Disposition of propargyl alcohol in rat and mouse after intravenous, oral, dermal and inhalation exposure.
1. The disposition of propargyl alcohol (PAL) radiolabelled with carbon-14 ([2,3-14C]PAL) was determined in the F344 rat and B6C3F1 mouse following intravenous (i.v.), oral, inhalation and dermal exposure. 2. By 72h following an i.v. (1 mg kg(-1) or oral (50 mg kg(-1) dose, 76-90% of the dose was excreted. Major routes of excretion by rat were urine (50-62%), CO2 (19-26%) and faeces (6-14%). Major routes of exerection by mouse were urine (30-40%), CO2 (22-26%) and faeces (10-20%). Less than 6% of the dose remained in tissues at 72 h. Biliary exeretion of radioactity by rat (62% in 4 h) was much greater than elimination in faeces (6% in 72 h), indicating that PAL metabolites underwent extensive enterohepatic recycling. 3. Dermal exposure studies demonstrated that dermal absorption of PAL was minimal due to its inherent volatility. 4. In the inhalation studies (1, 10 or 100 ppm for 6 h), 23-68% of the radioactivity to which animals were exposed was absorbed. The primary route of excretion was urine (23-53%), and significant portion was exhaled as volatile organics (15-30%). 5. PAL was extensively metabolized by both species. One metabolite was identified as 3,3-bis[(2-(acetylamino)-2-carboxyethyl)thio]-1-propanol, which is consistent with Banijamali et al. (1999).
Dix
K J
KJ
Research Triangle Institute, Research Triangle Park, NC 27709, USA.
Coleman
D P
DP
Fossett
J E
JE
Gaudette
N F
NF
Stanley
A P
AP
Thomas
B F
BF
Jeffcoat
A R
AR
D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000284:Administration, Oral; D000480:Alkynes / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D001646:Bile / Q000378:metabolism; D001944:Breath Tests; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005243:Feces; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D020005:Propanols / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000480:Alkynes; D002250:Carbon Radioisotopes; D020005:Propanols; C028255:propargyl alcohol