Correlation between acetone-potentiated CCl4-induced liver injury and blood concentrations after inhalation or oral administration.
In studies of acetone-potentiated liver injury induced by haloalkanes, acetone is usually given by gavage, whereas industrial exposure to acetone normally occurs by inhalation. It was of interest to verify if the route of administration influences the potentiation. Male Sprague-Dawley rats were exposed for 4 hr to acetone vapors or treated orally with acetone; the minimal effective dose (MED) levels for potentiating CCl4-induced liver injury were estimated to be 2500 ppm and 0.25 ml/kg, respectively. Groups were treated with acetone using 0.4, 1, 2, 4, or 6 times the MED. Half of each group was killed at various time intervals after treatment for blood acetone measurements by gas chromatography; the other half was challenged with CCl4 (0.1 ml/kg, ip) 18 hr after acetone, and killed 24 hr later. Plasma alanine aminotransferase (ALT) activity and bilirubin concentrations were measured. Inhalation and oral administration of acetone both potentiated CCl4 toxicity. Rats exposed repetitively to acetone vapors (10 daily exposures) and subsequently challenged with CCl4 exhibited liver toxicity that was not significantly different from that of rats subjected to a single exposure. Correlations between ALT activities and maximal blood acetone concentrations were found to be linear (positive) and significant for both routes. For a given blood acetone concentration, however, toxicity was least severe following acetone exposure by inhalation. When the concept of threshold concentrations was applied to the data, the severity of the toxic response was dependent on the blood acetone concentration above the threshold, irrespective of the route of administration.
D000096:Acetone / Q000008:administration & dosage / Q000378:metabolism; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride; D004357:Drug Synergism; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000096:Acetone; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase; D001663:Bilirubin