Test No. 478: Genetic Toxicology: Rodent Dominant Lethal Test

Dominant lethal (DL) effects cause embryonic or foetal death. Induction of a dominant lethal event after exposure to a test substance (liquid, solid, vapour or gas, …) indicates that the substance has affected germinal tissue of the test species. Dominant lethals are generally accepted to be the result of chromosomal aberrations (structural and numerical anomalies), but gene mutations and toxic effects cannot be excluded.

This Test Guideline recommends rats or mice as the test species. Generally, male animals are exposed to the test substance and mated to untreated virgin females. The most widely used is the single administration of the test substance by oral or by intraperitoneal injection. Normally, three dose levels should be used. The various germ cell stages can be tested separately by the use of sequential mating intervals. The females are sacrificed after an appropriate period of time, and the contents of the uteri are examined to determine the numbers of implants and live and dead embryos. The calculation of the dominant lethal effect is based on comparison of the live implants per female in the treated group to the live implants per female in the control group.

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