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. 1998 Feb;55(2):126–131. doi: 10.1136/oem.55.2.126

Dioxin exposure and non-malignant health effects: a mortality study

A C Pesatori, C Zocchetti, S Guercilena, D Consonni, D Turrini, P A Bertazzi
PMCID: PMC1757550  PMID: 9614398

Abstract

OBJECTIVE: To investigate, in a population heavily exposed to 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), the possible unusual occurrence of diseases other than cancer. METHODS: Five year extension of the follow up of the cohort involved in the Seveso accident. Soil measurements identified three exposure zones: (A) highest contamination, (B) substantial, and (R) low but higher than background contamination. Blood TCDD measurements, although limited in number, confirmed zone exposure ranking. The 15 year mortality in the exposed cohort was compared with that of a large population in the surrounding non- contaminated territory. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated with Poisson regression techniques. RESULTS: The already noted increased occurrence of cardiovascular deaths was confirmed, in particular in zone A, among males for chronic ischaemic heart disease (five deaths, RR 3.0, 95% CI 1.2 to 7.3), and among females for hypertensive disease (three deaths, RR 3.6, 95% CI 1.2 to 11.4) and chronic rheumatic heart disease. Novel findings were the increase of chronic obstructive pulmonary disease, most notably among males in zone A (four deaths, RR 3.7, 95% CI 1.4 to 9.9) and females in zone B (seven deaths, RR 2.4, 95% CI 1.1 to 5.1); and from diabetes, which was significantly increased in females in zone B (13 deaths, RR 1.9, 95% CI 1.1 to 3.2). In zone R, chronic ischaemic heart disease (males and females), hypertension (females), and diabetes (females) showed less pronounced, although significant excesses. CONCLUSIONS: As well as high TCDD exposure, the accident caused a severe burden of strain in the population. Both these factors might have contributed to the noted increased risks (in particular, circulatory and respiratory). The cardiovascular and immune toxicity of TCDD, as well as its complex interaction with the endocrine system, might be relevant to the explanations of these findings. These results, although not conclusive, concur with previous data in suggesting cardiopulmonary and endocrine effects in humans highly exposed to TCDD.

 

