Hematological effects of four ethylene glycol monoalkyl ethers in short-term repeated exposure in rats

Abstract

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.

Interactive effect of combined exposure to ethylene glycol ethers and ethanol on hematological parameters in rats

“…The various hematological changes observed during exposure to EGAEs are typical of hemolytic anemia with an associated reticulocytosis and hyperplasia of both bone marrow (erythroid elements) and spleen (extramedullary hemopoiesis) [26]. The results presented in this paper confirm previous observations that continued exposure to BE, contrary to ME and EE, resulted in significantly less pronounced hematological changes [6]. While the majority of hematological effects were dramatic at the beginning of the exposure, later these alterations clearly regressed despite continued weekly exposure to these compounds.…”

“…Although ethanol has been reported to cause anorexia and weight loss [23,24], it seems that EGAEs alone may be one of the main reasons for retardation of body weight gain. The body weight alterations observed previously in rats exposed to EGAEs alone [6] seem to confirm of this suggestion.…”

“…These ethers may cause local toxicity, i.e., skin irritation and sensitization in susceptible humans [1] and also, systemic toxicity. The primary systemic toxicity of these chemicals in animals include reproductive, developmental and hematological effects [2][3][4][5][6]. Similar effects have been observed in exposed workers.…”

The effects of 2-methoxyethanol and 2-ethoxyethanol on hematological changes induced by 2-butoxyethanol

“…So far, hematological toxicity of EGEs in humans and animals has been well documented [12][13][14]16,19]. In this study a short-chain EGEs (ME and EE) in a relatively low dose (1.25 mM/kg/day) exerted weak hematotoxic effects evidenced by reduction in RBC, PCV, HGB, WBC and LYM in peripheral blood.…”

Evaluation of Workers Exposed to Ethylene Glycol Monomethyl Ether and Ethylene Glycol Monomethyl Ether Acetate

“…Additionally, increased embryonic and fetal death, reduced fetal body weight and malformations of fetuses were also found 8) . Hematological effects of subacute poisoning include decreased white blood cell count (mainly neutrophils), macrocytic anemia and abnormal leukocytes [9][10][11] .…”