The Developmental Toxicity of Bisphenol A in Rats and Mice

Morrissey, Richard E.; George, Julia D.; Price, Catherine J.; Tyl, Rochelle W.; Marr, Melissa C.; Kimmel, Carole A.

doi:10.1093/toxsci/8.4.571

Cited by 73 publications

(86 citation statements)

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“…Previous studies have indicated that administration of BPA to rats showed no adverse reproductive toxicity (Morrissey et al, 1987;Cagen et al, 1999). Howdeshell et al (1999) demonstrated that prenatal treatment with BPA significantly reduced the number of days between vaginal opening and the first vaginal estrus, which correlated highly with the first post-pubertal ovulation.…”

Section: Discussionmentioning

confidence: 97%

Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.

et al. 2001

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The potential estrogenic activities of bisphenol-A were investigated in vitro (E-screen and estrogen receptor competitive binding bioassays) and in vivo (uterotrophic assay). Uterotrophic responses were evaluated using mature ovariectomized Sprague-Dawley female rats treated subcutaneously with bisphenol A (1, 5, 10, 50, and 100 mg/kg/day), E2 (0.3 /kg), and DES (0.3 /kg) for 3 consecutive days. In a MCF-7 cell proliferation assay, E2 and DES used as positive estrogens induced maximum proliferation of MCF-7 cells at 1.0 nM, whereas BPA slightly induced MCF-7 cell proliferation at a higher level of 0.1 M and maximum proliferation at 10 M. In a competitive binding assay, E2 and DES showed inhibition of 17 -[ 3 H]estradiol binding to the rat uterus ER with an IC50 of 1.0 nM and 0.5 M, respectively. However, BPA had an IC50 of 5 M, which was approximately 5,000 or 10,000-fold greater than the IC50 of E2 and DES. In uterotrophic assays, uterus (wet and blotted) and vagina weights were significantly increased at the dose of BPA 100 mg/kg/day in OVX Sprague-Dawley rats. These studies demonstrate that BPA exhibits weak estrogenic activity in all experimental systems, and thus its migration from epoxy resins or polycarbonate products should be controlled not to exceed a safety levels for humans.

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Section: Discussionmentioning

confidence: 97%

Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.

et al. 2001

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“…During organogenesis in mice, BPA treatment at maternally toxic doses was reported to produce foetal toxicosis, manifested adversely as a decrease in both foetal body weight and gravid uterine weight [36]. Shah et al [17] observed, in foetal rat liver, low but significant levels of UGT activity towards DES and the accumulated DES conjugates [17].…”

Section: Discussionmentioning

confidence: 99%

Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver

Yokota

Iwano

Endo

et al. 1999

Biochemical Journal

154

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Bisphenol A, an environmental oestrogenic chemical, was found to conjugate highly with glucuronic acid in male rat liver microsomes studied in vitro. In the various isoforms tested (1A1, 1A3, 1A5, 1A6, 1A7 and 2B1), glucuronidation of bisphenol A and of diethylstilboestrol, a synthetic crystalline compound possessing oestrogenic activity and known to be glucuronidated by liver microsomes, was catalysed by an isoform of UDP-glucuronosyltransferase (UGT), namely UGT2B1, which glucuronidates some endogenous androgens. UGT activity towards bisphenol A in liver microsomes and in UGT2B1 expressed in yeast AH22 cells (22.9 and 0.58 nmol/min per mg of microsomal proteins respectively) was higher than that towards diethylstilboestrol (75.0 and 4.66 pmol/min per mg of microsomal proteins respectively). UGT activities towards both bisphenol A and diethylstilboestrol were distributed mainly in the liver but were also observed at substantial levels in the kidney and testis. Northern blot analysis disclosed the presence of UGT2B1 solely in the liver, and about 65% of the male rat liver microsomal UGT activities towards bisphenol A were absorbed by the anti-UGT2B1 antibody. These results indicate that bisphenol A, in male rat liver, is glucuronidated by UGT2B1, an isoform of UGT.

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“…3.2.1.1 Evaluation of pre-or perinatal growth and development: Morrissey et al (1987), supported by NTP/NCTR, examined the effects of prenatal bisphenol A exposure in rats and mice in a study conducted according to GLP. Studies are also available as NTP publications for rats (NTP, 1985c) and mice (NTP, 1985b).…”

Section: Experimental Animalmentioning

confidence: 99%

“…Data for prostate weight were reported by Nagel et al (1997). Daily sperm production was determined in 8 control males/group and 5 treated Morrissey et al (1987). m,k Statistically significant increase, decrease; 2 no statistically significant change.…”

Section: Utility (Adequacy) For Cerhr Evaluation Processmentioning

confidence: 99%

“…Rat Studies: Prenatal studies with oral dosing of rats consistently demonstrated an absence of malformations at doses up to 1000 mg/kg bw/day (Morrissey et al, 1987;Kim et al, 2001b). Reduced fetal survival and body weights at birth or during the postnatal period were reported in studies with oral exposures occurring throughout the entire gestation and/or lactation periods (Tyl et al, 2000a(Tyl et al, , 2002bKim et al, 2001b).…”

Section: Experimental Animal Studies Considered Bymentioning

confidence: 99%

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NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

Chapin

Adams

Boekelheide

et al. 2008

Birth Defects Research Pt B

404

304

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The Developmental Toxicity of Bisphenol A in Rats and Mice

Cited by 73 publications

References 0 publications

Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.

Potential estrogenic effects of bisphenol-A estimated by in vitro and in vivo combination assays.

Glucuronidation of the environmental oestrogen bisphenol A by an isoform of UDP-glucuronosyltransferase, UGT2B1, in the rat liver

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

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