title: Mercapturic acids of acrylamide and glycidamide as biomarkers of the internal exposure to acrylamide in the general population.
abstract: Acrylamide (AA), a widely used industrial monomer which is categorised to be carcinogenic, was found to be generated in starch-containing foods during the heating process. This discovery has caused reasonable concern about possible health risks to humans due to dietary acrylamide uptake. In order to gain more information on human metabolism of acrylamide and to contribute to the assessment of the human carcinogenic risk due to AA uptake we measured the mercapturic acid of AA and its epoxide glycidamide (GA) i.e. N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-(R,S)-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) in human urine. The relation between AAMA and GAMA is important in this context because GA is thought to be the ultimate carcinogenic metabolite of AA. The median levels in smokers (n=13) were found to be about four times higher than in non-smokers (n=16) with median levels of 127 microg/l versus 29 microg/l for AAMA and 19 microg/l versus 5 microg/l for GAMA. Therefore cigarette smoke proved to be an important source of acrylamide exposure. The level of AAMA in the occupationally non-exposed collective (n=29) ranged from 3 to 338 microg/l, the level of GAMA from <LOD to 45 microg/l. The ratio of GAMA:AAMA varied from 0.03 to 0.53, median was 0.16 which is in reasonable agreement with results of different studies on rats. Thus the metabolic conversion of acrylamide to its genotoxic epoxide glycidamide seems to occur to a comparable extent in rats and humans. Consequently, risk estimations by various authorities based on experimental data obtained in rats are supported by our findings. Besides we also measured the haemoglobin adducts of AA and GA in the blood of 26 participants. From these results compared to the mercapturic acids, we deduce a steady state for AA uptake, and we demonstrate a higher reactivity of GA in comparison to AA towards haemoglobin compared to glutathione in humans.
authors.affiliation: Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstrasse 25/29, D-91054 Erlangen, Germany.
authors.forename: Melanie Isabell
authors.initials: MI
authors.lastname: Boettcher
authors.forename: Thomas
authors.initials: T
authors.lastname: Schettgen
authors.forename: Birgitta
authors.initials: B
authors.lastname: Kütting
authors.forename: Monika
authors.initials: M
authors.lastname: Pischetsrieder
authors.forename: Jürgen
authors.initials: J
authors.lastname: Angerer
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism / Q000652:urine*; D020106:Acrylamide / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000378:metabolism / Q000652:urine; D005247:Feeding Behavior; D005260:Female; D005506:Food Contamination; D008401:Gas Chromatography-Mass Spectrometry; D005858:Germany; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D004852:Epoxy Compounds; D006454:Hemoglobins; D020106:Acrylamide; C071834:glycidamide; D000111:Acetylcysteine