基于生理学的药代动力学模型
生物信息学
双酚S
体内
体外
药理学
人口
生物
双酚
计算生物学
化学
药代动力学
医学
生物化学
生物技术
基因
有机化学
环氧树脂
环境卫生
标识
DOI:10.1016/j.jhazmat.2020.122856
摘要
Combined risk assessment of endocrine effects of bisphenol A (BPA) and its analogues, such as bisphenols S, F, and AF (BPS, BPF, and BPAF), is challenging due to lack of related common toxicity metrics. This study conducted a population-based in vitro-to-in vivo extrapolation using physiologically based pharmacokinetic (PBPK) models coupled with Monte Carlo simulations to convert ToxCast in vitro estrogen receptor (ER) assays to human equivalent doses (HEDs). The ER pathway-based HEDs were compared with HEDs from animal studies and used to assess the combined risks for different populations across different countries/regions in a probabilistic manner. The estimated ER pathway-based HEDs for the four bisphenols (BPs) matched the animal-derived HEDs. The HEDs for the ER gene transcription (the common biological process target among BPs) were 0.40 (2.5th–97.5th percentiles: 0.06–5.42), 4.43 (0.69–53.84), 3.30 (0.51–626.57), and 1.12 (0.16–9.73) mg/kg/day for BPA, BPS, BPF, and BPAF, respectively. Results suggest a potentially moderate concern for combined risks of activating the ER pathway for toddlers and adults with high dietary exposures. This study presents in vitro-based credible HEDs for the four BPs and represents an advancement in the application of in vitro–in silico-based alternative approaches in human health risk assessment.
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