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ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS
Citation:
Stoker, T E., S C. Laws, J M. Ferrell, AND R L. Cooper. ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
ABILITY OF THE MALE RAT PUBERTAL ASSAY TO DETECT ENVIRONMENTAL CHEMICALS THAT ALTER THYROID HORMONE HOMEOSTASIS
Stoker, Tammy E.1; Laws, Susan C.1; Ferrell, Janet M.1; Cooper, Ralph L.1.
Endocrinology Branch, RTD, NHEERL, ORD, U.S. EPA, RTP, NC, 27711.
The U.S EPA Endocrine Disruptor Screening Program Tier 1 male pubertal protocol was designed to detect alterations in reproductive development and thyroid function. However, little is known about the efficacy of this protocol as a screen for thyrotoxicants with different mechanisms of action. We evaluated three environmental chemicals which reported to alter thyroid hormones: DE-71, thiram, and ammonium perchlorate. DE-71, a polybrominated diphenyl ether mixture which increases the clearance of thyroid hormone, was administered from postnatal day 23 to 53 by gavage to male Wistar rats. DE-71 decreased T4 (3, 30 and 60 mg/kg) and T3 (30 and 60 mg/kg) and increased TSH (30 and 60 mg/kg). The altered homeostasis of thyroid hormone by DE-71 was accompanied by altered histopathology of the thyroid tissue (decreased colloid area, increased follicular cell height) following exposure to 60 mg/kg. Thiram, a dithiocarbamate fungicide reported to inhibit thyroperoxidase activity (T4 to T3) in vitro, was administered at doses of 12.5 to 50 mg/kg. Thiram decreased T4 at 50 mg/kg and decreased TSH at 25 and 50 mg/kg. No differences in T3 or thyroid histology were observed. Thiram also decreased luteinizing hormone at 50 mg/kg and testosterone at all doses. The decreased LH was likely due to the ability of thiram to inhibit norepinephrine synthesis, which is important for normal GnRH function. Perchlorate, an ingredient in rocket fuel, paints, and lubricants and a competitive inhibitor of iodide uptake by the thyroid gland, was administered at 62.5, 125, 250, and 500 mg/kg. Perchlorate decreased T4 and increased TSH at doses of 125 to 500 mg/kg. Thyroid histology was altered at all doses. These results demonstrate that the male pubertal protocol is sensitive to the effects of thyrotoxicants that act through a variety of mechanisms. This abstract does not necessarily reflect EPA policy.