Phase III interlaboratory study of FETAX part 3. FETAX validation using 12 compounds with and without an exogenous metabolic activation system
Phase III interlaboratory study of FETAX part 3. FETAX validation using 12 compounds with and without an exogenous metabolic activation system
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FETAX 的 III 期实验室间研究第 3 部分。使用 12 种化合物（有或没有外源代谢激活系统）进行 FETAX 验证
DOI：
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发表时间：
1999
影响因子：
3.3
通讯作者：
Angela M. Gaudet‐Hull
中科院分区：
文献类型：
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作者：
J. Bantle;R. Finch;D. J. Fort;E. Stover;M. Hull;Marie Kumsher‐King;Angela M. Gaudet‐Hull
FETAX（蛙胚胎致畸试验-非洲爪蟾）是一种96小时全胚胎发育毒性筛选试验，可用于生态毒理学和采用体外代谢活化系统时检测哺乳动物发育毒物。一个标准化的美国测试与材料协会（ASTM）指南进行FETAX已经出版，沿着一个配套的地图集，有助于胚胎分期和识别畸形。作为ASTM过程的一部分，进行了实验室间验证研究，以评价FETAX的可重复性和可靠性，并评价12种化合物的潜在致畸危害。三个不同的实验室参与了这项研究。所有三个参与实验室都具有丰富的检测经验。根据变异系数判断，FETAX实验室内和实验室间的变异性非常低。使用采用代谢活化系统（MAS）的FETAX实验的两个主要标准评估了潜在的致畸危害。这些是致畸指数TI（TI = 96-h lc 50/96-h ec 50（畸形））和抑制生长的最小浓度（MCIG）。根据该标准，当MCIG浓度低于MAS 96-h lc 50的30%水平时与对照组存在显著差异时，认为化合物具有致畸性。根据本研究和其他研究的结果，构建了一个决策表，以评价其他研究。还评价了造成的畸形的严重程度，特别是在MAS 96-h ec 50（畸形）附近。四种化合物为非致畸性，但两种化合物具有明显的致畸性。其余6种化合物被列为可疑致畸剂。鉴于制作适当的决策表的困难，对结果进行了讨论。事实证明，只要在测距过程中小心行事，技术人员经过充分培训，FETAX就能产生可重复和可靠的数据。MAS在使用FETAX预测哺乳动物发育风险中是必不可少的，并且仍需要进一步发展。版权所有© 1999年约翰威利父子有限公司。
FETAX (Frog Embryo Teratogenesis Assay—Xenopus) is a 96‐h whole‐embryo developmental toxicity screening assay that can be used in ecotoxicology and in detecting mammalian developmental toxicants when an in vitro metabolic activation system is employed. A standardized American Society for Testing and Materials (ASTM) guide for the conduct of FETAX has been published, along with a companion atlas that helps in embryo staging and in identifying malformations. As part of the ASTM process, an interlaboratory validation study was undertaken to evaluate the repeatability and reliability of FETAX and to evaluate the potential teratogenic hazard of 12 compounds. Three different laboratories participated in the study. All three participating laboratories had extensive experience with the assay. FETAX intralaboratory and interlaboratory variability, as judged by coefficients of variation, were very low. Potential teratogenic hazard was evaluated using two major criteria from FETAX experiments employing metabolic activation systems (MAS). These were the teratogenic index TI (TI = 96‐h lc50/96‐h ec50 (malformation)) and the minimum concentration that inhibits growth (MCIG). A compound was considered teratogenic by this criterion when the MCIG was significantly different from controls at concentrations below the 30% level of the MAS 96‐h lc50. Based on the results of this and other studies, a decision table was constructed in order to evaluate additional studies. Severity of malformations caused, especially near the MAS 96‐h ec50 (malformation), were also evaluated. Four compounds were non‐teratogenic but two compounds were clearly teratogenic. The remaining six compounds were ranked as equivocal teratogens. The results were discussed in light of the difficulty of producing an adequate decision table. FETAX proved to yield repeatable and reliable data as long as care was taken during range‐finding and technicians were adequately trained. The MAS was essential in using FETAX to predict developmental hazard in mammals, and still requires further development. Copyright © 1999 John Wiley & Sons, Ltd.
新西兰白兔灌胃乙二醇的发育毒性评价。
DOI：
10.1006/faat.1993.1052
发表时间：
1993
期刊：
Fundamental and applied toxicology : official journal of the Society of Toxicology
影响因子：
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作者：
Tyl,RW;Price,CJ;Marr,MC;Myers,CB;Seely,JC;Heindel,JJ;Schwetz,BA
通讯作者：
Schwetz,BA