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哈伯定律在标准制定和风险评估中的应用。

The use of Haber's law in standard setting and risk assessment.

作者信息

Gaylor D W

机构信息

National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, 72079, Jefferson, AR 72079, USA.

出版信息

Toxicology. 2000 Aug 14;149(1):17-9. doi: 10.1016/s0300-483x(00)00228-6.

Abstract

Haber's Law simply states that the incidence and/or severity of a toxic effect depends on the total exposure, i.e. exposure concentration (c) rate times the duration time (t) of exposure (c x t). This rule, within constraints, is often used in setting exposure guidelines for toxic substances. Establishing reference doses (acceptable daily intakes) for long-term exposures when only the results of short-term studies are available requires the use of an uncertainty (safety) factor. The value of this uncertainty factor often approximates a value comparable to Haber's Law for extrapolation from short-term to long-term exposure durations. As a default procedure, cancer risk estimates are generally based on the average lifetime daily dose which is derived from the total cumulative exposure, i.e. Haber's (c x t). This has been shown both theoretically and empirically to be valid within a factor of 20 for carcinogenesis. This provides some credence for the use of an additional safety factor of 10, in some instances, for exposures of children to carcinogens. Finally, a generalization of Haber's Law, exposure concentration raised to a power times exposure duration, is discussed.

摘要

哈伯定律简单地表明,毒性效应的发生率和/或严重程度取决于总暴露量,即暴露浓度(c)乘以暴露持续时间(t)(c×t)。在一定限制条件下,该规则常用于设定有毒物质的暴露指南。当仅有短期研究结果时,确定长期暴露的参考剂量(可接受的每日摄入量)需要使用一个不确定度(安全)因子。这个不确定度因子的值通常近似于一个与哈伯定律相当的值,用于从短期暴露持续时间外推到长期暴露持续时间。作为默认程序,癌症风险评估通常基于从总累积暴露量得出的平均终身每日剂量,即哈伯定律中的(c×t)。理论和实证研究均表明,这在致癌作用方面在20倍的范围内是有效的。这为在某些情况下对儿童接触致癌物使用额外的10倍安全因子提供了一定可信度。最后,讨论了哈伯定律的一种推广形式,即暴露浓度的幂次方乘以暴露持续时间。

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