(Q)SARs for human toxicological endpoints: a literature search

The goal here was to describe human toxicological SARs (structure-activity relationships) available in the literature and used by the US EPA (Environmental Protection Agency). The CSR laboratory investigated implementation of SARs for the effect assessment. SARs correlate the molecular structure with biological-chemical or physico-chemical activity. These correlations are quantified in quantitative structure-activity relationships (QSARs). The (Q)SARs described are roughly divided into rule-based SARs and statistical SARs. The rule-based SAR uses similar chemicals (collected in chemical categories) having the same mechanism of action and descriptors for this mechanism was to predict the effect of other similar chemicals. The statistical SAR bases its prediction on statistical derived descriptors of more heterogeneous groups of chemicals. The development of SARs during the years has brought the two types of SARs together. The QSARs found need further validation before they can be used for the effect evaluation. QSAR methodology can be implemented. Predicting the effect of a chemical similar to an already assessed chemical or chemical category is used at RIVM/CSR on an ad-hoc basis for effect assessment. (Q)SAR methodology, chemical categories, and SAR features such as electronic effects should be implemented more systemically; this will increase the expertise of using SARs and the transparency of the effect assessment