4,5-T or its contaminant TCDD, picloram, or cacodylic acid) and laryngeal cancer.
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From page 198... ...
Studies Reviewed in LAO Fingerhut et al., 1991 NIOSH cohort 1-year exposure, 20-year latency 3 2.7 (0.~7.8) Manz et al., 1991 German production workers 2 2.0 (0.2-7.1)
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From page 199... ...
. Among the other risk factors are occupational exposure to asbestos, chromium' nickel, aromatic hydrocarbons, radioactive ores, and inorganic arsenic.
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From page 200... ...
Data on cigarette-smoking p atterns and other exposures were not reported, but arsenic was among the other chemicals to which some residents of Chapaevsk may have been exposed. Because of confounding by multiple exposures and because of the ecologic-study design, results ofthis study cannot be taken as strong evidence of an association with herbicide or TCDD exposure.
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From page 201... ...
. Increased Risk of Disease Among Vietnam Veterans Ranch Hand participants show a markedly increaser!
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From page 202... ...
Studies Reviewed in Update 1998 Garnbini et al., 1997 Italian rice growers Kogevinaset al, 1997 Phenoxy herbicides 36 cohorts Exposed to TCDD or higher PCDD Exposed to no or lower PCDD Becher et al., 1996 Gennan chemical production workers Ott and Zober, 1996 BASE cleanup workers Ramlow et al., 1996 Pentachlorophenol production workers Studies Reviewed in Update 1996 Aspetal., 1994 Blair et al., 1993 Bloemen et al., 1993 Kogevinas et al., 1993 Lynge, 1993 Studies Reviewed in LAO Bueno de Mesquita et al., 1993 Phenoxy herbicide workers Swaen et al., 1992 Herbicide appliers Coggon et al., 1991 Phenoxy herbicide production workers Finnish herbicide appliers US farmers from 23 states White males Nonwhite males Dow 2,4-D production workers Female herbicide spraying and production workers Danish male production workers Fingerhut et al., 1991 Green, 1991 Manz et al., 1991 Saracci et al., 1991 McDuffie et al., 1990 Zober et al., 1990 Wiklund et al., 1989a Bond et al., 1988 Coggon et al., 1986 TCDD-exposed workers >l-year exposure; >20-year latency Herbicide sprayers in Ontario Phenoxy herbicide production workers Herbicide spraying and production workers Probably exposed subgroup Saskatchewan farmers applying herbicides TCDD reactor accident workers High exposure Chloracne Pesticide appliers in Sweden Dow 2,4-D production workers (15-year latency) Respiratory cancer Low cumulative exposure Medium cumulative exposure High cumulative exposure MCPA production workers Background exposure Low-grade expos~e 202 45 225 148 47 6 18 37 2 13 0.8 (0.6-1.1)
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From page 203... ...
Zone R females 71 0.8 (0.7-1.1) Studies Reviewed in Update 1998 Bertazzi et al., 1997 Seveso residents—15-year follow-up Zone A males Zone B males Zone B females Zone R males Zone R females Swedish fishermen mortality East coast West coast Svensson et al., 1995 34 2 176 29 16 I.0 (0.3-2.5)
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From page 204... ...
Studies Reviewed in Update 1998 Crane et al., 1997a Australian military Vietnam veterans 212 1.3 (1.1-1.5) Crane etal., 1997b Australian nationalservice Vietnam veterans 27 2.2~1.1~.3)
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From page 205... ...
Agent Orange reports, the committee finds that there is inadequate or insufficient evidence to determine whether an association exists between exposure to the chemicals of interest (2,4-D, 2,4,5-T or its contaminant TCDD, picloram, or cacodylic acid) and bone cancer.
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From page 206... ...
Collins et al., 1993 Monsanto 2,4-D production workers 2 5.0 (0.~18.1) Studies Reviewed in LAO Roncoetal., 1992 Danish male self-employed farm workers 9 0.9 *
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From page 207... ...
AFHS, 1996 Air Force Ranch Hand veterans 0 Studies Reviewed in TAO Breslin etal., 1988 Army Vietnam veterans 27 0.8~0.~1.7) Manne Vietnam veterans 11 1.4~0.1-21.5)
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From page 208... ...
since Update 2000 (IOM, 20011. Synthesis Findings Tom prior occupational, environmental, and veteran studies show sufficient evidence to link herbicide exposure to STS.
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From page 209... ...
D (or higher-chlorinated dioxins) Workers exposed to any phenoxy herbicide or chlorophenol Workers exposed in 1953 accident Pentachlorophenol production workers Studies Reviewed in Update 1996 Kogevinas et al., 1995 IARC cohort Mack, 1995 US cancer registry data (SEER program)
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From page 210... ...
5.1 matched Costani et al., 2000 Residents near a chemical plant in Mantua, Italy Studies Reviewed in Update 2000 20 SMR = 2.25 (1.3-3.5) Bertazzi et al., 2001 Seves~20-year follow-up 0 *
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From page 211... ...
R females Seveso residents 10 year follow up Zone R males Zone B females VIETNAM VETERANS Studies Reviewed in Update 3000 AFHS, 2000 AIHW, 1999 CDVA, 1998a CDVA, 1998b Studies Reviewed in Update 1998 Clapp, 1997 Crane et al., 1997a Crane et al., 1997b Bertazzi et al., India, Bertazzi et al., 1989b, AFHS, 1996 Visintainer et al., 1995 Air Force Ranch Hand veterans Australian Vietnam veterans male Australian Vietnam veterans male Australian Vietnam veterans female Massachusetts Vietnam Veterans Australian military Vietnam veterans Australian national service Vietnam veterans Comparison group Ranch Hand veterans Compansons Vietnam veterans Watanabe and Kang, 1995 US Marines in Vietnam Studies Reviewed in Update 1996 Kogan and Clapp, 1988 Kang et al., 1986 Lawrence et al., 1985 Greenwald et al., 1984 Studies Reviewed in LAO Watanabe et al., 1991 Bullman et al., 1990 Michalek et al., 1990 Breslin et al., 1988 Fett et al., 1987 Anderson et al., 1986a,b Breslin et al., 1986 a Given when available. b Self-reported medical history.
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From page 212... ...
The ACS estimates that about 1,900 people will die Tom nonmelanocytic skin cancer in 2002. TABLE 6-~8 Average Annual Cancer Incidence (per 100,000)
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From page 213... ...
Suskind and fIertzberg, 1984 Monsanto production workers 8 1.6 * VIETNAM VETERANS Studies Reviewed in Update 2000 AFHS, 2000 Air Force Ranch Hand veterans 325 1.3 (1.1-1.6)
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From page 214... ...
Cancer incidence and mortality were analyzed in a cohort of 504 forestry workers in Sweden (Thorn et al., 2000~. The cohort included 261 workers exposed to phenoxy herbicides and 243 nonexposed workers.
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Key Terms
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