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DOI10.1002/bdrb.21132
Exposure-Based Validation List for Developmental Toxicity Screening Assays
Daston, George P.1; Beyer, Bruce K.2; Carney, Edward W.3; Chapin, Robert E.4; Friedman, Jan M.5; Piersma, Aldert H.6,7; Rogers, John M.8; Scialli, Anthony R.9,10
发表日期2014-12-01
ISSN1542-9733
卷号101期号:6页码:423-428
英文摘要

Validation of alternative assays requires comparison of the responses to toxicants in the alternative assay with in vivo responses. Chemicals have been classified as positive or negative in vivo, despite the fact that developmental toxicity is conditional on magnitude of exposure. We developed a list of positive and negative developmental exposures, with exposure defined by toxicokinetic data, specifically maternal plasma C-max. We selected a series of 20 chemicals that caused developmental toxicity and for which there were appropriate toxicokinetic data. Where possible, we used the same chemical for both positive and negative exposures, the positive being the C-max at a dose level that produced significant teratogenicity or embryolethality, the negative being the C-max at a dose level not causing developmental toxicity. It was not possible to find toxicokinetic data at the no-effect level for all positive compounds, and the negative exposure list contains C-max values for some compounds that do not have developmental toxicity up to the highest dose level tested. This exposure-based reference list represents a fundamentally different approach to the evaluation of alternative tests and is proposed as a step toward application of alternative tests in quantitative risk assessment (C) 2014 Wiley Periodicals, Inc.


英文关键词in vitro methods;validation;developmental toxicity
语种英语
WOS记录号WOS:000346705300003
来源期刊BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY
来源机构美国环保署
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/61733
作者单位1.Procter & Gamble, Cincinnati, OH USA;
2.Sanofi US Inc, Dept Disposit Safety & Anim Res Preclin Safety, Bridgewater, NJ USA;
3.Dow Chem Co USA, Midland, MI 48674 USA;
4.Pfizer Worldwide R&D, Groton, CT USA;
5.Univ British Columbia, Dept Med Genet, Child & Family Res Inst, Vancouver, BC V5Z 1M9, Canada;
6.RIVM, Utrecht, Netherlands;
7.Univ Utrecht, IRAS, Utrecht, Netherlands;
8.US EPA, Tox Assessment Div, NHEERL, ORD, Res Triangle Pk, NC 27711 USA;
9.Reprod Toxicol Ctr, Washington, DC USA;
10.George Washington Univ, Sch Med, Washington, DC USA
推荐引用方式
GB/T 7714
Daston, George P.,Beyer, Bruce K.,Carney, Edward W.,et al. Exposure-Based Validation List for Developmental Toxicity Screening Assays[J]. 美国环保署,2014,101(6):423-428.
APA Daston, George P..,Beyer, Bruce K..,Carney, Edward W..,Chapin, Robert E..,Friedman, Jan M..,...&Scialli, Anthony R..(2014).Exposure-Based Validation List for Developmental Toxicity Screening Assays.BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY,101(6),423-428.
MLA Daston, George P.,et al."Exposure-Based Validation List for Developmental Toxicity Screening Assays".BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY 101.6(2014):423-428.
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