title: Application of the KeratinoSens™ assay for assessing the skin sensitization potential of agrochemical active ingredients and formulations.
abstract: Assessment of skin sensitization potential is an important component of the safety evaluation process for agrochemical products. Recently, non-animal approaches including the KeratinoSens™ assay have been developed for predicting skin sensitization potential. Assessing the utility of the KeratinoSens™ assay for use with multi-component mixtures such as agrochemical formulations has not been previously evaluated and is a significant need. This study was undertaken to evaluate the KeratinoSens™ assay prediction potential for agrochemical formulations. The assay was conducted for 8 agrochemical active ingredients (AIs) including 3 sensitizers (acetochlor, meptyldinocap, triclopyr), 5 non-sensitizers (aminopyralid, clopyralid, florasulam, methoxyfenozide, oxyfluorfen) and 10 formulations for which in vivo sensitization data were available. The KeratinoSens™ correctly predicted the sensitization potential of all the AIs. For agrochemical formulations it was necessary to modify the standard assay procedure whereby the formulation was assumed to have a common molecular weight. The resultant approach correctly predicted the sensitization potential for 3 of 4 sensitizing formulations and all 6 non-sensitizing formulations when compared to in vivo data. Only the meptyldinocap-containing formulation was misclassified, as a result of high cytotoxicity. These results demonstrate the promising utility of the KeratinoSens™ assay for evaluating the skin sensitization potential of agrochemical AIs and formulations.
authors.affiliation: The Dow Chemical Company, Midland, MI, United States. Electronic address: rssettivari@dow.com.
authors.forename: Raja S
authors.initials: RS
authors.lastname: Settivari
authors.affiliation: Dow AgroSciences LLC, Indianapolis, IN, United States.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Gehen
authors.affiliation: Dow AgroSciences LLC, Indianapolis, IN, United States.
authors.forename: Ricardo Acosta
authors.initials: RA
authors.lastname: Amado
authors.affiliation: The Dow Chemical Company, Midland, MI, United States.
authors.forename: Nicolo R
authors.initials: NR
authors.lastname: Visconti
authors.affiliation: The Dow Chemical Company, Midland, MI, United States.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Boverhof
authors.affiliation: The Dow Chemical Company, Midland, MI, United States.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Carney
mesh_terms: D016573:Agrochemicals / Q000633:toxicity*; D000826:Animal Testing Alternatives; D001681:Biological Assay; D002460:Cell Line; D017449:Dermatitis, Allergic Contact; D006241:Haptens / Q000633:toxicity*; D006801:Humans
chemical_list: D016573:Agrochemicals; D006241:Haptens
keywords: Agrochemical formulations; In vitro; KeratinoSens test; Skin sensitization