0.05).CONCLUSION:The mutagenesis of Leflunomide 3-methyl-isomer was not observed in these tests.

Objective To establish and evaluate the animal model induced by inhalation injury of airborne fine particulate matter (PM2?5). Methods We manufactured equipment for rats aerosol inhalation with PM2?5. The effects of several facters such as concentrations(100 ± 10 μg/m3、150 ± 10 μg/m3、200 ± 10 μg/m3 )、time(1w、2w、4w、8w、12w)、method (non?exposed intratracheal instillation method and aerosol inhalation) and animals (Wistar rats, BN rats and guinea pigs) were investigated to establish the model. The respiratory rate, forced vital capacity ratio of forced expiratory volume ( FEV1/FVC) and arterial partial pressure of oxygen ( PO2 ) were measured, the pathological changes of bronchial and lung tissues under light microscope were observed. The success animal model was builded as the pneumonia was observed from the pathological changes of lung tissue. Results The Wistar rats exposed to PM2?5 aerosol inhalation for 8 weeks, we can see that the weight growth rate of rat decreased, WBC count and mononuclear cells count increased, the macrophages ratio decreased in BALF, the respiratory rate of lung increased while arterial PO2 and FEV1/FVC decreased, inflammation and pulmonary fibrosis changes were observed by bronch and pulmonary pathology, inflammatory changes with a dose?response relationship were observed. Exposed to PM2?5 aerosol inhalation for different time(1 w、2 w、4 w、8 w、12 w)with same dose, the score issue lesions of lung and bronchus in Wistar rats increased and the 8w group is obvious. The Wistar rats exposed to PM2?5 with different method ( aerosol inhalation and non?exposed intratracheal instillation method) for 8w, the aerosol inhalation worked as effectively as perfusion while mortality rate of aerosol inhalation is lower. Different animals ( Wistar rats, BN rats and guinea pigs) exposed to PM2?5 aerosol inhalation for 8w, the same results were observed with three method respectively while mortality rate of Wistar rats lower. Conclusions The optional conditions that the Wistar rats were continuously inhaled for 8w PM2?5 with a dose of 150 ± 10 μg/m3 were established. The animal model could be used on a national scale, especially in Fujian province. The results would be useful for the development of the research of the prevention and countermeasures of PM2?5 pollution.