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Metabolism and hemoglobin adducts following intraperitoneal, dermal, or inhalation exposure
Sumner, S. C. J., Williams, C. C., Snyder, R. W., Krol, W., & Fennell, T. R. (2002). Acrylamide: Metabolism and hemoglobin adducts following intraperitoneal, dermal, or inhalation exposure. The Toxicologist, Supplement to Toxicological Sciences, 66(1-S), 227. Article 1112.
Occupational exposure to acrylamide (AM) via dermal contact or inhalation may occur during use as an intermediate in the production of polymers, or during the use of AM-containing grouting materials. In this study, AM-derived urinary metabolites and hemoglobin adducts were measured in rats and mice following inhalation exposure and in rats following intraperitoneal (ip) and dermal administration. No mortality occurred from a 6-hr exposure to 5.6 ppm AM-vapor. Rats exposed for 6 hr to 3 ppm [13C /14C]AM-vapor had a lower uptake (90 μmol [14C]AM equiv /kg bw) than mice (245 μmol/kg bw). AM-derived 14C was excreted in 24-hr urine and feces (42% of recovered 14C in rats, 51% mice) or recovered in tissues (56% rats, 46% mice). Following dermal application of 162 mg/kg [14C]AM for 6 hr, 22% of the applied dose was absorbed and distributed to the excreta (44%) or tissues (53%) by 24 hr. Following ip administration of [13C]AM, 62% of the dose was excreted in 0-24-hr urine. In rats, metabolites derived from AM conjugation with glutathione (AM-GSH) accounted for 69% (ip), 52% (dermal), and 64% (inhalation) of the urinary metabolites. In mice, the AM-GSH pathway accounted for only 27% of the urinary metabolites. Remaining metabolites were derived from oxidation of AM to glycidamide (GA). Hemoglobin adducts of AM [N-(2-carbamoylethyl)valine, AAVal] and GA [N-(2-carbamoyl-2-hydroxyethyl)valine, GAVal] were analyzed by liquid chromatography mass spectrometry. AAVal in rats was 12900 ± 652 (ip), 6398 ± 2979 (dermal), and 1207 ± 127 fmol/mg globin (inhalation), while GAVal was 9031 ± 464 (ip), 10010 ± 3149 (dermal), and 1339 ± 206 fmol/mg globin (inhalation). ln mice, AAVal was 1431 ± 509, and GAVal was 4853 ± 564 fmol/mg (inhalation). GAVal:AAVal ratios were 0.7 (i.p. rat), 1.56 (dermal rat), 1.3 (inhalation rat), and 3.4 (inhalation mouse). This study demonstrates marked species and route differences in the metabolism and internal dose (Hbadducts) of AM and GA. [Funded by the Polyelectrolye Producers Group]
