Hematological effects of exposure to mixtures of selected ethylene glycol alkyl ethers in rats

Abstract

Exposure to various ethylene glycol monoalkyl ethers (EGAEs) is known to result in hemolytic effect caused by their metabolites, appropriate alkoxyacetic acids, generated via both alcohol dehydrogenase and aldehyde dehydrogenase. It has been shown in many studies that administration of single doses of EGAEs to rats lead to dose- and time-dependent hemolytic anemia. The repeated exposure to isopropoxyethanol (IPE), and butoxyethanol (BE), contrary to methoxyethanol (ME) and ethoxyethanol (EE), resulted in significantly less pronounced hematological changes. While the majority of hematological effects were dramatic at the beginning of the exposure, later these changes clearly regressed despite continued weekly exposure to these ethers. The gradual recovery from the hemolytic anemia may be associated with tolerance development to the hemolytic effect of IPE and BE. ME demonstrated high hematotoxicity, which increased progressively and reached a maximum at the end of 4 week exposure, whereas EE revealed moderate hematological effects. It might be suspected that ME and EE may modified of IPE hemolytic activity in rats simultaneously treated with these compounds. In the rats co-exposed to IPE and ME subcutaneously at a relatively low doses of 0.75 mM + 0.75 mM for 4 weeks, a significantly less pronounced hematological changes at the beginning of the exposure in comparison with animals treated with IPE (0.75 mM) alone were observed. At the later period, i.e., at the end of 4 weeks exposure, the hematological alterations in the same animals were markedly pronounced and progressively elevated with exposure time, except for mean corpuscular volume (MCV) values, which were significantly lower in comparison with IPE group. ME at the higher dose of 1.25 mM/kg and EE at both doses of 0.75 and 1.25 mM/kg did not modify the hematotoxicity of IPE (at doses of 0.75 mM and 1.25 mM) at the beginning of the exposure, whereas increased its harmful effects at the end of the treatment. The amelioration in the majority of the hematological parameters at the beginning of the exposure may be caused by inhibitory effect of ME on IPE metabolism. On the contrary, an accumulation of the methoxyacetic acid and ethoxyacetic acid, toxic metabolites of ME and EE, respectively, and no tolerance development to the hemolytic effect of these two chemicals may be responsible for elevated hematological alterations at the end of the exposure.

Ethylene glycol monomethyl ether-induced testicular oxidative stress and time-dependent up-regulation of apoptotic, pro-inflammatory, and oncogenic markers in rats

“…Following testicular exposures, EGEs are activated in affected cells by the action of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) respectively [ 18 ]. Methoxyacetic acid (MAA), a metabolite of EGME is responsible for the teratogenicity, hematotoxicity, gonadotoxicity, immunotoxicity, and embryotoxicity of EGME [ 5 , [19] , [20] , [21] ]. Severe effects of EGEs on sperm and testes as a whole have been documented in humans [ 5 ], but have not been fully investigated.…”

28-day inhalation toxicity of 3-methoxybutyl chloroformate in rats

“…Hematological indices including HGB and HCT are influenced by various factors. Several studies indicated that pulsed electric field exposure [ 14 ], herbal extracts [ [15] , [16] ], and chemicals [ 17 ] can influence hematological parameters, but in this study, alteration ranges were minimal and within the normal range, thus it is difficult to judge directly by test substance [ 18 ]. Generally, increased RDW indicates the presence of cell of different sized and related with iron deficiency anemia if accompanied by a decrease of MCV.…”

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

“…For example, ME attenuated hematotoxic action of isopropoxyethanol (IPE) in rats at the beginning of the exposure increased its harmful effects at the end of the treatment [18]. Aliphatic alcohols, i.e., ethanol, n-propanol, and n-butanol, almost completely inhibited the hemolytic effect of BE in rats, and significantly reduced the urinary excretion of butoxyacetic acid (BAA), a metabolite of BE.…”

“…Control rats (1 group) were given the equivalent volume of saline. The applied doses and route of administration were chosen based on the previous work output [18].…”

“…Data on the hematological analyses has been described elsewhere [18]. Hematological analyses were systematically checked.…”