INHALATION TOXICOLOGY OF DIMETHYLACETAMIDE (DMAC) IN MICE AND RATS - AGE-RELATED EFFECTS ON LETHALITY AND TESTICULAR INJURY

Two 10-day inhalation toxicity studies were conducted with dimethylace tamide (DMAC, CAS no. 127-19-5). In one study, pubescent Crl:CD-1 mice (35 days old) were exposed to DMAC at 30, 100, 310, 490, or 700 ppm f or 6 h/day, 5 days/wk for 10 days. Although well tolerated up to 310 p pm, exposure to 490 ppm or greater caused severe clinical signs and mo rtality. Hematologic changes in these groups included reduced erythroc yte and platelet counts, reduced hemoglobin concentration, and reduced hematocrit. Relative testes weights were decreased and relative liver weights were increased. In addition, centrilobular hepatocellular nec rosis and hypertrophy, lymphoid organ atrophy and necrosis, bone marro w hypoplasia, and cortical adrenal gland necrosis occurred; these path ologic changer were not seen in mice from these groups sacrificed afte r a 14-day recovery period. Testicular damage, consisting of degenerat ion of seminifierous tubules and oligospermia, occurred in a concentra tion-dependent manner in mice exposed to from 310 to 700 ppm DMAC. In the mice showing lesser testicular injury, some evidence of reversibil ity war; seen after a 14-day recovery period. Since the toxicity of DM AC was thought to be attributable to the use of pubescent mice, a seco nd study was conducted with older, young adult mice (62 days old) and with rats (47 days old) at concentrations of 0, 52, 150, 300, and 480 ppm DMAC. While no mice died in this study, similar but morphologicall y less severe testicular lesions were noted but only at 480 ppm; sperm counts and tester weights in all groups were similar to controls. No adverse effects on body weights, clinical signs, testicular weights, o r pathology were round in rats at any exposure level. The no-observed- adverse-effect level in this study was 100 ppm DMAC for pubescent mice and 300 ppm for young adult mice. Pubescent mice appeared to be more sensitive to the testicular effects of DMAC than young adult rats or m ice.