Experimental exposure to 1,1,1,3,3-pentafluoropropane (HFC-245fa): uptake and disposition in humans.
The aim of this study was to determine the toxicokinetics of inhaled 1,1,1,3,3-pentafluoropropane (HFC-245fa) in humans. Five healthy volunteers of each sex were exposed in random order to 0, 100, or 300 ppm HFC-245fa for 2 h at light exercise (50 W) in an exposure chamber. Capillary blood, urine, and exhaled air were sampled up to 22 h postexposure and analyzed for HFC-245fa. In addition, the metabolites fluoride, 3,3,3-trifluoropropionic acid (TFPA), and trifluoroacetic acid (TFAA) were analyzed in urine. Symptoms of irritation and central nervous system effects were rated in visual analogue scales. Various biochemical (aspartate-amino transferase, alanine-amino transferase, alkaline phosphate, glutamyl transferase, urate, creatine kinase [CK], and CK muscle brain) and inflammatory markers (serum amyloid A protein, fibrinogen, D-dimer, C-reactive protein, and interleukin-6) in plasma were analyzed. The initial increase in blood was fast and an apparent steady state was reached within a few minutes at both exposure levels. The postexposure decrease in blood was equally fast and parallel to that in exhaled air. Only minor amounts of unchanged HFC-245fa were excreted in breath (0.7% of inhaled) and urine (0.001%). The observed time courses in blood and breath agreed reasonably well those obtained by physiologically based pharmacokinetic (PBPK) modeling. The PBPK simulations indicate a relative uptake during exposure of 2.1%. TFPA was not detected in urine, and no increase in TFAA or fluoride above background was seen, suggesting little or no metabolism, the calculated minimum detectable metabolism being 0.001% of the inhaled amount. The symptom ratings revealed no HFC-245fa-related effects. None of the biochemical markers was affected. The changes in inflammatory markers, some of which are statistically significant, were not consistent with an inflammatory response.
Ernstgård
Lena
L
Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. lena.ernstgard@ki.se
Andersen
Melvin
M
Dekant
Wolfgang
W
Sjögren
Bengt
B
Johanson
Gunnar
G
D000328:Adult; D001273:Atmosphere Exposure Chambers; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests; D002490:Central Nervous System / Q000187:drug effects; D005260:Female; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D019570:Inhalation Exposure / Q000032:analysis*; D008297:Male; D011795:Surveys and Questionnaires; D055815:Young Adult; D005466:Fluorocarbons
D015415:Biomarkers; D006845:Hydrocarbons, Fluorinated; C403631:1,1,1,3,3-pentafluoropropane; D005466:Fluorocarbons