Metabolism and distribution of acrylamide in rats and mice following inhalation exposure or dermal application

Abstract

Acrylamide (AM) is used in the manufacture of polymers and is a known neurological toxicant. The epoxide intermediate of AM, glycidamide, is a known mutagen. In this study, the metabolism of AM was evaluated following inhalation exposure or dermal application. No mortality was observed for male F344 rats or B6C3Fl mice exposed to AM vapor at ~ 5.7 ppm for 6 hr via nose-only inhalation. Urine, feces, expired air, and tissues were collected from rats and mice following a 6-hr nose-only exposure to ~ 2.9 ppm [1,2,3- 13C]AM and [2,3- 14C]AM. Samples were also obtained from rats following a 24-hr dermal application of 162 mg/kg [ 14C]AM in distilled water. Following dermal application, ~ 22% (~ 112 μmol) of the applied dose was absorbed and largely distributed to excreta (~44% of the recovered dose in urine, feces, and washes) and tissues (~53%). Rats exposed to the mixture of ~2.9 ppm [ 13C/ 14C]AM-vapor retained ~18 μmol of AM, while mice retained ~ 8 μmol. Following inhalation exposure, excreta (urine, feces, and wash; 42% of the recovered radioactivity for rats, 51% for mice) and tissues (56% rats, 46% mice) were the major source of [ 14C]AM-equivalents. Route differences in the metabolism and distribution of AM are important considerations in the development of models for assessing the potential risk from human exposure. [This study was funded by the Polyelectrolyte Producers Croup.]