Document Detail


Toxicokinetics of acrylamide in humans after ingestion of a defined dose in a test meal to improve risk assessment for acrylamide carcinogenicity.
MedLine Citation:
PMID:  16492914     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
High amounts of acrylamide in some foods result in an estimated daily mean intake of 50 microg for a western style diet. Animal studies have shown the carcinogenicity of acrylamide upon oral exposure. However, only sparse human toxicokinetic data is available for acrylamide, which is needed for the extrapolation of human cancer risk from animal data. We evaluated the toxicokinetics of acrylamide in six young healthy volunteers after the consumption of a meal containing 0.94 mg of acrylamide. Urine was collected up to 72 hours thereafter. Unchanged acrylamide, its mercapturic acid metabolite N-acetyl-S-(2-carbamoylethyl)cysteine (AAMA), its epoxy derivative glycidamide, and the respective metabolite of glycidamide, N-acetyl-S-(2-hydroxy-2-carbamoylethyl)cysteine (GAMA), were quantified in the urine by liquid chromatography-mass spectrometry. Toxicokinetic variables were obtained by noncompartmental methods. Overall, 60.3 +/- 11.2% of the dose was recovered in the urine. Although no glycidamide was found, unchanged acrylamide, AAMA, and GAMA accounted for urinary excretion of (mean +/- SD) 4.4 +/- 1.5%, 50.0 +/- 9.4%, and 5.9 +/- 1.2% of the dose, respectively. Apparent terminal elimination half-lives for the substances were 2.4 +/- 0.4, 17.4 +/- 3.9, and 25.1 +/- 6.4 hours. The ratio of GAMA/AAMA amounts excreted was 0.12 +/- 0.02. In conclusion, most of the acrylamide ingested with food is absorbed in humans. Conjugation with glutathione exceeds the formation of the reactive metabolite glycidamide. The data suggests an at least 2-fold and 4-fold lower relative internal exposure for glycidamide from dietary acrylamide in humans compared with rats or mice, respectively. This should be considered for quantitative cancer risk assessment.
Authors:
Uwe Fuhr; Melanie I Boettcher; Martina Kinzig-Schippers; Alexandra Weyer; Alexander Jetter; Andreas Lazar; Dirk Taubert; Dorota Tomalik-Scharte; Panagiota Pournara; Verena Jakob; Stefanie Harlfinger; Tobias Klaassen; Albrecht Berkessel; Jürgen Angerer; Fritz Sörgel; Edgar Schömig
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology     Volume:  15     ISSN:  1055-9965     ISO Abbreviation:  Cancer Epidemiol. Biomarkers Prev.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-22     Completed Date:  2006-06-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9200608     Medline TA:  Cancer Epidemiol Biomarkers Prev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  266-71     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University Hospital, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany. uwe.fuhr@uk-koeln.de
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MeSH Terms
Descriptor/Qualifier:
Absorption
Acrylamide / administration & dosage,  pharmacokinetics*,  toxicity
Adult
Animals
Carcinogens / pharmacokinetics
Cookery / methods
Dietary Fats
Epoxy Compounds / urine
Female
Half-Life
Humans
Male
Risk Assessment
Solanum tuberosum / chemistry
Species Specificity
Time Factors
Chemical
Reg. No./Substance:
0/Carcinogens; 0/Dietary Fats; 0/Epoxy Compounds; 5694-00-8/glycidamide; 79-06-1/Acrylamide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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