Abstract
In order to identify biological indicators of exposure to trimethylbenzenes, the metabolism of pseudocumene (1,2,4-trimethylbenzene) was investigated in rabbits. After oral administration of this compound, urine was collected for several days and analyzed for the presence of acidic metabolites. Isolation techniques included steam-distillation, direct extraction of urine by ethyl acetate, preparative thin-layer and column chromatography of the extract. The metabolites were identified by microanalysis, followed by TLC, gas chromatography-mass spectrometry, infrared and ultraviolet spectroscopy. Two major urinary metabolites were identified, namely 2,4-dimethylbenzoic acid and 3,4-dimethylhippuric acid. The presence of these acidic metabolites in urine is a good indication of exposure to pseudocumene.
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References
Bakke OM, Scheline RR (1970) Hydroxylation of aromatic hydrocarbons in the rat. Toxicol Appl Pharmacol 16:691–700
Bättig K, Granjean E, Rossi L, Rickenbacher H (1958) Toxikologische Untersuchungen über Trimethylbenzol. Arch Gewerbepath 16:555–556
Bättig K, Grandjean E, Turrian V (1956) Gesundheitsschäden nach langdauernder Trimethylbenzol Exposition in einer Malerwerkstatt. Z Praeventivmed 1:389–403
Bray HG, Humphris BG, Thorpe WV (1949) Metabolism of derivatives of toluene. 3.o-,m-, andp-xylenes. Biochem J 45:241–244
Bray HG, Thorpe WV, Wood PB (1949) The fate of certain organic acids and amides in the rabbit. 8. Toluic acids and amides. Biochem J 45:45–50
Cameron GR, Paterson JLH, De Saram GSW, Thomas JC (1938) The toxicity of some methyl derivatives of benzene with special reference to pseudocumene and heavy coal tar naphtha. J Pathol 46:95–107
El Masri AM, Smith JN, Williams RT (1956) Studies in detoxication. 69. The metabolism of alkylbenzenes:n-propylbenzene andn-butylbenzene with further observations on ethylbenzene. Biochem J 64:50–56
Fabre R, Truhaut R, Laham S (1960a) Recherches sur le métabolisme comparé des xylènes ou diméthylbenzènes. Arch Mal Prof 21:314–328
Fabre R, Truhaut R, Laham S (1960b) Étude du métabolisme des xylènes ou diméthylbenzènes chez le rat, le cobaye et le lapin. Comptes Rendus Acad Sci 250:2655–2659
Gerarde HW (1959) Toxicological studies on hydrocarbons. III. The biochemorphology of the phenylalkanes and phenylalkenes. AMA Arch Ind Health 19:403–418
Laham S, Potvin M, Matutina E (1969) Metabolic studies on toxic compounds. 5. Identification of new methylhippuric acids. Mikrochim Acta (Wien) 654–659
Lazarew NW (1929) Über die Giftigkeit verschiedener Kohlenwasserstoffdämpfe. Naunyn-Schmiedebergs Arch Exp Pathol Pharmacol 143:223–233
Mikulski PI, Wiglusz R (1975) The comparative metabolism of mesitylene, pseudocumene, and hemimellitene in rats. Toxicol Appl Pharmacol 31:21–31
Ogata M, Tomokuni K, Takatsuka Y (1969) Quantitative determination in urine of hippuric acid andm- orp-methylhippuric acid, metabolites of toluene andm- orp-xylene. Brit J Indust Med 26:330–334
Ogata M, Tomokuni K, Takatsuka Y (1970) Urinary excretion of hippuric acid andm- orp-methylhippuric acid in the urine of persons exposed to vapours of toluene andm- orp-xylene as a test of exposure. Brit J Indust Med 27:43–50
Rossi L, Grandjean E (1957) L'eliminazione urinaria dei fenoli in animali espositi al trimetilbenzolo. Med Lav 48:523–532
Smith JN, Smithies RH, Williams RT (1954) Studies in detoxication. 55. The metabolism of alkylbenzenes: a) glucuronic acid excretion following the administration of alkylbenzenes; b) elimination of toluene in the expired air of rabbits. Biochem J 56:317–320
Srbova J, Teisinger J (1953) O metabolismu toluenu. Prac Lék 5:259–263
Teisinger J, Srbova J (1954) Vztah vylucovani kiseliny benzoove v moci K maximalne pripustne davce toluenu ve vzduchu. Prac Lék 6:332–335
Williams RT (1959) Detoxication mechanisms. 2nd edn. John Wiley and Sons, New York
Woronow A (1929) Über die morphologischen Veränderungen des Blutes und der bluterzeugenden Organe unter dem Einflusse des Benzols und dessen Abkömmlinge. Arch Pathol Anat Physiol 271:173–190
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J. Cerf is a recipient of a visiting fellowship from the Natural Sciences and Engineering Research Council of Canada
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Cerf, J., Potvin, M. & Laham, S. Acidic metabolites of pseudocumene in rabbit urine. Arch Toxicol 45, 93–100 (1980). https://doi.org/10.1007/BF01270906
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DOI: https://doi.org/10.1007/BF01270906