Zhu Xia, Cao Li, Liu Yufei, Tang Xinyao, Miao Yeqiu, Zhang Jing, Zhang Lishi, Jia Zhenchao, Chen Jinyao
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Second People's Hospital of Yibin City, Yibin, China.
J Appl Toxicol. 2024 Mar;44(3):428-444. doi: 10.1002/jat.4552. Epub 2023 Oct 14.
Bisphenol AF (BPAF), as one of structural analogs of BPA, has been increasingly used in recent years. However, limited studies have suggested its adverse effects similar to or higher than BPA. In order to explore the general toxicity and genotoxicity of subacute exposure to BPAF, the novel 28-day multi-endpoint (Pig-a assay + micronucleus [MN] test + comet assay) genotoxicity evaluation platform was applied. Male rats were randomly distributed into seven main experimental groups and four satellite groups. The main experimental groups included BPAF-treated groups (0.5, 5, and 50 μg/kg·bw/d), BPA group (10 μg/kg·bw/d), two solvent control groups (PBS and 0.1% ethanol/99.9% oil), and one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw). The satellite groups included BPAF high-dose recovery group (BPAF-HR), oil recovery group (oil-R), ENU recovery group (ENU-R), and PBS recovery group (PBS-R). All groups received the agents orally via gavage for 28 consecutive days, and satellite groups were given a recovery period of 35 days. Among all histopathologically examined organs, testis and epididymis damage was noticed, which was further manifested as blood-testis barrier (BTB) junction protein (Connexin 43 and Occludin) destruction. BPAF can induce micronucleus production and DNA damage, but the genotoxic injury can be repaired after the recovery period. The expression of DNA repair gene OGG1 was downregulated by BPAF. To summarize, under the design of this experiment, male reproductive toxicity of BPAF was noticed, which is similar to that of BPA, but its ability to induce micronucleus production may be stronger than that of BPA.
双酚AF（BPAF）作为双酚A（BPA）的结构类似物之一，近年来其使用量日益增加。然而，有限的研究表明其不良影响与BPA相似或高于BPA。为了探究亚急性暴露于BPAF的一般毒性和遗传毒性，应用了新型的28天多终点（Pig-a试验+微核[MN]试验+彗星试验）遗传毒性评估平台。雄性大鼠被随机分为七个主要实验组和四个卫星组。主要实验组包括BPAF处理组（0.5、5和50μg/kg·bw/d）、BPA组（10μg/kg·bw/d）、两个溶剂对照组（PBS和0.1%乙醇/99.9%油）以及一个阳性对照组（N-乙基-N-亚硝基脲，40mg/kg bw）。卫星组包括BPAF高剂量恢复组（BPAF-HR）、油恢复组（oil-R）、ENU恢复组（ENU-R）和PBS恢复组（PBS-R）。所有组连续28天经口灌胃给予相应试剂，卫星组给予35天的恢复期。在所有经组织病理学检查的器官中，发现睾丸和附睾受损，进一步表现为血睾屏障（BTB）连接蛋白（连接蛋白43和闭合蛋白）的破坏。BPAF可诱导微核产生和DNA损伤，但恢复期后遗传毒性损伤可得到修复。BPAF使DNA修复基因OGG1的表达下调。总之，在本实验设计下，观察到BPAF对雄性具有生殖毒性，这与BPA相似，但其诱导微核产生的能力可能比BPA更强。
