Important aspects of the evidence for TCDD carcinogenicity in man

Most of the evidence for the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in humans has centered on whether TCDD causes soft-tissue sarcomas (STS) and malignant lymphomas (ML). Recently, reports from two of the largest occupational cohort studies have become available. A critical reappraisal of these and other recent reports indicates that it is unlikely that TCDD causes malignant lymphomas in humans. For STS, the evidence for an etiologic role for TCDD is not convincing. However, more data and further clarification are needed before a clear and objective evaluation can be made. Factors such as level of exposure, sex, and host susceptibility may be critical determinants of whether cancer occurs; there is evidence from both humans and animals that these factors play a role, and therefore these factors should be considered in future evaluations. There is a serious need to rule out the possibility that observed effects are due to other concomitant exposures. Consideration of the carcinogenic effects of TCDD in animals reveals consistency with the human data and points to other cancers such as those of the thyroid gland and lung, for example, which are more likely candidates for investigating the role of TCDD in their occurrence, while at the same time providing a basis for a better understanding and interpretation of the human data. There are now sufficient epidemiologic studies in place that will provide a better climate for a definitive evaluation in the near future.