Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Toxicol Lett. 2012 Feb 25;209(1):21-9. doi: 10.1016/j.toxlet.2011.11.028. Epub 2011 Dec 4.
The aim of this study was to determine the toxicokinetics of inhaled 1,1-difluoroethane (HFC-152a) in humans. Healthy volunteers were exposed to 0, 200 or 1000 ppm 1,1-difluoroethane for 2h at light exercise in an exposure chamber. Capillary blood, urine and exhaled air were sampled up to 22 h post-exposure and analyzed for 1,1-difluoroethane. Fluoride and other potential metabolites were analyzed in urine. Symptoms of irritation and central nervous system effects were rated and inflammatory markers were analyzed in blood. Within a few minutes of exposure to 200 and 1000 ppm, 1,1-difluoroethane increased rapidly in blood and reached average levels of 7.4 and 34.3 μM, respectively. The post-exposure decreases in blood were fast and parallel to those in exhaled air. The observed time courses in blood and breath agreed well with those obtained with the PBPK model. The PBPK simulations indicate a net uptake during exposure to 1000 ppm of 6.6 mmol (6.7%) which corresponds to the amount exhaled post-exposure. About 20 μmol excess fluoride (0.013% of inhaled 1,1-difluoroethane on a molar basis) was excreted in urine after exposure to 1000 ppm, compared to control. No fluorine-containing metabolites were detected in urine. Symptom ratings and changes in inflammatory markers revealed no exposure-related effects.
本研究旨在确定人类吸入 1,1-二氟乙烷（HFC-152a）的毒代动力学。健康志愿者在轻体力活动下于暴露室内暴露于 0、200 或 1000 ppm 的 1,1-二氟乙烷 2 小时。在暴露后 22 小时内采集毛细血管血、尿液和呼出的空气样本，并分析 1,1-二氟乙烷。尿液中分析了氟化物和其他潜在代谢物。对刺激症状和中枢神经系统效应进行评分，并分析血液中的炎症标志物。在暴露于 200 和 1000 ppm 的几分钟内，1,1-二氟乙烷在血液中迅速增加，分别达到平均水平 7.4 和 34.3 μM。暴露后的血液下降速度快且与呼出空气中的下降速度平行。在血液和呼吸中观察到的时间过程与 PBPK 模型获得的结果非常吻合。PBPK 模拟表明，在暴露于 1000 ppm 时，净吸收率为 6.6 mmol（6.7%），这与暴露后呼出的量相对应。与对照相比，在暴露于 1000 ppm 后，尿液中排出了约 20 μmol 过量的氟化物（基于摩尔数，为吸入的 1,1-二氟乙烷的 0.013%）。尿液中未检测到含氟代谢物。症状评分和炎症标志物的变化未显示出与暴露相关的影响。
