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Preliminary toxicity studies on bis-[beta-(N,N-dimorpholino) ethyl] selenide (MOSE). A new radioimaging agent
Abstract:
The present study describes the acute toxicity of MOSE, a proposed radioimaging agent for brain scintigraphy . Acute intraperitoneal administration of MOSE in mice revealed an LD50 between 1.35 and 6.25 g/kg, with convulsions preceding death. Intravenous administration of MOSE in rats resulted in an LD50 between 400 and 800 mg/kg, with death also preceded by convulsions. The rabbit was more sensitive to the acute effects of MOSE than the rat. The LD50 for MOSE given i.v. in the rabbit was 80 mg/kg. The predominant toxic sign was convulsions, which immediately preceded death at high doses. At intermediate doses convulsions were elicited, followed by a period of lethargy which gave way to hyperactivity on the following day. Normal appearances were restored within a week. Hematology and blood chemistries were similar to controls, except for increased serum LDH in animals receiving MOSE when sampled two weeks after dosing. Repeated administration of MOSE by the intravenous route in rabbits at a dose rate of 1 mg/kg/da, five days per week for two weeks, resulted in no signs of toxicity. Hematology, clinical chemistry, and histology revealed no changes in animals receiving MOSE when compared to control. It was concluded that barring any unusual susceptibility in man, the proposed diagnostic dose to man is unlikely to precipitate any acute toxic effects.
Insights
MOSE, a radioimaging agent for brain scintigraphy, showed acute toxicity in animal models, with convulsions preceding death. However, the proposed diagnostic dose in humans is unlikely to cause acute toxic effects.
Area of Science:
- Pharmacology
- Toxicology
- Radiopharmaceutical Science
Background:
- MOSE is a potential radioimaging agent for brain scintigraphy.
- Understanding its acute toxicity is crucial for safe clinical application.
Purpose of the Study:
- To evaluate the acute toxicity of MOSE in preclinical animal models.
- To determine the safety profile of MOSE for human diagnostic use.
Main Methods:
- Acute intraperitoneal and intravenous administration of MOSE in mice, rats, and rabbits.
- LD50 determination and observation of toxic signs.
- Repeated dose toxicity study in rabbits.
- Hematology, clinical chemistry, and histology analyses.
Main Results:
- Acute LD50 values varied by species and administration route, with convulsions as the primary toxic sign.
- Rabbits were more sensitive than rats.
- Repeated low-dose administration in rabbits showed no toxicity.
- Hematological and biochemical parameters remained largely unchanged, except for transient LDH increase.
Conclusions:
- MOSE exhibits dose-dependent acute toxicity in animals, primarily characterized by convulsions.
- The proposed diagnostic dose for human brain scintigraphy is considered safe based on preclinical data.
- Further investigation into specific toxicological endpoints may be warranted.