QSAR Models for Human Carcinogenicity: An Assessment Based on Oral and Inhalation Slope Factors.

Carcinogenicity is a crucial endpoint for the safety assessment of chemicals and products. During the last few decades, the development of quantitative structure-activity relationship ((Q)SAR) models has gained importance for regulatory use, in combination with in vitro testing or expert-based reasoning. Several classification models can now predict both human and rat carcinogenicity, but there are few models to quantitatively assess carcinogenicity in humans. To our knowledge, slope factor (SF), a parameter describing carcinogenicity potential used especially for human risk assessment of contaminated sites, has never been modeled for both inhalation and oral exposures. In this study, we developed classification and regression models for inhalation and oral SFs using data from the Risk Assessment Information System (RAIS) and different machine learning approaches. The models performed well in classification, with accuracies for the external set of 0.76 and 0.74 for oral and inhalation exposure, respectively, and r2 values of 0.57 and 0.65 in the regression models for oral and inhalation SFs in external validation. These models might therefore support regulators in (de)prioritizing substances for regulatory action and in weighing evidence in the context of chemical safety assessments. Moreover, these models are implemented on the VEGA platform and are now freely downloadable online.

Impact of REACH legislation on the production and importation of CMR (carcinogen, mutagen and reproductive) and explosive chemicals in Italy from 2011 to 2015.

On 1 June 2007, the European Commission issued the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) to protect both the environment and human health. We analyzed the impact of REACH in the Italian market considering the presence of chemicals, their diversity, importation and production during the period 2011-2015, with particular attention to products with toxic or explosive properties. There was a reduction of the chemicals on the market, in terms of tons but also the absolute numbers of types of compounds. The production reduction was particularly noticeable for explosive chemicals: -14.7%. CMR products did not show any statistically significant reduction in term of tons: -2.3%.