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Toxicokinetics and internal exposure of acrylamide: new insight into comprehensively profiling mercapturic acid metabolites as short-term biomarkers in rats and Chinese adolescents

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Toxicokinetics and internal exposure of acrylamide: new insight into comprehensively profiling mercapturic acid metabolites as short-term biomarkers in rats and Chinese adolescents

Content Provider	Springer Nature Link
Author	Wang, Qiao Chen, Xinyu Ren, Yiping Chen, Qing Meng, Zhen Cheng, Jun Zheng, Yunyan Zeng, Weijiang Zhao, Qingning Zhang, Yu
Copyright Year	2016
Abstract	Acrylamide is classified as a probable carcinogen to humans and generated from Maillard reaction. Currently, the short-term exposure to acrylamide was evaluated via external diet sources in vitro or two main mercapturic acid metabolites: N-acetyl-S-(2-carbamoylethyl)-l-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-l-cysteine (GAMA) in vivo. In the present work, we comprehensively profiled four mercapturic acid metabolites and evaluated their internal exposure in rats and Chinese adolescents. The cumulative excretion of mercapturic acid metabolites contributes 38.4–73.0 and 43.8–63.6 % of total in vivo metabolites of acrylamide in male and female rats, respectively, when 1, 10, and 50 mg/kg bw of acrylamide were orally administered. Toxicokinetic study revealed that the conversion of acrylamide into glycidamide and glutathione coupling process is highly related to the gender and oral gavage dose via evaluating kinetic parameters, accumulative excretion percentages, and molar ratios of oxidative to reductive metabolism. In human study, a total of 101 Chinese adolescents (41 men and 60 women) were enrolled and served with a meal of potato chips, corresponding to a single-dose (12.6 μg/kg bw) exposure to acrylamide. Toxicokinetic work showed that AAMA is an early and predominant metabolite appearing as a biomarker in urine. N-acetyl-S-(2-carbamoylethyl)-l-cysteine-sulfoxide (AAMA-sul), an oxidative product from AAMA, exhibits a higher peak concentration than GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-l-cysteine (iso-GAMA) during the whole 48-h toxicokinetic period. The internal exposure via four mercapturic acid metabolites is associated with the gender and body mass index characteristics. Thus, current study aims at mercapturic acid metabolites as urinary biomarkers and provides comprehensive insights into the short-term internal exposure to acrylamide.
Starting Page	2107
Ending Page	2118
Page Count	12
File Format	PDF
ISSN	03405761
Journal	Archives of Toxicology
Volume Number	91
Issue Number	5
e-ISSN	14320738
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-10-13
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Acrylamide Toxicokinetics Internal exposure Mercapturic acid Biomarker Pharmacology/Toxicology Occupational Medicine/Industrial Medicine Environmental Health Biomedicine
Content Type	Text
Resource Type	Article
Subject	Health, Toxicology and Mutagenesis Medicine Toxicology

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