title: Bisphenol-A exposures and behavioural aberrations: median and linear spline and meta-regression analyses of 12 toxicity studies in rodents.
abstract: 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<0.001 vs. females). Overall, our study showed that developmental exposures to low-doses of bisphenol-A, e.g. ≤120 μg/day, were associated to behavioural aberrations in offspring.
authors.affiliation: Cancer Risk Factor Branch, Cancer Prevention and Research Institute, Tuscany Tumor Institute, Via Cosimo il Vecchio 2, 50139 Florence, Italy. Electronic address: m.peluso@ispo.toscana.it.
authors.forename: Marco E M
authors.initials: ME
authors.lastname: Peluso
authors.affiliation: Cancer Risk Factor Branch, Cancer Prevention and Research Institute, Tuscany Tumor Institute, Via Cosimo il Vecchio 2, 50139 Florence, Italy.
authors.forename: Armelle
authors.initials: A
authors.lastname: Munnia
authors.affiliation: IRCSS San Martino Hospital - National Cancer Research Institute, Largo R. Benzi 10, 16132 Genoa, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Ceppi
mesh_terms: D000374:Aggression / Q000187:drug effects; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D016014:Linear Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D018570:Risk Assessment; D012737:Sex Factors; D065853:Spatial Learning / Q000187:drug effects; D013997:Time Factors; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol-A; Developmental exposures; Median and linear spline and meta-regression; Rodents