The U.S. EPA
Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect
endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as
thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant
ammonium perchlorate as an
endocrine disruptor.
Ammonium perchlorate is a primary ingredient in rocket fuel,
fertilizers, paints, and
lubricants. Over the past 50 years,
potassium perchlorate has been used to treat
hyperthyroidism in humans.
Perchlorate alters
thyroid hormone secretion by competitively inhibiting
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 based on a pilot study of oral dosing. Doses of 125-500 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 useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of
iodide). This study also found that
perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.