Distribution studies in CD-1 mice administered [14C]muconaldehyde.
Trans,trans-muconaldehyde (muconaldehyde, MUC), a microsomal hematotoxic ring-opened metabolite of benzene, has been proposed to play a role in benzene hematotoxicity. In the present study, [14C]muconaldehyde was administered to CD-1 mice and the distribution of [14C]muconaldehyde equivalents was investigated. The study was carried out to evaluate whether [14C]muconaldehyde equivalents could reach the bone marrow. [14C]Muconaldehyde at a dose of 2 mg/kg was administered intraperitoneally (3.4 microCi/mouse) and by intravenous injection (2.7 microCi/mouse). The amount of [14C]muconaldehyde equivalents was measured in the bone marrow, blood, liver, lung, kidney and spleen at 0.25, 0.5, 1, 2, 4, and 24 h after [14C]MUC administration. The results indicate that 0.044% or 0.018% of the total dose administered when given i.v. or i.p., respectively, reached the bone marrow. The elimination of the radioactivity in all organs had at least two phases. The bone marrow, kidney, and lung had a rapid first phase (t1/2 0.5-1.2 h) and a slower second phase (t1/2 2.8-15.7 h). In the liver, a slow first phase (t1/2 3.7 h) was followed by a more rapid second phase (t1/2 1.5 h). The level of radioactivity in blood and bone marrow was significantly higher when [14C]muconaldehyde was administered intravenously compared with intraperitoneally, demonstrating that the route of administration affects the distribution of [14C]muconaldehyde equivalents.
Zhang
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Z
Joint Graduate Program in Toxicology, Rutgers University/UMDNJ-Robert Wood Johnson Medical School, Piscataway 08855-1179, USA.
Cooper
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K
Goldstein
B D
BD
Witz
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G
D000042:Absorption; D000447:Aldehydes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001853:Bone Marrow / Q000378:metabolism*; D005269:Femur / Q000378:metabolism; D006207:Half-Life; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014018:Tissue Distribution
D000447:Aldehydes; D000935:Antifungal Agents; C034476:muconaldehyde