Rubin, BS, MK Murray, DA Damassa, JC King and AM Soto. 2001. Perinatal Exposure to Low Doses of Bisphenol A Affects Body Weight, Patterns of Estrous Cyclicity, and Plasma LH Levels. Environmental Health Perspectives 109: 675-680.
In experiments with rats, Rubin et al. confirm results obtained by Howdeshell et al. (1999) on the effects of early exposure to bisphenol A on adult female weight, and extend the understanding of bisphenol A impacts to include effects on other aspects of reproduction.
Their results are important for three reasons.
- First, they provide additional confirmation from an independent, non-industry based laboratory that exposure to low-level bisphenol A has adverse effects. They thus contribute significantly to resolving debates about the reality of low-dose impacts of bisphenol A.
- Second, they report a non-monotonic relationship between dose and effect. In the female offspring, the lower of the two BPA doses produced a larger and more persistent effect on body weight relative to the higher dose. This is consistent with the nonmonotonic or inverted-U-shaped dose-response curve that reported for the imact of bisphenol A on prostate wet weight."
- Third, their results on estrous cyclicity and plasma LH levels extend the suite of endpoints affected by bisphenol A. The more the compound is studied by independent laboratories, the wider is the range of impacts detected.
What did they do?
Rubin et al. exposed pregnant female rats to bisphenol A from day 6 of pregancy through to the end of lactation. BPA exposure was via drinking water. They then examined the impact of two levels of exposure to bisphenol A, compared to controls, on aspects of growth, development and hormonal status of the offspring whose exposure had begun in the womb.
Because BPA was delivered via drinking water available through drinking bottles, Rubin et al. could not calculate the precise amount of BPA consumed by the females. Some leakage may have occurred. They estimate that the low level of exposure delivered up to 0.1 mg/kg body weight/day and the high level delivered 1.2 mg/kg bw/day. The actual exposure may have been significantly lower than this upper estimate. While this entailed contamination levels much lower than most studies on the effect of BPA (usually >10 mg/kg), it was much higher than levels used by vom Saal and his colleagues (<.01ppm).
What did they find?
- At birth, bisphenol A exposed pups were heavier than control animals. For females, this effect persisted through adulthood, even though exposure to BPA ended at weaning. Females receiving the low dose of BPA showed a larger effect than animals receiving the higher dose.
- According to the authors, "most females exposed perinatally to high-dose BPA failed to exhibit evidence of regular estrous cycles when examined at 4 months (only 21% exhibited regular estrous cycles) and at 6 months [only 23% exhibited regular estrous cycles (Figure 3A)]. The defect in the pattern of estrous cyclicity varied in individual females and was not easily defined."
- They also observed differences in adult hormonal status as a result of perinatal BPA exposure: females receiving the higher dose exposures had low plasma LH levels.
- No differences in time to sexual maturity were observed.