Toxicokinetics of 1,1,1,2-tetrafluoroethane (HFC-134a) in male volunteers after experimental exposure.
The aim of this study was to determine the uptake and disposition of inhaled 1,1,1,2-tetrafluoroethane (HFC-134a) in humans. Ten male volunteers were exposed to 500 ppm HFC-134a (2 h, 50 W exercise). The HFC-134a levels were monitored in blood, exhaled air and urine up to 19 h post-exposure. The concentration in blood increased rapidly, reaching a plateau of 9.4+/-1.9 microM (mean+/-S.D.) within 30 min, followed by a fast post-exposure decrease. HFC-134a in expired air decreased rapidly as well and in parallel with that in blood. The post-exposure urinary excretion was 0.002% of the inhaled amount, and the half-time was 58 min (pooled data). A physiologically based toxicokinetic (PBTK) model was developed for further analysis. Experimental and simulated time courses in blood and exhaled air agreed well in all 10 subjects. Further, the late decay in blood was consistent with a wash-out of HFC-134a from fat tissues, with a half-time of 114+/-21 min. The simulated relative uptake during exposure was 3.7+/-0.5%. No remarkable findings were observed in the electrocardiographic recordings. Fibrinogen in plasma increased 1 day after exposure, whereas no effects on C-reactive protein, serum amyloid A protein, D-dimer or uric acid were seen. Further studies are needed to investigate the possible inflammatory response.
Gunnare
Sara
S
Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. sara.gunnare@ki.se
Ernstgård
Lena
L
Sjögren
Bengt
B
Johanson
Gunnar
G
D000328:Adult; D000465:Algorithms; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000175:diagnosis; D002097:C-Reactive Protein / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects; D002986:Clinical Trials as Topic; D004562:Electrocardiography / Q000187:drug effects; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000493:pharmacokinetics* / Q000633:toxicity*; D019570:Inhalation Exposure; D007509:Irritants; D008297:Male; D015233:Models, Statistical; D012039:Regional Blood Flow / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014018:Tissue Distribution; D014527:Uric Acid / Q000378:metabolism; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D002097:C-Reactive Protein; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen; D006845:Hydrocarbons, Fluorinated; D007509:Irritants; D000685:Serum Amyloid A Protein; D014527:Uric Acid; C036309:fibrin fragment D; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons