Saint Mary's College of California, Department of Biology, Moraga, CA, USA.
Saint Mary's College of California, Department of Biology, Moraga, CA, USA.
Ecotoxicol Environ Saf. 2021 Jun 15;216:112210. doi: 10.1016/j.ecoenv.2021.112210. Epub 2021 Apr 15.
Bisphenol A (BPA) is a ubiquitous industrial chemical found in everyday plastic products and materials. Due to scientific findings on the reproductive, developmental, and cellular defects caused by BPA and heightened public awareness, manufacturers have begun to use new chemicals in place of BPA in "BPA-free" products. These alternatives are chemical analogs of BPA and include dozens of new compounds that have undergone relatively little testing and oversight, including: bisphenol S (BPS), bisphenol AF (BPAF), and the recently developed tetramethyl bisphenol F (TMBPF; the monomer of valPure V70). Here, we used adult female rat adipose-derived stem cells (rASCs) and human mesenchymal stem cells (hMSCs) to compare the toxicities and potencies of these BPA alternatives in vitro. Rat and human stem cells were exposed to BPA (1-10 μM), 17β-estradiol (E2; 10 μM), BPS (1-100 μM), BPAF (3×10-30 μM), TMBPF (0.01-50 μM), or control media alone (with 0.01% ethanol) for varying time intervals from 10 min to 24 h. We found significantly decreased cell viability and massive apoptosis in rat and human stem cells treated with each BPA analog, as early as 10 min of exposure, and at low, physiologically relevant doses. BPAF showed extreme cytotoxicity in a dose-dependent manner (LC =0.014 μM (rASCs) and 0.009 μM (hMSCs)), whereas TMBPF showed a bimodal response, with low and high concentrations being the most toxic (LC =0.88 μM (rASCs) and 0.06 μM (hMSCs)). Activated caspase-6 levels increased in nearly all cells treated with the BPA analogs indicating the majority of cell death was due to caspase-6-mediated apoptosis. These results in both rat and human stem cells underscore the toxicity and potency of these BPA analogs, and establish a rank order of potency of: BPAF>TMBPF>BPA>BPS. Further, these and other recent findings indicate that these newer BPA analogs may be 'regrettable substitutions,' being worse than the original parent compound and lacking proper testing and regulation. This work brings to light the need for further toxicological characterization, better regulation, greater public awareness, and the development of safer, more sustainable chemicals and non-plastic products.
双酚 A (BPA) 是一种普遍存在于日常塑料产品和材料中的工业化学物质。由于科学研究发现 BPA 会对生殖、发育和细胞造成缺陷，并且公众对此的认识不断提高，制造商已开始在“不含 BPA”的产品中使用新的化学物质替代 BPA。这些替代品是 BPA 的化学类似物，包括数十种新化合物，它们的测试和监管相对较少，其中包括：双酚 S (BPS)、双酚 AF (BPAF) 和最近开发的四甲基双酚 F (TMBPF; valPure V70 的单体)。在这里，我们使用成年雌性大鼠脂肪来源的干细胞 (rASCs) 和人骨髓间充质干细胞 (hMSCs) 来比较这些 BPA 替代品在体外的毒性和效力。大鼠和人干细胞暴露于 BPA(1-10 μM)、17β-雌二醇 (E2; 10 μM)、BPS(1-100 μM)、BPAF(3×10-30 μM)、TMBPF(0.01-50 μM) 或单独对照培养基 (含 0.01%乙醇)，暴露时间从 10 分钟到 24 小时不等。我们发现，大鼠和人干细胞在接触每种 BPA 类似物后，即使在低剂量、生理相关剂量下，也会在 10 分钟内出现明显的细胞活力下降和大量细胞凋亡。BPAF 表现出极高的细胞毒性，呈剂量依赖性(LC =0.014 μM(rASCs)和 0.009 μM(hMSCs))，而 TMBPF 则表现出双模态反应，低浓度和高浓度毒性最大(LC =0.88 μM(rASCs)和 0.06 μM(hMSCs))。用 BPA 类似物处理的几乎所有细胞中，活化的半胱天冬酶-6 水平均升高，表明大多数细胞死亡是由于半胱天冬酶-6 介导的细胞凋亡。这些在大鼠和人干细胞中的结果突出了这些 BPA 类似物的毒性和效力，并确定了它们的效力顺序：BPAF>TMBPF>BPA>BPS。此外，这些和其他最近的研究结果表明，这些新的 BPA 类似物可能是“令人遗憾的替代品”，比原始母体化合物更差，并且缺乏适当的测试和监管。这项工作揭示了需要进一步进行毒理学特征描述、更好的监管、提高公众意识以及开发更安全、更可持续的化学品和非塑料产品的必要性。
