A battery of in silico models application for pesticides exerting reproductive health effects: Assessment of performance and prioritization of mechanistic studies.

Autor: Kolesnyk S; L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Kyiv, Ukraine; Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, Basel 4056, Switzerland; Swiss Centre for Human Applied Toxicology, University of Basel, Missionsstrasse 64, Basel 4055, Switzerland. Electronic address: serhii.kolesnyk@unbas.ch., Prodanchuk M; L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Kyiv, Ukraine., Zhminko P; L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Kyiv, Ukraine., Kolianchuk Y; L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Kyiv, Ukraine., Bubalo N; L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Kyiv, Ukraine., Odermatt A; Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, Basel 4056, Switzerland; Swiss Centre for Human Applied Toxicology, University of Basel, Missionsstrasse 64, Basel 4055, Switzerland., Smieško M; Swiss Centre for Human Applied Toxicology, University of Basel, Missionsstrasse 64, Basel 4055, Switzerland; Computational Pharmacy, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, Basel 4056, Switzerland.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2023 Dec; Vol. 93, pp. 105706. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1016/j.tiv.2023.105706
Abstrakt: Given the high attention to endocrine disrupting chemicals (EDC), there is an urgent need for the development of rapid and reliable approaches for the screening of large numbers of chemicals with respect to their endocrine disruption potential. This study aimed at the assessment of the correlation between the predicted results of a battery of in silico tools and the reported observed adverse effects from in vivo reproductive toxicity studies. We used VirtualToxLab (VTL) software and the EndocrineDisruptome (ED) online tool to evaluate the binding affinities to nuclear receptors of 17 pesticides, 7 of which were classified as reprotoxic substances under Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP). Then, we aligned the results of the in silico modelling with data from ToxCast assays and in vivo reproductive toxicity studies. We combined results from different in silico tools in two different ways to improve the characteristics of their predictive performance. Reproductive toxicity can be caused by various mechanisms; however, in this study, we demonstrated that the use of a battery of in silico tools for assessing the binding to nuclear receptors can be useful for identifying hazardous compounds and for prioritizing further studies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Ltd.)
Databáze: MEDLINE
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