Toxicity Assessment of 4-Amino-2-Nitrotoluene

Abstract

4-Amino-2-nitrotoluene (4A2NT; CAS 119-32-4) is a degradation product of 2,4-dinitrotoluene. The toxicity data on 4A2NT are limited. Therefore, we collected toxicity data from rats to assess environmental and human health effects from exposures. The approximate lethal dose for both sexes was 5000 mg/kg. A 14-day toxicity study in rats was conducted with 4A2NT in the feed at concentrations of 0, 125, 250, 500, 1000, and 2000 ppm. Based on a 14-day oral dose range toxicity study with 4A2NT in the feed, 2000 ppm was selected as highest concentration for a subsequent 90-day study. An oral 90-day subchronic toxicity study in rats was conducted with concentrations of 0, 500, 1000, or 2000 ppm of 4A2NT in the feed. The calculated consumed doses of 4A2NT in the feed were 0, 27, 52, or 115 mg/kg/d for males and 0, 32, 65, or 138 mg/kg/d for females. A no-observed adverse effect level could not be determined. The lowest observed adverse effect level was 27 mg/kg/d for males and 32 mg/kg/d for female rats based upon decreased body weight gain. The decreased body weight gain in male rats was the most sensitive adverse event observed in this study and was used to derive a benchmark dose (BMD). A BMD of 23.1 mg/kg/d and BMD with 10% effect level of 15.5 mg/kg/d were calculated for male rats, which were used to derive an oral reference dose (RfD). The human RfD of 1.26 μg/kg/d was derived using current United States Environmental Protection Agency guidelines.