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ASSESSMENT OF DE-71, A COMMERCIAL POLYBROMINATED DIPHENYL ETHER (PBDE) MIXTURE, IN THE EDSP MALE AND FEMALE PUBERTAL PROTOCOLS
Citation:
Stoker, T E., S C. Laws, K M. Crofton, J M. Hedge, J M. Ferrell, AND R L. Cooper. ASSESSMENT OF DE-71, A COMMERCIAL POLYBROMINATED DIPHENYL ETHER (PBDE) MIXTURE, IN THE EDSP MALE AND FEMALE PUBERTAL PROTOCOLS. TOXICOLOGICAL SCIENCES 78(1):144-155, (2004).
Impact/Purpose:
scientific research
Description:
DE-71, a commercial mixture, was used to test the sensitivity of the female and male pubertal protocol to detect thyroid active chemicals. These protocols are being evaluated for the U.S. EPA's Endocrine Disruptor Screening Program as part of a Tier I Screening Battery. To examine the ability of these protocols to screen for chemicals with this mechanism of action for disruption of thyroid hormone homeostasis, we examined male and female Wistar rats following DE-71 (DE) exposure. Rats were dosed by gavage daily with 0, 3, 30 or 60 mg/kg DE in corn oil from postnatal day (PND) 23-53 in the male or PND 22-41 in the female. In addition, we also examined the temporal effects of DE-71 on the liver enzymes and thyroid hormones by measuring the liver and thyroid hormone endpoints in another group of males and females following only 5 days of dosing (PND 21 to 26 in females and PND 23 to 28 in males). T4 was significantly decreased at 30 and 60 mg/kg following five-day exposures and in the 21 day exposed females. Doses of 3, 30 and 60 mg/kg decreased T4 in 31 day exposed males. T3 was decreased and TSH was elevated only by 30 and 60 mg/kg in the 31 day exposed males. Increased liver-to- body weight ratios coincided with a significant induction of UDGPT (uridinediphosphate-glucuronosyltransferase; 2-4 fold), EROD and PROD (ethoxy- and pentoxy-resorufin-O-deethylase) at the two highest doses. Of the androgen dependent tissues, seminal vesicle (SV) and ventral prostate (VP) weights were reduced at 60 mg/kg, while testes and epididymal weights were not affected. Preputial separation (PPS) was also significantly delayed by doses of 30 and 60 mg/kg. In the female, the 60 mg/kg dose also caused a 1.8 day delay in the age of vaginal opening. Based upon the thyroid hormone response data, this study provides evidence that the 31 day alternative Tier 1 male protocol is a more sensitive test protocol than the 5 day or female pubertal protocol for thyrotoxic agents that act via up-regulation of hepatic metabolism. This apparent greater sensitivity may be due a greater body burden attained following the longer dosing regimen as compared to that of the female protocol, or to gender specific differences in thyroid hormone metabolism. Also, the delay in PPS and reduction in SV and VP weights may indicate a modification or inhibition of endogenous androgenic stimulation directly by DE-71 or a secondary effect that occurs in response to a DE-induced change in thyroid hormones.