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Selected References

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  1. Allen J. R., Barsotti D. A., Van Miller J. P., Abrahamson L. J., Lalich J. J. Morphological changes in monkeys consuming a diet containing low levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Food Cosmet Toxicol. 1977 Oct;15(5):401–410. doi: 10.1016/s0015-6264(77)80004-7. [DOI] [PubMed] [Google Scholar]
  2. Axelson O., Steenland K. Indirect methods of assessing the effects of tobacco use in occupational studies. Am J Ind Med. 1988;13(1):105–118. doi: 10.1002/ajim.4700130107. [DOI] [PubMed] [Google Scholar]
  3. Bertazzi A., Pesatori A. C., Consonni D., Tironi A., Landi M. T., Zocchetti C. Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin. Epidemiology. 1993 Sep;4(5):398–406. doi: 10.1097/00001648-199309000-00004. [DOI] [PubMed] [Google Scholar]
  4. Bertazzi P. A. Industrial disasters and epidemiology. A review of recent experiences. Scand J Work Environ Health. 1989 Apr;15(2):85–100. doi: 10.5271/sjweh.1867. [DOI] [PubMed] [Google Scholar]
  5. Bertazzi P. A., Zocchetti C., Pesatori A. C., Guercilena S., Sanarico M., Radice L. Mortality in an area contaminated by TCDD following an industrial incident. Med Lav. 1989 Jul-Aug;80(4):316–329. [PubMed] [Google Scholar]
  6. Bertazzi P. A., Zocchetti C., Pesatori A. C., Guercilena S., Sanarico M., Radice L. Ten-year mortality study of the population involved in the Seveso incident in 1976. Am J Epidemiol. 1989 Jun;129(6):1187–1200. doi: 10.1093/oxfordjournals.aje.a115240. [DOI] [PubMed] [Google Scholar]
  7. Bond G. G., McLaren E. A., Brenner F. E., Cook R. R. Incidence of chloracne among chemical workers potentially exposed to chlorinated dioxins. J Occup Med. 1989 Sep;31(9):771–774. doi: 10.1097/00043764-198909000-00017. [DOI] [PubMed] [Google Scholar]
  8. Bond G. G., Ott M. G., Brenner F. E., Cook R. R. Medical and morbidity surveillance findings among employees potentially exposed to TCDD. Br J Ind Med. 1983 Aug;40(3):318–324. doi: 10.1136/oem.40.3.318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brewster D. W., Bombick D. W., Matsumura F. Rabbit serum hypertriglyceridemia after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). J Toxicol Environ Health. 1988;25(4):495–507. doi: 10.1080/15287398809531227. [DOI] [PubMed] [Google Scholar]
  10. Brewster D. W., Matsumura F. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) reduces lipoprotein lipase activity in the adipose tissue of the guinea pig. Biochem Biophys Res Commun. 1984 Jul 31;122(2):810–817. doi: 10.1016/s0006-291x(84)80106-0. [DOI] [PubMed] [Google Scholar]
  11. Calvert G. M., Hornung R. W., Sweeney M. H., Fingerhut M. A., Halperin W. E. Hepatic and gastrointestinal effects in an occupational cohort exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin. JAMA. 1992 Apr 22;267(16):2209–2214. [PubMed] [Google Scholar]
  12. Calvert G. M., Willie K. K., Sweeney M. H., Fingerhut M. A., Halperin W. E. Evaluation of serum lipid concentrations among U.S. workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch Environ Health. 1996 Mar-Apr;51(2):100–107. doi: 10.1080/00039896.1996.9936001. [DOI] [PubMed] [Google Scholar]
  13. Canga L., Levi R., Rifkind A. B. Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity: decreased beta-adrenergic responsiveness and evidence of increased intracellular calcium. Proc Natl Acad Sci U S A. 1988 Feb;85(3):905–909. doi: 10.1073/pnas.85.3.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Caramaschi F., del Corno G., Favaretti C., Giambelluca S. E., Montesarchio E., Fara G. M. Chloracne following environmental contamination by TCDD in Seveso, Italy. Int J Epidemiol. 1981 Jun;10(2):135–143. doi: 10.1093/ije/10.2.135. [DOI] [PubMed] [Google Scholar]
  15. Dickson L. C., Buzik S. C. Health risks of "dioxins": a review of environmental and toxicological considerations. Vet Hum Toxicol. 1993 Feb;35(1):68–77. [PubMed] [Google Scholar]
