Paper Details
- Koji Morishita (External Relations Department, KYOWA HAKKO BIO CO., LTD. / koji.morishita@kyowa-kirin.co.jp)
1) Research & Innovation Center, KYOWA HAKKO BIO CO., LTD. , 2) External Relations Department, KYOWA HAKKO BIO CO., LTD.
Repeated-dose oral toxicity of L-hydroxyproline (Hyp) was assessed in male and female SD rats by gavage for 28 days at dose level of 40, 200, 1,000 or 4,000 mg/kg/day. The reversibility of treatment-related changes was also examined by providing 14-day recovery period in the control group and 4,000 mg/kg group. In the results, reduced body weight gain with decreased food consumption was noted in males at 4,000 mg/kg/day. The histopathological evaluation revealed increased incidences of focal dilatation of the renal tubules with narrowing of the tubular cell liner and focal interstitial fibroplasia in the kidney of males at 1,000 and 4,000 mg/kg and females at 4,000 mg/kg. The lack of kidney specific serum chemical or urinalysis findings supported that the renal changes were very mild. Based on the above results, it was concluded that the no observed adverse effect level (NOAEL) of Hyp was 200 mg/kg/day.