Toxicological Sciences 66, 105-116 (2002)
Copyright © 2002 by the Society of Toxicology
ENDOCRINE TOXICOLOGY |
Developmental Exposure to Brominated Diphenyl Ethers Results in Thyroid Hormone Disruption
,1
* Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina;
Neurotoxicology Division and
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina
The objective of the current study was to characterize the effects of DE-71 (a commercial polybrominated diphenyl ether mixture containing mostly tetra- and penta-bromodiphenyl ethers) on thyroid hormones and hepatic enzyme activity in offspring, following perinatal maternal exposure. Primiparous Long-Evans rats were orally administered DE-71 (0, 1, 10, and 30 mg/kg/day) in corn oil from gestation day (GD) 6 to postnatal day (PND) 21. Serum and liver samples obtained from dams (GD 20 and PND 22), fetuses (GD 20), and offspring (PNDs 4, 14, 36, and 90) were analyzed for circulating total serum thyroxine (T4) and triiodothyronine (T3), or hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD), and uridine diphosphoglucuronosyl transferase (UDPGT) activity. There were no significant effects of treatment on maternal body weight gain, litter size, or sex ratio, nor were there any effects on any measures of offspring viability or growth. Serum T4 was reduced in a dose-dependent manner in fetuses on GD 20 (at least 15%) and offspring on PND 4 and PND 14 (50 and 64% maximal in the 10 and 30 mg/kg/day groups, respectively), but recovered to control levels by PND 36. Reduction in serum T4 was also noted in GD 20 dams (48% at highest dose), as well as PND 22 dams (44% at highest dose). There was no significant effect of DE 71 on T3 concentrations at any time in the dams or the offspring. Increased liver to body weight ratios in offspring were consistent with induction of EROD (maximal 95-fold), PROD (maximal 26-fold) or UDPGT (maximal 4.7-fold). Induction of PROD was similar in both dams and offspring; however, EROD and UDPGT induction were much greater in offspring compared to dams (EROD = 3.8-fold; UDPGT = 0.5-fold). These data support the conclusion that DE-71 is an endocrine disrupter in rats during development.
Key Words: brominated diphenyl ether; development; thyroid hormone; hepatic enzyme activity; endocrine disrupter; rat.
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