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

Serhii Kolesnyk; Mykola Prodanchuk; Petro Zhminko; Yana Kolianchuk; Nataliia Bubalo; Alex Odermatt; Martin Smieško

doi:10.1016/j.tiv.2023.105706

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

Toxicol In Vitro. 2023 Dec:93:105706. doi: 10.1016/j.tiv.2023.105706. Epub 2023 Oct 4.

Authors

Serhii Kolesnyk¹, Mykola Prodanchuk², Petro Zhminko², Yana Kolianchuk², Nataliia Bubalo², Alex Odermatt³, Martin Smieško⁴

Affiliations

¹ 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.
² L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Kyiv, Ukraine.
³ 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.
⁴ 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.

PMID: 37802305
DOI: 10.1016/j.tiv.2023.105706

Abstract

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.

Keywords: Endocrine disrupting chemicals; In silico; In vivo; Pesticides; Reproductive toxicity.

MeSH terms

Computer Simulation
Endocrine Disruptors* / metabolism
Endocrine Disruptors* / toxicity
Endocrine System / metabolism
Pesticides* / toxicity
Receptors, Cytoplasmic and Nuclear
Reproductive Health

Substances

Pesticides
Endocrine Disruptors
Receptors, Cytoplasmic and Nuclear