Historical vehicle and positive control micronucleus data in mice and rats

Abstract

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 this assay, the historical vehicle and positive control data form an important component in the assay performance and data interpretation. Also, in light 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 questioned by the scientific community, especially in laboratories which have demonstrated assay reproducibility and conduct studies under Good Laboratory Practice regulations. In this paper, mouse and rat vehicle and positive control MN data, collected manually, are described as a reference for a period of 12 years (1987–1998) in our laboratory. The vehicles generally included a variety of aqueous solutions and suspensions and cyclophosphamide dosed intraperitoneally at 20 mg/kg (rats) or 40 mg/kg (mice) served as positive control, in all studies. Based on combined sex data (430 animals), for CD 1 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 (220 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 are comparable to the literature database and the positive control response was ≥4-fold over vehicle control, in all studies. These data demonstrate the reproducibility of positive control response in MN assay in our laboratory and support the MN Assay Expert Panel’s view that the use of positive control may not be necessary in every study.