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口服双酚 F 后的药代动力学和毒性评估。

Pharmacokinetics and toxicity evaluation following oral exposure to bisphenol F.

机构信息

Bio Technology Division, GLP 2 Center, Korea Conformity Laboratories (KCL), 8, Gaetbeol-ro 145 beon-gil, Yeonsu-gu, Incheon, 21999, South Korea.

Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.

出版信息

Arch Toxicol. 2022 Jun;96(6):1711-1728. doi: 10.1007/s00204-022-03246-w. Epub 2022 Apr 4.

DOI:10.1007/s00204-022-03246-w
PMID:35376969
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9095523/
Abstract

Bisphenol F is a substitute material for bisphenol A and is widely used in household products as a raw material for polycarbonate resin, epoxy resin, and plastic reinforcement. It is known to be mainly used in food containers, thermal paper for receipts, and coatings for water pipes. In some countries, bisphenol F has been detected in drinking water and human urine samples. However, due to the lack of safety evaluation data on bisphenol F, it is difficult to establish appropriate guidelines for the proper use of the substance, and social anxiety is increasing accordingly. This study investigated the use, exposure route, and distribution flow of bisphenol F, a household chemical. To determine the no-observed-adverse-effect level (NOAEL) and target organ of bisphenol F after exposure, a single-dose oral toxicity, dose-range finding (28 day oral), repeated dose toxicity (90 day oral), and genotoxicity (reverse mutation, chromosomal abnormality, in vivo micronucleus test) tests were performed. The pharmacokinetic profile was also obtained. The test results are as follows: in the pharmacokinetic study, it was confirmed that single oral exposure to BPF resulted in systemic exposure; in single oral dose toxicity test, the approximate lethal dose was found to be 4000 mg/kg and confusion and convulsion was shown in the test animals; NOAEL was determined to be 2 mg/kg/day for male and 5 mg/kg/day for female, and the no-observed-effect level (NOEL) was determined to be 2 mg/kg/day for males and 1 mg/kg/day for females, and the target organ was the small intestine; genotoxicity tests confirmed that BPF does not induce genotoxicity.

摘要

双酚 F 是双酚 A 的替代品,广泛用作聚碳酸酯树脂、环氧树脂和塑料增强剂的原料。已知它主要用于食品容器、收据用热敏纸和水管涂料。在一些国家,饮用水和人体尿液样本中检测到了双酚 F。然而,由于缺乏双酚 F 的安全评估数据,难以制定关于该物质正确使用的适当准则,因此社会焦虑感相应增加。本研究调查了家用化学品双酚 F 的使用、暴露途径和分布情况。为了确定双酚 F 暴露后的无观察不良效应水平(NOAEL)和靶器官,进行了单次口服毒性、剂量范围研究(28 天口服)、重复剂量毒性(90 天口服)和遗传毒性(回复突变、染色体异常、体内微核试验)测试。还获得了药代动力学特征。测试结果如下:在药代动力学研究中,证实单次口服暴露于 BPF 会导致全身暴露;在单次口服剂量毒性测试中,发现近似致死剂量为 4000mg/kg,试验动物出现了混乱和抽搐;确定雄性的 NOAEL 为 2mg/kg/天,雌性的 NOAEL 为 5mg/kg/天,未观察到效应水平(NOEL)确定为雄性 2mg/kg/天,雌性 1mg/kg/天,靶器官为小肠;遗传毒性测试证实 BPF 不会引起遗传毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a6/9095523/6db0d1fe6ebe/204_2022_3246_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a6/9095523/6db0d1fe6ebe/204_2022_3246_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a6/9095523/9bccd879123e/204_2022_3246_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/56a6/9095523/6db0d1fe6ebe/204_2022_3246_Fig7_HTML.jpg

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