Disease relevance of Ethyleneglycol monomethyl ether

• 2-Methoxyethanol (2-ME) is an industrial solvent that induces developmental and testicular toxicity in laboratory animals [1].
• At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occurred at both 100 and 50 ppm [2].
• We previously demonstrated that combined exposure to radiofrequency (r.f.; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent 2-methoxyethanol (2ME) produces enhanced teratogenicity in rats [3].
• Methoxy-, ethoxy- and n-butoxy acetic acids, known urinary metabolites of the corresponding alkoxyethanol solvents, were administered by gavage to rats as a single oral dose equimolar with 500, 250 or 100 mg 2-methoxyethanol/kg body weight [4].
• Cell death was analyzed in neurulating mouse embryos after in vivo doses of 2-methoxyethanol (2-ME) that produce anterior neural tube defects [5].

Psychiatry related information on Ethyleneglycol monomethyl ether

• Paw development of CD-1 mice is uniquely sensitive to 2-methoxyethanol (ME) given by gavage (po) on gestation day (gd) 11 (copulation plug day = gd 0) [6].

High impact information on Ethyleneglycol monomethyl ether

• To map periplasmic residues, accessible cysteines were blocked in whole cells by pretreatment with 4-acetamido-4'-maleimidylstilbene-2, 2' disulfonic acid before the cells were lysed in the presence of mPEG [7].
• The glycolethers 2-methoxyethanol (2-ME), 2-ethoxyethanol (2-EE), and 2-butoxyethanol are widely used organic solvents with teratogenic, spermatotoxic, and hematotoxic effects due to the respective alkoxyacetic acid metabolites formed via alcohol dehydrogenase (ADH) [8].
• These data demonstrate that rat testis germ cells contain relatively high levels of cyclophilin A whose nuclease activity is associated with spermatocyte apoptosis induced by 2-methoxyethanol [9].
• Recent investigations in our laboratory revealed divalent cation-dependent endonuclease activity in testes from 2-methoxyethanol-treated rats, which was able to cleave substrate DNA into a pattern of DNA fragmentation consisting of approximately 180-200 base pairs [9].
• Monomethoxypolyethylene glycol (mPEG) of average molecular weight 5000 was transformed in a series of synthetic steps to a new activated form of PEG, a stable thiol-protected intermediary, for reaction with cysteine residues in proteins under mild conditions to produce PEG--protein conjugates as possible candidates for therapeutics [10].

Chemical compound and disease context of Ethyleneglycol monomethyl ether

• These lesions may play a role in the resorption, reduction in fetal body weight, and syndactyly or oligodactyly attributed to 2-methoxyethanol and 2-methoxyacetic acid [11].
• The toxicity of 2-methoxyethanol and 2-ethoxyethanol was underestimated due to a lack of metabolic capacity in the EST [12].
• Ethylene glycol monomethyl ether (EGME) exhibits testicular toxicity and ethylene glycol monobutyl ether (EGBE) is a solvent with haemolytic effects in rats [13].
• Comparative testicular toxicity of bis(2-methoxyethyl) ether and 2-methoxyethanol in rats [14].
• Biotransformation of 2-methoxyethanol (2-ME) by alcohol and aldehyde dehydrogenases is an established factor in the toxicity of this useful solvent [15].

Biological context of Ethyleneglycol monomethyl ether

• Propylene glycol monomethyl ether (PGME) was shown not to cause testicular atrophy or to affect the development of rats at 600 ppm by inhalation, whereas EGME caused testicular atrophy at 300 ppm and showed teratogenic potential at 100 ppm [16].
• 2-Methoxyethanol (ME) induces paw malformations in CD-1 mice when given by gavage on gestation day (gd) 11 (vaginal plug + day = gd 0) [17].
• The results demonstrate that metabolic activation is required for 2-methoxyethanol to exert toxicity to the male reproductive system [18].
• Separation of L-PAM from its products of hydrolysis was accomplished with a mu-Bondapak C18 column, a solvent system composed of 2-methoxyethanol/0.1% acetic acid, and solvent programming with a step gradient [19].
• Calcium homeostasis in pregnant rats treated with ethylene glycol monomethyl ether (EGME) [20].

