Veterans and Agent Orange Update 2000 (2001) / Chapter Skim
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6 Epidemiologic Studies
6 Epidemiologic Studies
Pages 132-247
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From page 132... ...
Tables 6-1, 6-2, and 6-3 (which begin on page 182) provide a brief overview of the epidemiologic studies reviewed in both the prior reports and this document.
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From page 133... ...
, Seveso, and Ranch Hand cohorts. Typically, the risks between exposure to herbicides and specific health outcomes are updated every 3 to 5 years.
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From page 134... ...
Production Workers National Institute for Occupational Safety and Health In 1978, NIOSH began a study to identify all U.S. workers potentially exposed to TCDD between 1942 and 1984 (Fingerhut et al., 1991~.
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From page 135... ...
Occupationally exposed individuals were compared to a referent group composed of age-, neighborhood-, race-, and sex-matched individuals with no self-reported occupational exposure to TCDD. The relationship between serum TCDD concentrations (measured as picograms per gram of lipid)
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From page 136... ...
were conducted. 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; Ramlow et al., 1996~.
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From page 137... ...
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~. VAO, Update 1996, and Update 1998 highlight these studies.
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From page 138... ...
SMRs and relative risks were calculated by cause of death in two cohorts: 549 male workers exposed to phenoxy herbicides, chlorophenols, and contaminants; and 140 male workers exposed as a result of an accident at the plant. Flesch-Janys (1997)
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From page 139... ...
Other Chemical Plants Previous studies have reviewed health outcomes among chemical workers in the United Kingdom exposed to TCDD as a result of an industrial accident in 1968 (May, 1982,1983; Jennings et al., 1988~; production workers in the former USSR involved in the production of 2,4-D (Bashirov, 1969~; factory workers in Prague, Czechoslovakia, who exhibited symptoms of TCDD toxicity 10 years after occupational exposure to 2,4,5-T (Pazderova-Vejlupkova et al., 1981~; 2,4D and 2,4,5-T production workers in the United States (Poland et al., 1971~; white male workers employed at a chemical plant in the United States manufacturing flavors and fragrances (Thomas, 1987~; and the long-term immune system effects of TCDD in 11 industrial workers involved in production and maintenance operations at a German chemical factory producing 2,4,5-T (Tone et al., 1996~. VAO and Update 1998 detail these studies.
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From page 140... ...
and among a cohort of rice growers in the Novara Province of northern Italy (Gambini et al., 1997~; cancer incidence among farmers licensed to spray pesticides in the southern Piedmont area of Italy (Corrao et al., 1989) and among female Danish gardeners (Hansen et al., 1992~; sperm abnormalities among Argentinean farmers (Lerda and Rizzi, 1991~; cancer birth defects among the offspring of Norwegian farmers (Kristensen et al., 1997~; and immunological changes in 10 farmers who mixed and applied commercial formulations containing the chlorophenoxy herbicides (Faustini et al., 1996~.
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From page 141... ...
Forestry Workers Studies have been conducted among forestry workers potentially exposed to the types of herbicides used in Vietnam. These studies include a cohort mortality study among men employed at a Canadian public utility (Green, 1987, 1991)
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From page 142... ...
Herbicide and Pesticide Sprayers 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) , mortality among pesticide appliers in Florida (Blair et al., 1983)
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From page 143... ...
Additional case-control studies and an expanded case series were conducted on phenoxy herbicide and chlorophenol exposure and the risks of malignant lymphoma, NHL, and multiple myeloma (Pearce et al., 1985, 1986a,b, 1987~. Elevated leukemia mortality in geographic patterns for white males in the central part of the United States prompted a study of the leukemia mortality of Nebraska farmers (Blair and Thomas, 1979~.
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From page 144... ...
in terms of occupational and environmental risk factors (Liou et al., 1997~; PD by looking at various rural factors, including exposure to herbicides and wood preservatives (Seidler et al., 1996~; PD by examining occupational risk factors (Semchuk et al., 1993~; and birth defects among agricultural workers (Nurminen et al., 1994~. Those earlier studies are discussed in detail in VAO, Update 1996, or Update 1998.
