Metabolic fate and disposition of 1,1,1,2-tetrafluoroethane (HFC134a) in rat following a single exposure by inhalation.
1. The metabolic fate and disposition of [U-14C]-1,1,1,2-tetrafluoroethane ([U-14C]-HFC134a) has been determined in the male and female rat following a 1 h single exposure by inhalation to atmospheres of 10,000 ppm. 2. Of the inhaled dose, approx. 1% was recovered in urine, faeces and expired air postexposure indicating that absorption of this fluorocarbon across the lung is poor. Of this 1%, approx, two-thirds were exhaled within 1 h of the cessation of exposure as unchanged HFC134a. The remaining radioactivity was exhaled as [14C]-carbon dioxide or excreted in urine and faeces as trifluoroacetic acid. 3. Carbon dioxide was the major metabolite of HFC134a accounting for 0.22 and 0.27% of the inhaled dose in the male and female rat, respectively. Urinary excretion accounted for 0.09% of the dose and faecal excretion 0.04% of the dose by both sexes. 4. Total metabolism measured as the sum of the radioactivities in urine, faeces and as carbon dioxide amounted to 0.34 and 0.40% of the inhaled dose in male and female, respectively. 5. There were no major sex differences in the rates, routes or amounts of radiolabel excreted. Analysis of a range of tissues at 5 days postexposure showed a relatively uniform distribution of radioactivity. There was no evidence for a specific uptake of HFC134a or a metabolite into any organ or tissue analysed, including fat.
Ellis
M K
MK
Investigative Toxicology Section, ZENECA Central Toxicology Laboratory, Alderley Park, Macclesfield, UK.
Gowans
L A
LA
Green
T
T
Tanner
R J
RJ
D000042:Absorption; D000280:Administration, Inhalation; D000818:Animals; D002245:Carbon Dioxide / Q000032:analysis / Q000378:metabolism; D002250:Carbon Radioisotopes; D002606:Charcoal; D005243:Feces / Q000737:chemistry; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D014018:Tissue Distribution; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D002245:Carbon Dioxide; D002250:Carbon Radioisotopes; D002606:Charcoal; D006845:Hydrocarbons, Fluorinated; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons