title: An in vivo rodent model for identifying and characterizing acaricides.
abstract: Evaluation of candidate acaricides in livestock or companion animals is expensive, time-consuming, and usually requires large quantities of test material. To identify promising substances at the earliest possible stage of the development process, robust and predictive surrogate animal models, capable of rapidly characterizing potency with minimal compound requirements, are necessary. The objective of this study was to generate an in vivo surrogate animal bioassay capable of rapidly and accurately predicting the topical activity of acaricides emerging from in vitro acaricide bioassays. The rat acaricide test (RAT) requires adult rats, Rattus norvegicus (Berkenhout, 1769), a flexible tick containment device fastened to their dorso-thoracic region, and the nymphal stage of the lone star tick, Amblyomma americanum (L.). The feeding kinetics of A. americanum nymphs on rats was assessed, and compound efficacies were determined by measuring tick survivorship and engorgement weight on acaricide-treated animals. Results from this bioassay demonstrated efficacy with fipronil, ivermectin, permethrin, and chlorpyrifos, and dose-response relationships for each acaricide were determined. The rank order of potencies was fipronil > ivermectin > chlorpyrifos = permethrin for nymphal mortality and fipronil > ivermectin > chlorpyrifos > permethrin for inhibition of nymphal engorgement. The activity of permethrin against nymphs in the RAT was positively correlated with potency values for technical and commercial permethrin formulations against adult A. americanum infestations on cattle. The RAT proved to be an economical, rapid surrogate animal bioassay that together with the in vitro acaricide bioassay can be used for the rapid identification, characterization, and prioritization of candidate acaricides.
authors.affiliation: Elanco Animal Health Research and Development, A Division of Eli Lilly & Company, 2001 W. Main Street, Greenfield, IN 46140, USA.
authors.forename: Jesus A
authors.initials: JA
authors.lastname: Gutierrez
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhao
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Kemper
authors.forename: Philip R
authors.initials: PR
authors.lastname: Plummer
authors.forename: Steven M
authors.initials: SM
authors.lastname: Bauer
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Hutchens
authors.forename: Charles K
authors.initials: CK
authors.lastname: Smith
authors.forename: W Hunter
authors.initials: WH
authors.lastname: White
mesh_terms: D000818:Animals; D002417:Cattle; D004390:Chlorpyrifos; D004305:Dose-Response Relationship, Drug; D005260:Female; D007306:Insecticides / Q000008:administration & dosage; D007559:Ivermectin; D023421:Models, Animal; D009758:Nymph; D026023:Permethrin; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013987:Ticks
chemical_list: D007306:Insecticides; D011720:Pyrazoles; D026023:Permethrin; D007559:Ivermectin; D004390:Chlorpyrifos; C082360:fipronil