Spontaneous Micronucleus Formation in an Integrated Bone Marrow Micronucleus Assay in Wistar Han Rats

Abstract

Multiple end-point in vivo assays can alleviate the need for multiple repeated in vivo assays, thereby reducing time, the costs involved and extensive use of laboratory animals in targeted preclinical experiments. The International conference on harmonization (Ich) guideline S2 (R1) recommends the use of the integrated micronucleus study. One option is to integrate the micronucleus end-points into a repeat dose study. a 4-week repeated dose toxicity study is one of the approaches often included in a preclinical toxicity study schedule. Thus, ten 4-week repeated dose toxicity studies were conducted in a Wistar han rat model that included integrated micronucleus end-point determinations. Those studies used common vehicles and determined different routes of administration that permitted the collection of background data of spontaneous micronucleus formation. The studies conformed to standard operation procedures (SOP), respective study protocols of the testing facility, and related regulatory guidelines. The micronucleus background data obtained from the Wistar han rat model was compared to data obtained from Sprague Dawley rats in an acute exposure design. It was concluded that micronucleus background responses were very similar between the Wistar han (repeated-dose design) and Sprague Dawley rats (acute dose design). These background data will serve as reference values for future integrated micronucleus studies. We also reported particular clinical pathology parameters (e.g., hematology, coagulation and biochemistry) and the relative organ weight data collected from the animals that participated in these studies. Journal of Environmental Immunology and Toxicology 2014; 1:159-166