Uterotrophic Activity of Bisphenol A in the Immature Mouse

Tinwell, H.; Joiner, R.L.; Pate, Ian; Soames, Anthony R.; Foster, John R.; Ashby, John

doi:10.1006/rtph.2000.1412

Cited by 56 publications

(53 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As a result of our study, BPA was shown to have weak estrogenic activity compared to E2 and DES. Moreover, BPA produced estrogenic activity at low dosage (100 mg/kg/day) compared with a previously published study (Ashby and Tinwell, 1998;Tinwell et al, 2000). Although the estrogenic effects of BPA at low dosage were obvious in vivo 3-day uterotrophic assay, it is not clear whether the estrogenlike effect would be apparent at environmentally relevant dosages in humans.…”

Section: Discussionmentioning

confidence: 64%

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

et al. 2001

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 64%

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

et al. 2001

View full text Add to dashboard Cite

show abstract

“…When all of the data were merged no significant utero trophic effects were seen (Table 1). However, the few positive responses observed were statistically significant and considered unlikely to Overall mean ± 10.2 ± 10.0 ± 10.5 ± 12.5 ± S.9± 10.5 ± 9.1 ± 9.6 ± 13.0 ± 11.0 ± 9.6 ± 10.5 ± 10.9 ± 11.3 ± 11.4 ± 12.0± SD (n) 4.4 (110) 1.8 (8) Tinwell et al, 2000).…”

Section: Uterotrophic Activity Of Low Doses Of Bpa In the Mousementioning

confidence: 99%

Problems Associated with the Recognition and Confirmation of Low-Dose Endocrine Toxicities

Ashby

2003

Nonlinearity in Biology, Toxicology, Medicine

View full text Add to dashboard Cite

Our attempts to confirm reports oflow-dose/hormetic effects in rodent endocrine toxicity studies are reviewed. It is concluded that our present failure to confirm any such effects is due, in large part, to a general lack of understanding of confounding influences and the failure of most investigators to confirm their findings before publication. The major potential confounding factor is suggested to be variability of the parameters under study within control groups, a factor that assumes increased importance when attempting to demonstrate weak low-dose effects. This is illustrated by our studies with bisphenol A in the mouse uterotrophic assay and of finasteride in the Hershberger antiandrogenicity assav. In both of these cases our ability to demonstrate a low-dose effect is dependent on whether concurrent or recent control values are used.Key Words: low dose, control variability, endocrine disruption, hormesis, antiandrogen, estrogen DISCUSSIONThe available literature on hormetic dose-response effects for chemicals has been reviewed (Calabrese, 2002). These usuallv involve a stimulatory effect at low doses and an inhibitory effect at high doses, albeit the reverse can sometimes be observed. Few of these reports relate to classical. toxicologv, but the prospect that effects may been seen for a chemical below its classicallv derived "no adverse effect level" (NOAEL) is of obvious interest. Our experiences over the past 6 years when attempting to confirm examples of effects reported for chemicals in rodents exposed at doses below the previously accepted 1'\O/\EL value (low-dose effects) are reviewed in the following text.

show abstract

“…It was revealed that significant differences were noted at the doses which induced a wet uterine weight increase, at least 1.4-fold over control, with the uterine weight/body weight ratio higher than 0.1%. In our study immature hamsters were sensitive to the s.c. (27) failed to define BPA as reproducibly active in immature mouse uterotrophic assay at the doses ranging from 0.02 to 300 µg/kg. In a more recent study, the sensitivity of immature mice and rats to s.c. injection of DES was the same as in our study on hamsters (1 µg/kg/d) (3).…”

Section: Discussionmentioning

confidence: 99%

Usefulness of immature golden hamster (Mesocricetus auratus) as a model for uterotrophic assay

Radko

Minta

Jasik

et al. 2015

Bulletin of the Veterinary Institute in Pulawy

View full text Add to dashboard Cite

The present study assessed the sensitivity of immature hamster uterotrophic assay to reference oestrogen agonists/antagonists in order to develop a sensitive model for evaluation of endocrine-active compounds in diets. After performing a baseline for control animals, the sensitivity of immature females (postnatal day 18) to reference compounds was evaluated in a three-day uterotrophic assay. The absolute and adjusted dry uterine weights, fold induction over control for absolute wet uterine weight, and wet uterine weight/body weight ratio (%) were used as endpoints. The significantly active doses for reference oestrogens were as follows: 0.6 µg/kg for 17α-ethinyloestradiol (s.c.); 1 µg/kg/day (s.c.) and 40 µg/kg (p.o.) for diethylstilboestrol; 40 mg/kg (s.c.) and 160 mg/kg (p.o.) for bisphenol A. Co-treatment with tamoxifen at a dose of 1 mg/kg significantly antagonised the uterotrophic effect induced by 1 µg/kg 17α-ethinyloestradiol, and showed the attenuated proliferative effect in histopathological examination. We found immature hamster uterotrophic assay as a sensitive model that could be a good alternative to the rat assay.

show abstract

Uterotrophic Activity of Bisphenol A in the Immature Mouse

Cited by 56 publications

References 19 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.

Problems Associated with the Recognition and Confirmation of Low-Dose Endocrine Toxicities

Usefulness of immature golden hamster (Mesocricetus auratus) as a model for uterotrophic assay

Contact Info

Product

Resources

About