Toxicity of a 90-day repeated oral dose of a collagen peptide derived from skate (Raja kenojei) skin: a rat model study

Collagen peptides are widely employed as therapeutic materials due to their numerous beneficial properties, including for the following uses: antiaging, antioxidant applications, antibacterial applications, wound healing, tissue engineering, medication delivery, and cosmetics. Although collagen peptides are useful in these applications, to our knowledge, few published studies have been undertaken on their repeated-dose toxicity. We evaluated the possible subchronic toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in Sprague-Dawley rats by administering repeated oral doses over 90 days. Rats of both sexes were assigned randomly to one of four experimental groups, respectively receiving 0, 500, 1000, or 2000 mg/kg/day of CPSS. At all doses tested, repeated oral CPSS administration had no treatment-related adverse effects in terms of clinical signs, body weight, food consumption, detailed clinical observation, sensory reactivity, functional assessment, urinalysis, ophthalmic examination, gross pathology, hematology, serum biochemistry, hormone analysis, organ weight, and histopathology. Even though there were some alterations in hematologic parameters, serum biochemistry parameters, organ weight, and histopathological findings, these did not follow a dose-response pattern and were within historical limits for control rats. The oral no-observed-adverse-effect level (NOAEL) of the CPSS was 2000 mg/kg/day for both male and female rats in the applied experimental circumstances, and no target organs were identified.