Improved basis for cancer risk assessment of acrylamide from food : Determination of glycidamide in vivo doses

Acrylamide is formed in heat processing of many common foods. According to animal cancer tests acrylamide is a carcinogen. To estimate the cancer risk from exposure via food, the response at high doses in the cancer tests with rats has to be extrapolated to the exposure levels in humans. Acrylamide is biotransformed to the epoxide glycidamide, which is assumed to be the cancer-risk increasing agent. Therefore in vivo doses of both acrylamide and glycidamide should be measured in rats and humans and related to the acrylamide intake. In vivo doses (area under the time-concentration curve, AUC) of reactive compounds can be determined from measured reaction products, adducts, to hemoglobin (Hb). A study in mice showed that the food matrix does not have an influence on the absorbed amount of acrylamide from food. There was a linear dose-response of Hb-adduct levels from acrylamide and glycidamide. For cancer risk assessment it is important to describe variations between individuals in intake and in AUC. Hb-adduct levels of acrylamide and glycidamide were studied in two large groups. In non-smokers the acrylamide and glycidamide-adduct levels varied with a factor of 5 and 8, respectively. The influence of other compounds in the diet on metabolic formation/elimination of glycidamide was demonstrated by associations between the ratio of glycidamide-to-acrylamide-adduct levels and alcohol intake. Furthermore, a non-linearity between glycidamide and acrylamide-adduct levels was shown at low exposure levels. AUCs from acrylamide and glycidamide in rats exposed as in the cancer tests were measured and compared with AUCs in humans exposed to acrylamide through food. The AUC of glycidamide per given dose of acrylamide was somewhat higher in humans than in the rats. Altogether the generated data could be used to improve the cancer risk estimate of acrylamide in food. The obtained data strengthen earlier preliminary cancer risk estimates of acrylamide.At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 5: Manuscript