Experimental exposure to 1,1,1,3,3-pentafluoropropane (HFC-245fa): Uptake and disposition in humans

Abstract

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. © The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology.