• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. Apr 1998; 106(Suppl 2): 625–633.
PMCID: PMC1533388
Research Article

The Seveso studies on early and long-term effects of dioxin exposure: a review.

Abstract

The industrial accident that occurred in the town of Seveso, Italy, in 1976 exposed a large population to substantial amounts of relatively pure 2,3,7,8-tetrachlorodibenzo-p-dioxin. Extensive monitoring of soil levels and measurements of a limited number of human blood samples allowed classification of the exposed population into three categories, A (highest exposure), B (median exposure), and R (lowest exposure). Early health investigations including liver function, immune function, neurologic impairment, and reproductive effects yielded inconclusive results. Chloracne (nearly 200 cases with a definite exposure dependence) was the only effect established with certainty. Long-term studies were conducted using the large population living in the surrounding noncontaminated territory as reference. An excess mortality from cardiovascular and respiratory diseases was uncovered, possibly related to the psychosocial consequences of the accident in addition to the chemical contamination. An excess of diabetes cases was also found. Results of cancer incidence and mortality follow-up showed an increased occurrence of cancer of the gastrointestinal sites and of the lymphatic and hematopoietic tissue. Experimental and epidemiologic data as well as mechanistic knowledge support the hypothesis that the observed cancer excesses are associated with dioxin exposure. Results cannot be viewed as conclusive. The study is continuing in an attempt to overcome the existing limitations (few individual exposure data, short latency period, and small population size for certain cancer types) and to explore new research paths (e.g., differences in individual susceptibility).

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.7M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Huff JE, Salmon AG, Hooper NK, Zeise L. Long-term carcinogenesis studies on 2,3,7,8-tetrachlorodibenzo-p-dioxin and hexachlorodibenzo-p-dioxins. Cell Biol Toxicol. 1991 Jan;7(1):67–94. [PubMed]
  • Holmstedt B. Prolegomena to Seveso. Ecclesiastes I 18. Arch Toxicol. 1980 Apr;44(4):211–230. [PubMed]
  • 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. [PubMed]
  • di Domenico A, Silano V, Viviano G, Zapponi G. Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. IV. Vertical distribution of TCDD in soil. Ecotoxicol Environ Saf. 1980 Sep;4(3):327–338. [PubMed]
  • di Domenico A, Silano V, Viviano G, Zapponi G. Accidental release of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at Sèveso, Italy. VI. TCDD levels in atmospheric particles. Ecotoxicol Environ Saf. 1980 Sep;4(3):346–356. [PubMed]
  • Fanelli R, Bertoni MP, Castelli MG, Chiabrando C, Martelli GP, Noseda A, Garattini S, Binaghi C, Marazza V, Pezza F. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxic effects and tissue levels in animals from the contaminated area of Seveso, Italy. Arch Environ Contam Toxicol. 1980;9(5):569–577. [PubMed]
  • Fanelli R, Bertoni MP, Bonfanti M, Castelli MG, Chiabrando C, Martelli GP, Noè MA, Noseda A, Garrattini S, Binaghi C, et al. 2,3,7,8-Tetrachlorodibenzo-p-dioxin levels in cow's milk from the contaminated area of Seveso, Italy. Bull Environ Contam Toxicol. 1980 Apr;24(4):634–639. [PubMed]
  • Caramaschi F, del Corno G, Favaretti C, Giambelluca SE, Montesarchio E, Fara GM. Chloracne following environmental contamination by TCDD in Seveso, Italy. Int J Epidemiol. 1981 Jun;10(2):135–143. [PubMed]
  • Mocarelli P, Needham LL, Marocchi A, Patterson DG, Jr, Brambilla P, Gerthoux PM, Meazza L, Carreri V. Serum concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin and test results from selected residents of Seveso, Italy. J Toxicol Environ Health. 1991 Apr;32(4):357–366. [PubMed]
  • Landi MT, Needham LL, Lucier G, Mocarelli P, Bertazzi PA, Caporaso N. Concentrations of dioxin 20 years after Seveso. Lancet. 1997 Jun 21;349(9068):1811–1811. [PubMed]
  • Pirkle JL, Wolfe WH, Patterson DG, Needham LL, Michalek JE, Miner JC, Peterson MR, Phillips DL. Estimates of the half-life of 2,3,7,8-tetrachlorodibenzo-p-dioxin in Vietnam Veterans of Operation Ranch Hand. J Toxicol Environ Health. 1989;27(2):165–171. [PubMed]
  • Assennato G, Cervino D, Emmett EA, Longo G, Merlo F. Follow-up of subjects who developed chloracne following TCDD exposure at Seveso. Am J Ind Med. 1989;16(2):119–125. [PubMed]
  • Filippini G, Bordo B, Crenna P, Massetto N, Musicco M, Boeri R. Relationship between clinical and electrophysiological findings and indicators of heavy exposure to 2,3,7,8-tetrachlorodibenzo-dioxin. Scand J Work Environ Health. 1981 Dec;7(4):257–262. [PubMed]
  • Barbieri S, Pirovano C, Scarlato G, Tarchini P, Zappa A, Maranzana M. Long-term effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the peripheral nervous system. Clinical and neurophysiological controlled study on subjects with chloracne from the Seveso area. Neuroepidemiology. 1988;7(1):29–37. [PubMed]
  • Whitlock JP., Jr Genetic and molecular aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin action. Annu Rev Pharmacol Toxicol. 1990;30:251–277. [PubMed]
  • 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. [PMC free article] [PubMed]
  • Mocarelli P, Marocchi A, Brambilla P, Gerthoux P, Young DS, 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]
  • Bisanti L, Bonetti F, Caramaschi F, Del Corno G, Favaretti C, Giambelluca SE, Marni E, Montesarchio E, Puccinelli V, Remotti G, et al. Experiences from the accident of Seveso. Acta Morphol Acad Sci Hung. 1980;28(1-2):139–157. [PubMed]
  • Tenchini ML, Crimaudo C, Pacchetti G, Mottura A, Agosti S, De Carli L. A comparative cytogenetic study on cases of induced abortions in TCDD-exposed and nonexposed women. Environ Mutagen. 1983;5(1):73–85. [PubMed]
  • Rehder H, Sanchioni L, Cefis F, Gropp A. Pathologisch-embryologische Untersuchungen an Abortusfällen im Zusammenhang mit dem Seveso-Unglück. Schweiz Med Wochenschr. 1978 Oct 21;108(42):1617–1625. [PubMed]
  • Mastroiacovo P, Spagnolo A, Marni E, Meazza L, Bertollini R, Segni G, Borgna-Pignatti C. Birth defects in the Seveso area after TCDD contamination. JAMA. 1988 Mar 18;259(11):1668–1672. [PubMed]
  • Mocarelli P, Brambilla P, Gerthoux PM, Patterson DG, Jr, Needham LL. Change in sex ratio with exposure to dioxin. Lancet. 1996 Aug 10;348(9024):409–409. [PubMed]
  • Bertazzi PA, Zocchetti C, Pesatori AC, 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. [PubMed]
  • Bertazzi PA, Zocchetti C, Guercilena S, Consonni D, Tironi A, Landi MT, Pesatori AC. Dioxin exposure and cancer risk: a 15-year mortality study after the "Seveso accident". Epidemiology. 1997 Nov;8(6):646–652. [PubMed]
  • Pesatori AC, Zocchetti C, Guercilena S, Consonni D, Turrini D, Bertazzi PA. Dioxin exposure and non-malignant health effects: a mortality study. Occup Environ Med. 1998 Feb;55(2):126–131. [PMC free article] [PubMed]
  • Bertazzi A, Pesatori AC, Consonni D, Tironi A, Landi MT, Zocchetti C. Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin. Epidemiology. 1993 Sep;4(5):398–406. [PubMed]
  • Bertazzi PA. Industrial disasters and epidemiology. A review of recent experiences. Scand J Work Environ Health. 1989 Apr;15(2):85–100. [PubMed]
  • Kelling CK, Menahan LA, Peterson RE. 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. [PubMed]
  • Hermansky SJ, Holcslaw TL, Murray WJ, Markin RS, Stohs SJ. 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. [PubMed]
  • Brewster DW, Bombick DW, 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. [PubMed]
  • Canga L, Levi R, Rifkind AB. 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. [PMC free article] [PubMed]
  • Kociba RJ, Keyes DG, Beyer JE, Carreon RM, Wade CE, Dittenber DA, Kalnins RP, Frauson LE, Park CN, Barnard SD, et al. 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. [PubMed]
  • Allen JR, Barsotti DA, Van Miller JP, Abrahamson LJ, Lalich JJ. 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. [PubMed]
  • Gasiewicz TA, Neal RA. 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. [PubMed]
  • Brewster DW, 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. [PubMed]
  • Speizer FE, Tager IB. Epidemiology of chronic mucus hypersecretion and obstructive airways disease. Epidemiol Rev. 1979;1:124–142. [PubMed]
  • 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. [PubMed]
  • Ott MG, 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. [PMC free article] [PubMed]
  • Kogevinas M, Becher H, Benn T, Bertazzi PA, Boffetta P, Bueno-de-Mesquita HB, Coggon D, Colin D, Flesch-Janys D, Fingerhut M, et al. Cancer mortality in workers exposed to phenoxy herbicides, chlorophenols, and dioxins. An expanded and updated international cohort study. Am J Epidemiol. 1997 Jun 15;145(12):1061–1075. [PubMed]
  • Fingerhut MA, Halperin WE, Marlow DA, Piacitelli LA, Honchar PA, Sweeney MH, Greife AL, Dill PA, Steenland K, Suruda AJ. Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. N Engl J Med. 1991 Jan 24;324(4):212–218. [PubMed]
  • Bueno de Mesquita HB, Doornbos G, Van der Kuip DA, Kogevinas M, Winkelmann R. Occupational exposure to phenoxy herbicides and chlorophenols and cancer mortality in The Netherlands. Am J Ind Med. 1993 Feb;23(2):289–300. [PubMed]
  • Kogevinas M, Kauppinen T, Winkelmann R, Becher H, Bertazzi PA, Bueno-de-Mesquita HB, Coggon D, Green L, Johnson E, Littorin M, et al. Soft tissue sarcoma and non-Hodgkin's lymphoma in workers exposed to phenoxy herbicides, chlorophenols, and dioxins: two nested case-control studies. Epidemiology. 1995 Jul;6(4):396–402. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...