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Article

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

1
Laboratory of Chemistry and Environmental Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy
2
Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands
3
Kode Chemoinformatics s.r.l., 56125 Pisa, Italy
*
Authors to whom correspondence should be addressed.
Molecules 2021, 26(1), 127; https://doi.org/10.3390/molecules26010127
Received: 2 December 2020 / Revised: 24 December 2020 / Accepted: 25 December 2020 / Published: 29 December 2020
(This article belongs to the Special Issue Environmental Toxicology)
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. View Full-Text
Keywords: cancer slope factor; in silico method; QSAR; prioritization cancer slope factor; in silico method; QSAR; prioritization
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    Doi: https://doi.org/10.5281/zenodo.4385768
MDPI and ACS Style

Toma, C.; Manganaro, A.; Raitano, G.; Marzo, M.; Gadaleta, D.; Baderna, D.; Roncaglioni, A.; Kramer, N.; Benfenati, E. QSAR Models for Human Carcinogenicity: An Assessment Based on Oral and Inhalation Slope Factors. Molecules 2021, 26, 127. https://doi.org/10.3390/molecules26010127

AMA Style

Toma C, Manganaro A, Raitano G, Marzo M, Gadaleta D, Baderna D, Roncaglioni A, Kramer N, Benfenati E. QSAR Models for Human Carcinogenicity: An Assessment Based on Oral and Inhalation Slope Factors. Molecules. 2021; 26(1):127. https://doi.org/10.3390/molecules26010127

Chicago/Turabian Style

Toma, Cosimo, Alberto Manganaro, Giuseppa Raitano, Marco Marzo, Domenico Gadaleta, Diego Baderna, Alessandra Roncaglioni, Nynke Kramer, and Emilio Benfenati. 2021. "QSAR Models for Human Carcinogenicity: An Assessment Based on Oral and Inhalation Slope Factors" Molecules 26, no. 1: 127. https://doi.org/10.3390/molecules26010127

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