B.M. de Rooij · D.A. Rijksen · J.N.M. Commandeur · N.P.E. Vermeulen ( ) Leiden-Amsterdam Center for Drug Research (LACDR), Division of Molecular Toxicology, Department of Pharmacochemistry, Free University, De Boelelaan 1083, NL-1081 HV Amsterdam, The Netherlands P.J. Boogaard Shell International Chemicals BV, Molecular Toxicology, Shell Research and Technology Centre, Amsterdam, The Netherlands Arch Toxicol (1996) 70: 635—639  Springer-Verlag 1996 ORIGINAL INVESTIGATION Ben M. de Rooij · Pieter J. Boogaard · De ´ sire ´ e A. Rijksen Jan N.M. Commandeur · Nico P.E. Vermeulen Urinary excretion of N -acetyl- S -allyl-L-cysteine upon garlic consumption by human volunteers Received: 17 November 1995/Accepted: 14 February 1996 Abstract N-Acetyl-S-allyl-L-cysteine (allylmercapturic acid, ALMA) was previously detected in urine from humans consuming garlic. Exposure of rats to allyl halides is also known to lead to excretion of ALMA in urine. ALMA is a potential biomarker for exposure assessment of workers exposed to allyl halides. It is not known whether garlic consumption can lead to urinary concentrations of ALMA which may interfere with biological monitoring of exposure to allyl halides by determination of urinary ALMA. Therefore, this study was undertaken to determine the cumulative excretion and the excretion kinetics of ALMA in urine of humans consuming garlic. Six human volunteers were given orally two garlic tablets, each containing 100 mg garlic extract (each representing 300 mg fresh garlic). Three of the volunteers consumed additional garlic after the garlic tablet intake. Urine samples were collected up to 24 h after the intake of the garlic tablets. ALMA was identified in the urine using gas chromatography-mass spectrometry (GC-MS) and determined quantitatively with a limit of detection of 0.10 g/ml with gas chroma- tography with sulphur selective detection. The total amount of ALMA found in urine of volunteers who consumed two garlic tablets was 0.43$0.14 mg (n"3). In the urine of the three volunteers who con- sumed not only two garlic tablets but also additional fresh garlic, a significantly higher amount of ALMA was excreted in the urine, 1.4$0.2 mg (n"3). The elimination half-life of ALMA, estimated from urinary excretion rate versus time curves, was 6.0$1.3 h (n"5). One volunteer, who ate additional garlic, showed an irregular elimination profile and was ex- cluded from this estimation. The highest urinary con- centration of ALMA found in this study was 2.2 g/ml. In a preliminary biological monitoring study of expo- sure in workers with potential exposure to allyl chlor- ide (AC) up to the occupational exposure limit of 1 ppm (8-h TWA), we recently found urinary ALMA concen- trations up to 4 g/ml. Based on the results presented here, we conclude that garlic consumption is a poten- tial confounder when monitoring human exposure to allylhalides and other chemicals leading to ALMA ex- cretion when ALMA is used as a biomarker of expo- sure. Key words Allyl chloride · Biological monitoring · Garlic · Mercapturic acid · Urine Introduction N-Acetyl-L-cysteine-S-conjugates or mercapturic acids (MAs) are frequently used as biomarkers of elec- trophilic chemicals in biomonitoring and toxicological studies (Vermeulen 1989; Van Welie et al. 1992). Elec- trophilic compounds may react either spontaneously or enzymatically with the endogenous tripeptide glutathione (-Glu-Cys-Gly; GSH) forming glutathione conjugates. So-called MAs are formed from these GSH-conjugates by removal of the -glutamyl- and glycine moieties by -glutamyl transpeptidase and dipeptidases, respectively followed by N-acetylation of the resulting L-cysteine conjugates by cysteine conju- gate N-acetyl transferase. MAs have been analysed in rat and human urine samples with chromatographic methods such as high pressure liquid chromatography (HPLC), gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) (Van Welie et al. 1992). Allylmercapturic acid (ALMA) has