The xylene isomers are metabolised by oxidation of the methyl groups. The initial products of biotransformation are methylbenzyl alcohols, which are metabolised to methylbenzaldehydes by alcohol dehydrogenase. Then aldehyde dehydrogenase is involved in the conversion to methylbenzoic acids (toluic acids) (Miller and Edwards, 1999). These are then conjugated with glycine and excreted as methylhippuric acids (MHA, toluric acids) (Sedivec and Flek, 1976). The isomer of methylhippuric acid excreted depends on the isomer of xylene to which an individual has been exposed; o-xylene is metabolised to o-methylhippuric acid, m-xylene to m-methylhippuric acid and p-xylene to p-methylhippuric acid. The urinary concentrations of methylhippuric acids correlate with the exposure concentration of xylene isomers (Inoue et al., 1993).

Metabolism of xylene is rapid (Senczuk and Orlowski, 1978) with methylhippuric acid detectable in urine within 2 hours of exposure (Sedivec and Flek, 1976). The different isomers of xylene may be metabolised at slightly different rates; p-xylene may be metabolised more quickly than m- and o-xylene (Sedivec and Flek, 1976; Kawai et al., 1991). In volunteers exposed to a 1:1:1 mixture of the 3 isomers the concentration of the methylhippuric acids in the initial urine sample were: p-methylhippuric acid 41.5%, o-methylhippuric acid 23.8% and m-methylhippuric acid 34.7%. When the hippuric acid concentrations were calculated for all urine samples the percentages evened out at 33% each (Sedivec and Flek, 1976). However, in a more recent study in exposed workers metabolism of m-xylene appeared to be favoured over that of the other isomers. This was independent of the concentrations of the isomers in the mixture to which the workers were exposed (Miller and Edwards, 1999).

Xylenols are formed by hydroxylation of the aromatic ring. In volunteers exposed to the different isomers, 2,3-xylenol and 3,4-xylenol were found after exposure to o-xylene; 2,4-xylenol and 2,6-xylenol after exposure to m-xylene; and 2,5-xylenol after p-xylenol exposure. The highest concentration of xylenols is observed just after cessation of exposure (Sedivec and Flek, 1976; Riihimaki et al., 1979). This is also the case with the methylhippuric acid metabolites (Riihimaki et al., 1979).

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