Developmental neurotoxicity study of dietary bisphenol A in Sprague-Dawley rats.
This study was conducted to determine the potential of bisphenol A (BPA) to induce functional and/or morphological effects to the nervous system of F(1) offspring from dietary exposure during gestation and lactation according to the Organization for Economic Cooperation and Development and U.S. Environmental Protection Agency guidelines for the study of developmental neurotoxicity. BPA was offered to female Sprague-Dawley Crl:CD (SD) rats (24 per dose group) and their litters at dietary concentrations of 0 (control), 0.15, 1.5, 75, 750, and 2250 ppm daily from gestation day 0 through lactation day 21. F(1) offspring were evaluated using the following tests: detailed clinical observations (postnatal days [PNDs] 4, 11, 21, 35, 45, and 60), auditory startle (PNDs 20 and 60), motor activity (PNDs 13, 17, 21, and 61), learning and memory using the Biel water maze (PNDs 22 and 62), and brain and nervous system neuropathology and brain morphometry (PNDs 21 and 72). For F(1) offspring, there were no treatment-related neurobehavioral effects, nor was there evidence of neuropathology or effects on brain morphometry. Based on maternal and offspring body weight reductions, the no-observed-adverse-effect level (NOAEL) for systemic toxicity was 75 ppm (5.85 and 13.1 mg/kg/day during gestation and lactation, respectively), with no treatment-related effects at lower doses or nonmonotonic dose responses observed for any parameter. There was no evidence that BPA is a developmental neurotoxicant in rats, and the NOAEL for developmental neurotoxicity was 2250 ppm, the highest dose tested (164 and 410 mg/kg/day during gestation and lactation, respectively).
Stump
Donald G
DG
Developmental and Reproductive Toxicology, WIL Research Laboratories, LLC, Ashland, Ohio 44805-8946, USA. dstump@wilresearch.com
Beck
Melissa J
MJ
Radovsky
Ann
A
Garman
Robert H
RH
Freshwater
Lester L
LL
Sheets
Larry P
LP
Marty
M Sue
MS
Waechter
John M
JM
Dimond
Stephen S
SS
Van Miller
John P
JP
Shiotsuka
Ronald N
RN
Beyer
Dieter
D
Chappelle
Anne H
AH
Hentges
Steven G
SG
D000014:Abnormalities, Drug-Induced; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000254:growth & development; D005260:Female; D007774:Lactation / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000196:embryology / Q000473:pathology; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D000098826:Bisphenol A Compounds
D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds