Derivation of noncancer reference values for acrylonitrile

Dose-response assessments were conducted for the noncancer effects of acrylonitrile (AN) for the purposes of deriving subchronic and chronic oral reference dose (RfD) and inhalation reference concentration (RfC) values. Based upon an evaluation of available toxicity data, the irritation and neurological effects of AN were determined to be appropriate bases for deriving reference values. A PBPK model, which describes the toxicokinetics of AN and its metabolite 2-cyanoethylene oxide (CEO) in both rats and humans, was used to assess the dose-response data in terms of an internal dose measure for the oral RfD values, but could not be used in deriving the inhalation RfC values. Benchmark dose (BMD) methods were used to derive all reference values. Where sufficient information was available, data-derived uncertainty factors were applied to the points of departure determined by BMD methods. From this assessment, subchronic and chronic oral RfD values of 0.5 and 0.05 mg/kg/day, respectively, were derived. Similarly, subchronic and chronic inhalation RfC values of 0.1 and 0.06 mg/m(3), respectively, were derived. Confidence in the reference values derived for AN was considered to be medium to high, based upon a consideration of the confidence in the key studies, the toxicity database, dosimetry, and dose-response modeling.