PNNL

Abstract

Internal dosimetry of acrylamide (AA, 2-propenamide; CASRN: 79-06-1) and its active metabolite glycidamide (GA) can be estimated using either a biomarker of internal exposure or a physiologically based toxicokinetic (PBTK) model. The US EPA posted human health reference values for AA (U.S. EPA, 2010; http://www.epa.gov/iris/toxreviews/0286tr.pdf) based on AA and GA hemoglobin adduct levels in rats and humans as a biomarker of exposure. Sweeney et al. (2010) subsequently published an updated PBTK model, providing the opportunity to directly compare estimates from both approaches, and the resulting impact on the human equivalent dose (HED, oral exposures), the human equivalent concentration (HEC, inhalation exposure), and final reference values. Both approaches yielded similar AA HED and HEC values for the most sensitive noncancer effect of neurotoxicity, and identical oral reference doses (RfD) of 2 x 10-3 mg AA/kg. The inhalation reference concentrations were nearly identical: RfC = 0.006 mg/m3 and 0.007 mg/m3, biomarker and PBTK results, respectively. HED and HEC values for carcinogenic potential were also very similar yielding oral cancer slope factors of 0.4 and 0.5 / [mg AA/kg-d], from the biomarker and PBTK results, respectively, and identical inhalation unit risks of 0.1 / (mg AA/m3). This concordance in estimated HEDs and HECs increases confidence in these values and the resulting reference values. Advantages and specific application of each approach are discussed. [Caveat: the reference values derived with the PBPK model were part of this research exercise, and will not replace the values currently posted on IRIS.]