期刊
BIRTH DEFECTS RESEARCH
卷 114, 期 16, 页码 972-982出版社
WILEY
DOI: 10.1002/bdr2.1984
关键词
adverse outcome pathway; Daston list; embryo; embryotoxicity; gastruloid; risk assessment; teratogen
资金
- Alternatives Research and Development Foundation
- National Institute of Child Health and Human Development [R03 HD101735, R03 HD102502]
- NIH Centers of Biomedical Research Excellence Phase 3 to the Institute for Biogenesis Research [P30 GM131944]
Pluripotent stem cells have been explored as nonanimal alternatives for assessing developmental toxicity of chemicals, but no standard assay has been established. This article discusses issues in improving stem cell assays and their acceptance as the cornerstone in predictive developmental toxicology. It suggests establishing standardized reference lists of chemicals to validate and compare individual assays. Stem cell assays, though not replacing human or animal tests, can serve as practical alternatives to identify chemical exposures that disrupt embryogenesis.
In the past few decades, pluripotent stem cells have been explored as nonanimal alternatives to assess the developmental toxicity of chemicals. To date, numerous versions of stem cell-based assays have been reported that are allegedly effective. Nonetheless, none of the assays has become the gold standard in developmental toxicity assessment. Why? This article discusses several issues in the hope of facilitating the refinement of stem cell assays and their acceptance as the cornerstone in predictive developmental toxicology. Each stem cell assay is built on a limited representation of embryogenesis, so that multiple assays are needed to detect the diverse effects of various chemicals. To validate and compare the strengths and weaknesses of individual assays, standardized lists of reference chemicals should be established. Reference lists should consist of exposures defined by toxicokinetic data, namely maternal plasma concentrations that cause embryonic death or malformations, and also by the effects on the molecular machineries that control embryogenesis. Although not entirely replacing human or animal tests, carefully selected stem cell assays should serve as practical and ethical alternatives to proactively identify chemical exposures that disturb embryogenesis. To achieve this goal, unprecedented levels of coordination and conviction are required among research and regulatory communities.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据