Toxicol Ind Health. 2019 Mar;35(3):196-203. doi: 10.1177/0748233719825528.
1,1,2,2-Tetrafluoroethane (HFC-134) is a colorless gas used as a foam expansion agent and heat transfer fluid. HFC-134 has a low acute inhalation toxicity with an LC of >244,000 ppm. The no-observed adverse effect level (NOAEL) and lowest-observed adverse effect level for cardiac sensitization (in epinephrine-challenged beagle dogs) were 75,000 and 100,000 ppm, respectively. A subacute 4-week GLP inhalation toxicity study exposed male and female Crl: CDBR rats (10/sex) to 0, 2000, 10,000, or 50,000 ppm via whole-body inhalation. Transient and non-dose-response-related body weight changes were observed throughout the exposure period, but no statistically significant, test substance-related adverse effects were observed in any clinical observations, chemistry, hematology, or pathology. This study identified a NOAEL for HFC-134 of 50,000 ppm, the highest exposure level tested. HFC-134 is not genotoxic in in vitro studies; however, no in vivo studies are available. No developmental or maternal toxicity was found in female rats exposed to HFC-134 up to 50,000 ppm via whole-body inhalation in two different studies. Based on data for a similar material (HFC-134a), HFC-134 is not expected to be extensively metabolized or to cause genetic toxicity or carcinogenicity. The HFC-134 workplace environmental exposure level (WEEL) is based primarily on the subacute 4-week inhalation toxicity study in rats with the NOAEL of 50,000 ppm selected as the point of departure for the derivation of the 8-h TWA, health-based WEEL value. The developmental toxicity study also had a NOAEL of 50,000 ppm and was the highest exposure level tested. The subacute inhalation NOAEL was adjusted to account for interindividual variability, subacute to chronic duration, animal to human extrapolation, daily duration of exposure, and residual uncertainty. In addition, the lack of adverse effects noted in the toxicology studies for HFC-134a was considered. The resulting 8-h TWA WEEL value of 1000 ppm is expected to provide a significant margin of safety against the production of any potential adverse health effects in workers following long-term inhalation exposure to HFC-134.
1,1,2,2-四氟乙烷（HFC-134）是一种无色气体，用作泡沫膨胀剂和传热流体。HFC-134的急性吸入毒性较低，LC>244,000 ppm。心脏致敏的未观察到不良反应水平（NOAEL）和最低观察到不良反应水平（在肾上腺素激发的比格犬中）分别为75,000 ppm和100,000 ppm。一项为期4周的亚急性GLP吸入毒性研究通过全身吸入使雄性和雌性Crl:CDBR大鼠（每组10只）暴露于0、2000、10,000或50,000 ppm的环境中。在整个暴露期间观察到短暂的、与剂量无关的体重变化，但在任何临床观察、化学、血液学或病理学检查中均未观察到与受试物质相关的具有统计学意义的不良反应。该研究确定HFC-134的NOAEL为50,000 ppm，这是测试的最高暴露水平。在体外研究中，HFC-134没有遗传毒性；然而，尚无体内研究。在两项不同的研究中，通过全身吸入暴露于高达50,000 ppm的HFC-134的雌性大鼠未发现发育毒性或母体毒性。基于类似物质（HFC-134a）的数据，预计HFC-134不会被广泛代谢，也不会导致遗传毒性或致癌性。HFC-134工作场所环境暴露水平（WEEL）主要基于大鼠为期4周的亚急性吸入毒性研究，选择50,000 ppm的NOAEL作为推导基于健康的8小时时间加权平均（TWA）WEEL值的出发点。发育毒性研究的NOAEL也为50,000 ppm，这是测试的最高暴露水平。对亚急性吸入NOAEL进行了调整，以考虑个体间变异性、亚急性到慢性的持续时间、动物到人的外推、每日暴露持续时间以及残留不确定性。此外，还考虑了HFC-134a毒理学研究中未观察到不良反应这一情况。由此得出的8小时TWA WEEL值为1000 ppm，预计能为长期吸入暴露于HFC-134的工人预防任何潜在不良健康影响提供显著的安全边际。
