Disposition of [¹⁴C]N,N-Dimethyl-p-Toluidine in F344 Rats and B6C3F1 Mice

Abstract

N,N-Dimethyl-p-toluidine (DMPT) is used as a polymerization accelerator, in industrial glues, and as an intermediate in dye and pesticide synthesis. There is potential for human exposure to DMPT. The disposition of oral and intravenous (iv) doses of [¹⁴C]DMPT in F344 rats and B6C3F1 mice was investigated. A single iv (2.5 mg/kg) or oral (2.5, 25, or 250 mg/kg) dose of [¹⁴C]DMPT (1–25 μCi) was administered in an aqueous vehicle to male rats and mice. The 25-mg/kg oral dose was administered to females to investigate possible gender differences in disposition. However, no striking gender differences were observed. Since toxicity studies conducted elsewhere used a corn oil vehicle, the 250-mg/kg oral dose also was administered in corn oil to male rats; disposition was not dependent on vehicle. Excreta (through 24 h) and tissues collected at sacrifice were analyzed for total radioactivity. Dose-dependent differences in toxicity and disposition were observed. Toxicity at the 250-mg/kg oral dose to male mice was consistent with acute renal failure. At the same dose, male rats exhibited clinical signs of toxicity through 12 h but were clinically normal by 24 h. At lower oral doses, [¹⁴C]DMPT-derived radioactivity was well absorbed and rapidly excreted, primarily in urine.

This project was funded with federal funds from the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Department of Health and Human Services, under contract N01-ES-25483. The authors thank Krystal Pacheco, Mark Gurule, Rena Marr, Denise Marks, and Zhengyu Gao for technical assistance and Vicki Fisher for manuscript preparation. We also thank Dr. L. T. Burka of NIEHS and Drs. J. D. McDonald and W. M. Weber of LRRI for critical review of the manuscript.