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中国人群镉暴露的贝叶斯毒代动力学建模。

Bayesian toxicokinetic modeling of cadmium exposure in Chinese population.

机构信息

School of Public Health/Key Laboratory of Public Health Safety, Ministry of Education, Department of Nutrition and food science, Fudan University, Shanghai 200032, China.

Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA.

出版信息

J Hazard Mater. 2021 Jul 5;413:125465. doi: 10.1016/j.jhazmat.2021.125465. Epub 2021 Feb 19.

Abstract

Cadmium (Cd) is a toxic heavy metal widely present in the environment. Estimating its internal levels for a given external exposure using toxicokinetic (TK) models is key to the human health risk assessment of Cd. In this study, existing Cd TK models were adapted to develop a one-compartment TK model and a multi-compartment physiologically based toxicokinetic (PBTK) model by estimating the characteristics of Cd kinetics based on Cd exposure data from 814 Chinese residents. Both models not only considered the effect of gender difference on Cd kinetics, but also described the model parameters in terms of distributions to reflect individual variability. For both models, the posterior distributions of sensitive parameters were estimated using the Markov chain-Monte Carlo method (MCMC) and the approximate Bayesian computation-MCMC algorithm (ABC-MCMC). Validation with the test dataset showed 1.4-22.5% improvement in the root mean square error (RMSE) over the original models. After a systematic literature search, the optimized models showed acceptable prediction on other Chinese datasets. The study provides a method for parameter optimization of TK models under different exposure environment, and the validated models can serve as new quantitative assessment tools for the risk assessment of Cd in the Chinese population.

摘要

镉(Cd)是一种广泛存在于环境中的有毒重金属。使用毒代动力学(TK)模型估计给定外暴露水平下的内部水平,是进行镉对人体健康风险评估的关键。在这项研究中,我们对现有的镉 TK 模型进行了改编,通过估算 814 名中国居民的镉暴露数据,建立了一个单室 TK 模型和一个多室基于生理学的毒代动力学(PBTK)模型,以评估镉动力学的特征。这两个模型不仅考虑了性别差异对镉动力学的影响,还根据分布情况描述了模型参数,以反映个体差异。对于这两个模型,我们使用马尔可夫链-蒙特卡罗方法(MCMC)和近似贝叶斯计算-MCMC 算法(ABC-MCMC)估计了敏感参数的后验分布。使用测试数据集进行验证表明,与原始模型相比,均方根误差(RMSE)提高了 1.4-22.5%。经过系统的文献检索,优化后的模型对其他中国数据集的预测也表现出了较好的效果。该研究为不同暴露环境下 TK 模型的参数优化提供了一种方法,验证后的模型可作为中国人群镉风险评估的新的定量评估工具。

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