2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident.

In 1976, near Seveso, Italy, an industrial accident caused the release of large quantities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) into the atmosphere, resulting in the highest levels of the toxicant ever recorded in humans. The contaminated area was divided into three zones (A, B, R) corresponding to decreasing TCDD levels in soil, and cohort including all residents was enumerated. The population of the surrounding noncontaminated area (non-ABR) was chosen as referent population. Two decades after the accident. plasma TCDD levels were measured in 62 subjects randomly sampled from the highest exposed zones (A and B) and 59 subjects from non-ABR, frequency matched for age, gender, and cigarette smoking status. Subjects living in the exposed areas have persistently elevated plasma TCDD levels (range = 1.2-89.9 ppt; geometric mean = 53.2 and 11.0 ppt for Zone A and Zone B, respectively). Levels significantly decrease by distance from the accident site (p = 0.0001), down to general population values (4.9 ppt) in non-ABR, thus validating the original zone classification based on environmental measurements. Women have higher TCDD levels than men in the entire study area (p = 0.0003 in Zone B; p = 0.007 in non-ABR). This gender difference persists after adjustment for location within the zone, consumption of meat derived from locally raised animals, age, body mass index, and smoking. There is no evidence for a gender difference in exposure, so variation in metabolism or elimination due to body fat or hormone-related factors may explain this finding. Elevated TCDD levels in women may contribute to adverse reproductive, developmental, and cancer outcomes. ImagesFigure 1

[1]  S. Yufit Role of electronic factors in the formation of a standard, quasi-stable mixture of toxic polychlorinated dibenzo-para-dioxins and polychlorinated dibenzofurans , 1999 .

[2]  S Guercilena,et al.  Dioxin Exposure and Cancer Risk: A 15‐Year Mortality Study after the “Seveso Accident” , 1997, Epidemiology.

[3]  R. Jackson,et al.  Serum dioxin levels in Seveso, Italy, population in 1976. , 1997, Teratogenesis, carcinogenesis, and mutagenesis.

[4]  A. Schecter,et al.  Dioxins and dioxin-like chemicals in blood and semen of American Vietnam veterans from the state of Michigan. , 1996, American journal of industrial medicine.

[5]  M. G. Ott,et al.  Cause specific mortality and cancer incidence among employees exposed to 2,3,7,8-TCDD after a 1953 reactor accident. , 1996, Occupational and environmental medicine.

[6]  P. Brambilla,et al.  Change in sex ratio with exposure to dioxin , 1996, The Lancet.

[7]  H. Becher,et al.  Elimination of polychlorinated dibenzo-p-dioxins and dibenzofurans in occupationally exposed persons. , 1996, Journal of toxicology and environmental health.

[8]  R. Tripathi,et al.  Pharmacokinetics of TCDD in veterans of Operation Ranch Hand: 10-year follow-up. , 1996, Journal of toxicology and environmental health.

[9]  D. Silverman,et al.  A study of gender-based cytochrome P4501A2 variability: a possible mechanism for the male excess of bladder cancer. , 1995, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[10]  L S Birnbaum,et al.  Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants. , 1995, European journal of pharmacology.

[11]  W. Halperin,et al.  Total serum testosterone and gonadotropins in workers exposed to dioxin. , 1994, American journal of epidemiology.

[12]  P. Bertazzi,et al.  Chemical, Environmental, and Health Aspects of the Seveso, Italy, Accident , 1994 .

[13]  M. DeVito,et al.  Toxicology of Dioxins and Related Chemicals , 1994 .

[14]  J. Huff Dioxins and Mammalian Carcinogenesis , 1994 .

[15]  R. Peterson,et al.  Developmental and Reproductive Toxicity of Dioxins and Other Ah Receptor Agonists , 1994 .

[16]  N. Kerkvliet Immunotoxicology of Dioxins and Related Chemicals , 1994 .

[17]  Maria Teresa Landi,et al.  Cancer Incidence in a Population Accidentally Exposed to 2,3,7,8‐Tetrachlorodibenzo-para‐dioxin , 1993, Epidemiology.

[18]  C. Sengstag,et al.  Caffeine, estradiol, and progesterone interact with human CYP1A1 and CYP1A2. Evidence from cDNA-directed expression in Saccharomyces cerevisiae. , 1992, Drug metabolism and disposition: the biological fate of chemicals.

[19]  M. Kogevinas,et al.  Cancer mortality in workers exposed to chlorophenoxy herbicides and chlorophenols , 1991, The Lancet.

[20]  D. Flesch‐Janys,et al.  Cancer mortality among workers in chemical plant contaminated with dioxin , 1991, The Lancet.

[21]  P. Brambilla,et al.  Serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy. , 1991, Journal of toxicology and environmental health.

[22]  G. Clark,et al.  Ovarian hormones enhance 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated increases in cell proliferation and preneoplastic foci in a two-stage model for rat hepatocarcinogenesis. , 1991, Cancer research.

[23]  P. A. Honchar,et al.  Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1991, The New England journal of medicine.

[24]  R. Suskind The association of selected cancers with service in the US military in Vietnam. , 1990, Archives of internal medicine.

[25]  R. Hornung,et al.  Estimation of Average Concentration in the Presence of Nondetectable Values , 1990 .

[26]  The association of selected cancers with service in the US military in Vietnam. II. Soft-tissue and other sarcomas. The Selected Cancers Cooperative Study Group. , 1990, Archives of internal medicine.

[27]  A. Zober,et al.  Thirty-four-year mortality follow-up of BASF employees exposed to 2,3,7,8-TCDD after the 1953 accident , 1990, International archives of occupational and environmental health.

[28]  I. Dewhurst,et al.  Polychlorinated Dibenzo-p-dioxins and Polychlorinated Dibenzofurans: The Risks to Human Health. A Review , 1989, Human toxicology.

[29]  G. Bond,et al.  Update of mortality among chemical workers with potential exposure to the higher chlorinated dioxins. , 1989, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[30]  J. Holder,et al.  Analysis of 2,3,7,8-TCDD tumor promotion activity and its relationship to cancer☆ , 1989 .

[31]  M. Rao,et al.  Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the Syrian golden hamster. , 1988, Carcinogenesis.

[32]  H. Kang,et al.  Soft tissue sarcoma and military service in Vietnam: a case-control study. , 1987, Journal of the National Cancer Institute.

[33]  L L Needham,et al.  High-resolution gas chromatographic/high-resolution mass spectrometric analysis of human serum on a whole-weight and lipid basis for 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1987, Analytical chemistry.

[34]  M. G. Ott,et al.  Cohort mortality study of chemical workers with potential exposure to the higher chlorinated dioxins. , 1987, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[35]  J. Pirkle,et al.  2,3,7,8-Tetrachlorodibenzo-p-dioxin levels in adipose tissue of exposed and control persons in Missouri. An interim report. , 1986, JAMA.

[36]  K. Wiklund,et al.  Soft tissue sarcoma risk in Swedish agricultural and forestry workers. , 1986, Journal of the National Cancer Institute.

[37]  Neil Pearce,et al.  Update on soft tissue sarcoma and phenoxyherbicides in New Zealand , 1986 .

[38]  Knapik Jj,et al.  Height, weight, percent body fat, and indices of adiposity for young men and women entering the U.S. Army. , 1983 .

[39]  E. Glover,et al.  Tumour promotion by TCDD in skin of HRS/J hairless mice , 1982, Nature.

[40]  J. Harington Environmental Health Perspectives , 1976 .