ToxSci Advance Access published online on September 6, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm234
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Urinary metabolites as biomarkers of acrylamide exposure in mice following dietary crisp bread administration or subcutaneous injection
a Norwegian Institute of Public Health, Division of Environmental Medicine, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway b Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, 0315 Oslo, Norway d Matforsk, Norwegian Food Research Institute, Osloveien 1, 1430 Aas, Norway
Corresponding author Jan Erik Paulsen, Norwegian Institute of Public Health, Division of Environmental Medicine, P.O. Box 4404 Nydalen, NO-0403 Oslo, Norway, Tel: +47 22 04 23 53, Fax: +47 22 04 22 43, e-mail: jan.erik.paulsen{at}fhi.no,
Received January 18, 2007; revision received August 24, 2007; accepted August 31, 2007
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Abstract |
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Heat-treated carbohydrate rich foods may contain high levels of acrylamide (AA). Crisp bread is a significant dietary AA source in the Nordic countries. We studied whether urinary metabolites of AA could be candidate biomarkers of AA intake and internal dose in mice following dietary crisp bread administration or subcutaneous (sc) injection. The crisp bread was experimentally baked to contain 3 different concentrations of AA: 0.19, 1.02, 2.65 mg/kg, giving dietary exposures to AA of 0.024±0.002, 0.14±0.02 and 0.29±0.04 mg/kg bw/day (mean±SD), respectively. A linear relationship was found between dietary AA exposure and urinary AA metabolites. On average 55% of the ingested dose was recovered as urinary AA metabolites, and the molar proportions between the urinary metabolites showed similar proportions for the different doses. Urine AA metabolites were measured after sc injection of AA at doses of 0.05, 0.5, 5 and 50 mg/kg bw and the urinary recovery for the three lowest doses was, 54%. With the highest dose, 80% was recovered in urine and the changed pattern of urinary metabolites indicated saturation of the metabolic conversion of AA to glycidamide. These results indicate that urinary metabolites of AA are good biomarkers of AA intake and internal dose up to 5 mg/kg bw/day. After sc injection of [14C]AA, 92% of the radioactivity was found in the urine and 2% in faeces, liver, blood and intestinal content (6% was not detected), demonstrating that sc AA was highly systemically available, that the major part AA metabolites was excreted, and that a significant portion of urinary AA metabolites (most likely glyceramide) was not accounted for by the present analytical method. Since the urinary recovery of AA after crisp bread feeding and sc injection was practically identical, an indicative "bioavailability" of AA from crisp bread was suggested to be approximately complete.
Key Words: Urine; biomarkers; dietary exposure; acrylamide; glycidamide; food; bioavailability; crisp bread.
* These authors have contributed equally