LACK OF MUTAGENIC EFFECTS OF HALOTHANE IN MAMMALS INVIVO

Rodents were exposed in vivo to various clinical doses of halothane to observe structural chromosome aberrations, micronuclei, sister chromatid exchanges (SCE), dominant lethal mutations and interferences with phases of the cell cycle. The frequency of chromosome aberrations in bone marrow cells was not increased after exposing Chinese hamsters to 1% halothane once for 3 h, twice for 3 h (exposures 24 h apart), or to 0.5% for 24 h. The analysis of SCE in bone marrow cells was negative after exposing hamsters to 1% halothane for 3 h, or to 0.5% for 12 h. In halothane-exposed female mice (0.75% for 16 h), oocyte maturation (meiotic stages) was delayed. Another group of exposed female mice (1% for 5 h) were mated with untreated males. The number of dead implants was not increased as compared to controls. In liver cells of 16 day old living embryos, monosomic and trisomic cells were not observed. Male mice were exposed to 1% halothane for 1 h per day for 48 days. On the evening of the 48th day, they were mated with untreated females. Dominant lethal mutations were not increased as compared to controls. In erythrocytes of the chronically exposed male mice, the frequency of micronuclei was not significantly enhanced. Halothane does not induce mutations under the in vivo conditions tested in this study.