Characterization of methemoglobinemia induced by 3,5-xylidine in rats

The objective of this study was to characterize the dose effect and kinetics of methemoglobinemia in rats following oral or intravenous administration of 3,5-xylidine (XYL). The first set of experiments involved the intravenous administration of 0.06, 0.12, 0.24, 0.48, or 0.60 mmol XYL/kg to groups of 3 rats each and the serial sampling of blood from the tail vein of individual animals for the determination of methemoglobin levels. An additional series of experiments involved the oral administration of 0.24, 0.48, 0.72, 0.96, 1.2, 1.8, 2.4, or 4.8 mmol XYL/kg and the serial sampling of blood for the determination of methemoglobin levels. The results showed a dose-dependent induction of methemoglobinemia by XYL in the rat, for both routes of administration. The maximal percent methemoglobin observed in the treated animals was 28.90 +/- 0.34% and 32.67 +/- 2.14% for the intravenous (0.6 mmol/kg) and oral (4.8 mmol/kg) routes, respectively. The dose levels of 0.06 mmol/kg (iv) and 0.96 mmol/kg (po) were the no-observable-adverse-effect levels with respect to XYL-induced methemoglobinemia in the rat. The dose-effect information on XYL-induced methemoglobinemia obtained in this study may be useful for the characterization of noncarcinogenic risks of acute human exposure to this chemical.