Thirty-four-year mortality follow-up of BASF employees exposed to 2,3,7,8-TCDD after the 1953 accident

  • Andreas Zober
  • Peter Messeren
  • Peter Hubert
Original Articles


2,3,7,8-Tetrachlorodibenzodioxin (TCDD) was formed in an uncontrolled decomposition reaction at BASF Aktiengesellschaft on 17 November 1953. This report presents the findings of a 34-year mortality follow-up study of 247 workers who were partly heavily exposed; 78 thereof had died. We divided these employees into three cohorts based on the amount and reliability of the exposure information. The mortality was compared with the national mortality rates in the Federal Republic of Germany (FRG) and is presented in terms of standardized mortality ratios (SMRs) together with 90% confidence intervals (CI) for different periods of time since the first exposure. In general, the overall mortality of these workers was similar to the rates of the national population. The SMR for all malignant neoplasms based on 23 deaths was 117 (90% CI: 80, 166), suggesting no overall increase in cancer among those employees. When workers with chloracne were examined separately, the SMR for all malignant neoplasms was not significantly elevated overall (SMR 139; 87, 211), but it was for the time period 20 or more years after the first exposure (SMR 201; 122, 315). Results for 22 causes of death as well as additional information on the type of exposure and skin findings are presented and discussed in relation to the current literature. In general, our results do not appear to support a strong association between cancer mortality and TCDD, but they do suggest that some hazard may have been produced.

Key words

Industrial accident TCDD Mortality study Chloracne Carcinogenicity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Assennato G, Cervino D, Emmett EA, Longo G, Merlo F (1989) Follow-up of subjects who developed chloracne following TCDD exposure at Seveso. Am J Ind Med 16:119–125PubMedGoogle Scholar
  2. Baader EW, Bauer HJ (1951) Industrial intoxication due to pentachlorphenol. Ind Med Surg 20:286–290PubMedGoogle Scholar
  3. Bauer H, Schulz KH, Spiegelberg U (1961) Berufliche Vergiftung bei der Herstellung von Chlorphenol-Verbindungen. Arch Gewerbepathol Gewerbehyg 18:538–555CrossRefPubMedGoogle Scholar
  4. Beck H, Eckart K, Mathar W, Wittkowski R (1989) Levels of PCDD's and PCDF's in adipose tissue of occupationally exposed workers. Chemosphere 18:507–516CrossRefGoogle Scholar
  5. Becker N, Frentzel-Beyme R, Wagner G (1984) Atlas of Cancer Mortality in the Federal Republic of Germany. Springer, Berlin Heidelberg NewYorkGoogle Scholar
  6. Bertazzi PA, Zocchetti C, Pesatori AC, Guercilena S, Sanarico M, Radice L (1989) Ten-year mortality study of the population involved in the Seveso incident in 1976. Am J Epidemiol 129:1187–1200PubMedGoogle Scholar
  7. Bettmann (1901) “Chlor-Akne”, eine besondere Form von professioneller Hauterkrankung. Dtsch Med Wochenschr 27:437–440Google Scholar
  8. Bleiberg J, Wallen M, Brodkin R, Applebaum JL (1964) Industrially acquired porphyria. Arch Dermatol 89:793–797PubMedGoogle Scholar
  9. Bond GG, Ott MG, Brenner FE, Cook RR (1983) Medical and morbidity surveillance findings among employees potentially exposed to TCDD. Br J Ind Med 40:318–324PubMedGoogle Scholar
  10. Bond GG, Cook RR, Brenner FE, McLaren EA (1987) Evaluation of mortality patterns among chemical workers with chloracne. Chemosphere 16:2117–2121Google Scholar
  11. Bond GG, McLaren EA, Lipps TE, Cook RR (1989) Update of mortality among chemical workers with potential exposure to the higher chlorinated dioxins. J Occup Med 31:121–123PubMedGoogle Scholar
  12. Butler MG (1937) Acneform dermatosis produced by ortho(2chlorophenyl)phenol sodium and tetra-chlorphenol sodium. Arch Derm Syph 35:251–254Google Scholar
