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ASSESSMENT OF DE-71, A COMMERCIAL POLYBROMINATED DIPHENYLETHER (PBDE) MIXTURE, IN THE EDSP MALE PUBERTAL PROTOCOL
Citation:
Stoker, T E., J M. Ferrell, J M. Hedge, K M. Crofton, R L. Cooper, AND S C. Laws. ASSESSMENT OF DE-71, A COMMERCIAL POLYBROMINATED DIPHENYLETHER (PBDE) MIXTURE, IN THE EDSP MALE PUBERTAL PROTOCOL. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
ASSESSMENT OF DE-71, A COMMERCIAL POLYBROMINATED DIPHENYL ETHER (PBDE) MIXTURE, IN THE EDSP MALE PUBERTAL PROTOCOL. T.E. Stoker1, J. Ferrell1, J.M. Hedge2, K. M. Crofton2, R.L. Cooper1 and S.C. Laws1. 1 Reprod. Tox. Div., 2 Neurotox. Div., NHEERL, ORD, USEPA, RTP, NC.
PBDEs are environmental contaminants that disrupt thyroid hormone homeostasis. To examine the ability of the Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol to detect thyroid active xenobiotics, we examined the thyroid and reproductive endpoints of male Wistar rats following DE-71(DE) exposure. Males were dosed daily with 0, 3, 30 or 60 mg/kg DE in corn oil from postnatal day (PND) 23-53. Thyroid measures were also made on PND 28 to compare a 5 day protocol with this 31 day protocol. T4 was significantly decreased at 30 and 60 mg/kg (74 and 81% below control, respectively) on PND 28 and at 3, 30 and 60 mg/kg (20, 80, and 86% below control, respectively) on PND 53. T3 was only decreased by 30 and 60 mg/kg (25 and 20% below control) on PND 53. TSH was increased on PND 53 at 30 and 60 mg/kg (64 and 113% increase). 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) predominantly at the two highest doses. EROD increased 10-14 fold by PND 28 and 53, while PROD increased 12-23 fold by PND 28 and 78-83 fold by PND 53. Of the androgen dependent tissues, seminal vesicle (SV) and ventral prostate (VP) wt were reduced at 60 mg/kg, while testes and epididymal wts were not affected. Preputial separation (PPS) was significantly delayed at 30 and 60 mg/kg by 2.0 and 2.3 days, respectively. Serum testosterone was decreased, but not significantly, at 60 mg/kg. Thus, the 31-day dosing required in the male pubertal protocol will detect thyroid hormone alterations of DE at doses as low as 3 mg/kg, while the 5 day exposure LOEL was 30 mg/kg. This data provides evidence that the 31 day alternative Tier 1 protocol is a sensitive test for thyrotoxic agents that act via up-regulation of hepatic metabolism. The delay in PPS and reduction in SV and VP wt may indicate a modification of endogenous androgenic stimulation directly by DE or a secondary effect that occurs in response to a DE-induced change in thyroid hormones. (This abstract does not necessariliy reflect EPA policy).