Toxicological properties of closantel

Area of Science:

• Veterinary Pharmacology and Toxicology
• Animal Health and Safety

Background:

• Closantel is an anthelmintic drug used in veterinary medicine.
• Understanding its safety profile is crucial for responsible animal treatment.

Purpose of the Study:

• To evaluate the acute, subacute, and chronic toxicity of closantel in laboratory animals.
• To assess the safety margin and potential adverse effects of closantel in target animal species (sheep, cattle, bulls, rams, ewes).
• To investigate the reproductive, developmental, mutagenic, and carcinogenic potential of closantel.

Main Methods:

• Acute, subacute, and chronic toxicity studies were conducted in rats and dogs.
• Repeated dose toxicity studies (40 weeks) were performed in sheep via oral and intramuscular routes.
• Reproduction studies (including a three-generation study in rats), embryotoxicity/teratogenicity tests in rats and rabbits, peri/postnatal studies in rats, and reproductive studies in target animals (bulls, rams, ewes) were conducted.
• Mutagenicity was assessed using Salmonella Ames test, Drosophila melanogaster sex-linked recessive lethal test, and mouse dominant lethal test.
• Carcinogenicity was evaluated in mice and rats.

Main Results:

• Closantel demonstrated good tolerability in acute, subacute, and chronic toxicity studies.
• No adverse effects were observed in rats and dogs at oral doses up to 40 mg/kg, except for focal swelling of the epididymis in male rats at 40 mg/kg.
• Sheep exhibited an acceptable safety margin with repeated oral and intramuscular dosing.
• Fertility was not affected, with only slight effects in male rats at 40 mg/kg. No embryotoxic or teratogenic potential was found.
• Peri- and postnatal parameters, as well as reproduction parameters in target animals, were unaffected.
• Closantel showed no mutagenic potential in various assays and was not carcinogenic in mice and rats.
• Clinical doses were well tolerated in sheep and cattle with no serious side effects.

Conclusions:

• Closantel possesses a favorable safety profile in laboratory animals and target veterinary species.
• The drug is well-tolerated at clinical doses, with a wide safety margin.
• Closantel does not present risks for reproduction, development, mutagenicity, or carcinogenicity.