Lack of mutagenic effects of halothane in mammals in vivo.
Rodents were exposed in vivo to various clinical doses of halothane to observe structural chromosome aberrations, micronuclei, sister chromatid exchanges (SCEs), 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 per cent halothane once for 3 h, twice for 3 h (exposures 24 h apart), or to 0.5 per cent for 24 h. The analysis of SCEs in bone marrow cells was also negative after exposing hamsters to 1 per cent halothane for 3 h, or to 0.5 per cent for 12 h. In halothane-exposed female mice (0.75 per cent for 16 h), oocyte maturation (meiotic stages) was delayed. Another group of exposed female mice (1 per cent 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, neither monosomic nor trisomic cells were observed. Male mice were exposed to 1 per cent halothane for 1 h per day for 48 days. On the evening of the forty-eighth day, they were mated with untreated females. Dominant lethal mutations were not increased as compared to controls. In erythrocytes of these chronically exposed male mice, the frequency of micronuclei was not significantly enhanced. The authors conclude that halothane does not induce mutations under the in vivo conditions tested in this study.