Department of Environmental Toxicology, Uppsala University, SE-752 36 Uppsala, Sweden.
Centre for Reproductive Biology in Uppsala (CRU), Uppsala, Sweden.
Toxicol Sci. 2020 Dec 1;178(2):239-250. doi: 10.1093/toxsci/kfaa152.
The plastic component bisphenol A (BPA) impairs reproductive organ development in various experimental animal species. In birds, effects are similar to those caused by other xenoestrogens. Because of its endocrine disrupting activity, BPA is being substituted with other bisphenols in many applications. Using the chicken embryo model, we explored whether the BPA alternatives bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS) can induce effects on reproductive organ development similar to those induced by BPA. Embryos were exposed in ovo from embryonic day 4 (E4) to vehicle, BPAF at 2.1, 21, 210, and 520 nmol/g egg, or to BPA, BPF, or BPS at 210 nmol/g egg and were dissected on embryonic day 19. Similar to BPA, BPAF and BPF induced testis feminization, manifested as eg testis-size asymmetry and ovarian-like cortex in the left testis. In the BPS-group, too few males were alive on day 19 to evaluate any effects on testis development. We found no effects by any treatment on ovaries or Müllerian ducts. BPAF and BPS increased the gallbladder-somatic index and BPAF, BPF and BPS caused increased embryo mortality. The overall lowest-observed-adverse-effect level for BPAF was 210 nmol/g egg based on increased mortality, increased gallbladder-somatic index, and various signs of testis feminization. This study demonstrates that the BPA replacements BPAF, BPF, and BPS are embryotoxic and suggests that BPAF is at least as potent as BPA in inducing estrogen-like effects in chicken embryos. Our results support the notion that these bisphenols are not safe alternatives to BPA.
塑料成分双酚 A（BPA）会损害各种实验动物物种的生殖器官发育。在鸟类中，其影响与其他外源性雌激素相似。由于其内分泌干扰活性，BPA 在许多应用中被其他双酚替代。本研究使用鸡胚模型，探讨了 BPA 的替代物双酚 AF（BPAF）、双酚 F（BPF）和双酚 S（BPS）是否会引起类似于 BPA 的生殖器官发育效应。胚胎从胚胎第 4 天（E4）开始在鸡胚中接受暴露，给予对照物、2.1、21、210 和 520 nmol/g 卵的 BPAF，或 210 nmol/g 卵的 BPA、BPF 或 BPS，并在胚胎第 19 天进行解剖。与 BPA 相似，BPAF 和 BPF 诱导睾丸女性化，表现为左睾丸的 eg 睾丸大小不对称和卵巢样皮质。在 BPS 组中，第 19 天存活的雄性鸡太少，无法评估对睾丸发育的任何影响。我们没有发现任何处理对卵巢或缪勒管有影响。BPAF 和 BPS 增加了胆囊体指数，BPAF、BPF 和 BPS 导致胚胎死亡率增加。基于死亡率增加、胆囊体指数增加和各种睾丸女性化迹象，BPAF 的最低观察到的不良效应水平为 210 nmol/g 卵。这项研究表明，BPA 的替代物 BPAF、BPF 和 BPS 具有胚胎毒性，并表明 BPAF 在诱导鸡胚雌激素样效应方面至少与 BPA 一样有效。我们的结果支持这些双酚类物质不是 BPA 的安全替代品的观点。
