RISK ASSESSMENT OF THYROID FOLLICULAR CELL TUMORS

Thyroid follicular cell tumors arise in rodents from mutations, pertur bations of thyroid and pituitary hormone status with increased stimula tion of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only known human thyroid carcinogen is io nizing radiation. It is not known for certain whether chemicals that a ffect thyroid cell growth lead to human thyroid cancer. The U.S. Envir onmental Protection Agency applies the following science policy positi ons: 1) chemically induced rodent thyroid tumors are presumed to be re levant to humans; 2) when interspecies information is lacking, the def ault is to assume comparable carcinogenic sensitivity in rodents and h umans; 3) adverse rodent noncancer thyroid effects due to chemically i nduced thyoid-pituitary disruption are presumed to be relevant to huma ns; 4) linear dose-response considerations are applied to thyroid canc er induced by chemical substances that either do not disrupt thyroid f unctioning or lack mode of action information; 5) nonlinear thyroid ca ncer dose-response considerations are applied to chemicals that reduce thyroid hormone levels, increase TSH and thyroid cell division, and a re judged to lack mutagenic activity; and 6) nonlinear considerations may be applied in thyroid cancer dose-response assessments on a case-b y-case basis for chemicals that disrupt thyroid-pituitary functioning and demonstrate some mutagenic activity Required data for risk assessm ent purposes is mode of action information on mutagenicity, increases in follicular cell growth (cell size and number) and thyroid gland wei ght, thyroid-pituitary hormones, site of action, correlations between doses producing thyroid effects and cancer, and reversibility of effec ts when dosing ceases.