The chronic toxicity of atropine administered intramuscularly to rabbits

Abstract

A dose of atropine sulfate estimated at 5 ± 3% of the LD 50 produced signs of toxicity in a minimal number of young male rabbits after 100 days of daily intramuscular injection, 10 ± 2% in half the animals and 15 ± 3% in all the animals. The clinical signs of toxicity included mydriasis, anorexia, impaired growth, oligodipsia, oliguria, fever, anemia, leucocytosis, hypocholesterolemia, and alkaluria. The volume and chloride content of respiratory tract fluid were unaffected. The pathologic signs of toxicity included loss of weight and edema of most organs, hepatitis, pulmonary thrombosis, inhibition of spermatogenesis, thymic atrophy, and toxic changes in the gall bladder, spleen, and pancreas. Areas of inflammation, fibrosis, and endarterities obliterans were present in the tissues of the injected limb and produced impaired movements after 2–3 months of drug administration. Death was most commonly due to convulsions and respiratory failure. Ability to survive was related to ability to maintain food intake.