Blood clearance tests for detecting 2,3,7,8-tetrachlorodibenzo-p-dioxin hepatotoxicity in rats and rabbits

Abstract

The objective was to determine if a blood clearance test would detect liver dysfunction in rats and rabbits treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Guinea pigs were included as a negative control, because TCDD does not produce detectable hepatotoxicity in this species. TCDD was given as a single dose to male rats (25 microgram/kg, po), rabbits (25 microgram/kg, ip) and guinea pigs (2 microgram/kg, ip) and liver function was assessed 10 days later by determining blood clearance of indocyanine green (ICG) and ouabain. Activity in serum of sorbitol dehydrogenase (SDH), glutamic pyruvic transaminase (SGPT) and gamma glutamyl transpeptidase (gamma GTP) were also measured and light microscopy performed on the liver. The results showed that hepatotoxicity in the rabbit could be detected by a reduction in ICG blood clearance and an elevation in SDH activity. In the rat, ouabain blood clearance was reduced and SDH activity elevated. None of the liver function tests were altered in the guinea pig. These results underline the usefulness of blood clearance tests using ICG and ouabain in detecting TCDD hepatotoxicity in animals.