Pharmacokinetics and metabolism of 14C-1,3-dichloropropene in the Fischer 344 rat and the B6C3F1 mouse.
1. 14C-1,3-dichloropropene (14C-DCP) is rapidly absorbed and eliminated in both the male F344 rat and B6C3F1 mouse following oral administration of 1 or 50 mg kg(-1) (rat) or 1 or 100 mg kg(-1) (mouse). 2. It is extensively metabolized in both species. Urinary excretion was the major route of elimination, accounting for 50.9-61.3 and 62.5-78.6% of the administered dose in rat and mouse, respectively. 3. Urinary elimination half-lives ranged from 5 to 6 h (rat) and from 7 to 10 h (mouse). Elimination via faeces or as 14CO2 accounted for 14.5-20.5 and 13.7-17.6% of the administered dose, respectively. 4. Metabolites arising from glutathione conjugation account for 36-55 and 48-50% of the administered dose in excreted from rats and mice, respectively. Hydrolysis of the 3-chloro moiety of DCP accounted for 24-37 and 29% of the dose administered to rats and mice, respectively. Two novel dimercapturic acid conjugates were also identified at low levels that might arise via initial hydrolysis of DCP or of epoxidation of DCP-glutathione conjugate or of DCP itself. Structural confirmation of these dimercapturates was obtained via analysis of deuterium retention from D4-DCP in the male F344 rat. 5. Only quantitative differences are seen between the overall metabolic profile of DCP in these two species.
Health and Environmental Research & Consulting Department, The Dow Chemical Co., Midland, MI 48674, USA. mjbartels@dow.com
M J
MJ
Bartels
S C
SC
Hansen
C M
CM
Thornton
K A
KA
Brzak
A L
AL
Mendrala
F K
FK
Dietz
P J
PJ
Kastl
D000498:Allyl Compounds / Q000378:metabolism* / Q000493:pharmacokinetics*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005243:Feces / Q000737:chemistry; D006207:Half-Life; D006843:Hydrocarbons, Chlorinated; D007202:Indicators and Reagents; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011916:Rats, Inbred F344; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D014018:Tissue Distribution
D000498:Allyl Compounds; D006843:Hydrocarbons, Chlorinated; D007202:Indicators and Reagents; C023891:1,3-dichloro-1-propene