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Evaluation of the Toxicity of Bisphenol A (BPA) in Male and Female Sprague-Dawley Rats Exposed Orally from Gestation Day 6 through Postnatal Day 90

Publications

Toxicity evaluation of bisphenol A administered by gavage to Sprague Dawley rats from gestation day 6 through postnatal day 90. Delclos KB, 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. Toxicol Sci. 2014 May;139(1):174-97. doi: 10.1093/toxsci/kfu022. PMID: 24496637.
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 day 1 after birth to termination. The primary focus was on seven equally spaced BPA doses (2.5-2700 μg/kg bw/day). Also included were a naïve 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 μg/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.

Toxicity Evaluation of Bisphenol A Administered by Gavage to Sprague Dawley Rats From Gestation Day 6 Through Postnatal Day 90. Delclos KB, 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. Toxicol Sci. 2016 Sep;153(1):212. doi: 10.1093/toxsci/kfw123. PMID: 27506224.
Although details of the statistical analyses performed are included in the Supplementary Materials provided with this article, it should have been noted that the pairwise comparisons of dose groups to the vehicle control were not corrected for multiple comparisons for the data reported in Tables 4 and 7–9. By convention, histopathology data are not corrected in National Toxicology Program studies.
Abstract:
Erratum for Toxicity evaluation of bisphenol A administered by gavage to Sprague Dawley rats from gestation day 6 through postnatal day 90. [Toxicol Sci. 2014]

Study Tables

Individual Animal Data