  13. Cook RR, Townsend JC, Ott MG, Silverstein LG (1980) Mortality experience of employees exposed to 2,3,7,8-TCDD. J Occup Med 22:530–532Google Scholar
  14. Cook RR, Bond GG, Olson RA, Ott MG, Gondek MR (1986) Evaluation of the mortality experience of workers exposed to chlorinated dioxins. Chemosphere 15:1769–1776CrossRefGoogle Scholar
  15. Cook RR, Bond GG, Olson RA, Ott MG (1987) Update of the mortality experience of workers exposed to chlorinated dioxins. Chemosphere 16:2111–2116CrossRefGoogle Scholar
  16. Dalderup LM, Zellenrath D (1983) Dioxin exposure: 20 year follow up. Lancet II:1134–1135Google Scholar
  17. Dugois P, Maréchal J, Colomb L (1958) Acné chlorique au 2,4,5 trichlorophenol. Arch Mal Prof 19:626–627PubMedGoogle Scholar
  18. Dugois P, Amblard P, Aimard M, Deshors G (1968) Acné chlorique collective et accidentelle d'un type nouveau. Bull Soc Fr Dermatol Syph 75:260–261Google Scholar
  19. EPA (1985) Report: health assessment document for polychlorinated dibenzo-p-dioxins. (EPA/600/8-84/014F). Washington, D.C.Google Scholar
  20. Eriksson M, Hardell L, Berg NO, Moller T, Axelson O (1981) Soft-tissue sarcomas and exposure to chemical substances: a case-referent study. Br J Ind Med 38:27–33PubMedGoogle Scholar
  21. Fuss S (1938) Chloracne. Zentralbl Haut Geschl Krankh 57:250Google Scholar
  22. Gardner MJ (1986) Considerations in the choice of expected numbers for appropriate comparisons in occupational cohort studies. Med Lav 77:23–47PubMedGoogle Scholar
  23. Gardner MJ, Altman DG (1989) Statistics with confidence. British Medical Journal, LondonGoogle Scholar
  24. Goldmann P (1972a) Schwerste akute Chlorakne durch Trichlorphenol-Zersetzungsprodukte. Arbeitsmed Sozialmed Arbeitshyg 7:12–18CrossRefPubMedGoogle Scholar
  25. Goldmann P (1972b) Schwerste akute Chlorakne — eine Massenintoxikation durch 2,3,6,7-Tetrachlordibenzodioxin. Proceedings of the International Conference Medichem, 27–29 April, Ludwigshafen, pp 220–227Google Scholar
  26. Goldmann P (1973) Schwerste akute Chlorakne, eine Massenintoxikation durch 2,3,6,7-Tetrachlordibenzodioxin. Hautarzt 24:149–152Google Scholar
  27. Greenlee WF (1988) Dioxin carcinogenesis — a perspective. cmCIIT-Activities 8:2–6Google Scholar
  28. Grimmer H (1954) Beruflich bedingte Akne durch chlorierte aromatische Kohlenwasserstoffe. Zentralbl Arbeitsmed Arbeitsschutz 5:76–83Google Scholar
  29. Hardell L, Sandstrom A (1979) A case-control study: soft tissue sarcomas and exposure to phenoxyacetic acids or chlorophenols. Br J Cancer 39:711–717PubMedGoogle Scholar
  30. Hardell L, Eriksson M (1988) The association between soft tissue sarcomas and exposure to phenoxyacetic acids — a new casereferent study. Cancer 62:652–656PubMedGoogle Scholar
  31. Hay A, Silbergeld E (1985) Assessing the risk of dioxin exposure. Nature 315:102Google Scholar
  32. Herxheimer K (1899) Über Chlorakne. Münch Med Wochenschr 46:278Google Scholar
  33. Hill ID (1972) Computing man years at risk. Br J Prev Soc Med 26:132–134Google Scholar
  34. Hoar SK, Blair A, Holmes FF, Boysen DC, Robel JR, Hoover R, Flammen JF (1986) Agricultural herbicide use and risk of lymphoma and soft tissue sarcoma. JAMA 256:1151–1157Google Scholar
  35. Hoffmann H (1957) Neue Erfahrungen mit hochtoxischen Chlorkohlenwasserstoffen. Arch Exp Pathol Pharmacol 232:228–230Google Scholar
  36. Hofmann MF, Meneghini CL (1962) A proposito delle follicolosi da idrocarburi clorosostituiti (acne clorica). G Ital Dermatol 103:427–450Google Scholar
  37. IARC (1987) IARC monographs on the evaluation of carcinogenic risks to humans, supplement 7. IARC, Lyon, pp 350–354Google Scholar
  38. Jensen NE (1972) Chloracne: three cases. Proc R Soc Med 65:21–22Google Scholar
  39. Jirasek L, Kalensky J, Kubec K, Pazderova J, Lukas E (1976) Chlorakne, Porphyria cutanea tarda und andere Intoxikationen durch Herbizide. Hautarzt 27:328–333Google Scholar
