Bayesian analysis of physiologically based toxicokinetic (PBTK) modeling for pentachlorophenol exposure in pregnant women

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2024-05-26 DOI:10.1016/j.tiv.2024.105853

Chunfeng Wu , Yajiao Tan , Xiaoyi Wei , Xun Li , Sifei Sun , Bing Lyu , Zhen Shen , Xiao Wei , Shuo Xiao , Yuanyuan Ruan , Jun Yu , Gengsheng He , Weiwei Zheng , Jingguang Li

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Abstract

Pentachlorophenol (PCP) is a persistent organic compound that is widely present in the environment. The estimation of internal exposure levels for a given external exposure using toxicokinetic models is key to the human health risk assessment of PCP. The present study developed a physiologically based multicompartmental pharmacokinetic (PBTK) model to describe and predict the behavior of pentachlorophenol (PCP) in an organism. The model consists of stomach, intestines, adipose tissue, kidneys and fast- and poorly perfused tissues that are interconnected via blood circulation. We constructed a PBTK model of PCP in rats and extrapolated it to human dietary PCP exposure. The toxicokinetic data of PCP in human tissues and excreta were obtained from the published literature. Based on the collected PCP dietary survey and internal exposure data of pregnant women in Shanghai, Bayesian statistical analysis was performed for the model using Markov chain Monte Carlo (MCMC) simulation. The posterior distributions of the sensitive parameters were estimated, and the model was parameter optimized and validated using the pregnant women's test dataset. The results showed that the root mean square error (RMSE) improved 37.3% compared to the original model, and a systematic literature search revealed that the optimized model achieved acceptable prediction results for other datasets in China. A PCP metabolism model based on the exposure characteristics of pregnant women in China was constructed in the present study. The model provides a theoretical basis for the study of PCP toxicity and risk assessment.

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对孕妇接触五氯苯酚的生理毒物动力学（PBTK）模型进行贝叶斯分析。

五氯苯酚（PCP）是一种广泛存在于环境中的持久性有机化合物。利用毒物动力学模型估算特定外部暴露的内部暴露水平是五氯苯酚人体健康风险评估的关键。本研究开发了一种基于生理学的多室药代动力学（PBTK）模型，用于描述和预测五氯苯酚（PCP）在生物体内的行为。该模型由胃、肠道、脂肪组织、肾脏以及通过血液循环相互连接的快灌注和低灌注组织组成。我们在大鼠体内构建了五氯苯酚的 PBTK 模型，并将其推断为人类从饮食中摄入五氯苯酚的情况。五氯苯酚在人体组织和排泄物中的毒物动力学数据来自已发表的文献。根据收集到的上海孕妇五氯苯酚膳食调查和体内暴露数据，采用马尔科夫链蒙特卡洛（MCMC）模拟对模型进行了贝叶斯统计分析。对敏感参数的后验分布进行了估计，并对模型进行了参数优化和使用孕妇测试数据集进行了验证。结果表明，与原始模型相比，均方根误差（RMSE）降低了 37.3%，通过系统的文献检索发现，优化后的模型在中国其他数据集上也取得了可接受的预测结果。本研究根据中国孕妇的暴露特点构建了五氯苯酚代谢模型。该模型为研究五氯苯酚的毒性和风险评估提供了理论依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.