Embryotoxic/teratogenic potential of halothane.
The embryotoxic/teratogenic potential of halothane was evaluated on the basis of available data obtained in an extensive literature search. It was found that halothane induced ultrastructural visible changes in the offspring of rats exposed to concentrations of 10 ppm during gestation. These consisted of degenerative changes in the cerebral cortex and, in particular, the weakening of cell membranes and the vacuolisation of the Golgi-complex. Macroscopically visible morphological changes were seen in rats only after exposure to concentrations equivalent to 320-fold (1600 ppm) the MAK value (maximum concentration value at the workplace). Furthermore, behavioural disorders were seen when exposure to concentrations greater than or equal to 10 ppm occurred during gestation and after parturition. In mice, only macroscopical investigations were performed. The first disturbances scored were only visible as retardation in the offspring, and occurred after exposure to concentrations of halothane 200-fold (1000 ppm) the MAK-value. In the rabbit, anaesthetic concentrations of 22000 ppm halothane did not result in an embryotoxic/teratogenic effect. The individual epidemiological findings in humans were discussed controversially. The studies are inconclusive in establishing an embryotoxic/teratogenic risk following sole exposure to halothane at the MAK level, since mixed exposures occurred and data on the concentrations of halothane in the inhaled air were missing. Therefore, the decision on whether halothane can impair intrauterine development is primarily based on the animal experimental findings. As long as a threshold value has not been established for the observed lesions, halothane should not be inhaled during pregnancy.
Berufsgenossenschaft der chemischen Industrie, Heidelberg, Federal Republic of Germany.
C
C
Baeder
M
M
Albrecht
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D004622:Embryo, Mammalian / Q000187:drug effects*; D005260:Female; D006221:Halothane / Q000009:adverse effects*; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009784:Occupational Diseases / Q000139:chemically induced*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced; D051381:Rats
D006221:Halothane