EPA conducts risk assessments on chemicals for carcinogenicity under the guidance provided in its cancer risk assessment guidelines (U.S. EPA, 1986a; 1996). From time to time scientific developments prompt the Agency to reexamine procedures that are generally applied. That is the case with the review of some chemicals that have produced thyroid follicular cell tumors in experimental animals. The purpose of this document is to describe the procedures EPA will use to evaluate these tumors and the data that are needed to make these judgments.

The report presents science policy guidance that describes the procedures the Agency will use in the evaluation of potential human cancer hazard and dose-response assessments from chemicals that are animal thyroid carcinogens. The Forum Report describes when, under clearly specified conditions, chemical carcinogenesis in thyroid follicular cells can be analyzed as a nonlinear phenomenon, rather than assuming low dose linearity as EPA customarily does for carcinogenic compounds.

Four hypothetical case studies are summarized which illustrate how to evaluate toxicological data and make hazard and dose-response estimation choices. The procedures and considerations developed in the Forum Report embody current scientific knowledge of thyroid carcinogenesis and evolving science policy. Should significant new information become available, the Agency will update its guidance accordingly.

Citation

U.S. EPA. Assessment of Thyroid Follicular Cell Tumors. U.S. Environmental Protection Agency, Washington, DC, EPA/630/R-97/002, 1998.

Document Details and Links

Default assumptions that in the absence of relevant data help guide EPA in the use of animal data in evaluating potential human hazards and risks include the following:

1. Tumors in animals are indicators of potential carcinogenic hazards in humans
2. Humans are generally as sensitive or more sensitive to effects of chemicals than are test animals
3. For carcinogens, dose and response maintain a linear relationship from high dose to zero dose, based on an assumption that chemicals act by affecting DNA directly to cause mutations

This paper reviews the evidence concerning these presumptions for thyroid follicular cell tumors and indicates that they do not entirely hold for some thyroid carcinogens. Data requirements for substantiating and describing thyroid effects of a chemical are elaborated.

• Assessment of Thyroid Follicular Cell Tumors (PDF)(51 pp, 255 K, March 1998, 630-R-97-0)
• Assessment of Thyroid Follicular Cell Tumors: Appendix A: Case Study of Compounds (PDF)(118 pp, 4 MB)