  40. Karmaus W (1986) Der Dioxin-Unfall bei BASF 1953 und der Nachweis einer Krebsursache beim Menschen. In: Elsner G, Karmaus W, Lißner L (eds) Muß Arbeit krank machen? VSA, Hamburg, pp 158–167Google Scholar
  41. Kimmig J, Schulz KH (1957) Chlorierte aromatische zyklische Äther als Ursache der sogenannten Chlorakne. Naturwissenschaften 44:337–338Google Scholar
  42. Kociba RJ, Keyes DG, Beyer JE, Carreon RM, Wade CE, Dittenber DA, Kalnins RP, Franson LE, Park CN, Bernard SD, Hummel RA, Humiston CG (1978) Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-TCDD in rats. Toxicol Appl Pharmacol 46:279–303CrossRefPubMedGoogle Scholar
  43. Lauer H (1986) Das „Untersuchungsprogramm Dioxin” der Berufsgenossenschaft der chemischen Industrie. Arbeitsmed Sozialmed Präventivmed 21:206–207Google Scholar
  44. Lehnert G, Szadkowski D (1985) Zur Humankanzerogenität von 2,3,7,8-TCDD. Arbeitsmed Sozialmed Präventivmed 20:225–232Google Scholar
  45. Leserforum Dioxin (1986) Arbeitsmed Sozialmed Präventivmed 21:153–175Google Scholar
  46. Lever WF, Schaumburg-Lever G (1983) Histopathology of the skin, 6th edn. Lippincott, Philadelphia, pp 577–579Google Scholar
  47. MAK-Werte. Toxikologisch-arbeitsmedizinische Begründung (1986) 2,3,7,8-TCDD. Verlag Chemie, WeinheimGoogle Scholar
  48. May G (1973) Chloracne from the accidental production of tetrachlorodibenzodioxin. Br J Ind Med 30:276–283PubMedGoogle Scholar
  49. May G (1982) Tetrachlorodibenzodioxin: a survey of subjects ten years after exposure. Br J Ind Med 39:128–135PubMedGoogle Scholar
  50. Monk M (1987) Epidemiology of suicide. Epid Rev 9:51–69Google Scholar
  51. Moses M, Lilis R, Crow KD, Thornton J, Fischbein A, Anderson HA, Selikoff IJ (1984) 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 5:161–182Google Scholar
  52. MRC (Medical Research Council) (1984) Environmental Epidemiology Unit. Expected numbers in cohort studies. Scientific report no 6. MRC, SouthamptonGoogle Scholar
  53. NN (1954) Hautschädigungen durch unbekannte Zersetzungsprodukte. BASF, Ludwigshafen. Arbeitsschutz im Werk 3:11–12Google Scholar
  54. Oliver RM (1975) Toxic effects of 2,3,7,8-TCDD in laboratory workers. Br J Ind Med 32:49–53Google Scholar
  55. Ott MG, Holder BB, Olson RD (1980) A mortality analysis of employees engaged in the manufacture of 2,4,5-T. J Occup Med 22:47–50Google Scholar
  56. Ott MG, Olson RA, Cook RR, Bond GG (1987) Cohort mortality study of chemical workers with potential exposure to the higher chlorinated dioxins. J Occup Med 29:5,422–429PubMedGoogle Scholar
  57. Patterson DG, Fingerhut MA, Roberts DW, Needham LL, Haring Sweeney M, Marlow DA, Andrews JS, Halperin WE (1989) Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Am J Ind Med 16:135–146PubMedGoogle Scholar
  58. Pazderova-Vejlupkova J, Nêmcova M, Pickova J, Jirasek L (1981) The development and prognosis of chronic intoxication by TCDD in men. Arch Env Health 36:5–11Google Scholar
  59. Pitot HC, Goldsworthy T, Campbell HA, Poland A (1980) Quantitative evaluation of the promotion by 2,3,7,8-TCDD of hepatocarcinogenesis from diethylnitrosamine. Cancer Res 40:3616–3620Google Scholar
  60. Poland AP, Smith D, Metter G, Possick P (1971) A health survey of workers in a 2,4-D and 2,4,5-T plant. Arch Environ Health 22:316–327Google Scholar
  61. Poland A, Palen D, Glover E (1982) Tumour promotion by TCDD in skin of HRS/J hairless mice. Nature 300:271–273PubMedGoogle Scholar
  62. Reggiani G (1981) Toxicology of TCDD. Reg Toxicol Pharmacol 1:211–243Google Scholar
  63. Reggiani G (1988) The Seveso, Italy episode — July 10, 1976. In: Young AL, Reggiani GM (eds) Agent orange. Elsevier, Amsterdam New York Oxford, pp 225–269Google Scholar
  64. Rubinstein LJ (1972) Atlas of tumor pathology, second series, fascicle 6. Tumors of the central nervous system. Armed Forces Institute of Pathology, Washington, D.C.Google Scholar
