Evaluation of substance-P toxicity with single dose and repeated dose in rats

Toxicity study evaluating the effects of intravenous injection of SP with single- and repeated-dose in rats was performed. Single 100, 50, and 10 mg/kg doses of SP were administered and animals were monitored for 14 days. Although 10 mg/kg dose did not affect behavior and survival, 100 and 50 mg/kg doses elicited mortality, suggesting the minimum lethal dose (MLD) of SP to be between 10 and 50 mg/kg. To evaluate the toxicity of repeated dosing, rats were injected twice first two days per week with 30, 10, and 3 mg/kg of SP over 2 weeks and evaluated for survival, behavior, hematological factors, and organ weight. All rats administered with 10 and 3 mg/kg SP survived with minor changes in behavior and hematological indices. Thus, certain poison dose was estimated to be approximately 3 mg/kg, indicating that application of SP below 3 mg/kg may not be associated with toxicity.