Acute toxicity of muroctasin in mice, rats and dogs

Acute toxicity of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin), a synthetic muramyl dipeptide derivative, was studied in Std-ddy mice, Std-Wistar rats and beagle dogs by subcutaneous and intravenous administration. Subcutaneous LD50 values were 436 mg/kg for male, 625 mg/kg for female in mice, 761 mg/kg for male, 801 mg/kg for female in rats and more than 200 mg/kg for dogs. Toxic signs included screaming, decrease of locomotor activity, weakness, emaciation and loss of hair, crust formation, necrosis and ulceration around the injection site in all species. Death occurred within 7 days after treatment. Pathological examination revealed inflammation around the injection site. In dogs a subcutaneous cavity with puruloid fluid and enlargement of the axillary lymphnodes were seen in addition. No marked toxic signs and pathological findings were observed in mice and rats after intravenous administration of 90 mg/kg, a critical dose of treatment.