A subchronic toxicity study of two inhaled aerosolized atropine sulfate formulations in rats and dogs.
The potential subchronic (21 days) toxicity of inhaled metered aerosol formulations (solution and suspension) of atropine sulfate was investigated in rats and dogs. The doses administered to rats were 0.78 and 2.5 mg/kg/day (solution) or 1.4 and 3.2 mg/kg/day (suspension). In the dog, the daily doses achieved were 0.5 and 1.3 mg/kg/day, regardless of formulation. In both species, sham control animals inhaled air only and vehicle control animals inhaled either placebo solution or placebo suspension. There was no mortality or other evidence of a toxic effect of atropine sulfate. The expected mydriatic effect of atropine sulfate was seen in both species and, similarly, the pupillary light reflex was impaired in rats and dogs receiving either formulation of atropine sulfate at both dose levels. Reduced salivation was also noted and ophthalmologic examinations in both species were unremarkable. In dogs, atropine sulfate (high-dose) caused tachycardia but there was no evidence of an adverse effect on the electrocardiogram or on systolic blood pressure. In both species, atropine sulfate did not alter body weight, food consumption or clinical pathology parameters. Necropsy observations and histopathological findings revealed no effect of atropine sulfate in either species although, in the rat, adrenal gland hypertrophy in both sexes followed inhalation of the suspension at both dose levels. With this possible exception, nothing but the expected pharmacological effects of atropine sulfate were seen in either rats or dogs.
Lulham
G
G
Bio-Research Laboratories Ltd., Montreal, Quebec, Canada.
Procter
B
B
Losos
G
G
Osborne
B
B
Clawson
R
R
Chesney
C
C
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001285:Atropine / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004435:Eating / Q000187:drug effects; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011680:Pupil / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012025:Reflex, Pupillary / Q000187:drug effects; D012472:Salivation / Q000187:drug effects; D013045:Species Specificity
D000336:Aerosols; D001285:Atropine