One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorization of Chemicals) is to fulfill the gaps in data concerned with properties of chemicals affecting the human health. (Q)SAR models are accepted as a suitable source of information. The EU funded CAESAR project aimed to develop models for prediction of 5 endpoints for regulatory purposes. Carcinogenicity is one of the endpoints under consideration.

The regulatory agencies should fulfil the data gap in toxicity for new chemicals including nano-sized compounds, like metal oxides nanoparticles (MeO_x NPs) according to the registration, evaluation, authorisation and restriction of chemicals (REACH) legislation policy. This study demonstrates the perspective capability of neural network models for prediction of cytotoxicity of MeO_x NPs to bacteria Escherichia coli (E. coli) for the widest range of metal oxides extracted from Periodic table. The counter propagation artificial neural network (CP ANN) models for prediction of cytotoxicity of MeO_x NPs for data sets of 17, 36 and 72 metal oxides were employed in the study. The cytotoxicity of studied metal oxide NPs was correlated with (i) χ-metal electronegativity (EN) by Pauling scale and composition of metal oxides characterised by (ii) number of metal atoms in oxide, (iii) number of oxygen atoms in oxide and (iv) charge of metal cation in oxide. The paper describes the models in context of five OECD principles of validation models accepted for regulatory use. The recommendations were done for the minimal number of cytotoxicity tests needs for evaluation of the large set of MeO_x with different oxidation states. The methodology is expected to be useful for potential hazard assessment of MeO_x NPs and prioritisation for further testing and risk assessment.

The aim of this article is to show the main aspects of quantitative structure activity relationship (QSAR) modeling for regulatory purposes. We try to answer the question; what makes QSAR models suitable for regulatory uses. The article focuses on directions in QSAR modeling in European Union (EU) and Russia. Difficulties in validation models have been discussed.