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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.

Experimental Exposure to 1,1,1,3,3-Pentafluoropropane (HFC-245fa): Uptake and Disposition in Humans