# Preliminary Safety Assessment for Mandarin Orange Peel Administration to Dogs Based on Physical Conditions and Blood Examination Parameters

## TL;DR

Mandarin orange peel is safe for dogs at high doses, with no major health issues observed in blood tests or physical conditions.

## Contribution

This study provides the first comprehensive safety assessment of mandarin orange peel in dogs, confirming its suitability for canine cognitive support.

## Key findings

- Mandarin orange peel was well tolerated in dogs at doses up to 10 g/head/day.
- No significant dose-dependent abnormalities were observed in clinical signs, hematology, or biochemistry.
- MOP composition and residue levels met Japanese pet food safety standards.

## Abstract

What are the main findings?
Mandarin orange peel (MOP) administration at 2–10 g/head/day was well tolerated in healthy Beagle dogs.No significant dose-dependent abnormalities were observed in clinical signs, hematology, or biochemistry.

Mandarin orange peel (MOP) administration at 2–10 g/head/day was well tolerated in healthy Beagle dogs.

No significant dose-dependent abnormalities were observed in clinical signs, hematology, or biochemistry.

What are the implications of the main findings?
MOP is a safe dietary intervention for older dogs, even at doses exceeding anticipated clinical levels.Comprehensive residue and composition screening confirms its suitability for use in canine cognitive support.

MOP is a safe dietary intervention for older dogs, even at doses exceeding anticipated clinical levels.

Comprehensive residue and composition screening confirms its suitability for use in canine cognitive support.

Background/Objectives: Mandarin orange peel (MOP) is rich in bioactive polymethoxyflavones, including hesperidin and nobiletin, which have shown neuroprotective effects in rodent models. However, comprehensive safety data in dogs are required to support its development as a therapeutic intervention for canine cognitive dysfunction syndrome. In this study, the safety profile of a standardized MOP formulation was evaluated in four healthy Beagle dogs. Methods: Initially, compositional analysis was performed, and 202 pesticide residues and psoralens were screened to ensure compliance with Japanese pet food safety standards. Subsequently, a dose-escalation study was conducted in which dogs received oral MOP at 2, 6, and 10 g/head/day for 3–4 weeks at each dose level. Clinical signs, hematology, and serum biochemistry were monitored throughout the study period. Results: The MOP powder composition and residue levels remained within regulatory safety limits. In the dose-escalation study, no significant dose-dependent abnormalities were observed in physical or clinicopathological parameters. One dog exhibited transient loose stools at higher doses and a temporary elevation in alkaline phosphatase levels at 2 g/head/day; however, these symptoms resolved spontaneously despite continued administration. Conclusions: MOP was safe and well tolerated in dogs even at 10 g/head/day (787–952 mg/kg/day), which is approximately five times the anticipated clinical dose. The observed fluctuations in active ingredient concentrations remained within the acceptable range for natural products and did not affect overall safety. Combined with comprehensive screening for residues, these results indicate that MOP is a high-quality and safe dietary intervention for older dogs.