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

Andrzej Starek, Katarzyna Miranowicz-Dzierżawska, Beata Starek-Świechowicz

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DOI: 10.4236/health.2010.29155                

Abstract

The study of the interaction of three glycol ethers, i.e. 2-methoxyethanol (ME), 2-ethoxyethanol (EE) and 2-butoxyethanol (BE) administered subcutaneously for 4 weeks and ethanol simultaneously given as 10% w/v solution for drinking in male rats, was carried out from a toxicodynamic point of view. Administered alone, ME (2.5 and 5.0 mM/kg), EE (2.5 and 5.0 mM/kg) or BE (0.75 and 1.25 mM/kg) resulted in a decrease of red blood cells (RBC), packed cell volumes (PCV), and hemoglobin concentration (HGB), as well as an increase in mean corpuscular volume (MCV) and reticulocyte count (Ret). In the rats co-ex- posed to ethanol and EGAEs, a significantly less pronounced hematological changes in comparison with animal exposed to these ethers alone were seen. The rats simultaneously exposed to ethanol and both ME and EE at the lower dose demonstrated mainly protection from the alterations in leukocyte system. In contrast, in the rats which consumed ethanol and were simultaneously treated with the higher dose of ME or EE (5.0 mM/kg) the amelioration of same hematological parameters were displayed. The intake of ethanol along with BE treatment at both doses resulted in markedly ameliorated hematological parameters, compared to those which were changed by BE alone. In conclusion, the decrease of the hemolytic effects of EGAEs is ethanol dependent. Ethanol is a substrate of alcohol dehydrogenase (ADH), and affinity of this enzyme to ethanol is greater than that to glycol ethers. It is possible that ethanol results in the change in EGAEs metabolism.

Keywords

Ethylene Glycol Alkyl Ethers; Ethanol; Repeated Exposure; Toxicodynamic Interactions

