Thyroid gland neoplasia: non-genotoxic mechanisms

There are two basic mechanisms whereby chemicals produce thyroid gland neoplasia in rodents. The first involves chemicals that exert a direct carcinogenic effect in the thyroid gland and the other involves chemicals which, through a variety of mechanisms, disrupt thyroid function and produce thyroid gland neoplasia secondary to hormone imbalance. There are important species differences in thyroid gland physiology between rodents and humans which may account for a marked species difference in the inherent susceptibility for neoplasia secondary to hormone imbalance. Thus, it is important to consider mechanism in the evaluation of potential cancer risks. There would be little if any risk for apparently nongenotoxic chemicals that act secondary to hormone imbalance at exposure levels that do not disrupt thyroid function. Further, the degree of thyroid dysfunction produced by a chemical would present a major toxicological problem before such exposure would increase the risk for neoplasia for humans.