Title
Improving the applicability of (Q)SARs for percutaneous penetration in regulatory risk assessment.
Author
Bouwman, T.
Cronin, M.T.
Bessems, J.G.
van de Sandt, J.J.
TNO Kwaliteit van Leven
Publication year
2008
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.
Subject
Health
xenobiotic agent
article
biological model
chemistry
drug effect
European Union
government regulation
human
legal aspect
physiology
prediction and forecasting
quantitative structure activity relation
risk assessment
skin absorption
European Union
Government Regulation
Humans
Models, Biological
Predictive Value of Tests
Quantitative Structure-Activity Relationship
Risk Assessment
Skin Absorption
Xenobiotics
To reference this document use:
http://resolver.tudelft.nl/uuid:20a903c1-c23d-4d66-9100-93dbec457c4b
DOI
https://doi.org/10.1177/0960327107085829
TNO identifier
240735
ISSN
0960-3271
Source
Human & experimental toxicology, 27 (4), 269-276
Document type
article