Abstract |
The pharmacokinetics of 1,2-dichloropropane (DCP) was evaluated in Fischer 344 rats following oral and inhalation exposure. Three groups of 4 rats/sex were administered either single doses of 1 or 100 mg/kg 14C-DCP by gavage, or 7 daily oral doses of 1 mg/kg/day non-radiolabled DCP followed by a single oral dose of 1 mg/kg 14C- DCP on day 8. Tissue, urine, and fecal analyses were conducted at 48 hours post-dosing. No signs of toxicity were observed at any dose. Radioactivity was distributed to all tissues, with the liver containing the highest 14C activity (0.229 to 0.41% of dose/g wet weight). The principle routes of elimination of radioactivity were in urine (37 to 52% of dose) and expired air (23 to 36%), with most occurring during the 1st 24 hours after dosing. Feces contained 5.5 to 7.9%, and tissues and carcass accounted for 7.1 to 10.6%. No parent DCP was noted in urine, but about 82% of radioactivity in expired air was parent compound. Three mercapturic acid metabolites of DCP were identified. No differences were noted between sexes or dose levels. Groups of 4 rats/sex/dose were exposed by inhalation (head only) to 5, 50, or 100 ppm 14C-DCP, 6 hours/day for 2 weeks. No signs of toxicity were observed. The overall disposition was similar tothat following oral administration, and dose-related saturation of metabolic sites was evident following both routes of administration. |