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From page 145... ...
Three counties have gastric cancer incidences close to the national average; two other counties have Sweden's highest incidences of gastric cancer. Individuals born in Sweden who were between 40 and 79 years of age and lived in one of five counties in Sweden during the study period were eligible for the study.
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From page 146... ...
Paper and Pulp Workers Workers in the paper and pulp industry may be exposed to TCDD and other dioxins that are generated during the bleaching process used in the production and treatment of some paper and paper products. VAO describes studies of workers potentially exposed to TCDD at paper and pulp mills and various health outcomes, including general mortality of workers at five mills in Washington, Oregon, and California (Robinson et al., 1986~; cancer incidence among male Finnish paper mill workers (Jappinen and Pukkala, 1991~; respiratory health in a New Hampshire mill (Henneberger et al., 1989~; and cause-specific mortality among white males employed in plants identified by the United Paperworkers International Union (Soles et al., 1989~.
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From page 147... ...
. Other studies looked at specific health effects associated with TCDD exposure among Seveso residents, including chloracne, birth defects, spontaneous abortions, crude birth and death rates (Bisanti et al., 1980~; chloracne and peripheral nervous system conditions (Barbieri et al., 1988~; hepatic enzyme-associated conditions (Ideo et al., 1982, 1985~; abnormal birth outcomes (Mastroiacovo et al., 1988~; cytogenetic abnormalities in maternal and fetal tissues (Tenchini et al., 1983~; neurological disorders (Boer)
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From page 148... ...
(1998) have updated the noncancer mortality causes for the 15 years from July 1976 to June 1991 for individuals living in zone A, B
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From page 149... ...
et al., 1992~; lymphomas and STS in Italy (Vineis et al., 1991~; neuropsychological effects in Germany (Peper et al., 1993~; young-onset Parkinson's disease in Oregon and Washington (Butterfield et al., 1993~; adverse health effects following an electrical transformer fire in Binghamton, New York (Fitzgerald et al., 1989~; skin cancer in Alberta, Canada (Gallagher et al., 1996~; NHL, HD, and chronic lymphocytic leukemia (CLL) in a rural Michigan community (Waterhouse et al., 1996~; HD, NHL, multiple myelomas, and acute myeloid leukemias in various regions of Italy (Masala et al., 1996~; inhalation exposure to TCDD and the effects of related compounds in wood preservatives on cell-mediated immunity in German day care center employees (Wolf and Karmaus,1995~; mortality and cancer incidence in two cohorts of Swedish fishermen for whom it is assumed that diet constitutes the primary exposure route (Svensson et al., 1995~; immune effects in hobby fishermen in the Frierfjord in southeastern Norway (Lovik et al., 1996~; and immunological effects of pre- and postnatal PCB or TCDD exposure in Dutch infants from birth to 18 months of age (WeisglasKuperus et al., 1995~.
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From page 150... ...
In these studies, exposure measures fall along a crude scale from individual levels for Ranch Hands, as reflected in serum dioxin measurements, to use of service in Vietnam as a surrogate for TCDD exposure in some state studies. It should also be noted that a variety of comparison groups have been used for the veteran cohort studies: (a)
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From page 151... ...
Since Ranch Hands and controls performed similar combat or combat-related jobs, many potential confounders related to the physical and psychophysiologic effects of combat stress and the Southeast Asia environment were potentially controlled (AFHS, 1982~. Rank was also used as a surrogate of exposure.
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From page 152... ...
. Serum dioxin levels were measured in 1982 (36 Ranch Hands; Pirkle et al., 1989~; 1987 (866 Ranch Hands; AFHS,199lb)
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From page 153... ...
A total of 1,261 Ranch Hands and 19,080 comparison veterans were included in the analysis. Exposure was based on military occupation.
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From page 154... ...
