No 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

Thyroid folliclar celi tumor arise in rodents from mutations, perturbations of thyroid and pituitay hormone status with increased sution of thyroid cell growth by thyroid-stimulating hormone (TSH), or a combination of the two. The only kown 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) chemical induced rodent thyroid tumors are presumed to be relevnt to humans; 2) when interspecies information is lacking the default is to asme comparble carcinogenic senitivity in rodents and humans; 3) adverse rodent noncancer thyroid effe due to chemically induced thyroid-pituity disruption are presumed to be relevant to humans; 4) linear dose-response considerations are applied to thyroid cancer induced by chemical substaces 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 mutanic acivity, and 6) nonlinear conideions may be applied in thyroid cancer dose-response assessments on a caseby-case basis for chemicalls that disrupt thyroid-pituitary functioning and demonstrate some mutagenic activity. Required data for risk asessment purposes is mode of action information on mutgenicity, increases in follicular cell growth (cell size and number) and thyroid gland weight, thyroid-pituitary honrones, site of action, correlations between doses producing thyroid effects and cancer, and reversibility of effet when dosing ceases. Key won iodide pump, microsomal enzyme induction, 5'-monodeiodinase, ris assessment, thyroid follicular cell tumors, thyroid hormone (T4, T3), thyroid p ida, throid-smulating hormone (TSH), UDP glucuronosyl trnsferase.

Although chloroform (CHCl3) is metabolized in vivo and in vitro to a substance that covalently interacts with protein and lipid, its potential for binding to DNA is low. In addition, most of the assays for genotoxicity are negative. However, many of the genotoxicity results are inconclusive because of inadequacies in the experimental protocols. The types of genotoxicity tests this report is based on include bacterial, yeast, host-mediated, Drosophila sex-linked recessive lethal, mammalian cell mutagenicity, sperm head abnormality, cytogenetic, and DNA damage. On the basis of presently available information, no definitive conclusion on the mutagenic potential of CHCl3 can be reached.

Background: In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion) and for the day (e.g., rest and low melatonin secretion). Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition.