Predicting mammalian metabolism and toxicity of pesticides in silico

Pest Management Science
Robert D Clark

Abstract

Pesticides must be effective to be commercially viable but they must also be reasonably safe for those who manufacture them, apply them, or consume the food they are used to produce. Animal testing is key to ensuring safety, but it comes late in the agrochemical development process, is expensive, and requires relatively large amounts of material. Surrogate assays used as in vitro models require less material and shift identification of potential mammalian toxicity back to earlier stages in development. Modern in silico methods are cost-effective complements to such in vitro models that make it possible to predict mammalian metabolism, toxicity and exposure for a pesticide, crop residue or other metabolite before it has been synthesized. Their broader use could substantially reduce the amount of time and effort wasted in pesticide development. This contribution reviews the kind of in silico models that are currently available for vetting ideas about what to synthesize and how to focus development efforts; the limitations of those models; and the practical considerations that have slowed development in the area. Detailed discussions are provided of how bacterial mutagenicity, human cytochrome P450 (CYP) metabolism, and bioavailab...Continue Reading

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Citations

Aug 25, 2020·Journal of Computer-aided Molecular Design·Robert D ClarkWalter S Woltosz
Jun 18, 2019·Journal of Biomolecular Structure & Dynamics·Revanth BathulaSarita Rajender Potlapally
Sep 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yi ZhangFan-Hao Meng
May 14, 2020·Journal of Applied Genetics·Gamze Aydın, Recep Liman
Jun 22, 2021·Toxicology Reports·Valeriya P KalyabinaValentina A Kratasyuk

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Software Mentioned

GastroPlus
MultiCASE
SimCyp®
ADMET Predictor
PK
[UNK]
Genetox
Sim®
ADMET
Genetox Expert Alerts in Toxicity Suite

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