Historical vehicle and positive control micronucleus data in mice and rats

The rodent bone marrow micronucleus (MN) assay has been widely used as part of an in vivo genotoxicity test battery in product safety evaluation. In t his assay, the historical vehicle and positive control data form an importa nt component in the assay performance and data interpretation. Also, in lig ht of minimizing animal use in research and still obtain required data from a study, the routine use of positive control in every MN assay has been qu estioned by the scientific community, especially in laboratories which have demonstrated assay reproducibility and conduct studies under Good Laborato ry Practice regulations. In this paper, mouse and rat vehicle and positive control MN data, collected manually, are described as a reference for a per iod of 12 years (1987-1998) in our laboratory. The vehicles generally inclu ded a variety of aqueous solutions and suspensions and cyclophosphamide dos ed intraperitoneally at 20 mg/kg (rats) or 40 mg/kg (mice) served as positi ve control, in all studies. Based on combined sex data (430 animals), for C D I mice, the vehicle control MN polychromatic erythrocyte (PCE) range was 0.9-3.1 with a mean of 1.75 per 1000 PCE and the positive control range (22 0 animals) was 8.8-42.1 with a mean of 23.1 MNPCE per 1000 PCE. Similarly, for Wistar rats, the vehicle control range (360 animals) was 1.3-5.3 with a mean of 2.6 MNPCE per 1000 PCE and the positive control range (240 animals ) was 10.4-33.8 MNPCE per 1000 PCE. Vehicle control ranges reported here ar e comparable to the literature database and the positive control response w as greater than or equal to4-fold over vehicle control, in all studies. The se data demonstrate the reproducibility of positive control response in MN assay in our laboratory and support the MN Assay Expert Panel's view that t he use of positive control may not be necessary in every study. (C) 2000 El sevier Science B.V. All rights reserved.