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EVALUATION OF AMMONIUM PERCHLORATE IN THE ENDOCRINE DISRUPTOR SCREENING AND TESTING PROGRAM'S MALE PUBERTAL PROTOCOL: ABILITY TO DETECT EFFECTS OF THYROID ENDPOINTS.
Citation:
STOKER, T. E., J. M. FERRELL, S. C. LAWS, R. L. COOPER, AND A. R. BUCKALEW. EVALUATION OF AMMONIUM PERCHLORATE IN THE ENDOCRINE DISRUPTOR SCREENING AND TESTING PROGRAM'S MALE PUBERTAL PROTOCOL: ABILITY TO DETECT EFFECTS OF THYROID ENDPOINTS. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 228(1):58-65, (2006).
Impact/Purpose:
To evaluate the ability of the male pubertal protocol to detect the thyrotoxicant ammonium perchlorate
Description:
The U.S EPA Endocrine Disruptor Screening Program Tier 1 male pubertal protocol was designed to detect reproductive development and thyroid function. One purpose of this in vivo protocol is to detect thyrotoxicants via a number of different mechanisms of action. Here we evaluate the ability of the male pubertal protocol to detect the thyrotoxicant ammonium perchlorate. Perchlorate is a primary ingredient in rocket fuel, paints, and lubricants. The thyrotoxicant effects of this compound are well characterized as a competitive inhibitor of iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats from postnatal day 23 to 53. Doses of 125 to 500 mg/kg perchlorate decreased T4 in a dose dependent manner. TSH was significantly increased in a dose responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is sensitive to the effects of thyrotoxicants which target the uptake of iodide. This study also demonstrated that a toxicant-induced hypothyroidism is without effects on postnatal reproductive development.