title: Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose in Future Studies. A Response to the Counterpoints.
abstract: We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). As a result of our publication, 2 counterviews were expressed. Both counterviews illustrate very valid points in their interpretation of our data. In this article, we would like to highlight clarifications based on several points and issues they have raised in their papers, namely, the dose-level selection, determining if MTD was exceeded in 26-week studies, and a discussion on the number of dose groups to be used in the studies.
authors.affiliation: BioReliance By SAFC, Rockville, Maryland, USA madhav.paranjpe@bioreliance.com.
authors.forename: Madhav G
authors.initials: MG
authors.lastname: Paranjpe
authors.affiliation: Virginia Commonwealth University, Richmond, Virginia, USA.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Denton
authors.affiliation: BioSTAT Consultants, Inc., Portage, Michigan, USA.
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Vidmar
authors.affiliation: PAREXEL International, Bethesda, Maryland, USA.
authors.forename: Reem H
authors.initials: RH
authors.lastname: Elbekai
mesh_terms: D000818:Animals; D001835:Body Weight; D015197:Carcinogenicity Tests / Q000379:methods* / Q000592:standards*; D004435:Eating; D005260:Female; D011905:Genes, ras; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008822:Mice, Transgenic; D012189:Retrospective Studies
keywords: MTD; Tg.rasH2 mice; alternative models in toxicology; carcinogenesis; preclinical research and development; toxicologic pathology; transgenic animals