Distribution of chloroform and methyl chloroform and their metabolites in pregnant mice

The distribution of radioactivity in pregnant mice was registered at different time intervals (0-24 h) after a 10-min period of inhalation of 14C-labelled chloroform and methyl chloroform. Autoradiographic and liquid scintillation methods were used to make possible the distinction between volatile (non-metabolized), water-soluble and firmly tissue-bound radioactivity. Methyl chloroform was retained longer in fat as compared to chloroform. Metabolites of chloroform were present in a much greater abundance than those of methyl chloroform and they were found preferentially in the respiratory tract (nasal mucosa, trachea and bronchi), liver and excretory organs. Tissue-bound activity after chloroform inhalation or i.p. injection to newborn mice was found in the respiratory tract and centrilobular areas of the liver. Volatile radioactivity was observed in the placenta and fetuses at short time intervals after inhalation of both chloroform and methyl chloroform at all stages of gestation. While a low level of radioactive metabolites of methyl chloroform was observed in the fetoplacental unit, metabolites of chloroform accumulated with time. This fact was especially marked in the amniotic fluid, where the peak level of radioactivity was observed at 4 h. In early gestation, metabolites accumulated in the embryonic neural tissues. Tissue-bound metabolites of chloroform were observed in the fetal respiratory epithelium in late gestation, indicating a capacity for drug metabolism in these cells in the late fetal period.