Neurotoxicity of BPA, BPS, and BPB for the hippocampal cell line (HT-22): An implication for the replacement of BPA in plastics.

Bisphenol A (BPA), a plastic additive, is ubiquitous in the environment and has endocrine disrupting effects. As many countries have prohibited the manufacture and sale of plastic products with BPA, BPA analogs have been used to replace BPA during production, including bisphenol S (BPS) and bisphenol B (BPB). To investigate the toxicities of BPA and its analogs on neurons, reactive oxygen species (ROS) assay, Annexin V-FITC (fluorescein) apoptosis detection assay, lactate dehydrogenase (LDH) cytotoxicity assay, and Cell Counting Kit-8 assay were conducted to comprehensively assess the influence of different concentrations of BPA, BPB, and BPS on ROS, apoptosis, damage, and proliferation for hippocampal HT-22 cells, respectively. Results showed that 6 h of exposure to bisphenols (BPs) could increase the ROS levels, 24 h and 48 h of exposure could induce higher apoptosis and LDH leakage rates for HT-22 cells, and 7 d of exposure could inhibit the cell proliferations. In addition, non-monotonic dose-response relationships were observed between the concentrations of bisphenols and the toxic effects mentioned above. The neurotoxic effects of BPA, BPB and BPS on HT-22 cells were in the increasing order of BPS, BPA, and BPB. In conclusion, these results showed that exposure to BPA and its analogs may result in adverse effects on hippocampal neuronal cell lines. BPS is a surrogate with lower neurotoxicity to replace BPA in production of plastic utensils.

Relationship between bisphenol A exposure and attention-deficit/ hyperactivity disorder: A case-control study for primary school children in Guangzhou, China.

Bisphenol A (BPA) is an endocrine-disrupting chemical. Studies have shown that the exposure to BPA is associated with attention-deficit/hyperactivity disorder (ADHD) during adolescent development. However the direct clinical evidence is limited. To investigate the possible association between environmental BPA exposure and the altered behavior of children, a case-control study was conducted with children aged 6-12 years in Guangzhou, China. Two hundred fifteen children diagnosed with ADHD and 253 healthy children from Guangzhou were recruited as the case and control groups, respectively. Urinary BPA and 8-hydroxy-2'-deoxyguanosine (8-OHdG, a biomarker of oxidative DNA damage) concentrations were determined by high-performance liquid chromatography/tandem spectrometry. The results showed that concentrations of urinary BPA for the case group were significantly higher than those for the control group (3.44 vs 1.70 µg/L; 4.63 vs 1.71 µg/g Crt. p < .001). A stepwise increase in the odds ratios for ADHD was observed with the increasing quartiles of children's urinary BPA (first quartile: reference category; second quartile adjusted OR: 1.79, 95% CI: 0.95-3.37; third quartile adjusted OR: 7.44, 95% CI: 3.91-14.1; fourth quartile adjusted OR: 9.41, 95% CI: 4.91-18.1). When the BPA levels were stratified by gender, the odds of ADHD among boys and girls increased significantly with urinary BPA concentrations (adjusted OR: 4.58, 95% CI: 2.84-7.37; adjusted OR: 2.83, 95% CI: 1.17-6.84). Urinary 8-OHdG concentrations in the ADHD children were significantly higher than those in the control group. Furthermore, the linear regression analysis results indicated that a significant relationship existed between BPA exposure and 8-OHdG levels (R = 0.257, p < .001). Our findings provide direct evidence that childhood BPA exposure may be related to ADHD and 8-OHdG concentrations for children. Moreover, BPA exposure could increase the higher occurrence of ADHD for boy than for girls.