Toxicity of Danshen Injection in Beagle's Dogs by Repeated iv Injection

ObjectiveTo re-evaluate the potential toxicity of Danshen Injection (DI) in Beagle's dogs by repeated iv injection.MethodsDI was iv given to the dogs at the doses of 0, 1.6, 5.4, and 16.0 g/(kg·d) (4 per sex per group) for 13 weeks. During the test period, the clinical signs, mortality, body weights, food consumption, rectal temperature, ophthalmoscopy, electrocardiography, urinalysis, hematology, serum biochemistry, organ weights, gross findings, and histopathology were examined.ResultsDogs iv given with DI at the doses of 0, 1.6, 5.4, and 16.0 g/(kg·d) for 13 weeks had no drug-related changes in mortality, body weight, food consumption, temperature, electrocardiography, ophthalmoscopy, urinalysis parameters, and organ weights. The hematological parameter data showed a significant decrease in red blood cells and hemoglobin concentration in the high-dose group and a significant increase in activated partial thromboplastin time suggesting an effect on haemopoiesis. For biochemical parameters, a significant decrease in glucose and a significant increase in total bilirubin were observed in the high-dose group, and the latter was considered to be toxicologically insignificant as lack of histopathological correlate. However, the histopathological examinations of the injection site showed that DI could cause dose-dependent focal inflammation.ConclusionThat the iv injection with DI into dogs at 16 g/(kg·d) for 13 weeks could cause the decreases in red blood cell parameters and glucose, as well as the lesions of the injection site. The no observed adverse effect level is 5.4 g/(kg·d), which suggests that safe clinical dosing be possible.