Anatomical context of Ethyleneglycol monomethyl ether

• F344 rats were treated with 2-methoxyethanol, a glycol ether that causes the death of pachytene spermatocytes in juvenile and adult rats [9].
• EGME has been shown to cause effects on the testis in rats after a single exposure to 600 ppm or above for 4 hr [16].
• Cyclophilin A staining was present in both control and 2-methoxyethanol-treated rat testes in a stage-dependent manner, with pachytene spermatocytes in stage-VIII-XIV seminiferous tubules most heavily stained [9].
• Patients were monitored by annual challenges with histamine in bronchi, and Dp allergen in bronchi, nose and conjunctiva. mPEG-modified extract was not inferior to unmodified Dp-extract; both were to some extent able to improve tolerance to Dp and histamine in bronchi and to Dp in nose and eyes [21].
• T cell transfer from mPEG-peptide pretreated mice down regulated, in recipient mice, Ab induction (after cell transfer) and Ab production (after two tAChR injections) toward alpha-chain peptides [22].

Associations of Ethyleneglycol monomethyl ether with other chemical compounds

• Ethylene glycol monomethyl ether (EGME) and propylene glycol monomethyl ether (PGME): inhalation fertility and teratogenicity studies in rats, mice and rabbits [23].
• Exposure to 2-methoxyethanol (ME) or its major metabolite, methoxyacetic acid (MA), results in spermatocyte depletion and testicular atrophy in experimental animals [24].
• A new method for simultaneous determination of alkoxyethanols (2-methoxyethanol, 2-ethoxyethanol, 2-isopropoxyethanol, and 2-butoxyethanol) by high-performance liquid chromatography (HPLC) with fluorescence detection has been developed [25].
• We have reported previously that methoxyacetaldehyde (MALD), a metabolite of 2-methoxyethanol, induces gpt gene mutations in Chinese hamster ovary (CHO)-AS52 cells but not hprt gene mutations in the standard CHO-K1-BH4 cells [26].
• Porous crystalline networks have been synthesized and include fatty acid esters during crystallization from both methanol and 2-methoxyethanol [27].

Gene context of Ethyleneglycol monomethyl ether

• The potent developmental toxicant, 2-methoxyethanol (2-ME), elicits exencephaly in near-term mouse fetuses following a single maternal treatment early on gestation day (gd) 8 [28].
• IFN was pegylated with methoxy-polyethylene glycol (mPEG, MW 2000 or 5000) [29].
• In corroboration, immunocytochemistry with antibodies to various kinases (PKCmu, zeta, and gamma, AKAP220, CaMKII, MLCK, and Src) showed increased staining around dying spermatocytes following EGME treatment in vivo [30].
• Treatment of these hu-PBL-SCID mice with a tolerogenic covalent conjugate of monomethoxypolyethylene glycol (mPEG) and an anti-ovalbumin, IgG1 murine monoclonal antibody, Mab-2, suppressed the human anti-mouse antibody responses to both the common (gamma 1,kappa) and the idiotypic determinants of Mab-2 [31].
• Ethylene glycol monomethyl ether (EGME) inhibits rat embryo ornithine decarboxylase (ODC) activity [32].

Analytical, diagnostic and therapeutic context of Ethyleneglycol monomethyl ether

• Immunotoxicity of 2-methoxyethanol following oral administration in Fischer 344 rats [33].
• The determination of free aromatic amine in water-soluble radiopaques by diazotization in 2-methoxyethanol-water, coupling with naphthylethylenediamine, and colorimetry of the azo dye has been automated [34].
• Effects were examined at week 2 after treatment for CP, EMS BLM and EGME and at weeks 5 and 6 for EGME [35].
• Species and strain comparisons of immunosuppression by 2-methoxyethanol and 2-methoxyacetic acid [36].
• Histopathologic changes in the extraembryonic and embryonic tissues induced by an intraperitoneal injection of 250 or 500 mg/kg of 2-methoxyethanol, or its metabolite, 2-methoxyacetic acid, via oral gavage were determined 48 hr after dosing CD-1 mice on day 11 of pregnancy [11].

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