2,4-PENTANEDIONE: EVALUATION OF THE GENOTOXIC POTENTIAL IN VITRO AND IN VIVO

The genotoxic potential of 2,4-pentanedione (2,4-PD; CAS No. 123-54-6) was assessed using a battery of in vitro and in vivo tests. In vitro studies showed no mutagenic activity in a Salmonella typhimurium reverse mutation test or in a Chinese Hamster Ovary (CHO) forward gene mutation test (HGPRT locus), either in the absence or in the presence of an Aroclor 1245-induced rat liver S9 metabolic activation system. Increased frequencies of sister chromatid exchanges in cultured CHO cells were observed both in the absence and in the presence of S9 activation. 2,4-PD was highly clastogenic to CHO cells in vitro in the absence, but not in the presence, of S9. 2,4-PD produced significant, doserelated increases in the incidence of micronucleated polychromatic erythrocytes (PCE) in the peripheral blood and bone marrow of Swiss Webster mice after a single intraperitoneal injection. However, there was no significant induction of micronuclei in the bone marrow of Sprague Dawley® rats dosed with 2,4-PD by a single intraperitoneal injection. When rats and mice were exposed to 2,4-PD vapor for 6 hr/day for 5 consecutive days at target concentrations up to 800 ppm, there were no significant exposure-related increases in the incidences of chromosomal aberrations or micronucleated PCE in bone marrow samples taken 24 hr after the 5th day of exposure in either species.