Longnecker and Michalek (2000) studied the relationship between serum dioxin levels and diabetes mellitus in Vietnam veterans who had never had contact with dioxin-contaminated herbicides (i.e., among the comparison veterans)
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From page 155... ...
Extrapolations were calculated based on a first-order elimination assumption of an exponential decrease in dioxin body burden with time; the half-life of 8.7 years is based on a sample of Ranch Hand participants with repeat dioxin measures over time. It is further limited to Ranch Hands with serum dioxin levels greater than 10 ppt measured at the 1987, 1992, or 1997 physical exam.
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From page 156... ...
All Ranch Hand veterans with available dioxin measurements were considered in Model 4 analyses, including those with levels less than 10 ppt who were excluded from Model 2 and treated as a separate category in Model 3. Models 2, 3, and 4 all use the same 1987 serum dioxin measures (or later where a 1987 value was not available)
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From page 157... ...
(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 page 158... ...
American Legion The American Legion conducted a cohort study of the health and well-being of Vietnam veterans who belonged to the American Legion, a voluntary veterans service organization. A series of studies examining physical health and reproductive outcomes, social-behavioral consequences, and PTSD were conducted on veterans who had served in Southeast Asia compared with veterans who served elsewhere (Snow et al., 1988; Stellman et al., 1988a,b,c)
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From page 159... ...
, and PTSD among monozygotic twins who served during the Vietnam era (Goldberg et al., l990~. After a published study indicating a potential association with testicular cancer in dogs that served in Vietnam (Hayes et al., 1990)
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From page 160... ...
is an epidemiologic study whose purpose is to determine whether exposure to the herbicides used in Vietnam may be responsible for any adverse health conditions observed in a cohort of Air Force personnel responsible for conducting aerial spray missions (the Ranch Hands)
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From page 161... ...
However, the committee's judgment is that continued research on the health of the Ranch Hand and Comparison veterans is likely to yield important information on the determinants of health and disease in males who served in the military during the Vietnam era and perhaps their offspring. If the records were to be retained and maintained and/or the research continued, this would have to be done with the full knowledge and consent of the AFHS population, and to be subject to controls that would respect the privacy of the participants.
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From page 162... ...
American Journal of Industrial Medicine 14:167-176. Alavanja MC, Merkle S
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From page 163... ...
1996. Cancer mortality in German male workers exposed to phenoxy herbicides and dioxins.
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From page 164... ...
American Journal of Industrial Medicine 32(3)
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From page 165... ...
workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. American Journal of Industrial Medicine 25:559-571.
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From page 166... ...
1989a. Comparison of Serum Levels of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin with Indirect Estimates of Agent Orange Exposure Among Vietnam Veterans: Final Report.
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From page 167... ...
1986. Evaluation of the mortality experience of workers exposed to the chlorinated dioxins.
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From page 168... ...
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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From page 169... ...
American Journal of Industrial Medicine 31(4)
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From page 170... ...
1991. A cohort mortality study of forestry workers exposed to phenoxy acid herbicides.
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From page 171... ...
1997. Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand.
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From page 172... ...
1999. Serum dioxin and cancer in veterans of Operation Ranch Hand.
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From page 173... ...
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 174... ...
1999a. Serum dioxin, insulin, fasting glucose, and sex hormonebinding globulin in veterans of Operation Ranch Hand.
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From page 175... ...
American Journal of Industrial Medicine 5:161-182. Musicco M, S ant M, Molinari S
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From page 176... ...
1993. Some occupational exposures as risk factors for malignant lymphomas.
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From page 177... ...
1991. Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols.
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From page 178... ...
1992. Phenoxy herbicides and chlorophenols: a case-control study on soft tissue sarcoma and malignant lymphoma.
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From page 179... ...
American Journal of Industrial Medicine 3:179-189. Thomas TL.
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From page 180... ...
American Journal of Industrial Medicine 11:685-691. Weisglas-Kuperus N
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From page 181... ...
1995. Paternal serum dioxin and reproductive outcomes among veterans of Operation Ranch Hand.
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