Experimental exposure to 1,1,1-trifluoroethane (HFC-143a): Uptake, disposition and acute effects in male volunteers

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• 作者：Sara Gunnare ; Lena Ernstgå ; rd ; Bengt Sjö ; gren ; Gunnar Johanson
• 关键词：Blood ; air partition coefficient ; Human ; Hydrofluorocarbon ; Inflammatory marker ; HFC-143a ; Physiologically based toxicokinetic model
• 刊名：Toxicology Letters
• 出版年：2007
• 期刊代码：49_03784274
• 类别：pha
• 出版时间：10 August 2007
• 卷：172
• 期：3
• 页码：120-130
• 文件大小：480 K

摘要

The aim of this study was to determine the toxicokinetics and some effects of 1,1,1-trifluoroethane (HFC-143a) in humans. Nine male volunteers were experimentally exposed to 500 ppm HFC-143a for 2 h during light physical exercise (50 W) in an exposure chamber. Blood, urine and exhaled air were sampled before, during and up to 19 h after exposure and analysed for HFC-143a by gas chromatography. These data were described by a physiologically based toxicokinetic (PBTK) model. The electrocardiograms of the volunteers were monitored during exposure. Before, during and after exposure the volunteers rated symptoms related to irritation and CNS-symptoms on a visual analogue scale. Inflammatory markers (C-reactive protein, serum amyloid A protein, D-dimer, fibrinogen) and uric acid were analysed in plasma collected before and 21 h after exposure. The exposures were performed after informed consent and ethical approval.

The plasma concentration of HFC-143a increased promptly at start of exposure, and decreased in the same manner post-exposure. A stable level of 4.8 ± 2.0 μM (mean ± S.D.) was reached within 30 min of exposure. The HFC-143a concentration in plasma and exhaled air decreased fast and in parallel when exposure was stopped. The urinary excretion of HFC-143a after exposure was 0.0007%of the inhaled amount. The half-time in urine, calculated from pooled data, was 53 min. The experimental and simulated time courses in blood and exhaled air were in agreement. The simulated relative uptake during the exposure was 1.6 ± 0.3%.

The fibrinogen level in plasma had increased by 11%1 day post-exposure. No statistically significant increase was seen for the other inflammatory markers or for uric acid. No effects of exposure were seen either in the electrocardiographic monitorings or as symptom ratings on the visual analogue scale.