Kinetics of carbaryl and malathion in combination in the rat

The disposition and metabolism of pesticides used in combination, especially carbaryl and malathion, is of considerable toxicological importance. Radioactivity was rapidly absorbed from the rat gastrointestinal tract (GIT) following the administration of 0.25 ml of 10 mg/kg [¹⁴C]carbaryl (0.80 μCi), 10/10 mg/kg [¹⁴C]carbaryl/malathion (0.80 μCi), 10 mg/kg [¹⁴C]malathion (1.03 μCi), or 10/10 mg/kg [¹⁴C]malathion/carbaryl (0.86 μCi). The administration of carbaryl or malathion, individually and in combination, followed a two-phase elimination model. The presence of malathion decreased the rate constants of absorption and β-phase elimination of [¹⁴C]carbaryl. In the mean time, the length of the distribution phase and the area under the curve of [¹⁴C]carbaryl were decreased by malathion administration. Although [¹⁴C]malathion’s absorption half-life was unchanged in the presence of carbaryl, increases were noted in the length of the distribution phase, β-phase elimination half-life, and area under the curve for malathion when administered simultaneously with carbaryl. Both combinations caused an increase in¹⁴C activity to be deposited in the fat as compared to the respectively labeled pesticide. However, only malathion increased the concentration of [¹⁴C]carbaryl remaining in the GIT tissues after the administration of the combined pesticides. The subcellular distribution of the liver indicated that the highest activity was present in the cytosol. These pesticides and their combinations were excreted primarily by the kidney, followed by the lung and the intestinal route. Although there was no alteration in the metabolic pathways due to the combinations, an increase in malaoxon and malathion diacid concentration in urine was observed after the administration of [¹⁴C]malathion/carbaryl as compared to [¹⁴C]malathion. The results from this study revealed that the combination of these pesticides altered fundamental pharmacokinetic parameters, which may explain some of the toxicities associated with exposure to these chemicals in combination.