Risk assessment of thyroid follicular cell tumors.

Abstract

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.ImagesFigure 1Figure 2Figure 3

Cancer Mortality in Agricultural Regions of Minnesota

“…In terms of etiology, the causative agent for the observed increase in thyroid cancer mortality is uncertain. To date, no pesticides have been proven to be carcinogenic to the human thyroid (25,27). Heavy use of chlorophenoxy herbicides in western Minnesota creates concern for elevated dioxin levels in this population.…”

“…Mechanistically, ETU decreases thyroxine and increases thyroidstimulating hormones, as well as causes thyroid and liver neoplasms in rodents. ETU is a thyroid peroxidase inhibitor in rodent studies, disrupting the thyroid-pituitary homeostasis (25,27). Besides their effect on the thyroid, EBDCs are also teratogenic in rodents, causing damaging effects in the gonads of both male and female rats, which successful for the more common forms of this disease, with a 5-year survival rate of over 90% (23)(24)(25).…”

“…ETU is a thyroid peroxidase inhibitor in rodent studies, disrupting the thyroid-pituitary homeostasis (25,27). Besides their effect on the thyroid, EBDCs are also teratogenic in rodents, causing damaging effects in the gonads of both male and female rats, which successful for the more common forms of this disease, with a 5-year survival rate of over 90% (23)(24)(25). Clearly mortality data underestimate the number of people with --result in decreased fertility and malformations in the offspring (28 Tables 1 and 3 (only four deaths were reported for each category), they are worth noting because the thyroid, testis, thymus, and other endocrine glands are organs susceptible to endocrine disruption.…”

Scientific Opinion on Polybrominated Diphenyl Ethers (PBDEs) in Food

“…transthyretin and thyroid binding globulin (Capen, 1997;Hill et al, 1998). In the case of PBDEs differences in changes in total serum T4 between rodents and humans may arise from the differences in activation of pregnane X receptors that leads to up-regulation of hepatic catabolic enzymes and a subsequent decline in circulating T4 concentrations (Schuetz et al, 1998).…”

Risk factors for thyroid cancer: A prospective cohort study

“…However, given that the incidence of thyroid cancer is consistently higher in women than in men 3,4 and the finding that estrogen receptors are present in papillary and follicular thyroid carcinomas (the 2 major histologic subtypes of thyroid cancer), 4 it has been hypothesized that hormonal factors may be involved in the etiology of thyroid cancer. Furthermore, there is experimental evidence that elevated thyroid-stimulating hormone (TSH) levels may play a role in the development of thyroid carcinomas [5][6][7][8][9] and epidemiologic evidence that smoking [10][11][12][13] and alcohol consumption 14 may be inversely associated with TSH production, which suggests that they might be inversely associated with thyroid cancer risk.…”