Oral and intraperitoneal LD[50] of thymoquinone, an active principle of Nigella sativa, in mice and rats

Thymoquinone is the major active principle of Nigella saliva [N. sativa] and constitutes about 30% of its volatile oil or ether extract. N. sativa oil and seed are commonly used as a natural remedy for many ailments. Using modern scientific techniques, a number of pharmacological actions of N. sativa have been investigated including immunostimulant, anti-inflammatory, anticancer, antioxidant, antihistaminic, antiasthmatic, hypoglycemic, antimicrobial and antiparasitic. There are only few reports regarding the toxicity of thymoquinone. The present study was carried out to determine LD[50] of thymoquinone both in mice and rats, orally as well as intraperitoneal, by the method of Miller and Tainter. Autopsy and histopathology of liver, kidney, heart and lungs were also determined. The LD[50] in mice after intraperitoneal injection was determined to be 104.7 mg/kg [89.7-119.7, 95% confidence interval] and after oral ingestion was 870.9 mg/kg [647.1-1094.8, 95% confidence interval]. Whereas, LD[50] in rats after intraperitoneal injection was determined to be 57.5 mg/kg [45.6-69.4, 95% confidence intervals] and after oral ingestion was 794.3 mg/kg [469.8-1118.8, 95% confidence intervals]. The LD[50] values presented here after intraperitoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects. Thymoquinone is a relatively safe compound, particularly when given orally to experimental animals