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

Archives of toxicology (2007-09-18)
Andrzej Starek, Wieslaw Szymczak, Lidia Zapor
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-Methoxyethanol, anhydrous, 99.8%
Sigma-Aldrich
2-Ethoxyethanol, ReagentPlus®, 99%
Sigma-Aldrich
2-Methoxyethanol, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Ethylene glycol butyl ether, ≥99%
Sigma-Aldrich
2-Methoxyethanol, ReagentPlus®, ≥99.0%, contains 50 ppm BHT as stabilizer
Sigma-Aldrich
2-Isopropoxyethanol, 99%
Supelco
Ethylene glycol butyl ether, analytical standard
Supelco
2-Ethoxyethanol, analytical standard
Sigma-Aldrich
2-Methoxyethanol, contains 50 ppm BHT as stabilizer, ACS reagent, ≥99.3%
Supelco
2-Methoxyethanol, analytical standard
Sigma-Aldrich
Ethylene glycol butyl ether, spectrophotometric grade, ≥99.0%
Sigma-Aldrich
2-Ethoxyethanol, spectrophotometric grade, ≥99%