Dosimetry of Acrylamide and Glycidamide Over the Lifespan in a 2-Year Bioassay of Acrylamide in Wistar Han Rats

Abstract

Acrylamide is an industrial chemical used to manufacture polymers, and is produced in foods during cooking at high heat. Hemoglobin adducts provide a long-lived dosimeter for acrylamide and glycidamide. This study determined acrylamide and glycidamide hemoglobin adducts (AAVal and GAVal) during a lifetime carcinogenesis bioassay. Exposure to acrylamide in drinking water began in utero in pregnant rats on gestation day 6. Dams were administered acrylamide until weaning, and male and female F1 rats were exposed for a further 104 weeks. Acrylamide concentration in drinking water was adjusted to provide a constant dose of 0.5, 1.5, and 3 mg/kg/day. Blood was collected from animals euthanized at 2, 60, 90, and 120 days and 53, 79, and 104 weeks after weaning. Low levels of AAVal and GAVal at postnatal day 24 suggested that little exposure to acrylamide occurred by placental or lactational transfer, and extensive metabolism to glycidamide occurred with a GAVal:AAVal ratio of 4. Adduct levels varied somewhat from 60 days to 2 years, with a GAVal:AAVal ratio of approximately 1. Adduct formation/day estimated at each timepoint at 3 mg/kg/day for AAVal was 1293 +/- 220 and 1096 +/- 338 fmol/mg/day for male and female rats, respectively. Adduct formation per day estimated at each timepoint at 3 mg/kg/day for GAVal was 827 +/- 78 fmol/mg/day for male rats, and 982 +/- 222 fmol/mg/day for female rats. The study has provided estimates of linearity for dose response, and variability in internal dose throughout an entire 2-year bioassay, including the early phases of pregnancy and lactation