Distribution of halothane and the metabolites trifluoroacetic acid and bromide in the conceptus after halothane inhalation by pregnant mice.

Mice in late stage of gestation were exposed to halothane at various concentrations for 1 hr, and were killed at different time intervals after discontinuance of inhalation. The concentration of halothane in maternal plasma decreased rapidly, and in the amniotic fluid the halothane never reached more than 20% of maternal plasma levels. Trifluoroacetic acid (TFA) and bromide, formed mainly by maternal metabolism of halothane, accumulated in foetus and amniotic fluid with time, and reached plateau levels in amniotic fluid between 4 and 24 hrs. TFA infused intravenously to the mother reached higher levels in amniotic fluid after long survival times, than in maternal plasma. Equilibrium dialysis experiments showed that TFA and trichloroacetic acid (TCA) (previously shown to accumulate in amniotic fluid) were bound to amniotic fluid macromolecules only to approximately 20-30 percent. This was at the same magnitude (or lower) as compared to binding in maternal plasma, suggesting that such binding did not contribute to the observed retention in the amniotic fluid. Other possible explanations for the slow accumulation and long-term retention in amniotic fluid are transport by bulk flow via foetus, excretion via foetal urine, or paraplacentally through endometrium and foetal membranes, followed by trapping in the amniotic fluid. The significance of this accumulation of metabolites of halogenated organic solvents and halothane for their foetotoxicity is not clear.