Serum Dioxin Concentrations and Breast Cancer Risk in the Seveso Women's Health Study (original) (raw)
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Risk Assessment for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) based on an Epidemiologic Study
American Journal of Epidemiology, 2001
recently concluded that 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD) is a human carcinogen. There have been few human studies and risk assessments with quantitative exposure data. The authors previously conducted exposure-response analyses based on estimated external TCDD exposure for 3,538 US male chemical workers and found a positive trend for all cancer with increasing cumulative exposure. In the present study, 1988 data from 170 workers with both estimated external exposure and known serum TCDD levels were used to derive the relation between the two. This derived relation was used to estimate serum TCDD levels over time for all 3,538 workers, and new doseresponse analyses were conducted by using cumulative serum level. A positive trend (p = 0.003) was found between estimated log cumulative TCDD serum level and cancer mortality. For males, the excess lifetime (75 years) risk of dying of cancer given a TCDD intake of 1.0 pg/kg of body weight per day, twice the background intake, was an estimated 0.05-0.9% above a background lifetime risk of cancer death of 12.4%. Data from this cohort are consistent with another epidemiologic risk assessment from Germany and support recent conclusions by the US Environmental Protection Agency.
Cancer risk for chemical workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin
Occupational and Environmental Medicine, 2003
Aims: To describe the long term mortality experience of a cohort of 2187 male chemical production workers previously exposed to substantial levels of dioxin. Methods: Vital status for a previously identified cohort was determined for an additional 10 years, to 1995. Dioxin exposures took place before 1983 and were sufficient to result in chloracne in 245 individuals. Mortality rates were compared with national figures and with a large pool of co-workers in unrelated production jobs. Results: All cancers combined (standardised mortality ratio (SMR) = 1.0, 95% CI 0.8 to 1.1) and lung cancer (SMR = 0.8, 95% CI 0.6 to 1.1) were at or below expected levels. Rates for soft tissue sarcoma (SMR = 2.4, 95% CI 0.3 to 8.6) and non-Hodgkin's lymphoma (SMR = 1.4, 95% CI 0.6 to 2.7) were greater than expected overall, but below expectation in the update period. No trend of increasing risk with increasing exposure was observed for these cancers. Workers who developed chloracne had very low all-cancer rates (SMR = 0.5, 95% CI 0.3 to 1.0), and lung cancer rates (SMR = 0.3, 95% CI 0.0 to 1.1). Conclusions: We found no coherent evidence of increased cancer risk from dioxin exposure in this cohort. Our study highlights the wide range of cancer rates and the lack of consistency across dioxin studies.
Cancer, Heart Disease, and Diabetes in Workers Exposed to 2,3,7,8-Tetrachlorodibenzo-p-dioxin
JNCI Journal of the National Cancer Institute, 1999
Background: In 1997, the International Agency for Research on Cancer classified 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) as a group 1 human carcinogen, based largely on four highly exposed industrial cohorts that showed an excess of all cancers combined. In this study, we extended the follow-up period for the largest of these cohorts by 6 years and developed a jobexposure matrix. Methods: We did cohort mortality analyses involving 5132 chemical workers at 12 U.S. plants by use of life table techniques (U.S. population referent) and Cox regression (internal referent). We conducted exposure-response analyses for 69% of the cohort with adequate work history data and adequate plant data on TCDD contamination. All P values are two-sided. Results: The standardized mortality ratio (SMR) for all cancers combined was 1.13 (95% confidence interval = 1.02-1.25). We found statistically significant positive linear trends in SMRs with increasing exposure for all cancers combined and for lung cancer. The SMR for all cancers combined for the highest exposure group was 1.60 (95% confidence interval = 1.15-1.82). SMRs for heart disease showed a weak increasing trend with higher exposure (P = .14). Diabetes (any mention on the death certificate) showed a negative exposureresponse trend. Internal analyses with Cox regression found statistically significant trends for cancer (15-year lag time) and heart disease (no lag). Conclusions: Our analyses suggest that high TCDD exposure results in an excess of all cancers combined, without any marked specificity. However, excess cancer was limited to the highest exposed workers, with exposures that were likely to have been 100-1000 times higher than those experienced by the general population and similar to the TCDD levels used in animal studies.
