Human inhalation pharmacokinetics of chlorodifluoromethane (HCFC22).
Two groups of three male volunteers were exposed to atmospheric concentrations of either 327 or 1833 mg m-3 chlorodifluoromethane (HCFC22) for 4 h. Blood, urine and expired air samples were taken during and after the exposure period and analysed for HCFC22. Urine samples were also analysed for fluoride ion. During the exposure period, blood concentrations of HCFC22 approached a plateau, and the average peak blood concentrations of 0.25 and 1.36 micrograms cm-3 were proportional to dose. HCFC22 concentrations in expired air were similar to the exposure concentration during the exposure period. The ratio between venous blood and breath concentrations of HCFC22 towards the end of the exposure period was on average 0.77, which is consistent with in vitro estimates of the partition coefficient. In the post-exposure period, three phases for the elimination of HCFC22 were identified, with estimated half-lives of 0.005, 0.2 and 2.6h. HCFC22 was detected in urine samples taken in the post-exposure period, and the rate of decline was consistent with the terminal rate of elimination estimated from blood and breath measurements. On average 2.1% of the inhaled HCFC22 was recovered in breath within 26 h of exposure. This is consistent with the low solubility in blood and fat. Minimal changes in fluoride ion concentrations in urine following exposure indicate that HCFC22 is unlikely to be metabolised to a significant extent. Following inhalational exposure HCFC22 is poorly absorbed and is rapidly eliminated from the body. Possible biological monitoring strategies could be based on measurements of HCFC22 in urine or breath samples collected after the end of an exposure period.
Woollen
B H
BH
Human Toxicology Team, ICI Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Marsh
J R
JR
Mahler
J D
JD
Auton
T R
TR
Makepeace
D
D
Cocker
J
J
Blain
P G
PG
D000328:Adult; D000395:Air Pollutants, Occupational / Q000493:pharmacokinetics*; D005617:Chlorofluorocarbons, Methane / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D008452:Maximum Allowable Concentration; D008657:Metabolic Clearance Rate; D016273:Occupational Exposure
D000395:Air Pollutants, Occupational; D005617:Chlorofluorocarbons, Methane; C009755:fluorocarbon 22