完整的急性毒性试验方案-不仅仅是LD50测定。

A Dayan
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引用次数: 6

摘要

任何实验者的目标都应该是以最经济的方式获得最大量的有用信息。在这种情况下,“有用”是指研究被检测化合物的主要或预期作用,以及检测对其的其他反应。为了进行有效的评估,包括更严格的统计,一个连续的或分级的答复和定量测量是可取的,尽管通过简单地分析是否存在答复可以做很多事情,即使这些是复杂的或依赖于主观标准。实验条件和诊断标准的一致性是必不可少的,无论是在单一的、探索性的还是比较试验中。因此,像其他实验一样,急性毒性试验的设计应该务实,既要确认被检查物质的特性,又要有一般或全面的覆盖,尽管不那么具体,以发现意外的行为。这两类方法的重要性或大或小,取决于该试验是作为先前未知物质的一般筛选的一部分,还是作为测定某一特定性质的特定控制措施。只有在有限的和高度人工的条件下进行的任何实验所应有的谨慎,才能将结果外推到人类或其他物种身上,但是在人类身上获得的经验往往表明了急性毒性数据的价值。
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Complete programme for acute toxicity testing - not only LD50 determination.

The objective of any experimenter should be to obtain the maximum amount of useful information in the most economical manner possible. In this context, 'useful' means study both of the principal or anticipated actions of the compound under examination, and also detection of additional responses to it. For efficient evaluation, including greater statistical rigour, a continuous or graded response and quantitative measurement is preferable, although much can be done by simply analysis of the presence or absence of responses, even if these are complex or dependent upon subjective criteria. Consistency of experimental conditions, and of diagnostic criteria are essential, whether in single, exploratory or comparative tests. Acute toxicity tests, like other experiments, should be designed pragmatically, therefore, confirming to the properties of the substance under examination, but also with general or holistic coverage, albeit less specific, to detect unanticipated actions. Greater or lesser weight may be given to these two classes of method, depending on whether the test is done as part of a general screen of a previously unknown substance, or as a specific control measure done to assay one particular property. Extrapolation of the results to man or other species is only possible with the caution proper to any experiment done under restricted and highly artificial conditions, but the value of acute toxicity data has often been shown by experience gained in man.

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