  16. Doss M., Sauer H., von Tiepermann R., Colombi A. M. Development of chronic hepatic porphyria (porphyria cutanea tarda) with inherited uroporphyrinogen decarboxylase deficiency under exposure to dioxin. Int J Biochem. 1984;16(4):369–373. doi: 10.1016/0020-711x(84)90134-4. [DOI] [PubMed] [Google Scholar]
  17. Fingerhut M. A., Halperin W. E., Marlow D. A., Piacitelli L. A., Honchar P. A., Sweeney M. H., Greife A. L., Dill P. A., Steenland K., Suruda A. J. Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. N Engl J Med. 1991 Jan 24;324(4):212–218. doi: 10.1056/NEJM199101243240402. [DOI] [PubMed] [Google Scholar]
  18. Flesch-Janys D., Berger J., Gurn P., Manz A., Nagel S., Waltsgott H., Dwyer J. H. 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. Am J Epidemiol. 1995 Dec 1;142(11):1165–1175. doi: 10.1093/oxfordjournals.aje.a117575. [DOI] [PubMed] [Google Scholar]
  19. Fox A. J., Collier P. F. Low mortality rates in industrial cohort studies due to selection for work and survival in the industry. Br J Prev Soc Med. 1976 Dec;30(4):225–230. doi: 10.1136/jech.30.4.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gasiewicz T. A., Neal R. A. 2,3,7,8-Tetrachlorodibenzo-p-dioxin tissue distribution, excretion, and effects on clinical chemical parameters in guinea pigs. Toxicol Appl Pharmacol. 1979 Nov;51(2):329–339. doi: 10.1016/0041-008x(79)90475-7. [DOI] [PubMed] [Google Scholar]
  21. Hermansky S. J., Holcslaw T. L., Murray W. J., Markin R. S., Stohs S. J. Biochemical and functional effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the heart of female rats. Toxicol Appl Pharmacol. 1988 Sep 15;95(2):175–184. doi: 10.1016/0041-008x(88)90154-8. [DOI] [PubMed] [Google Scholar]
  22. Idéo G., Bellati G., Bellobuono A., Bissanti L. Urinary D-glucaric acid excretion in the Seveso area, polluted by tetrachloro-dibenzo-p-dioxin (TCDD): five years of experience. Environ Health Perspect. 1985 May;60:151–157. doi: 10.1289/ehp.60-1568553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jirásek L., Kalenský J., Kubec K., Pazderová J., Lukás E. Acne chlorina, porphyria cutanea tarda a jiné projevy celkové intoxikace pri výrobe herbidic. II. Cesk Dermatol. 1974 Jun;49(3):145–157. [PubMed] [Google Scholar]
  24. Kelling C. K., Menahan L. A., Peterson R. E. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment on mechanical function of the rat heart. Toxicol Appl Pharmacol. 1987 Dec;91(3):497–501. doi: 10.1016/0041-008x(87)90072-x. [DOI] [PubMed] [Google Scholar]
  25. Kociba R. J., Keyes D. G., Beyer J. E., Carreon R. M., Wade C. E., Dittenber D. A., Kalnins R. P., Frauson L. E., Park C. N., Barnard S. D. Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol Appl Pharmacol. 1978 Nov;46(2):279–303. doi: 10.1016/0041-008x(78)90075-3. [DOI] [PubMed] [Google Scholar]
  26. Koopman-Esseboom C., Morse D. C., Weisglas-Kuperus N., Lutkeschipholt I. J., Van der Paauw C. G., Tuinstra L. G., Brouwer A., Sauer P. J. Effects of dioxins and polychlorinated biphenyls on thyroid hormone status of pregnant women and their infants. Pediatr Res. 1994 Oct;36(4):468–473. doi: 10.1203/00006450-199410000-00009. [DOI] [PubMed] [Google Scholar]
  27. Landi M. T., Needham L. L., Lucier G., Mocarelli P., Bertazzi P. A., Caporaso N. Concentrations of dioxin 20 years after Seveso. Lancet. 1997 Jun 21;349(9068):1811–1811. doi: 10.1016/s0140-6736(97)24025-0. [DOI] [PubMed] [Google Scholar]
  28. Lovati M. R., Galbussera M., Franceschini G., Weber G., Resi L., Tanganelli P., Sirtori C. R. Increased plasma and aortic triglycerides in rabbits after acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol. 1984 Aug;75(1):91–97. doi: 10.1016/0041-008x(84)90079-6. [DOI] [PubMed] [Google Scholar]
  29. Lucier G. W., Tritscher A., Goldsworthy T., Foley J., Clark G., Goldstein J., Maronpot R. 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. Cancer Res. 1991 Mar 1;51(5):1391–1397. [PubMed] [Google Scholar]
  30. Martin J. V. Lipid abnormalities in workers exposed to dioxin. Br J Ind Med. 1984 May;41(2):254–256. doi: 10.1136/oem.41.2.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. May G. Tetrachlorodibenzodioxin: a survey of subjects ten years after exposure. Br J Ind Med. 1982 May;39(2):128–135. doi: 10.1136/oem.39.2.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. McConnell E. E., Moore J. A. Toxicopathology characteristics of the halogenated aromatics. Ann N Y Acad Sci. 1979 May 31;320:138–150. [PubMed] [Google Scholar]
