Ethylene glycol monomethyl ether research-My contribution

Ethylene Glycol Monomethyl Ether (EGME) is enlisted among the group of solvents referred to as glycol ethers. Glycol ethers are alkyl ethers of ethylene glycol usually used in paints and this group is sub-divided into two classes: ethylene glycol ethers (EGEs) and propylene glycol ethers (PGEs). EGME belongs to the class of EGEs [1]. Synonyms for EGME are methyl oxitol, methyl cellosolve (commercially), methyl glycol, monomethyl ether, monomethyl glycol, monomethyl ethylene glycol ether or 2-methoxy ethanol [2].


Introduction
Ethylene Glycol Monomethyl Ether (EGME) is enlisted among the group of solvents referred to as glycol ethers.
Glycol ethers are alkyl ethers of ethylene glycol usually used in paints and this group is sub-divided into two classes: ethylene glycol ethers (EGEs) and propylene glycol ethers (PGEs). EGME belongs to the class of EGEs [1]. Synonyms for EGME are methyl oxitol, methyl cellosolve (commercially), methyl glycol, monomethyl ether, monomethyl glycol, monomethyl ethylene glycol ether or 2-methoxy ethanol [2]. The molecular formula is C 3 H 8 O 2 and the molecular weight is 76.09 g/mol 2 . The active biological oxidation product is Methoxy Acetic Acid (MAA). EGME is a reaction product of ethylene oxide and methanol. It is moderately volatile, highly infl ammable, and colorless with very good solubility properties. As a result of the simultaneous hydrophilic and lipophilic properties, it has wide consumer and industrial applications. EGME fi nds use as an anti-freeze additive in hydraulic fl uids and jet fuel. It is also used in stains, inks, paints and surface coating, photographic and photo lithographic processes, lacquers, production of food-contact plastics, textile and leather fi nishing, silk-screen printing, and in the semi-conductor industry [3,4].
In humans and several other species, exposure to EGME either by ingestion, dermal absorption and/or inhalation has been reported to cause reproductive, hematopoietic and developmental toxicities with emphasis on testicular damage [5]. The evidences of haematological toxicities as a result of exposure to EGME include marrow depression and decrease in red blood cells count, platelet count, packed cell volume, haemoglobin concentration, mean corpuscular and mean corpuscular haemoglobin; pancytopenia and leucopenia [6,7].
The evidences of reproductive toxicities as result of exposure to EGME or the active oxidation product, MAA, include decreased sperm production as a result of increased apoptosis of primary spermatocytes [8]; gene expression changes in germ cells and Leydig cells in-vitro [9]; hyper-secretion of progesterone from ovarian luteal cells both in-vivo and in-vitro; activation of caspases leading to apoptosis triggered by oxidative stress in spermatocytes [5]; prolonged estrus cycle, hypertrophy of corpora lutea evidenced by the presence of round to polygonal luteal cells with abundant vacuolated cytoplasm and ovulatory inhibition [10,11]; altered androgen-dependent processes in Leydig cells in-vitro [12]; affects microRNAs expression in the testes [13]; affects the antioxidant system and increase lipid peroxidation in the testes [14] and caused spermatocyte toxicity The study suggests that EGME exerts deleterious effects on the testes and epididymes by increasing the oxidative load in rats [18].
Our second study was conducted using co-administration of EGME with Paullinia pinnata methanol leaf extract. Paullinia pinnata (PP) is a medicinal plant whose parts are used for medicinal purposes traditionally in the treatment of various diseases including malaria, diarrhea and to help infertility which is currently a scourge globally. In this study, EGME was the infertility model. Sixty adult male Wistar rats were weightmatched into six groups of ten animals each. All administrations were done orally daily for twenty-one consecutive days as follows: Group I(control) -distilled water; Group II -1.5 ml/ kg body weight of 10% dimethyl sulfoxide (vehicle); Group III-EGME only (200 mg/kg); Group IV-PP only (200 mg/kg); Group V-EGME+PP at 100 mg/kg body weight and Group VI-EGME+PP at 200 mg/kg body weight. On day 22, blood was collected for the analysis of the reproductive hormones. The animals were euthanized, dissected in order to excise the testes, epididymes, seminal vesicles, prostate gland and brain, and weighed. The brain, testes and epididymes were processed and used for spermatozoa analysis, antioxidant and anti-infl ammatory assays, and histological examination appropriately. The plasma concentrations of the reproductive hormones including luteinizing hormone and follicle stimulating hormone were signifi cantly increased in the co-administered groups while the plasma testosterone concentration was decreased. Similarly, the spermatozoa parameters were affected. The testicular spermatozoa number, spermatozoa motility and viability were reduced in the EGME only and co-administered groups.
Antioxidant parameters including catalase and glutathione-Stransferase were affected in the epididymis, testes and brain in the EGME only and co-administered groups. The infl ammatory markers; nitric oxide and myeloperoxidase, were also variably affected in the testes and epididymes of the EGME only and co-administered groups. The results were complemented by the histological observations in the testes, and hypothalamus.
The conclusion was that P. pinnata leaves lack chemopreventive potential against ethylene glycol monomethyl ether-induced gonadotoxicity rather, it exacerbates the deleterious effects [19].

Conclusion
Taken together, the studies underscore the point that caution needs to be exercised in the exposure to EGME, especially in the light of co-exposure with herbal treatments.