Health effects of dioxin exposure: a 20-year mortality study.

Follow-up of the population exposed to dioxin after the 1976 accident in Seveso, Italy, was extended to 1996. During the entire observation period, all-cause and all-cancer mortality did not increase. Fifteen years after the accident, mortality among men in high-exposure zones A (804 inhabitants) and B (5,941 inhabitants) increased from all cancers (rate ratio (RR) = 1.3, 95% confidence interval (CI): 1.0, 1.7), rectal cancer (RR = 2.4, 95% CI: 1.2, 4.6), and lung cancer (RR = 1.3, 95% CI: 1.0, 1.7), with no latency-related pattern for rectal or lung cancer. An excess of lymphohemopoietic neoplasms was found in both genders (RR = 1.7, 95% CI: 1.2, 2.5). Hodgkin's disease risk was elevated in the first 10-year observation period (RR = 4.9, 95% CI: 1.5, 16.4), whereas the highest increase for non-Hodgkin's lymphoma (RR = 2.8, 95% CI: 1.1, 7.0) and myeloid leukemia (RR = 3.8, 95% CI: 1.2, 12.5) occurred after 15 years. No soft tissue sarcoma cases were found in these zones (0.8 expected). An overall increase in diabetes was reported, notably among women (RR = 2.4, 95% CI: 1.2, 4.6). Chronic circulatory and respiratory diseases were moderately increased, suggesting a link with accident-related stressors and chemical exposure. Results support evaluation of dioxin as carcinogenic to humans and corroborate the hypotheses of its association with other health outcomes, including cardiovascular- and endocrine-related effects.

[1]  M. G. Ott,et al.  Laboratory results for selected target organs in 138 individuals occupationally exposed to TCDD. , 1994, Chemosphere.

[2]  G. Franceschini,et al.  Increased plasma and aortic triglycerides in rabbits after acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1984, Toxicology and applied pharmacology.

[3]  J. B. Greig Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam , 1995 .

[4]  L. Bisanti,et al.  Experiences from the accident of Seveso. , 1980, Acta morphologica Academiae Scientiarum Hungaricae.

[5]  J. Brugge Origins of human cancer : a comprehensive review , 1991 .

[6]  E. S. Johnson Important aspects of the evidence for TCDD carcinogenicity in man. , 1993, Environmental health perspectives.

[7]  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.

[8]  N. Mantel,et al.  Clinical laboratory manifestations of exposure to dioxin in children. A six-year study of the effects of an environmental disaster near Seveso, Italy. , 1986, JAMA.

[9]  D. Consonni,et al.  2,3,7,8-Tetrachlorodibenzo-p-dioxin plasma levels in Seveso 20 years after the accident. , 1998, Environmental health perspectives.

[10]  T. Dragani,et al.  Carcinogenic Effects of Infantile and Long-Term 2,3,7,8-Tetrachlorodibenzo-P-Dioxin Treatment in the Mouse , 1987, Tumori.

[11]  F. Matsumura,et al.  Rabbit serum hypertriglyceridemia after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). , 1988, Journal of toxicology and environmental health.

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

[13]  M. Kogevinas,et al.  Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands. , 1993, American journal of industrial medicine.

[14]  P. Simpson,et al.  Statistical methods in cancer research , 2001, Journal of surgical oncology.

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

[16]  R. Levi,et al.  Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity: decreased beta-adrenergic responsiveness and evidence of increased intracellular calcium. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. Hay Toxic cloud over Seveso , 1976, Nature.

[18]  M. Kogevinas,et al.  Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers. , 1998, Environmental health perspectives.

[19]  D. Consonni,et al.  Dioxin exposure and non-malignant health effects: a mortality study. , 1998, Occupational and environmental medicine.

[20]  P. Crenna,et al.  Relationship between clinical and electrophysiological findings and indicators of heavy exposure to 2,3,7,8-tetrachlorodibenzo-dioxin. , 1981, Scandinavian journal of work, environment & health.

[21]  Jack Cuzick,et al.  Geographical and environmental epidemiology : methods for small-area studies , 1997 .

[22]  F. Matsumura,et al.  TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) reduces lipoprotein lipase activity in the adipose tissue of the guinea pig. , 1984, Biochemical and biophysical research communications.

[23]  G. Fara,et al.  Chloracne following environmental contamination by TCDD in Seveso, Italy. , 1981, International journal of epidemiology.

[24]  M. Kogevinas,et al.  Soft Tissue Sarcoma and Non‐Hodgkin's Lymphoma in Workers Exposed to Phenoxy Herbicides, Chlorophenols, and Dioxins: Two Nested Case‐Control Studies , 1995, Epidemiology.

[25]  G. Henriksen,et al.  Serum Dioxin and Diabetes Mellitus in Veterans of Operation Ranch Hand , 1997, Epidemiology.

