Starek Andrzej, Szymczak Wieslaw, Zapor Lidia
Department of Biochemical Toxicology, Medical College, Jagiellonian University, Krakow, Poland.
Arch Toxicol. 2008 Feb;82(2):125-36. doi: 10.1007/s00204-007-0236-z. Epub 2007 Sep 14.
This study was carried out to compare the hematological effects of 2-methoxyethanol (ME), 2-ethoxyethanol (EE), 2-isopropoxyethanol (IPE), and 2-butoxyethanol (BE) in short-term studies in rats. Male rats were subcutaneously treated with ME or EE at a dosage of 0, 1.25, 2.5 and 5.0 mM/kg in saline, 5 days per week, for 4 weeks. Other rats were exposed to IPE or BE at doses of 0, 0.25, 0.5, 0.75 and 1.25 mM/kg in the same manner. Administration of each chemical, except of ME, resulted in a time- and dose-dependent swelling of erythrocytes as evidenced by an increase in mean corpuscular volume (MCV). Subsequently, red blood cells (RBC), packed cell volumes (PCV), hemoglobin concentration (HGB), and mean cell hemoglobin concentration (MCHC) decreased. Furthermore, an increase in mean cell hemoglobin (MCH) and reticulocyte counts was observed. The onset of hemolysis induced by EE, IPE or BE was faster than after ME administration. While in rats exposed to ME hematological changes were strongly pronounced and progressively increased with exposure time beginning from the day 11, those in animals treated with EE were rather persisted at low constant level for all exposure period. In contrast, the rats exposed to IPE and BE demonstrated the dramatic hematological changes more pronounced in case of BE than IPE at the beginning of exposure (on day 4). Despite of exposure duration, these changes were regressed, although the decrease in RBC and MCHC and the increase in MCV and MCH in rats treated with highest doses of both compound (0.5, 0.75, and 1.25 mM/kg) were more persistent, probably due to selective hemolysis of the aged erythrocytes. In addition, significant leukopenia due to reduction of lymphocytes in rats exposed to ME was observed. In summary, this study demonstrated no tolerance to ME- and EE-induced intravascular hemolysis developed under these experimental conditions. On the contrary, tolerance to IPE- and BE-induced hemolysis in rats exposed to these compounds was prompted.
本研究旨在比较2-甲氧基乙醇（ME）、2-乙氧基乙醇（EE）、2-异丙氧基乙醇（IPE）和2-丁氧基乙醇（BE）在大鼠短期研究中的血液学效应。雄性大鼠每周皮下注射5天，连续4周，分别给予0、1.25、2.5和5.0 mM/kg剂量的ME或EE生理盐水溶液。其他大鼠以相同方式暴露于0、0.25、0.5、0.75和1.25 mM/kg剂量的IPE或BE。除ME外，每种化学物质的给药均导致红细胞呈时间和剂量依赖性肿胀，平均红细胞体积（MCV）增加证明了这一点。随后，红细胞（RBC）、血细胞压积（PCV）、血红蛋白浓度（HGB）和平均细胞血红蛋白浓度（MCHC）下降。此外，观察到平均细胞血红蛋白（MCH）和网织红细胞计数增加。EE、IPE或BE诱导溶血的开始速度比ME给药后更快。在暴露于ME的大鼠中，血液学变化从第11天开始强烈且随着暴露时间逐渐增加，而在接受EE治疗的动物中，在整个暴露期间这些变化相当稳定地维持在低水平。相比之下，暴露于IPE和BE的大鼠在暴露开始时（第4天）表现出显著的血液学变化，BE组比IPE组更明显。尽管暴露持续时间不同，但这些变化会消退，不过用两种化合物最高剂量（0.5、0.75和1.25 mM/kg）处理的大鼠中，RBC和MCHC的下降以及MCV和MCH的增加更持久，可能是由于衰老红细胞的选择性溶血。此外，观察到暴露于ME的大鼠因淋巴细胞减少而出现显著白细胞减少。总之，本研究表明在这些实验条件下，对ME和EE诱导的血管内溶血没有产生耐受性。相反，暴露于这些化合物的大鼠对IPE和BE诱导的溶血产生了耐受性。
