Investigation of the Low-Dose Response in the In Vivo Induction of Micronuclei and Adducts by Acrylamide

Acrylamide is an industrial chemical used in polymer manufacture.It is also formed in foods processed at high temperatures. Itinduces chromosome aberrations and micronuclei (MN) in somaticcells of mice, but not rats, and mutations in transgenic mice.This study evaluated the low-dose MN response in mouse bonemarrow and the shape of the dose-response curve. Mice were treatedorally with acrylamide for 28 days using logarithmically spaceddoses from 0.125 to 24 mg/kg/day, and MN were assessed in peripheralblood reticulocytes (RETs) and erythrocytes by flow cytometry.Liver glycidamide DNA adducts and acrylamide and glycidamideN-terminal valine hemoglobin adducts were also determined. Acrylamideproduced a weak MN response, with statistical significance at6.0 mg/kg/day, or greater, in MN-RETs and at 4.0 mg/kg/day orgreater in MN normochromatic erythrocytes (NCEs). The MN responsesat the lower doses were indistinguishable from the concurrentand historical controls. The adducts increased at a much differentrate than the MN. When the MN-NCE values were compared to administereddose, the response was consistent with a linear model. However,when hemoglobin or DNA adducts were used as the dose metric,the response was significantly nonlinear, and models that assumeda threshold dose of 1 or 2 mg/kg/day provided a better fit thana linear model. The MN-RET dose-response had greater variabilitythan the MN-NCE response and was consistent with linearity andwith a threshold at 1 or 2 mg/kg/day, regardless of the dosemetric. These data suggest a threshold for acrylamide in theMN test.