A study of the chronic toxicity of inhaled disodium cromoglycate in the squirrel monkey

Abstract

A chronic inhalation toxicological study of disodium cromoglycate (cromolyn sodium, intal) was performed in the squirrel monkey, Saimiri sciureus. Each of five experimental groups consisted of three male and three female monkeys. Groups I and II were exposed 6 hr/day, 7 days/week, for 1 year to aerosols containing a disodium cromoglycate blend in approximate concentrations of 0.5 and 0.05 mg/liter of air, respectively. Group III was similarly exposed to an aerosol containing 0.01 mg of lactose/liter of air. Group IV animals served as chamber controls, and the room controls (Group V) were maintained in the animal holding room throughout the study. A comprehensive toxicological evaluation of the monkeys was carried out prior to and throughout the study. At appropriate intervals observations were made of physical appearance, behavior, weight gain, and ophthalmoscopic appearance; electrocardiograms, systolic blood pressure measurements, hemograms, blood biochemical profiles, and urinalyses were also obtained. At termination, necropsies were conducted, and organ weights were determined. A variety of staining techniques was employed in the histopathological examination of tissues. Special attention was given to heart, kidney, and lung structures and to vascular and nerve tissues. Bone marrow smears and the distribution and morphology of mast cells in the lung were studied. Ultrastructural studies, using the electron microscope, were made of the lungs. No changes that could be attributed to the action of disodium cromoglycate were seen in any parameter. A special absorption study in five monkeys showed that the Group I animals absorbed about 60 times the recommended human dose.