Bisphenol-A exposures and behavioural aberrations: Median and linear spline and meta-regression analyses of 12 toxicity studies in rodents

Exposures to bisphenol-A, a weak estrogenic chemical, largely used for the production of plastic containers, can affect the rodent behaviour. Thus, we examined the relationships between bisphenol-A and the anxiety-like behaviour, spatial skills, and aggressiveness, in 12 toxicity studies of rodent offspring from females orally exposed to bisphenol-A, while pregnant and/or lactating, by median and linear splines analyses. Subsequently, the meta-regression analysis was applied to quantify the behavioural changes. U-shaped, inverted U-shaped and J-shaped dose-response curves were found to describe the relationships between bisphenol-A with the behavioural outcomes. The occurrence of anxiogenic-like effects and spatial skill changes displayed U-shaped and inverted U-shaped curves, respectively, providing examples of effects that are observed at low-doses. Conversely, a J-dose-response relationship was observed for aggressiveness. When the proportion of rodents expressing certain traits or the time that they employed to manifest an attitude was analysed, the meta-regression indicated that a borderline significant increment of anxiogenic-like effects was present at low-doses regardless of sexes (β) = -0.8%, 95% C.I. -1.7/0.1, P= 0.076, at ≤120. μg bisphenol-A. Whereas, only bisphenol-A-males exhibited a significant inhibition of spatial skills (β) = 0.7%, 95% C.I. 0.2/1.2, P= 0.004, at ≤100. μg/day. A significant increment of aggressiveness was observed in both the sexes (β). = 67.9,. C.I. 3.4, 172.5, P= 0.038, at >4.0. μg. Then, bisphenol-A treatments significantly abrogated spatial learning and ability in males (P