Gene mutation assays species used

Species. In vivo genotoxicity assays mainly use rodents (rats and mice), because they are small (standard animal facilities and low amount of test article needed) and because abundant toxicologic and metabolic data are available on these species. Most assays are also theoretically applicable to noiu odent animals, but limited data have been reported in the literature. Most of the assays are applicable to wild-type and readily available animal strains. It should nevertheless be noted that a few models require specific strains (e.g., some gene mutation assays). 

IPEC-US (intended clinical route)a Acute oral and dermal toxicity, skin and eye irritation, and skin sensitization. Bacterial gene mutation and chromosome damage. ADME (intended route). 28-day toxicity (2 species by intended clinical route) Short-term use studies. 90-day toxicity (most appropriate species). Teratology (rat and/or rabbit). Genotoxicity assays. Additional assays (conditional) 1 Short-/midterm studies. One-generation reproduction. Chronic toxicity (rodent and nonrodent) and carcinogenicity (conditional)... 

MBOCA induced gene mutations at the thymidine kinase (TK) locus in mouse lymphoma cells (Caspary et al. 1988 Myhr and Caspary 1988). Unscheduled DNA synthesis (UDS) was induced in HeLa cells (Martin and Mcdermid 1981), in rat primary hepatocytes at >10 pmol (McQueen et al. 1981 Mori et al. 1988 Williams et al. 1982), and in hamster (McQueen et al. 1981) and rabbit (McQueen and Wiliams 1987) hepatocytes. The concentration that tested positive in the mouse was 50 jmol (McQueen et al. 1981). Sensitivity to MBOCA showed species-specific variations rat > mouse > hamster > rabbit (McQueen et al. 1981, 1983). Because hepatocytes have their own metabolic activation systems, no exogenous metabolic activation is needed. In assays using attachment independence as an end point, MBOCA, at concentrations near the LC o, transformed baby hamster kidney (Daniel and Dehnel 1981 Styles 1981), rat embryo (Dunkel et al. 1981 Traul et al. 1981), and Balb/3T3 cells (Dunkel et al. 1981). Transformation assays have not been evaluated... 

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