Benchmark doses (BMD) extrapolated from in vitro cytotoxicity experiments in SH-SY5Y cells using the EFSA Bayesian BMD web app: The study case of imidacloprid

IF 3.1 Q2 TOXICOLOGY
Lenin J. Ramirez-Cando , Santiago J. Ballaz
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引用次数: 0

Abstract

Identifying possible chemical hazards is critical to establish toxicological risk assessment related to non-cancer health effects. The benchmark dose (BMD) is an estimate of the hazardous toxic level (dose or concentration) that produces a predetermined variation in the response rate of an adverse effect (exposure-related risk endpoint). Our goal was to assess how well Bayesian weighted averaging models enhances the imidacloprid-treated SH-SY5Y cells’ dose-toxicological response in the MTT cytotoxicity assay. Notably, the Gelman-Rubin statistics for our models were constantly between 0.9 and 1.0, and the effective sample size was greater than 150, which guaranteed practical sufficiency. We used a weighted average of posteriorly fitted models to estimate the final BMD = 26.40 and the lower confidence limit (BMDL) = 13.10. Including uncertainty factors (UF) in conjunction with MTT data into our risk analysis, we assessed the population’s imidacloprid exposure. The Point of Departure (PoD) at 5th percentil (8.14) indicated adverse effects. Moreover, a similar link was observed between the target human dose for minimal impact (HDMI) and the HD50 (dose hazardous to 50 % of people). The determined Reference Dose (RfD) of 0.0003 µM suggested a high toxicity risk associated with imidacloprid exposure. Summarizing, dose–response evaluations were enhanced by Bayesian model averaging, highlighting the significance of probabilistic modeling and toxicological understanding.
使用EFSA贝叶斯BMD web应用程序从SH-SY5Y细胞体外细胞毒性实验中推断出的基准剂量(BMD):以吡虫啉为例
确定可能的化学危害对于建立与非癌症健康影响有关的毒理学风险评估至关重要。基准剂量(BMD)是对有害毒性水平(剂量或浓度)的估计,该水平会在不良反应的反应率(暴露相关风险终点)中产生预定的变化。我们的目标是评估贝叶斯加权平均模型在MTT细胞毒性试验中增强吡虫啉处理的SH-SY5Y细胞的剂量毒理学反应的效果。值得注意的是,我们的模型的Gelman-Rubin统计量一直在0.9 ~ 1.0之间,有效样本量大于150,保证了实际的充分性。我们使用后拟合模型的加权平均值来估计最终BMD = 26.40,下限置信限(BMDL) = 13.10。包括不确定性因素(UF)和MTT数据纳入我们的风险分析,我们评估了人群的吡虫啉暴露。第5个百分位的起始点(PoD)(8.14)提示不良反应。此外,在人体最小影响目标剂量(HDMI)和HD50(对50%的人有害的剂量)之间也观察到类似的联系。确定的参考剂量(RfD)为0.0003µM,表明吡虫啉暴露具有高毒性风险。综上所述,贝叶斯模型平均增强了剂量-反应评估,突出了概率建模和毒理学理解的重要性。
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
Computational Toxicology
Computational Toxicology Computer Science-Computer Science Applications
CiteScore
5.50
自引率
0.00%
发文量
53
审稿时长
56 days
期刊介绍: Computational Toxicology is an international journal publishing computational approaches that assist in the toxicological evaluation of new and existing chemical substances assisting in their safety assessment. -All effects relating to human health and environmental toxicity and fate -Prediction of toxicity, metabolism, fate and physico-chemical properties -The development of models from read-across, (Q)SARs, PBPK, QIVIVE, Multi-Scale Models -Big Data in toxicology: integration, management, analysis -Implementation of models through AOPs, IATA, TTC -Regulatory acceptance of models: evaluation, verification and validation -From metals, to small organic molecules to nanoparticles -Pharmaceuticals, pesticides, foods, cosmetics, fine chemicals -Bringing together the views of industry, regulators, academia, NGOs
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