In vivo doses of acrylamide and glycidamide in humans after intake of acrylamide-rich food.
For assessment of cancer risk from acrylamide (AA) exposure through food, the relation between intake from food in humans and the in vivo doses (area under the concentration-time curve, AUC) of AA (AUC-AA) and of its genotoxic metabolite glycidamide (GA) (AUC-GA) is used as a basis for extrapolation between exposure levels and between species. In this study, AA-rich foods were given to nonsmokers: a high intake of 11 μg AA/kg body weight (bw) and day for 4 days or an extra (medium) intake of 2.5 μg AA/kg bw and day for a month. Hemoglobin (Hb)-adduct levels from AA and GA, measured in blood samples donated before and after exposures, were used for calculation of AUC-AA and AUC-GA using reaction rate constants for the adduct formation measured in vitro. Both AA- and GA-adduct levels increased about twofold after the periods with enhanced intake. AUC for the high and medium groups, respectively, in nanomolar hours per microgram AA per kilogram bw, was for AA 212 and 120 and for GA 49 and 21. The AA intake in the high group was better controlled and used for comparisons with other data. The AUCs per exposure dose obtained in the present human study (high group) are in agreement with those previously obtained at 10(2) times higher exposure levels in humans. Furthermore, the values of AUC-AA and AUC-GA are five and two times higher, respectively, than the corresponding values for F344 rats exposed to AA at levels as in published cancer bioassays.
Department of Materials and Environmental Chemistry, Environmental Chemistry unit, Arrhenius laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.
Anna C
AC
Vikström
Lilianne
L
Abramsson-Zetterberg
Marek
M
Naruszewicz
Ioannis
I
Athanassiadis
Fredrik N
FN
Granath
Margareta Å
MÅ
Törnqvist
D020106:Acrylamide / Q000008:administration & dosage* / Q000097:blood* / Q000633:toxicity; D000328:Adult; D019540:Area Under Curve; D001711:Biotransformation; D004435:Eating; D004852:Epoxy Compounds / Q000097:blood*; D005260:Female; D005502:Food; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D018570:Risk Assessment; D055815:Young Adult
D004852:Epoxy Compounds; D006454:Hemoglobins; D020106:Acrylamide; C071834:glycidamide