Developmental exposure to a commercial PBDE mixture, DE-71: neurobehavioral, hormonal, and reproductive effects.
Developmental effects of polybrominated diphenyl ethers (PBDEs) have been suspected due to their structural similarities to polychlorinated biphenyls (PCBs). This study evaluated neurobehavioral, hormonal, and reproductive effects in rat offspring perinatally exposed to a widely used pentabrominated commercial mixture, DE-71. Pregnant Long-Evans rats were exposed to 0, 1.7, 10.2, or 30.6 mg/kg/day DE-71 in corn oil by oral gavage from gestational day 6 to weaning. DE-71 did not alter maternal or male offspring body weights. However, female offspring were smaller compared with controls from postnatal days (PNDs) 35-60. Although several neurobehavioral endpoints were assessed, the only statistically significant behavioral finding was a dose-by-age interaction in the number of rears in an open-field test. Developmental exposure to DE-71 caused severe hypothyroxinemia in the dams and early postnatal offspring. DE-71 also affected anogenital distance and preputial separation in male pups. Body weight gain over time, reproductive tissue weights, and serum testosterone concentrations at PND 60 were not altered. Mammary gland development of female offspring was significantly affected at PND 21. Congener-specific analysis of PBDEs indicated accumulation in all tissues examined. Highest PBDE concentrations were found in fat including milk, whereas blood had the lowest concentrations on a wet weight basis. PBDE concentrations were comparable among various brain regions. Thus, perinatal exposure to DE-71 leads to accumulation of PBDE congeners in various tissues crossing blood-placenta and blood-brain barriers, causing subtle changes in some parameters of neurobehavior and dramatic changes in circulating thyroid hormone levels, as well as changes in both male and female reproductive endpoints. Some of these effects are similar to those seen with PCBs, and the persistence of these changes requires further investigation.
Kodavanti
Prasada Rao S
PR
Neurotoxicology Branch, Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US EPA, Research Triangle Park, North Carolina 27711, USA. kodavanti.prasada@epa.gov
Coburn
Cary G
CG
Moser
Virginia C
VC
MacPhail
Robert C
RC
Fenton
Suzanne E
SE
Stoker
Tammy E
TE
Rayner
Jennifer L
JL
Kannan
Kurunthachalam
K
Birnbaum
Linda S
LS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development; D018811:Maternal Exposure; D011247:Pregnancy; D011863:Radioimmunoassay; D051381:Rats; D020318:Rats, Long-Evans; D012098:Reproduction / Q000187:drug effects*; D013723:Teratogens / Q000633:toxicity*
D055768:Halogenated Diphenyl Ethers; D013723:Teratogens; C086401:pentabromodiphenyl ether