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Toxicol Sci 2014 Feb 4 [Epub ahead of print]

Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague-Dawley Rats from Gestation Day 6 through Postnatal Day 90.

Barry Delclos K, Camacho L, Lewis SM, Vanlandingham MM, Latendresse JR, Olson GR, Davis KJ, Patton RE, Gamboa da Costa G, Woodling KA, Bryant MS, Chidambaram M, Trbojevich R, Juliar BE, Felton RP, Thorn BT

Abstract

Bisphenol A (BPA) is a high production volume industrial chemical to which there is widespread human oral exposure. Guideline studies used to set regulatory limits detected adverse effects only at doses well above human exposures and established a no-observed-adverse-effect level (NOAEL) of 5 mg/kg body weight (bw)/day. However, many reported animal studies link BPA to potentially adverse effects on multiple organ systems at doses below the NOAEL. The primary goals of the subchronic study reported here were to identify adverse effects induced by orally (gavage) administered BPA below the NOAEL, to characterize the dose-response for such effects, and to determine doses for a subsequent chronic study. Sprague-Dawley rat dams were dosed daily from gestation day 6 until the start of labor, and their pups were directly dosed from one day after birth to termination. The primary focus was on seven equally spaced BPA doses (2.5-2,700 mug/kg bw/day). Also included were a naive control, two doses of ethinyl estradiol (EE2) to demonstrate the estrogen responsiveness of the animal model, and two high BPA doses (100,000 and 300,000 mug/kg bw/day) expected from guideline studies to produce adverse effects. Clear adverse effects of BPA, including depressed gestational and postnatal body weight gain, effects on the ovary (increased cystic follicles, depleted corpora lutea and antral follicles) and serum hormones (increased serum estradiol and prolactin and decreased progesterone), were observed only at the two high doses of BPA. BPA-induced effects partially overlapped those induced by EE2, consistent with the known weak estrogenic activity of BPA.


Category: Journal Article
PubMed ID: #24496637 DOI: 10.1093/toxsci/kfu022
Includes FDA Authors from Scientific Area(s): Toxicological Research
Entry Created: 2014-02-06
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