Veterans and Agent Orange Update 1998 (1999) / Chapter Skim
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6 Epidemiologic Studies
6 Epidemiologic Studies
Pages 169-264
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This chapter summarizes the epidemiologic studies and reports reviewed by the committee. Included are new studies published after Veterans and Agent Orange: Update 1996 (henceforth called Update 1996)
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The occupational section includes studies of production workers, agricultural and forestry workers (including herbicide and pesticide appliers) , and paper and pulp workers, as well as case-control studies of specific cancers and the association with exposures to herbicides or related compounds.
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workers potentially exposed to TCDD between 1942 and 1984 (Fingerhut et al., 1991~. In a total of 12 chemical companies, 5,000 workers were identified from personnel and payroll records as having been involved in production or maintenance processes associated with TCDD contamination.
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. Dow Chemical Company Several studies of Dow Chemical Company production workers are summarized in VAO and Update 1996.
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. Dow Chemical Company has also undertaken a large-scale cohort mortality study of workers exposed to herbicides in several Dow plants (Bond et al., 1988; Bloemen et al., 1993~.
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Two nested case-control studies were also undertaken to evaluate the relationship between soft-tissue sarcoma and non-Hodgkin's lymphoma (Kogevinas et al., 1995~. A cohort study of cancer incidence and mortality was conducted among 701 women occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins from seven countries (Kogevinas et al., 1993~.
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(1996) assessed cancer mortality among German workers in four phenoxy herbicide- and chlorophenol-producing facilities.
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Agricultural and Forestry Workers Cohort Studies of Agricultural Workers VAO and Update 1996 details a number of cohort studies examining health effects among those involved in agricultural activity, including proportionate mortality among Iowa farmers (Burmeister, 1981) , cancer mortality among Danish and Italian farmers (Ronco et al., 1992)
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Cohort Studies of Forestry Workers Studies have been conducted among forestry workers potentially exposed to herbicides used in Vietnam. These studies include a cohort mortality study among
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VAO describes these studies in greater detail. Cohort Studies of Herbicide/Pesticide Appliers A number of cohort studies have assessed health outcomes among herbicide and pesticide appliers including cancer mortality among Swedish railroad workers (Axelson and Sundell, 1974; Axelson et al., 1980)
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conducted a large retrospective cohort study of British Columbia sawmill workers potentially exposed chlorophenate wood preservatives. The researchers selected 23,829 cases from 11 sawmills that used chlorophenates, and 2,658 controls from 3 other sawmills.
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These included studies of STS from data provided by the Department of Oncology, University Hospital, Umea (Hardell and Sandstrom,1979~; the Cancer Registry of five southern counties, where MCPA, 2,4-D, and phenoxypropionic acids are used in agricultural areas (Eriksson et al., 1979, 1981~; the Regional Cancer Registry in Umea, Sweden (Hardell and Eriksson, 1988~; the Regional Cancer Registry at the University Hospital in Linkoping in southeastern Sweden (Wingren et al., 1990~; and the Regional Cancer Registry in Uppsala in central Sweden (Eriksson et al., 1990~. Based on these results, other researchers conducted cases-control studies of other health outcomes including HD, NEIL, and other lymphomas from the north
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Prompted by the Swedish studies of STS and exposure to phenoxy herbicides, a set of case-control studies was undertaken in New Zealand to evaluate the risks of phenoxyherbicide and chlorophenol exposure and STS incidence and mortality (Smith et al., 1983, 1984; Smith and Pearce, 1986~. Additional casecontrol studies and an expanded case series were conducted of phenoxy herbicide and chlorophenol exposure and the risks of malignant lymphoma, NHL, and multiple myeloma (Pearce et al., 1985, 1986a,b, 1987~.
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(1997) conducted a population-based case-control study of the occupational risk factors for subgroups of NHL patients using information contained in the CDC's Selected Cancers Study, a multicenter case-control study
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(1996) conducted a proportionate mortality study of neurodegenerative diseases and occupational risk factors.
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VAO and Update 1996 describe a number of other studies that look at various health outcomes and associated exposures to phenoxyherbicides or surrogate measures of exposure. The examined health outcomes include including ovarian cancer in the Piedmont region of Italy (Donna et al., 1984~; brain gliomas in two hospitals in Milan, Italy (Musicco et al., 1988~; STS and other cancers from the 15 regional cancer registries that constitute the National Cancer Register in England (Balarajan and Acheson, 1984~; STS and malignant lymphomas in the Victorian Cancer Registry of Australia (Smith and Christophers, 1992~; lymphoid cancer in Milan, Italy (LaVecchia et al., 1989~; STS among rice weeders in northern Italy (Vineis et al., 1986~; primary lung cancer among pesticide users in Saskatchewan (McDuffie et al., 1990~; renal cell carcinoma from the Denmark Cancer Registry (Mellemgaard et al., 1994~; Parkinson's disease in relation to occupational risk factors in Canada (Semchuk et al., 1993~; and birth defects among agricultural workers in Finland (Nurminen et al., 1994~.
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, and cancer incidence (Pesatori et al., 1992, 1993; Bertazzi et al., 1993~. A two-year prospective controlled study was conducted of workers potentially exposed to TCDD during cleanup of the most highly contaminated areas following the accident (Assennato et al., 1989b)
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VAO and Update 1996 discuss these studies in more thorough detail. Other Environmental Studies VAO and Update 1996 reported on numerous studies focusing on reproductive outcomes of potential environmental exposure in Oregon (U.S.
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Researchers identified 7,016 study participants who had been involved in earlier rounds of the longitudinal cohort study, and sent health surveillance questionnaires to them or their living relatives. Cause of death was determined for 99 percent of the individuals.
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Mothers were questioned about health status and history. VIETNAM VETERANS STUDIES Studies of Vietnam veterans who were potentially exposed to herbicides, including Agent Orange, have been conducted in the United States at the national
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To determine whether there are adverse health effects associated with exposure to herbicides, including Agent Orange, the Air Force made a commitment to the Congress and the White House in 1979 to conduct an epidemiologic study of Ranch Hands (AFHS,1982~. VAO and Update 1996 discuss the cohort in more detail.
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. Serum dioxin levels were measured in 1982 (36 Ranch Hands)
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conceived before the father's service in Southeast Asia. The 859 Ranch Hands children were stratified into four exposure categories including children of comparison veterans (current dioxin levels less than 10 ppt)
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physical health; (2) reproductive outcomes and child health; and (3)
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(1990) examined whether Army I Corps Vietnam veterans had cancer mortality experiences similar to other Army Vietnam era veterans, based on the study design of Breslin et al.
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from 1969 to 1985 identified all malignant lymphomas among male Vietnam era veterans. A pathologist reviewed pathology reports from VA medical centers that had 10 or more lymphoma cases and identified 770 cases of HD.
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A series of studies examining physical health and reproductive outcomes, social-behavioral consequences, and PTSD was conducted on 2,858 veterans who had served in Southeast Asia and 3,933 who served elsewhere (Snow et al., 1988; Stellman et al., 1988a-c)
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In the first study, detailed in VAO, the researchers identified cases of selected cancers from the Massachusetts Cancer Registry between 1982 and 1988 (Clapp et al., l991~. Data were linked to status as Vietnam era veterans or Vietnam bonus recipients.
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There were no direct measures or indirect estimates of veterans' exposure to herbicides or other chemical agents, and the authors suggest that any variations in mortality found in the study would "probably need to be attributed to service in Vietnam rather than exposure to particular agents." Cause-specific standardized mortality ratios were calculated and compared to death rates for the Australian male population. A second cohort study of Australian veterans compared mortality for the period 1982-1994 for 18,949 national servicemen who had served in Vietnam (veterans)
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American Journal of Industrial Medicine 14:167-176. Alavanja MC, Merkle S
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1996. Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.
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1993. Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in the Netherlands.
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workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. American Journal of Industrial Medicine 25:559-571.
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1993. The mortality experience of workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin in a trichlorophenol process accident.
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1986. Evaluation of the mortality experience of workers exposed to the chlorinated dioxins.
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American Journal of Industrial Medicine 22:305-312. Evans RG, Webb KB, Knutsen AP, Roodman ST, Roberts DW, Bagby JR, Garrett WA Jr, Andrews JS Jr.
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1986. Final Report: A Case-Control Mortality Study on the Association of Soft Tissue Sarcomas, Non-Hodgkin's Lymphomas, and Other Selected Cancers and Vietnam Military Service in Pennsylvania Males.
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1997. Mortality and cancer incidence among sawmill workers exposed to chlorophenate wood preservatives.
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1991. Cancer incidence among pulp and paper workers exposed to organic chlorinated compounds formed during chlorine pulp bleaching.
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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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1985. A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark.
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American Journal of Industrial Medicine 5:161-182. Musicco M, S ant M, Molinari S
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American Journal of Industrial Medicine 30(2)
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1991. Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols.
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. American Journal of Industrial Medicine 23 :845-858.
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American Journal of Industrial Medicine 18:665-673. Thomas TL, Kang H
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1980. The mortality experience of workers exposed to tetrachlorodibenzodioxin in a trichlorophenol process accident.
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264 VETERANS AND AGENT ORANGE: UPDATE 1998 Zober A, Messerer P Huber P
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