SummaryHuman ToxicityGeens et al. shows interesting information about the BPA intake in Belgian adults after consumption of canned beverages and foods. The critical discussion about the intake assessment based on urinary concentrations of BPA and its parallelism with that based on beverage and food consumption is relevant.Animal Toxicity

In September 2010 some studies very relevant for EFSAs risk assessment of BPA have been published. The most relevant is the study of Taylor et al., which presents also results in contrast with the literature. In particular, basing on toxicokinetics of BPA in primates and rodents and comparing the experimental results with what expected in humans, some considerations should be taken into account: 1) the reference methods used until now to estimate BPA in serum could be not so sensible, and the expected exposure to BPA could be underestimated. 2) toxicokinetics in monkeys and mice are similar, and in line with what expected for humans. 3) serum levels of unconjugated BPA in humans may reflect the possibility of sources of exposure other than the oral one.

Another relevant study is that of Jones et al. Apart the in vitro section (see over), authors suggest that the loss of BRCA1 function may enhance BPA effects via estrogen-related pathways also at doses, that reflect the levels of BPA measured in circulating blood of humans. Yu et al. have shown that mice exposed to 50 g/Kg BPA over 8 days from PND 23 to PND 30 showed alterations in the behavior in the adulthood. With the limitation that the authors used only one dose of exposure and did not show any biological endpoint, this study could have some relevance for EFSAs risk assessment of BPA.Cardoso et al. exposed pubertal male rats to 2.5 mg/Kg BW/Day BPA, and observed an inhibitory effect at the hypothalamic level mediated by Glutamic Acid (GLU). Hewitt et al, despite a relatively high exposure (30 mg/Kg BPA injected subcutaneously), showing an alteration in the gene expression pathway of uterine RNA, and a parallelism with other endocrine disruptors was made. Xu2 et al. (animal toxicity) tested a wide range of BPA concentrations (0.05-200 mg/Kg/d) during perinatal maternal exposure, observing alterations in NMDA receptor subunits, estrogen receptor beta, and aromatase cytochrome P450 expressions in the hippocampus of male rats followed by PND 4 to PND 56.Finally, there are few minor contributions:

Wang et al. studied the mitochondrial signaling pathway in BPA-induced germ cell apoptosis in testes of mice. However, the doses of exposure used (160-480 mg/Kg/D) are very high as compared to what established by recent literature. Finally, Minamiyama et al. show that ROS production induced by BPA exposure in rat sperm can influence the sperm function even when the sperm number and/or morphology remain unaltered. However, in this case the exposure doses are expressed in mg/L (e.g. nominal dose of exposure) and the intake remains unknown.In Vitro ToxicityApart the results of Jones et al, who demonstrated that BPA acts as a mitogen in mammary epithelial cells with loss of BRCA function in the range of BPA concentration between 0.01 and 1 M, other studies present interesting results, but with low relevance for risk assessment. In the same range of concentrations (low doses), Xu1 et al. (in vitro toxicity) observed significant effects on filopodia length changes, number and phosphorylation of NMDA receptor subunit NR2B in hippocampal neurons. Ashai et al., at high concentration (100 M) observed endoplasmic reticulum stress-associated apoptosis in mouse non-parenchimal hepatocytes. Bolli et al, with some experimental limits, showed an impairment of estradiol-induced protective effect against the cell growth of a colon cancer cell line induced by BPA exposure (1 M 1 mM). Finally, Dong et al. showed a rapid activation of Erk1/2 through the G protein-coupled receptor 30 (GPR30) in human breast cancer cells induced by 10 M BPA.