Degnan David J, Bramer Lisa M, Truong Lisa, Tanguay Robyn L, Gosline Sara M, Waters Katrina M
Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington, United States of America.
Sinnhuber Aquatic Research Laboratory, Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, United States of America.
PLoS Comput Biol. 2025 Jul 28;21(7):e1013337. doi: 10.1371/journal.pcbi.1013337. eCollection 2025 Jul.
Though chemical exposures are known to potentially have negative impacts on health, including contributing to chronic diseases such as cancer, the quantitative contribution of risk is not fully understood for every chemical. A commonly used approach to quantify levels of risk is to measure the proportion of organisms (such as a total number of zebrafish on a plate or mice in a cage) with abnormal behavioral responses or morphology at increasing concentrations of chemical exposure. A particular challenge with processing the proportional data from these assays is the appropriate estimation of chemical concentration levels that result in malformations or acute toxicity, as these values typically vary between experimental measurements. The recommended approach by the Environmental Protection Agency (EPA) is to fit benchmark dose curves with specific filters and model fitting steps, which are crucial to properly processing the proportional data. Several tools exist for the fitting of benchmark dose response curves, but none are standalone Python libraries built to process both morphological and behavioral data as proportions with all the EPA recommended filters, filter parameters, models, and model parameters. Thus, here we present the benchmark dose response curve (bmdrc) Python library, which was built to closely follow these EPA guidelines with helpful visualizations of filters and fitted model curves, and reports for reproducibility purposes. bmdrc is open-source and has demonstrated utility as a support package to an existing web portal for information on chemicals (https://srp.pnnl.gov). Our package will support any toxicology analysis where the response is a proportional value at increasing levels of a concentration of a chemical or chemical mixture.
尽管已知化学物质暴露可能对健康产生负面影响,包括导致癌症等慢性疾病,但并非每种化学物质的风险定量贡献都已完全明确。一种常用的量化风险水平的方法是,在化学物质暴露浓度不断增加的情况下,测量出现异常行为反应或形态的生物体比例(如培养皿中斑马鱼的总数或笼子里小鼠的数量)。处理这些试验中的比例数据时面临的一个特殊挑战是,要准确估计导致畸形或急性毒性的化学物质浓度水平,因为这些值在实验测量中通常会有所不同。美国环境保护局(EPA)推荐的方法是,通过特定的筛选器和模型拟合步骤来拟合基准剂量曲线,这对于正确处理比例数据至关重要。有几种工具可用于拟合基准剂量反应曲线,但没有一个是独立的Python库,能够按照EPA推荐的所有筛选器、筛选器参数、模型和模型参数,将形态学和行为数据作为比例进行处理。因此,我们在此展示基准剂量反应曲线(bmdrc)Python库,它的构建严格遵循这些EPA指南,提供筛选器和拟合模型曲线的直观可视化,并出于可重复性目的生成报告。bmdrc是开源的,已证明可作为现有化学品信息网站门户(https://srp.pnnl.gov)的支持包。我们的软件包将支持任何毒理学分析,其中反应是化学物质或化学混合物浓度增加时的比例值。