Objective:To observe the toxic reactions of beagle dogs caused by continuous po administration of the
co_naphthoquine,
including the toxic dose, the target organs, the safety range and the recovery after drug withdrawal.Methods:The dogs were randomly divided into three dose groups <17.5,87.5,140?mg/(kg·d)> and a blank control group. Each group consisted of 3 males and 3 females. The drug was given once a day for 14 successive days. Manifestations and behaviors of the dogs, hematology, blood chemistry, urinalysis, electrocardiogram, eyeground, necropsy, bone marrow and histopathology were examined. Twenty_four hours after the last dose, 4 dogs of each group were sacrificed and the remaining 2 dogs in each group were further observed for four weeks.Results:The results revealed that 140?mg/(kg·d) had serious toxicity. The main toxic manifestations of the dog were nausea and vomiting. Some animals demonstrated paroxysmal twitch, which stopped spontaneously without any treatment. After administration, extended Q_T interval , increase in GOT and GPT, erythropoietic suppression of the bone marrow, degenerative changes in the parenchymal cells of liver were observed. All of these changes were less serious in 87.5?mg/(kg·d)group than those in 140?mg/(kg·d)group. Conclusions:The dose of 140?mg/(kg·d) was toxic, 87.5?mg/(kg·d) had mild toxicity and 17.5?mg/(kg·d) was safe. The liver and bone marrow could be assumed as the most sensitive target organs. All of the changes were reversible after stopping treatment.