Test No. 485: Genetic toxicology, Mouse Heritable Translocation Assay

The mouse heritable translocation test detects structural and numerical chromosome changes in mammalian germ cells as recovered in first generation progeny.

The types of chromosome changes detected in this test system are reciprocal translocations. Carriers of translocations and XO-females show reduced fertility which is used to select first generation progeny for cytogenetic analysis. Translocations are cytogenetically observed in meiotic cells at diakinesis metaphase I of male individuals. The test is usually performed by analysis of male first generation progeny. About 500 first generation males per dose level are required. One dose level is tested, usually the highest dose associated with the production of minimal toxic effects, and administered by oral intubation or intraperitoneal injection. A single administration of the test substance or the administration of the test substance on 7 days/week for 35 days, are possible. The test substance can be solid, liquid, vapour or gaseous. For translocation heterozygosity one of two possible methods is used: fertility testing of first generation progeny; or cytogenetic analysis of all male first generation progeny are possible. A test substance producing neither a statistically significant increase in the number of translocations observed for at least one test point, nor a statistically significant, dose-related, increase in the number of translocations observed, is considered non-mutagenic in this system.

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