Postnatal hepatic and renal consequences of in utero exposure to halothane or its oxidative metabolite trifluoroacetic acid in the rat.
In utero exposure of rats to low levels of the anaesthetic halothane has been reported to produce ultrastructural changes in the liver and kidney at birth. The current study examined the postnatal functional capacities of the liver and the kidney following prenatal exposure to halothane. Halothane or its oxidative metabolite trifluoroacetic acid (TFAA) were given to Sprague-Dawley rats on gestational days 10-20. Halothane was administered by inhalation at concentration of 50 or 500 ppm 6 h-1 day-1, and TFAA was administered by gavage at doses of 75 or 150 mg kg-1 day-1. The exposed offsprings were examined on postnatal days 3, 12 or 49 for hepatic and renal biochemistry and/or function through measurements of several serum and urinary parameters. Neither halothane nor TFAA treatments had statistically significant effect on litter size, neonatal survival or postnatal growth. Both prenatal halothane and TFAA exposure produced changes in liver biochemistry of newborns, as indicated by significant increases in the serum activities of glutamate dehydrogenase and aspartate aminotransferase. In addition, TFAA caused a functional deficit of the proximal tubule in newborns, as evidenced by the significant increase in the urinary excretion of beta 2-microglobulin. However, these hepatic and renal alterations were restricted to the early postnatal period and were no longer observed by postnatal day 49. It is concluded that prenatal exposure to relatively low levels of halothane can cause slight and transient changes in the neonatal rat liver.
Saillenfait
A M
AM
Institut National de Recherche et de Sécurité, Vandoeuvre, France.
Roure
M B
MB
Ban
M
M
Gallissot
F
F
Langonné
I
I
Sabaté
J P
JP
Bonnet
P
P
D000367:Age Factors; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D005260:Female; D006221:Halothane / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D018811:Maternal Exposure; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014269:Trifluoroacetic Acid / Q000633:toxicity*
D018685:Anesthetics, Inhalation; D014269:Trifluoroacetic Acid; D006221:Halothane