  65. Schecter A, Ryan JJ (1988) Polychlorinated dibenzo-para-dioxin and dibenzofuran levels in human adipose tissues from workers 32 years after occupational exposure to 2,3,7,8-TCDD. Chemosphere 17:915–920Google Scholar
  66. Schmidt W, Boslet W (1956) Zur Kenntnis bleibender Hautveränderungen bei Chlorakne-Kranken. Berufsdermatol 4:109–123Google Scholar
  67. Schulz KH (1957) Klinische und experimentelle Untersuchungen zur Ätiologie der Chlorakne. Arch Klin Exp Dermatol 206:589–596Google Scholar
  68. Skene SA, Dewhurst IC, Greenberg M (1989) Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans: The risks to human health. A review. Human Toxicol 8:173–203Google Scholar
  69. Sobel W, Bond GG, Skowronski BJ, Brownson PJ, Cook RR (1987) A soft tissue sarcoma case control study in a large multichemical manufacturing facility. Chemosphere 16:2095–2099Google Scholar
  70. Stingily KO (1940) A new industrial chemical dermatitis. South Med J 33:1268–1272Google Scholar
  71. Suskind RR (1983) Long-term health effects of exposure to 2,4,5-T and/or its contaminants. Chemosphere 12:769Google Scholar
  72. Suskind RR, Hertzberg VS (1984) Human health effects of 2,4,5-T and its toxic contaminants. JAMA 251:2372–2380PubMedGoogle Scholar
  73. Telegina KA, Bikbulatova LI (1970) Affection of the follicular apparatus of the skin in workers occupied in production of butylether of 2,4,5-T. Vest Dermatol Venerol 44:35–38Google Scholar
  74. Thaler H (1987) Leberkrankheiten. Springer, Berlin Heidelberg New YorkGoogle Scholar
  75. Thiess AM, Frentzel-Beyme R (1977) Mortality study of persons exposed to dioxin following an accident which occurred in the BASF on 17 November 1953. Proceedings of the V. International Conference Medichem, San Francisco, 228–236 September 1977Google Scholar
  76. Thiess AM, Goldmann P (1976) Follow-up Report über das Trichlorphenol-Dioxin-Unfallgeschehen in der BASF AG vom 17. November 1953. Proceedings of the IV. International Conference Medichem, Haifa, 174–179, 7–10 September 1976Google Scholar
  77. Thiess AM, Frentzel-Beyme R, Link R (1982) Mortality study of persons exposed to dioxin in a trichlorophenol-process accident that occurred in the BASF AG on November 17, 1953. Am J Ind Med 3:179–189PubMedGoogle Scholar
  78. TRGS 910 (1988) Begründung für die Einstufung... 2,3,7,8-TCDD. Bundesarbeitsbl 3:88–89Google Scholar
  79. UBA (Umweltbundesamt) (1985) Sachstand Dioxine Berichte 5/85. E Schmidt, BerlinGoogle Scholar
  80. VDI (Verein Deutscher Ingenieure) (1987) Dioxin. VDI-Verlag, DüsseldorfGoogle Scholar
  81. Wicklund K, Dich J, Holm LE (1988) Soft tissue sarcoma risk in Swedish licensed pesticide applicators. J Occup Med 30:801–804PubMedGoogle Scholar
  82. Young AL, Reggiani GM (eds) (1988) Agent orange and its associated dioxin: assessment of a controversy. Elsevier, Amsterdam New York OxfordGoogle Scholar
  83. Zack JA, Gaffey WR (1983) A mortality study of workers employed at the Monsanto company plant in Nitro, West Virginia. In: Tucker RE, Young AL, Gray AP (eds) Human and environmental risks of chlorinated dioxins and related compounds. Plenum Press, New York, pp 575–591Google Scholar
  84. Zack JA, Suskind R (1980) The mortality analysis of employees engaged in the manufacture of 2,4,5trichlorophenoxyacetic acid. J Occup Med 22:11–14Google Scholar
  85. Zelikov AX, Danilov LN (1974) Professional dermatosis in a worker in 2,4,5-T production. Sov Med 7:145–146PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Andreas Zober
    • 1
  • Peter Messeren
    • 1
  • Peter Hubert
    • 2
  1. 1.Occupational Medical and Health Protection DepartmentBASF AktiengesellschaftLudwigshafenGermany
  2. 2.Occupational Safety and Employee Protection DepartmentBASF AktiengesellschaftLudwigshafenGermany

Personalised recommendations