| Combined pesticides are known to have increased insecticidal effect and decreased resistance, especially in combination of organophosphorus with pyrethroid insecticides. Subsequently, cases of poisoning were also increased gradually. The toxicities of phoxim and fenvalerate were determined individually and in mixture against mice. The LD50 of phoxim, fenvalerate and the mixture was 1470mg/kg, 21 5mg/kg and 464mg/kg respectively. The predictive LD50 of the mixture was 840.8mg/kg according to the joint action coefficient. The interaction between phoxim and fenvalerate was found synergistic. The symptoms of poisoning with the mixture in mice were hyperexcitability and tremors , but more severe and with a higher mortality than fenvalerate poisoning. Using ?C-Fenvalerate as tracing agent, a single dose of fenvalerate and mixture of fenvalerate and phoxim was given intravenously to mice. From 0.5 to 120 mm after the administration, nine blood samples were taken for measurements. Eight samples from brain, heart, liver and lung were also taken respectively from 8 to 960 mm. The samples were measured by 3-scintillation counter. The data of blood samples were analyzed by residual method for the estimation of toxicokinetic parameters. The toxicokinetics of fenvalerate was fitted to the two-compartment model with distribution phase Tta of 2.12 mm, elimination phase T1 of 77.9 mm and area under the blood dpm-time curve of 36271 dpm-in-V The toxicokinetics of fenvalerate in mixture was fitted to the two-compartment model with distribution phase T112,, of 3.22 mm, elimination phase T1 of 124 mm and area under the blood dpm-time curve of 59207 dpm-min-m1-1 Toxicokinetic parameters of fenvalerate were significantly different from those of the mixture. The result indicated that the metabolism of fenvalerate was postponed by phoxim. The lung has the highest concentration of ?C-fenvalerate residues and was close to liver 16 hours after intravenous administration. After intraperitoneal administration, however the highest concentration of ?C-fenvalerate residues was found in the liver, followed by the spleen and lung. The results suggested that the first-pass effect in liver altered the distribution of fenvalerate. Since pesticide workers are repeatedly exposed to low-concentration fenvalerate by respiration, pulmonal toxicity induced by the insecticide should be stressed. Although both phoxim and fenvalerate vere neurotoxic, little was knovn about the brain responses to them in molecular level, especially when combined. In this study, expression of c-fos and c-jun immediate- early genes was studied in mice after intraperitoneal administration of the insecticides. The levels of c-fos and c-jun rnRNA were determined by RT-PCR. A time-course study indicated that the induction of c-fos and c-jun mRNA was shown as early as 5 minutes, reached a peak at 15 minutes, and returned to the basal level at 24hour after exposure to fenvalerate. After exposure to combined insecticides, the levels of c-fos and c-jun mRNA did not change significantly, but the time course of c- fos mRNA was prolonged compared to that of fenvalerate exposure alone. The effects of insecticides on the activities of AchE, SOD, MAO, NO and MDA in brain of mice were also studied. The activities of SOD and MAO significantly decreased in all the phoxim group, fenvalerate group and mixture group, compared with the control gr... |
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