Hill R N, Crisp T M, Hurley P M, Rosenthal S L, Singh D V
Office of Prevention, Pesticides and Toxic Substances, U.S. Environmental Protection Agency, Washington, DC 20460 USA.
Environ Health Perspect. 1998 Aug;106(8):447-57. doi: 10.1289/ehp.98106447.
Thyroid follicular cell tumors arise in rodents from mutations, perturbations of thyroid and pituitary hormone status with increased stimulation of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only known human thyroid carcinogen is ionizing radiation. It is not known for certain whether chemicals that affect thyroid cell growth lead to human thyroid cancer. The U.S. Environmental Protection Agency applies the following science policy positions: 1) chemically induced rodent thyroid tumors are presumed to be relevant to humans; 2) when interspecies information is lacking, the default is to assume comparable carcinogenic sensitivity in rodents and humans; 3) adverse rodent noncancer thyroid effects due to chemically induced thyroid-pituitary disruption are presumed to be relevant to humans; 4) linear dose-response considerations are applied to thyroid cancer induced by chemical substances that either do not disrupt thyroid functioning or lack mode of action information; 5) nonlinear thyroid cancer dose-response considerations are applied to chemicals that reduce thyroid hormone levels, increase TSH and thyroid cell division, and are judged to lack mutagenic activity; and 6) nonlinear considerations may be applied in thyroid cancer dose-response assessments on a case-by-case basis for chemicals that disrupt thyroid-pituitary functioning and demonstrate some mutagenic activity. Required data for risk assessment purposes is mode of action information on mutagenicity, increases in follicular cell growth (cell size and number) and thyroid gland weight, thyroid-pituitary hormones, site of action, correlations between doses producing thyroid effects and cancer, and reversibility of effects when dosing ceases.
甲状腺滤泡细胞肿瘤在啮齿动物中由突变、甲状腺和垂体激素状态的紊乱（促甲状腺激素（TSH）对甲状腺细胞生长的刺激增加）或两者共同作用引起。已知的唯一人类甲状腺致癌物是电离辐射。目前尚不确定影响甲状腺细胞生长的化学物质是否会导致人类甲状腺癌。美国环境保护局采用以下科学政策立场：1）化学诱导的啮齿动物甲状腺肿瘤被推定为与人类相关；2）当缺乏种间信息时，默认假设啮齿动物和人类具有可比的致癌敏感性；3）化学诱导的甲状腺-垂体功能紊乱导致的啮齿动物非癌性甲状腺效应被推定为与人类相关；4）线性剂量反应考虑适用于不破坏甲状腺功能或缺乏作用方式信息的化学物质诱导的甲状腺癌；5）非线性甲状腺癌剂量反应考虑适用于降低甲状腺激素水平、增加TSH和甲状腺细胞分裂且被判定缺乏诱变活性的化学物质；6）对于破坏甲状腺-垂体功能并表现出一定诱变活性的化学物质，非线性考虑可能在甲状腺癌剂量反应评估中逐案应用。风险评估所需的数据是关于诱变性、滤泡细胞生长增加（细胞大小和数量）、甲状腺重量、甲状腺-垂体激素、作用部位、产生甲状腺效应和癌症的剂量之间的相关性以及给药停止后效应的可逆性的作用方式信息。
