Dioxin and cancer: a critical review
Introduction
This document is a three-part review of the evidence on the hypothetical cause–effect relationship between exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (hereafter, TCDD) and cancer in human beings. Part I focuses on the evidence available through 1997 with emphasis on the review done by the International Agency for Research on Cancer (IARC) in its 1997 Monograph 69 (IARC, 1997). IARC’s decision to place TCDD in Group 1 (agents with sufficient evidence of carcinogenicity for humans) is unsupportable because it depends on an analogy of mechanisms of carcinogenicity between animals and humans and on an inappropriate evaluation of the epidemiologic evidence.
Part II presents a similar approach to subsequent epidemiologic reports and concludes that the most recent literature further weakens the evidence concerning the potential carcinogenicity of TCDD in humans. Part III addresses the current version of the US Environmental Protection Agency’s ongoing risk assessment.
Because of the many negative studies of TCDD and cancer in humans and the weaknesses and inconsistencies even among the positive studies published before and since 1997, we suggest that the existing evidence would exclude TCDD from IARC’S Group 1.
Section snippets
Part I. The IARC evaluation
The carcinogenicity of TCDD for humans has been controversial for a long time, but it was its designation in 1997 as carcinogenic to humans (Group 1) by the IARC of the World Health Organization that focused the controversy on the specific issues of the epidemiologic evidence linking TCDD with cancer and on TCDD’s possible mode of action as a carcinogen (IARC, 1997). For decades, the necessary criterion for inclusion of an agent in Group 1 was that there existed sufficient evidence of
Part II. Epidemiologic studies after 1997
In this section we review epidemiologic studies appearing after the publication of the IARC Monograph 69. Special attention is given to studies that were published in major journals or that received wide publicity.
In the update of the NIOSH follow-up study, Steenland et al. (1999) state that, “In 1997, the International Agency for Research on Cancer (IARC) classified 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a group 1 human carcinogen, based largely on four highly exposed industrial cohorts
Part III. Comments on USEPA’s dose–response assessment and risk characterization of the potential human carcinogenicity of TCDD
As concluded previously, the data available to IARC for its 1997 monograph, and all data published subsequent to that review do not support a conclusion that TCDD is carcinogenic in humans. It is inappropriate, therefore, to engage in detailed evaluations of a potential dose–response relationship between TCDD and a cancer endpoint. Nevertheless, USEPA conducted such an evaluation in the Integrated Summary and Risk Characterization Section of its reassessment (US EPA, 2000). For this reason, it
Conclusion
It is clear from this review that the evidence does not support the IARC’s classification of TCDD as a Group 1 carcinogen. In fact, the evidence indicates that TCDD is not carcinogenic to human beings at low levels and that it may not be carcinogenic to them even at high levels.
Acknowledgements
The assistance of Pam Chapman and Sean Hays is gratefully acknowledged. The project was sponsored by the Chlorine Chemistry Council.
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