Thyroid Function and Thyroid Tumors in Toxaphene-Treated Rats

Environmental occurrence, analysis, and toxicology of toxaphene compounds.

“…The study in which neoplasms were found in the thyroid gland of the rat were conducted by the National Cancer Institute (218). In order to investigate whether the increased incidence in thyroid tumours seen in the rat in the National Cancer Institute bioassay of toxaphene may have had a nongenotoxic aetiology, Waritz et al (219) studied the thyroid function and thyroid tumours in male Crl:Cd BR (Sprague-Dawley derived) rats orally exposed to 75 mg toxaphene kg -1 day -1 for 28 days (the first 4 days, 100 mg toxaphene kg -1 day -1 was administered). Rats were sacrificed at day 0, 7, 14 and 28 of exposure.…”

Risk Assessment of Toxaphene and its Breakdown Products: Time for a Change?

“…Therefore, the results of the 1979 NCI bioassay are not appropriate to use for risk assessment purposes. Waritz et al (1996) demonstrated that toxaphene causes increased thyroid-stimulating hormone (TSH) production, resulting in thyroid follicular-cell hypertrophy and hyperplasia following short-term exposures. These findings are typical in the rat following cytochrome P-450 (P450) enzyme induction in the liver, which results in an increased metabolic inactivation of circulating thyroid hormone and subsequent stimulation of the thyroid by TSH (Waritz et al, 1996).…”

“…Waritz et al (1996) demonstrated that toxaphene causes increased thyroid-stimulating hormone (TSH) production, resulting in thyroid follicular-cell hypertrophy and hyperplasia following short-term exposures. These findings are typical in the rat following cytochrome P-450 (P450) enzyme induction in the liver, which results in an increased metabolic inactivation of circulating thyroid hormone and subsequent stimulation of the thyroid by TSH (Waritz et al, 1996). The rat is far more sensitive to this phenomenon than the human because of the relatively low reserve of circulating thyroid hormone in the rat compared to the human, the greatly reduced protein binding in the rat, and the shorter half-life of the circulating thyroid hormones.…”

Toxaphene [MAK Value Documentation, 2003]

“…Hormone analysis and the histological findings in rats (see Section 5.2.1) together with data from the literature led the authors to conclude that toxaphene is a cytochrome P450 inducer of phenobarbital type and causes induction of enzymes such as glucuronosyl transferases. This results in an increased breakdown of thyroxine (T 4 ) (Waritz et al 1996). As rats do not have the specific T 4 -binding globulins (Capen andMartin 1989, Curran andDeGroot 1991) which are essential for the storage of thyroid hormones, they are unable to compensate fluctuations in the T 4 level.…”

“…Histological examination of the thyroid gland at the end of the study revealed follicle cell hypertrophy and hyperplasia in all treated animals. The results are indicative of toxaphene-induced hyperactivity of the thyroid (Waritz et al 1996). In a 13-week feeding study with male and female Sprague-Dawley rats given toxaphene in the diet in concentrations of 0, 4, 20, 100 or 500 mg/kg diet (about 0, 0.4, 2, 10 and 50 mg/kg body weight), food consumption and body weight gains were not different from the control values in any of the dose groups.…”