Evaluation of gamma-hydroxybutyric acid for genotoxicity in the mouse micronucleus assay

Gamma-hydroxybutyric acid (GHB) is an endogenous compound found in the brain and other tissues of mammals. Neurotransmitter/neuromodulator functions have been ascribed to GHB, which has lately become a drug of abuse. In this study, we tested GHB for genotoxicity by measuring its ability to induce micronuclei in polychromatic erythrocytes (reticulocytes) in the peripheral blood of mice. Intraperitoneal injection with a dose of 25 mg/kg/day for 3 days or 50 mg/kg/day x 3 days resulted in a significant (by Dunnett's test) increase of 1.9- to 2.1-fold in micronuclei. However, because increases were small and because no consistent dose-dependent increase in induced micronuclear frequency could be demonstrated, our results do not conclusively show that GHB is an in vivo genotoxicant in mammals.