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一种基于暴露与效应关系考量的发育毒性评估分级系统。

A tier system for developmental toxicity evaluations based on considerations of exposure and effect relationships.

作者信息

Johnson E M

出版信息

Teratology. 1987 Jun;35(3):405-27. doi: 10.1002/tera.1420350314.

DOI:10.1002/tera.1420350314
PMID:3307013
Abstract

The backlog of untested chemicals and the rate at which new substances enter the marketplace exceed our capacity for developmental effects testing by standard in vivo methods. However, conservative use of two observations in a manner consistent with present day understanding of abnormal developmental biology can more accurately focus attention and resources on those agents in greatest need of complex testing for effects on in utero development. These two observations are 1) most chemicals are no more toxic to embryonic development than they are to adult homeostasis and 2) most human exposure to chemicals is de minimus, i.e., so small that it is inconsequential. Recently devised in vitro assays to quantitatively rank chemicals according to their developmental hazard index, when used in conjunction with more conventional in vivo methods and appropriate considerations of exposure, permit evaluation of a significantly larger number of chemicals than is currently achieved. The methods described apply a tier approach to establish testing priorities that markedly reduce the time, cost, and number of laboratory animals needed for evaluation of developmental toxicity.

摘要

未经测试的化学物质积压以及新物质进入市场的速度超过了我们采用标准体内方法进行发育效应测试的能力。然而,以与当今对异常发育生物学的理解相一致的方式保守地运用两项观察结果,能够更准确地将注意力和资源集中于那些最需要进行复杂的子宫内发育效应测试的化学物质。这两项观察结果是:1)大多数化学物质对胚胎发育的毒性并不比对成体体内平衡的毒性更大;2)大多数人类对化学物质的接触量极小,即小到无关紧要。最近设计的体外试验,用于根据化学物质的发育危害指数对其进行定量排序,当与更传统的体内方法以及对接触的适当考量结合使用时,能够评估比目前数量显著更多的化学物质。所描述的方法采用分层方法来确定测试优先级,这显著减少了评估发育毒性所需的时间、成本以及实验动物数量。

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