Methylhippuric acid

XYLENES (technical-grade) Methylhippuric acids in urine End of shift 1.5 g/g creatinine ... 

Daily average workplace xylene air and urinary methylhippuric acid in exposed workers, 155... 

FIGURE 5-5 Daily average workplace xylene air and urinary methylhippuric acid (MHA) in exposed workers. Source Jang et al. 2001. Reprinted with permission copyright 2001, International Archives of Occupational and Environmental Health. 

Occupational exposure to chemical substances almost invariably involves multiple chemicals. That situation may result in PK interactions, which may affect the relationship between the atmospheric concentration of the parent chemical and the associated biomarker concentration (Viau 2002). For example, such an interaction is known to occur between ethylbenzene and the xylene isomers (Jang et al. 2001). Commercial xylene contains about 20% ethylbenzene, which modifies the slope of the relationship between urinary methylhippuric acid (MHA) and airborne xylene concentrations. That kind of interaction is unlikely at the subparts-per-million exposure concentrations seen in the general population. But because the BEI for MHA was obtained from the relationship observed after exposure to commercial xylene, thereby taking the interaction into account, the slope of the relationship cannot be extrapolated to the subparts-per-million range. Similar PK interactions have been observed for other mixtures but only at concentrations nearing or exceeding the occupational exposure limits (Viau 2002), so it would be a priori reasonable to consider extrapolation of the relationship between biomarker concentrations and those of their parent chemicals. For example, Tardif et al. (1991) demonstrated that, provided inhalation exposure to a mixture of toluene and xylene was kept below their airborne occupational exposure limits, there were no PK interactions between the compounds that affected the linear relationship between airborne parent-chemical exposure and urinary-metabolite concentrations. However, such an interaction was apparent at higher concentrations. 

Hippuric acids, which are formed as phase II metabolic products from toluene, xylenes, benzoic acid, ethylbenzene, and closely related compounds, can be determined as biological markers of exposure. The formation of hippuric acid from toluene is shown Figure 13.9, and the formation of 4-methylhippuric acid from p-xylene is shown below ... 

Quantification. Gas Chromatography. In urine w and p-methylhippuric acids, sensitivity l.Opg/ml, AFID—M. Morin etal., J. Chromat., 1981, 210, 346-349. 

C10H11NO3 3-methylhippuric acid 27115-49-7 504.40 44.307 2 19492 C10H12O alpha-vinyl-alpha-methylbenzenemethanol 6051-52-1 502.76 44 150 2... 

HPLC methods are considered by the National Institute for Occupational Safety and Health (NIOSH) to be the reference methods (e.g., NIOSH 8301). However, these methods cannot separately quantify each isomer of hippuric acid and methylhippuric acids. 

Gas chromatographic methods are considered to be specific for determination of hippuric acid and methylhippuric acid, although they require a derivatization procedure with various reagents for example, several investigators have used diazomethane others have used trimethyl-silyl derivatives. 

The detection of urinary metabolites has also been used to detect occupational exposure or to confirm inhalation of volatile substances. Urinary metabolites such as phenol (benzene metaboEte), trichloroacetic acid (tetrachloroethylene), hippuric acid (toluene) and methylhippuric acid (xylene) have been detected and measured. Results are often... 

Xylene vapor is rapidly absorbed from the lungs, and xylene liquid and vapor are absorbed slowly through skin. More than 90% of the absorbed xylene is metabolized to methylhippuric acid, which is readily excreted in urine. On repeated administration, xylene auto-induces some P450 enzymes, which metabolize the methyl side chain to toluic acid (methylbenzoic acid), which is also rapidly excreted. Additional metabolites of xylenes are dimethylphenol and methylbenzyl alcohol (Langman 1994). 

Isotachophoresis has already been successfully applied to the analysis of urine of persons exposed to styrene, toluene, and xylene, for the contents of mandelic, phenylglyoxylic, hippuric and methylhippuric acids . For the clinical disgnostic of inborne metabolic disorders of purines and pyrimidines, it has been elaborated permitting the identification of different inborne disorders of the metabolism of these bases by the contents of characteristic metabolites excreted in urine (adenine, uric acid, xanthin, deoxyinosin, deoxyguanosin etc.). 

H. Matsui and T. Sekiya, High-performance Liquid Chromatographic Separation of Urinary Hippuric and o-, m- and p-methylhippuric Acids with a P-cyclodextrin-bonded Column, J. 

M. Korn, R. Hennings and M. Heilig, HPLC Determination of o-, m-, p-Methylhippuric Acids and Hippuric Acid in Urine of Xylene and Toluene Exposed Persons, 13th Annual Conference on Biochemical Analysis, Annual Meeting of the German Society for Clinical Chemistry. 

Figure 3.170 Separation of various aromatic suppressed conductivity injection volume monocarboxylic acids. Separator columns 2 50pL peaks (1) o-methylhippuric acid, (2)...

Figure 18.5 The permeability P is proportional to the oil-water partition coefficient K for p-methylhippuric acids (o) and p-toluic acids ( ) through lipid bilayer membranes. Source P Mayer, T-X Xiang, and BD Anderson, AAPS Pharm Sci 2, article 14 (2000).

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