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提高(定量)构效关系在经皮渗透监管风险评估中的适用性。

Improving the applicability of (Q)SARs for percutaneous penetration in regulatory risk assessment.

作者信息

Bouwman T, Cronin M T D, Bessems J G M, van de Sandt J J M

机构信息

Department of Food and Chemical Risk Analysis, TNO Quality of Life, Zeist, The Netherlands.

出版信息

Hum Exp Toxicol. 2008 Apr;27(4):269-76. doi: 10.1177/0960327107085829.

Abstract

The new regulatory framework REACH (Registration, Evaluation, and Authorisation of Chemicals) foresees the use of non-testing approaches, such as read-across, chemical categories, structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs). Although information on skin absorption data are not a formal requirement under REACH, data on dermal absorption are an integral part of risk assessment of substances/products to which man is predominantly exposed via the dermal route. In this study, we assess the present applicability of publicly available QSARs on skin absorption for risk assessment purposes. We explicitly did not aim to give scientific judgments on individual QSARs. A total of 33 QSARs selected from the public domain were evaluated using the OECD (Organisation for Economic Co-operation and Development) Principles for the Validation of (Q)SAR Models. Additionally, several pragmatic criteria were formulated to select QSARs that are most suitable for their use in regulatory risk assessment. Based on these criteria, four QSARs were selected. The predictivity of these QSARs was evaluated by comparing their outcomes with experimentally derived skin absorption data (for 62 compounds). The predictivity was low for three of four QSARs, whereas one model gave reasonable predictions. Several suggestions are made to increase the applicability of QSARs for skin absorption for risk assessment purposes.

摘要

新的监管框架《化学品注册、评估、授权和限制》(REACH)预计将采用非测试方法,如类推法、化学类别、构效关系(SAR)和定量构效关系(QSAR)。尽管根据REACH法规,皮肤吸收数据并非正式要求,但皮肤吸收数据是对人类主要通过皮肤接触的物质/产品进行风险评估的一个组成部分。在本研究中,我们评估了公开可用的QSAR在皮肤吸收风险评估中的适用性。我们明确无意对单个QSAR做出科学判断。从公共领域选取了33个QSAR,依据经济合作与发展组织(OECD)的(Q)SAR模型验证原则进行评估。此外,还制定了一些实用标准,以挑选最适合用于监管风险评估的QSAR。基于这些标准,选出了四个QSAR。通过将这些QSAR的结果与实验得出的皮肤吸收数据(针对62种化合物)进行比较,评估了它们的预测能力。四个QSAR中有三个的预测能力较低,而有一个模型给出了合理的预测结果。针对提高QSAR在皮肤吸收风险评估中的适用性,我们提出了一些建议。

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