  33. Mocarelli P., Marocchi A., Brambilla P., Gerthoux P., Young D. S., Mantel N. Clinical laboratory manifestations of exposure to dioxin in children. A six-year study of the effects of an environmental disaster near Seveso, Italy. JAMA. 1986 Nov 21;256(19):2687–2695. [PubMed] [Google Scholar]
  34. Moses M., Lilis R., Crow K. D., Thornton J., Fischbein A., Anderson H. A., Selikoff I. J. Health status of workers with past exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the manufacture of 2,4,5-trichlorophenoxyacetic acid: comparison of findings with and without chloracne. Am J Ind Med. 1984;5(3):161–182. doi: 10.1002/ajim.4700050303. [DOI] [PubMed] [Google Scholar]
  35. Ott M. G., Zober A. Cause specific mortality and cancer incidence among employees exposed to 2,3,7,8-TCDD after a 1953 reactor accident. Occup Environ Med. 1996 Sep;53(9):606–612. doi: 10.1136/oem.53.9.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ott M. G., Zober A., Germann C. Laboratory results for selected target organs in 138 individuals occupationally exposed to TCDD. Chemosphere. 1994 Nov-Dec;29(9-11):2423–2437. doi: 10.1016/0045-6535(94)90411-1. [DOI] [PubMed] [Google Scholar]
  37. Pazderova-Vejlupková J., Lukás E., Nemcova M., Pícková J., Jirásek L. The development and prognosis of chronic intoxication by tetrachlordibenzo-p-dioxin in men. Arch Environ Health. 1981 Jan-Feb;36(1):5–11. doi: 10.1080/00039896.1981.10667598. [DOI] [PubMed] [Google Scholar]
  38. Pesatori A. C. Dioxin contamination in Seveso: the social tragedy and the scientific challenge. Med Lav. 1995 Mar-Apr;86(2):111–124. [PubMed] [Google Scholar]
  39. Pluim H. J., de Vijlder J. J., Olie K., Kok J. H., Vulsma T., van Tijn D. A., van der Slikke J. W., Koppe J. G. Effects of pre- and postnatal exposure to chlorinated dioxins and furans on human neonatal thyroid hormone concentrations. Environ Health Perspect. 1993 Nov;101(6):504–508. doi: 10.1289/ehp.93101504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Poland A. P., Smith D., Metter G., Possick P. A health survey of workers in a 2,4-D and 2,4,5-T plan with special attention to chloracne, porphyria cutanea tarda, and psychologic parameters. Arch Environ Health. 1971 Mar;22(3):316–327. doi: 10.1080/00039896.1971.10665850. [DOI] [PubMed] [Google Scholar]
  41. Speizer F. E., Tager I. B. Epidemiology of chronic mucus hypersecretion and obstructive airways disease. Epidemiol Rev. 1979;1:124–142. doi: 10.1093/oxfordjournals.epirev.a036206. [DOI] [PubMed] [Google Scholar]
  42. Suskind R. R., Hertzberg V. S. Human health effects of 2,4,5-T and its toxic contaminants. JAMA. 1984 May 11;251(18):2372–2380. [PubMed] [Google Scholar]
  43. Tonn T., Esser C., Schneider E. M., Steinmann-Steiner-Haldenstätt W., Gleichmann E. Persistence of decreased T-helper cell function in industrial workers 20 years after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Environ Health Perspect. 1996 Apr;104(4):422–426. doi: 10.1289/ehp.96104422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Vanden Heuvel J. P., Lucier G. Environmental toxicology of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans. Environ Health Perspect. 1993 Apr;100:189–200. doi: 10.1289/ehp.93100189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zober A., Messerer P., Huber P. Thirty-four-year mortality follow-up of BASF employees exposed to 2,3,7,8-TCDD after the 1953 accident. Int Arch Occup Environ Health. 1990;62(2):139–157. doi: 10.1007/BF00383591. [DOI] [PubMed] [Google Scholar]
  46. di Domenico A., Silano V., Viviano G., Zapponi G. Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. II. TCDD distribution in the soil surface layer. Ecotoxicol Environ Saf. 1980 Sep;4(3):298–320. doi: 10.1016/0147-6513(80)90032-9. [DOI] [PubMed] [Google Scholar]

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