Rat two-generation reproductive toxicity study of bisphenol A

Ema, Makoto; Fujii, Sakiko; Furukawa, Masatoshi; Kiguchi, Masao; Ikka, Tsuguo; Harazono, Akira

doi:10.1016/s0890-6238(01)00160-5

Cited by 163 publications

(144 citation statements)

References 30 publications

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“…Ema et al (2001) (35) reported that administration of Bisphenol A at doses of 0.2/200 mg/Kg body weight per day did not cause significant changes in the reproductive parameters of the rats for two generations; however, our study showed that low doses of Bisphenol A caused reproductive toxicity.…”

Section: Discussioncontrasting

confidence: 65%

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

Hasanluyi

Khojasteh

Nejhad

2016

Thrita

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Background: Bisphenol A is a xenoestrogen, synthesized in large quantities for the production of polymers (polycarbonates, epoxy resins) and thermal paper, and is widely used in products of everyday use (packaging, containers and bottles). Data concerning the occurrence of BPA in food, water and indoor environments as well as its appearance in tissues and body fluids of the human body are available in the literature. Male accessory sex glands are also vulnerable to environmental endocrine disruptors with adverse effects in adulthood. The developing prostate gland is particularly sensitive to estrogens and high-dose exposures during a critical developmental window results in intraepithelial prostatic neoplasia (PIN) in adult rodent models. Bisphenol A is also an endocrine disruptor. High levels of BPA exposure correlate with increased risk of mammary gland, brain and prostate cancers and have adverse effects on the tissues of the prostate and seminal vesicles. Objectives: The aim of this study was to investigate the effects of BPA doses on the histological structure and ultrastructure of prostate and seminal vesicle glands. Methods: Forty male Wistar rats were randomly divided into four groups (n = 10): A control group and three treatment groups,

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Section: Discussioncontrasting

confidence: 65%

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

Hasanluyi

Khojasteh

Nejhad

2016

Thrita

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“…BPA was negative at 200 mg/kg/day in all laboratories and was positive over a range of 375-1000 mg/kg/day. This compares favorably with the absence of estrogen-mediated effects at doses up to 500 mg/kg/day, as well in the controversial low-dose range in two multigeneration studies (Ema et al 2001;Tyl et al 2002). The GN and MX uterotrophic results in protocol A are also consistent when compared with available developmental and other studies (Casanova et al 1999;Chapin et al 1997;Newbold et al 2001).…”

supporting

confidence: 57%

The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies.

Kanno

Onyon

Peddada

et al. 2003

Environ Health Perspect

133

111

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The Organisation for Economic Co-operation and Development has completed phase 2 of an international validation program for the rodent uterotrophic bioassay. The purpose of the validation program was to demonstrate the performance of two versions of the uterotrophic bioassay, the immature female rat and the adult ovariectomized rat, in four standardized protocols. This article reports the dose-response studies of the validation program; the coded single-dose studies are reported in an accompanying paper. The dose-response study design used five selected weak estrogen agonists, bisphenol A, genistein, methoxychlor, nonylphenol, and o,p -DDT. These weak agonists were administered in a prescribed series of doses to measure the performance and reproducibility of the protocols among the participating laboratories. All protocols successfully detected increases in uterine weights when the weak agonists were administered. Within each protocol, there was good agreement and reproducibility of the dose response among laboratories with each substance. Substance-specific variations were observed in the influence of the route of administration on the uterine response, the potency as related to the dose producing the first statistically significant increase in uterine weights, and the maximum increase in uterine weight. Substantive performance differences were not observed between the uterotrophic bioassay versions or among the standardized protocols, and these were judged to be qualitatively equivalent. It is noteworthy that these results were reproducible under a variety of different experimental conditions (e.g., animal strain, diet, housing, bedding, vehicle, animal age), indicating that the bioassay's performance as a screen is robust. In conclusion, both the intact, immature, and adult OVX versions, and all protocols appear to be reproducible and transferable across laboratories and are able to detect weak estrogen agonists.

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“…This study was not designed to find unusual effects or non-linear dose-response relationships or to address the issue of low-dose functional responses or non-linear responses. Ema et al (2001), supported by the Japanese Ministry of Health and Welfare, examined developmental toxicity endpoints, in a 2 generation rats study described in detail in Section 4.2.3.1. Two generations of rats were gavaged with 0, 0.0002, 0.002, 0.020, or 0.200 mg/kg bw/day bisphenol A (99.9% purity) before and during mating and throughout the gestation and lactation period.…”

Section: Experimental Animalmentioning

confidence: 99%

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

402

304

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Rat two-generation reproductive toxicity study of bisphenol A

Cited by 163 publications

References 30 publications

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

Investigation of the Effects of Bisphenol A on the Histology and Ultrastructure of Prostate and Seminal Vesicle Glands in Rats

The OECD program to validate the rat uterotrophic bioassay. Phase 2: dose-response studies.

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

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