Vehicle-dependent oral absorption and target tissue dosimetry of chloroform in male rats and female mice.
Chloroform-induced toxicity in rodents depends on oral dose regimen. We evaluated the absorption and tissue dosimetry of chloroform after gavage administration in various vehicles to male Fischer 344 rats and female B6C3F1 mice. Animals received a single dose of chloroform in corn oil, water, or aqueous 2% emulphor at doses (15-180 and 70-477 mg/kg for rats and mice) and dose volumes (2 and 10 ml/kg for rats and mice) used in previously reported toxicity studies. Blood, liver, and kidney chloroform concentration-time courses were determined. Gavage vehicle had minimal effects on chloroform dosimetry in rats. In mice, however, tissue chloroform concentrations were consistently greater for aqueous versus corn oil vehicle. At the low dose volume used for rats (2 ml/kg) gavage vehicle may not play a significant role in chloroform absorption and tissue dosimetry, at the higher dose volume used for mice (10 ml/kg), vehicle may be a critical factor.
Dix
K J
KJ
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Kedderis
G L
GL
Borghoff
S J
SJ
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002725:Chloroform / Q000493:pharmacokinetics*; D005260:Female; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D014677:Pharmaceutical Vehicles / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D012997:Solvents / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D014677:Pharmaceutical Vehicles; D012997:Solvents; D002725:Chloroform