Assessment of Xiao'er Xiexieting Keli-induced toxicity in juvenile rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Sufficient safety data on juvenile development is not available for Xiao'er Xiexieting Keli (XXTK), a Chinese herbal formula for pediatric diarrhea.

AIM OF THE STUDY: Considering the challenges associated with clinical trials of XXTK, this study was aimed at evaluating its toxicity in juvenile rats to obtain a basis for assessing its safety and dosage in children.

MATERIALS AND

METHODS

In acute toxicity study (Study 1), postnatal day (PND) 24 rats were orally administered 253.13 g/kg XXTK and observed over 14 days. In subacute toxicity study (Study 2), PND21 rats were administered 1.74, 8.71, or 32.66 g/kg XXTK daily for six consecutive weeks and allowed to recover for 4 weeks. Clinical signs, body weight, food intake, and timing of vaginal opening and preputial separation were recorded during the dosing period. Hematological, serum biochemical, and histopathological examinations, Irwin's test, and assessment of growth hormone levels, skeletal development, and immune-related indicators were performed mid-administration, and at culmination of dosing and recovery. Urinalysis, ophthalmological assessment, and Morris water maze test were conducted at the end of dosing and recovery periods.

RESULTS

No deaths or significant findings occurred in Study 1; maximum tolerated dose was 253.13 g/kg. In Study 2, all changes were reversible, mild, and without toxicological significance. The no-observed-adverse-effect level was 32.66 g/kg/day.

CONCLUSION

XXTK demonstrated a favorable toxicological safety profile in juvenile rats, supporting its potential for extended clinical use in children. Further evaluation of child development-related indicators and validation in pediatric clinical cohorts are recommended.