[26]  S Guercilena,et al.  Ten-year mortality study of the population involved in the Seveso incident in 1976. , 1989, American journal of epidemiology.

[27]  G. Lucier,et al.  Concentrations of dioxin 20 years after Seveso , 1997, The Lancet.

[28]  G Idéo,et al.  Urinary D-glucaric acid excretion in the Seveso area, polluted by tetrachloro-dibenzo-p-dioxin (TCDD): five years of experience. , 1985, Environmental health perspectives.

[29]  F. Coulston,et al.  Accidental exposure to dioxins : human health aspects , 1983 .

[30]  C. Fortunati The Seveso accident , 1985 .

[31]  J. Kiel,et al.  Serum dioxin, insulin, fasting glucose, and sex hormone-binding globulin in veterans of Operation Ranch Hand. , 1999, The Journal of clinical endocrinology and metabolism.

[32]  A. Schecter,et al.  Dioxin and dibenzofuran levels in human blood samples from Guam, Russia, Germany, Vietnam and the USA , 1992 .

[33]  C. Taylor,et al.  Stress factors in the development of coronary artery disease. , 1984, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[34]  S. Stohs,et al.  Biochemical and functional effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the heart of female rats. , 1988, Toxicology and applied pharmacology.

[35]  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.

[36]  Fabrizio Jossa,et al.  Long-Term Psychological Effects of Natural Disasters , 1996, Psychosomatic medicine.

[37]  G. Lucier,et al.  Animal models of human response to dioxins. , 1998, Environmental health perspectives.

[38]  P. Bertazzi,et al.  Industrial disasters and epidemiology. A review of recent experiences. , 1989, Scandinavian journal of work, environment & health.

[39]  Norman E. Breslow,et al.  The design and analysis of cohort studies , 1987 .

[40]  M. Kogevinas,et al.  Second follow-up of a Dutch cohort occupationally exposed to phenoxy herbicides, chlorophenols, and contaminants. , 1998, American journal of epidemiology.

[41]  J. Pickova,et al.  The development and prognosis of chronic intoxication by tetrachlordibenzo-p-dioxin in men. , 1981, Archives of environmental health.

[42]  R. Peterson,et al.  Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment on mechanical function of the rat heart. , 1987, Toxicology and applied pharmacology.

[43]  W. Castelli Lipids, risk factors and ischaemic heart disease. , 1996, Atherosclerosis.

[44]  K. Steenland,et al.  Cancer, heart disease, and diabetes in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1999, Journal of the National Cancer Institute.

[45]  R. Bertollini,et al.  Birth Defects in the Seveso Area After TCDD Contamination , 1988 .

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

[47]  H. Becher,et al.  Estimation of the cumulated exposure to polychlorinated dibenzo-p-dioxins/furans and standardized mortality ratio analysis of cancer mortality by dose in an occupationally exposed cohort. , 1998, Environmental health perspectives.

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

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

[50]  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.

[51]  M. Kogevinas,et al.  Earthquake-related stress and cardiac mortality. , 1986, International journal of epidemiology.

[52]  V. Silano,et al.  Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. II. TCDD distribution in the soil surface layer. , 1980, Ecotoxicology and environmental safety.

[53]  J. Landers,et al.  The Ah receptor and the mechanism of dioxin toxicity. , 1991, The Biochemical journal.

[54]  A. Schecter Dioxins and Health , 2003, Springer US.

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

[56]  C. Wade,et al.  Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. , 1978, Toxicology and applied pharmacology.

[57]  M. Kogevinas,et al.  Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study. , 1997, American journal of epidemiology.

[58]  F. Speizer,et al.  Epidemiology of chronic mucus hypersecretion and obstructive airways disease. , 1979, Epidemiologic reviews.

[59]  V. Silano,et al.  Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. , 1980, Ecotoxicology and environmental safety.

[60]  M. Tenchini,et al.  A comparative cytogenetic study on cases of induced abortions in TCDD-exposed and nonexposed women. , 1983, Environmental mutagenesis.

[61]  R. A. Neal,et al.  2,3,7,8-Tetrachlorodibenzo-p-dioxin tissue distribution, excretion, and effects on clinical chemical parameters in guinea pigs. , 1979, Toxicology and applied pharmacology.

[62]  M. Trevisan,et al.  Short‐Term Effect of Natural Disasters on Coronary Heart Disease Risk Factors , 1986, Arteriosclerosis.

[63]  D. Flesch‐Janys,et al.  Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of Germany. , 1995, American journal of epidemiology.

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

[65]  C. Esser,et al.  Persistence of decreased T-helper cell function in industrial workers 20 years after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1996, Environmental health perspectives.

[66]  J. Allen,et al.  Morphological changes in monkeys consuming a diet containing low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1977, Food and cosmetics toxicology.

[67]  Oldham Oli Lipid abnormalities in workers exposed to dioxin , 2022 .

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