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THE EFFECTS OF DE-71, A COMMERCIAL POLYBROMINATED DIPHENYL EITHER MIXTURE, ON FEMALE PUBERTAL DEVELOPMENT AND THYROID FUNCTION
Citation:
Laws, S C., J M. Ferrell, J M. Hedge, K M. Crofton, R L. Cooper, AND T E. Stoker. THE EFFECTS OF DE-71, A COMMERCIAL POLYBROMINATED DIPHENYL EITHER MIXTURE, ON FEMALE PUBERTAL DEVELOPMENT AND THYROID FUNCTION. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
THE EFFECTS OF DE-71, A COMMERICAL POLYBROMINATED DIPHENYL ETHER MIXTURE, ON FEMALE PUBERTAL DEVELOPMENT AND THYROID FUNCTION. S.C. Laws1, J. M. Ferrell1, J. M Hedge2, K. M. Crofton2, R.L. Cooper1, and T.E. Stoker1. 1Reprod. Tox. Div., 2Neurotox. Div., NHEERL, ORD, USEPA, RTP, NC.
PBDEs, widely used as flame-retardants, are persistent environmental contaminants that can alter thyroid homeostasis via their action on liver enzyme induction. DE-71 was used to test the sensitivity of the female pubertal protocol to detect thyroid active chemicals. This protocol is being evaluated for the U.S. EPA?s Endocrine Disruptor Screening Program as part of a Tier I Screening Battery. Wistar rats were gavaged from postnatal day (PND) 22 - 41 with DE-71 (0, 3, 30, 60 mg/kg) in corn oil. Females were monitored daily for vaginal opening (VO) as an assessment of pubertal development. To evaluate the temporal effects of DE-71 on serum thyroid hormones and liver microsomal EROD, PROD (ethoxy- and pentoxy-resorufin-O-deethylase) and UDPGT (uridinediphosphate-glucuronosyltransferase) activity, groups of animals were killed after 5 and 20 days of dosing. Serum total thyroxine (T4) was significantly decreased by 30 and 60 mg/kg at both time points. No significant changes were observed in triiodothyronine (T3), while a significant linear trend for increased thyroid stimulating hormone (1.6 X increase in the 60 mg/kg group) was detected in those animals exposed for 20 days. Increased liver to body weight (bw) ratios following exposure to 30 and 60 mg/kg were consistent with induction of hepatic enzymes. UDGPT activity was inducted 2.5 - 4 X over control. EROD and PROD activity were also induced at 30 and 60 mg/kg. EROD increased 5 -14 X, while PROD increased 10 and 72 X with 5 and 20-day exposures, respectively. The highest dose of DE-71 caused a small, yet statistically significant delay in the age of vaginal opening (i.e., 1.8 day delay vrs control). No treatment related changes were noted in growth, necropsy bw, or any reproductive tissue weights. In summary, these data demonstrate that this protocol will detect chemicals that alter thyroid hormone concentrations by inducing liver metabolic enzymes. This abstract does not necessarily reflect USEPA policy.