title: An in vitro approach for comparative interspecies metabolism of agrochemicals.
abstract: The metabolism and elimination of a xenobiotic has a direct bearing on its potential to cause toxicity in an organism. The confidence with which data from safety studies can be extrapolated to humans depends, among other factors, upon knowing whether humans are systemically exposed to the same chemical entities (i.e. a parent compound and its metabolites) as the laboratory animals used to study toxicity. Ideally, to understand a metabolite in terms of safety, both the chemical structure and the systemic exposure would need to be determined. However, as systemic exposure data (i.e. blood concentration/time data of test material or metabolites) in humans will not be available for agrochemicals, an in vitro approach must be taken. This paper outlines an in vitro experimental approach for evaluating interspecies metabolic comparisons between humans and animal species used in safety studies. The aim is to ensure, where possible, that all potential human metabolites are also present in the species used in the safety studies. If a metabolite is only observed in human in vitro samples and is not present in a metabolic pathway defined in the toxicological species already, the toxicological relevance of this metabolite must be evaluated.
authors.affiliation: Syngenta, Jealott's Hill International Research Centre, Bracknell, RG42 6EY, UK. Electronic address: paul.whalley@syngenta.com.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Whalley
authors.affiliation: ToxMetrics.com, LLC, Midland, MI USA. Electronic address: mjbartels@toxmetrics.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
authors.affiliation: DuPont Crop Protection, Stine-Haskell Research Center, Newark DE 19711, USA. Electronic address: karin.s.bentley-1@dupont.com.
authors.forename: Karin S
authors.initials: KS
authors.lastname: Bentley
authors.affiliation: Dow AgroSciences, 3B Park Square, Milton, Milton Park, Abingdon, Oxfordshire, OX14 4RN, UK. Electronic address: mcorvaro@dow.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Corvaro
authors.affiliation: BASF SE Crop Protection, Global Consumer Safety, 67117 Limburgerhof, Germany. Electronic address: dorothee.funk@basf.com.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Funk
authors.affiliation: DuPont Haskell Global Centers, USA. Electronic address: matthew.w.himmelstein@dupont.com.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Himmelstein
authors.affiliation: Bayer CropScience AG, 40789 Monheim Am Rhein, Germany. Electronic address: birgit.neumann2@bayer.com.
authors.forename: Birgit
authors.initials: B
authors.lastname: Neumann
authors.affiliation: ADAMA MAH BV Amsterdam NL Schaffhausen Branch, 8200 Schaffhausen, Switzerland. Electronic address: christian.strupp@adama.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Strupp
authors.affiliation: The Dow Chemical Company, Toxicology & Environmental Research and Consulting, Midland, MI 48674, USA. Electronic address: fzzhang@dow.com.
authors.forename: Fagen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Dow AgroSciences, 3B Park Square, Milton, Milton Park, Abingdon, Oxfordshire, OX14 4RN, UK. Electronic address: jmehta@dow.com.
authors.forename: Jyotigna
authors.initials: J
authors.lastname: Mehta
mesh_terms: D016573:Agrochemicals / Q000378:metabolism*; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D013045:Species Specificity
chemical_list: D016573:Agrochemicals
keywords: Agrochemicals; Comparative; Human; Interspecies; In vitro; Metabolism; Pesticide; Safety; Toxicology