Abstract
Background
Low-concentration atropine sulfate eye drops (LAED) are widely used in children to control myopia progression; however, their long-term safety and effects on children's development remain unclear.
Objective
To assess the safety and growth development effects of LAED in juvenile cynomolgus monkeys over one year.
Methods
Eighty-eight juvenile cynomolgus monkeys were randomly assigned to a negative control group or one of three treatment groups receiving daily LAED: 0.01 mg (0.01%), 0.02 mg (0.01%), or 0.08 mg (0.04%) per day, with 22 animals (11 males and 11 females) per group. The treatment period lasted 12 months, followed by a 2-month recovery observation. Toxicological, growth, and ophthalmological parameters were evaluated.
Results
No test substance-related changes were observed in food intake, body weight, body temperature, hematology, biochemical parameters, immunoglobulins, ECGs, blood pressure, urinalysis, bone marrow, or histopathology across all groups. Growth parameters exhibited age-consistent upward trends. The 0.04% LAED dose caused transient pupil dilation throughout the treatment period, which resolved upon withdrawal, attributed to the pharmacological effects of atropine sulfate. Toxicokinetic analysis revealed minimal systemic exposure, with no evidence of drug accumulation after prolonged use.
Conclusion
The no-observed-adverse-effect level (NOAEL) for 0.04% LAED (0.8 mg/monkey/day) in juvenile cynomolgus monkeys was established over a one-year period. No developmental or ocular toxicity was observed, providing a foundation for the clinical evaluation of LAED in delaying myopia progression in children.
Keywords
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