Relationship of Serum TCDD Concentrations and Age at Exposure of Female Residents of Seveso, Italy
Environmental Health Perspectives, 2003
In 1976, a chemical plant explosion near Seveso, Italy, resulted in the highest known exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in residential populations. In 1996, we initiated the Seveso Women's Health Study (SWHS), a historical cohort study of females who were ≤ 40 years old at the time of explosion and residents of the most heavily contaminated areas, zones A and B. Serum samples collected near the time of the explosion were analyzed for TCDD. We also analyzed pooled serum samples collected in 1976 from females who resided in zone non-ABR, the "unexposed" zone, to assess concurrent background exposures to other dioxins, furans, and coplanar polychlorinated biphenyls (PCBs). The median lipid-adjusted TCDD level for residents of zones A and B combined was 56 ppt (range = 2.5-56,000 ppt). Zone A residents had 5-fold higher TCDD levels (n = 67, median = 272 ppt) than did zone B residents (n = 814, median = 47 ppt). The youngest children had the highest TCDD levels, which decreased with age at explosion until approximately 13 years of age and were constant thereafter. Therefore, children living in zones A and B received a disproportionately higher exposure to TCDD as a result of the explosion. Zone of residence and age were the strongest predictors of TCDD level. Chloracne, nearby animal mortality, location (outdoors vs. indoors) at the time of explosion, and consumption of homegrown food were also related to serum TCDD levels. The serum pools from zone non-ABR residents had an average TCDD concentration of 20.2 ppt, and average total toxic equivalent (TEQ) concentration of 100.4 ppt. Therefore, background exposure to dioxins, furans, and PCBs unrelated to the explosion may have been substantial. As a consequence, previous SWHS studies that considered only TCDD exposure may have underestimated health effects due to total TEQ concentrations.
Leukemia, 1999
Dioxin is a polychlorinated hydrocarbon considered to be an almost ubiquitous contaminant of our environment. The environmental contamination arises mainly from combustion processes of different types, ranging from metal industry to forest fires, from urban traffic to waste incineration, and so on. Exposure to the highest dioxin levels was ascertained in the past in the chemical industry during the manufacture of some phenoxy acid herbicides, and after industrial accidents which affected both workers inside the establishment and/or the population in the outside environment (Bertazzi PA, Di Domenico A. Chemical, environmental, and health aspects of the Seveso, Italy, accident. In: Schecter A (ed). Dioxins and Health. Plenum Press: New York, 1994, pp 587-632). Recently, the International Agency for Research of Cancer convened a Working group to evaluate all the available scientific evidence concerning TCDD carcinogenicity. The evaluation was based on evidence from epidemiologic studies, which was considered limited, and from animal experiments which is indisputably positive. A series of mechanistic considerations led the working group to classify the compound in category 1, as a human carcinogen (International Agency for Research on Cancer. Polychlorinated dibenzo-para-dioxins and polychlorinated dibenzofurans. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, vol 69. International Agency for Research on Cancer: Lyon, 1997). The lymphatic and hemopoietic tissue is among the targets of the carcinogenic action of TCDD. The hypothesis was first suggested by a series of case-control studies carried out in Sweden in the late seventies and eighties. Elevated relative risks were found in several studies for NHL and HD, and also for multiple myeloma. However, exposure was poorly described, and characterized only in terms of compounds
1993
The association between exposure to chlorophenoxy herbicides contaminated with dioxins and occurrence of cancer has been studied mainly in male populations. In animal experiments, gender differences have been recorded in the cancer response to administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Mortality and cancer incidence in an international cohort of 701 women from an International Register of Workers occupationally exposed to chlorophenoxy herbicides, chlorophenols, and dioxins is examined. Cause-specific, national death rates and cancer incidence rates were used as referents. Cancer risk was not increased overall, with a standardized incidence ratio (SIR) of 96 and 95 percent confidence interval (CI) of 64-137, based on 29 cases. Among workers exposed to those chlorophenoxy herbicides contaminated with TCDD, excess cancer incidence (for all sites) was observed (SIR = 222, CI = 102-422, 9 cases); this was highest in the first 10 years after exposure. No excess was observed for breast cancer, the most common cancer in this cohort. Results on cancer mortality were consistent with those on incidence.