title: Toxicokinetics and internal exposure of acrylamide: new insight into comprehensively profiling mercapturic acid metabolites as short-term biomarkers in rats and Chinese adolescents.
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.
authors.affiliation: Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Yangtze Delta Region Institute of Tsinghua University, Jiaxing, 314006, Zhejiang, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, Zhejiang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, Zhejiang, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, Zhejiang, China.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Epidemiology and Health Statistics, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.
authors.forename: Weijiang
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
authors.forename: Qingning
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Department of Food Science and Nutrition, Zhejiang University, Hangzhou, 310058, Zhejiang, China. y_zhang@zju.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D020106:Acrylamide / Q000493:pharmacokinetics / Q000633:toxicity* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine*; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests / Q000379:methods; D055815:Young Adult
chemical_list: D015415:Biomarkers; C000625513:N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine; C569465:N-acetyl-S-(2-carbamoylethyl)cysteine; D020106:Acrylamide; D000111:Acetylcysteine
keywords: Acrylamide; Biomarker; Internal exposure; Mercapturic acid; Toxicokinetics