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Raymond, L.W., Williford, L.S. and Burke, W.A. (1998) Eruptive cherry angiomas and irritant symptoms after one acute exposure to the glycol ether solvent 2-butoxy- ethanol. Journal of Occupational and Environmental Medicine, 40(12), 1059-1064.
[2]	Hardin, B.D., Goad, P.T. and Burg, J.A.R. (1984) Developmental toxicity of four glycol ethers applied cutaneously to rats. Environmental Health Perspectives, 57, 69- 74.
[3]	Foster, P., Lloyd, S.C. and Blackburn, D.M. (1987) Comparison of the in vivo and in vitro testicular effects produced by methoxy-, ethoxy- and N-butoxyacetic acids in the rat. Toxicology, 43, 17-30.
[4]	Wier, P.J., Lewis, S.C. and Traul, K.A. (1987) A comparison of developmental toxicity evident at term to postnatal growth and survival using ethylene glycol monoethyl ether, ethylene glycol monobutyl ether and ethanol. Teratogenesis, Carcinogenesis and Mutagenesis, 7(1), 55-64.
[5]	Ghanayem, B.I., Long, P.H., Ward, S.M., Chanas, B., Nyska, M. and Nyska, A. (2001) “Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol. Experimental and Toxicologic Pathology, 53(2-3), 97-105.
[6]	Starek, A., Szymczak, W. and Zapór, L. (2008) Hematological effects of four ethylene glycol monoalkyl ethers in short-term repeated exposure in rats. Archives of Toxicology, 82(2), 125-136.
[7]	Cohen, R. (1984) Reversible subacute ethylene glycol monomethyl ether toxicity associated with microfilm production, a case report. American Journal of Industrial Medicine, 6, 441-446.
[8]	Larese, F., Fiorito, A. and Zotti, R.D. (1992) The possible haematological effects of glycol monomethyl ether in a frame factory. British Journal of Industrial Medicine, 49, 131-133.
[9]	Shih, T.-S., Hsieh, A.-T., Liao, G.-D., Chen, Y.-H. and Liou, S.-H. (2000) Haematological and spermatotoxic effects of ethylene glycol monomethyl ether in copper clad laminate factories. Occupational and Environmental Medicine, 57, 348-352.
[10]	Shih, T.-S., Hsieh, A.-T., Chen, Y.-H., Liao, G.-D., Chen, C.-Y., Chou, J.-S. and Liou, S.-H. (2003) Follow up study of haematological effects in workers exposed to 2-methoxyethanol. Occupational and Environmental Medicine, 60, 130-135.
[11]	Kim, Y., Lee, N., Sakai, T., Kim, K.S., Yang, J.S., Park, S., Lee, C.R., Cheong, H.K. and Moon, Y. (1999) Evaluation of exposure to ethylene glycol monoethyl ether acetates and their possible haematological effects on shipyard painters. Occupational and Environmental Medicine, 56(6), 378-382.
[12]	Wang, R.S., Suda, M., Gao, X., Wang, B., Nakajima, T. and Honma, T. (2004) Health effects of exposure to ethylene glycol monoethyl ether in female workers. Industrial Health, 42(4), 447-451.
[13]	Haufroid, V., Thirion, F., Mertens, P., Buchet, J.-P. and Lison, D. (1997) Biological monitoring of workers exposed to low levels of 2-butoxyethanol. International Archives of Occupational and Environmental Health, 70(4), 232-236.
[14]	Ghanayem, B.I., Burka, L.T. and Mattews, H.B. (1989) Structure-activity relationship for the in vitro hematotoxicity of N-alkoxyacetic acids, the toxic metabolites of glycol ethers. Chemico-Biological Interactions, 70(3-4), 339-352.
[15]	Dartsch, P.C., Hildenbrand, S., Gfrorer, W., Kimmel, R. and Schmahl, F.W. (1999) Cytotoxic effects of 2-butoxyethanol in vitro are related to butoxyacetaldehyde, an intermediate oxidation product. Environmental Toxicology and Pharmacology, 7(2), 135-142.
[16]	Moss, E.J., Thomas, L.V., Cook, W.M., Walters, D.G., Foster, P.M.D., Creasy, D.M. and Gray, T.J.B. (1985) The role of metabolism in 2-methoxyethanol induced testicular toxicity. Toxicology and Applied Pharmacology, 79(3), 480-489.
[17]	Ghanayem, B.I., Burka, L.T. and Matthews, H.B. (1987) Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity, role of alcohol and aldehyde dehydrogenases. The Journal of Pharmacology and Experimental Therapeutics, 242(1), 222-231.
[18]	Nagano, K., Nakayama, E., Oobayashi, H., Nishizawa, T., Okuda, H. and Yamazaki, K. (1984) Experimental studies on toxicity of ethylene glycol alkyl ethers in Japan. Environmental Health Perspectives, 57, 75-84.
[19]	Starek, A., Szabla, J. and Starek-?wiechowicz, B. (2007) Pyrazole and methylpyrazole for the treatment of 2-bu- toxyethanol poisoning. Acta Poloniae Pharmaceutica, 64(1), 93-100.
[20]	R?mer, K.G., Balge, F. and Freundt, K.J. (1985) Ethanol induced accumulation of ethylene glycol monoalkyl ethers in rats. Drug and Chemical Toxicology, 8(4), 255- 264.
[21]	Morel, G., Lambert, A.M., Rieger, B. and Subra, I. (1996) Interactive effect of combined exposure to glycol ethers and alcohols on toxicodynamic and toxicokinetic parameters. Archives of Toxicology, 70, 519-525.
[22]	Wi?niewska-Knypl, J.M. and Wrońska-Nofer, T. (1994) Biological markers of oxidative stress induced by ethanol and iron overload in rats. International Journal of Occupational Medicine & Environmental Health, 7, 355-363.
[23]	Strbak, V., Benicky, J., Macho, L., Jezova, D. and Nikodemova, M. (1998) Four-week ethanol intake decreases food intake and body weight but does not affect plasma leptin, corticosterone, and insulin levels in pubertal rats. Metabolism, 47(6), 1269-1273.
[24]	Gupta, V. and Gill, K.D. (2000) Influence of ethanol on lead distribution and biochemical changes in rats exposed to lead. Alcohol, 20, 9-17.
[25]	Carpenter, C.P., Pozzani, U.C., Weil, C.S., Nair, J.H. and Keck, G.A. (1956) The toxicity of butyl cellosolve solvent. A.M.A. Archives of Industrial Health, 14(2), 114- 131.
[26]	Grant, D., Sulsh, S., Jones, H.B., Gangolli, S.D. and Butler, W.H. (1985) Acute toxicity and recovery in the hemopoietic system of rats after treatment with ethylene glycol monomethyl and monobutyl ethers. Toxicology and Applied Pharmacology, 77(2), 187-200.
[27]	Krasavage, W.J. (1986) Subchronic oral toxicity of ethylene glycol monobutyl ether in male rats. Fundamental and Applied Toxicology, 6(2), 349-355.
[28]	Ghanayem, B.I., Ward, S.M., Blair, P.C. and Matthews, H.B. (1990) Comparison of the hematologic effects of 2-butoxyethanol using two types of hematology analyzers. Toxicology and Applied Pharmacology, 106(2), 341- 345.
[29]	Starek, A., Jarosz, J. and Szymczak, W. (2004) Comparison of the hemolytic activity of isopropoxyethanol and phenoxyethanol. International Journal of Occupational Medicine & Environmental Health, 17, 339-346.
[30]	Starek, A., Szabla, J., Szymczak, W. and Zapór, J. (2006) Comparison of acute haematotoxicity of 2-methoxye- thanol, 2-ethoxyethanol and 2-butoxyethanol in male rats. Acta Toxicoogica, 14, 63-71.
[31]	Williams, W.C., Riddle, M.M., Copeland, C.B., Andrews, D.L., Smialowicz, R.J. (1995) Immunological effects of 2-methoxyethanol administered dermally or orally to Fischer 344 rats. Toxicology, 98(1-3), 215-223.
[32]	Miller, R.R., Hermann, E.A., Young, J.T., Landry, T.D. and Calhoun, L.L. (1984) Ethylene glycol monomethyl ether and propylene glycol monomethyl ether, metabolism, disposition, and subchronic inhalation toxicity studies. Environmental Health Perspectives, 57, 233-239.
[33]	Smialowicz, R.J., Williams, W.C., Riddle, M.M., Andrews, D.L., Luebeke, R.W. and Copeland, C.B. (1992) Comparative immunosuppression of various glycol ethers orally administered to Fischer 344 rats. Fundamental and Applied Toxicology, 18(4), 621-627.
[34]	Smialowicz, R.J., Riddle, M.M. and Williams, W.C. (1993) Methoxyacetaldehyde, an intermediate metabolite of 2-methoxyethanol, is immunosuppressive in the rat. Fundamental and Applied Toxicology, 21(1), 1-7.
[35]	Lockley, D.J., Howes, D. and Williams, F.M. (2005) Cutaneous metabolism of glycol ethers. Archives of Toxicology, 79(3), 160-168.
[36]	Coomes, M.W., Norling, A., Pohl, R.J., Muller, D. and Fouts, I.R. (1983) Foreign compound metabolism by isolated skin cells from the hairless mouse. The Journal of Pharmacology and Experimental Therapeutics, 225(3), 770-777.
[37]	Lockley, D.J., Howes, D. and Williams, F.M. (2002) Percutaneous penetration and metabolism of 2-ethoxy- ethanol. Toxicology and Applied Pharmacology, 180(2), 74-82.