A sub-chronic (13 weeks) oral toxicity study in rats and an in vitro genotoxicity study with Korean pine nut oil (PinnoThin TG™)

Abstract

In this paper a sub-chronic (13 weeks) toxicity study in rats and an in vitro genotoxicity study with Korean pine ( Pinus koraiensis Siebold & Zucc.) nut oil, KPNO (PinnoThin™) are described. Both studies were performed in compliance with GLP, and in line with OECD guidelines applicable. In the sub-chronic toxicity study, no clinical signs, abnormalities in functional observation tests or ophthalmologic examinations or changes in body weight or food intake were noted at any of the doses of KPNO tested. Various changes in clinical biochemistry parameters were noted. Whilst these changes were not consistent in both sexes, and neither associated with any histopathological changes, nor dose-related, these were not considered to be toxicologically relevant. No toxicologically significant changes were noted in haematological parameters. There were a few histopathological observations such as a periportal vacuolation of the liver in all dose groups including the control, and renal tubular mineralisation in most females of the high dose group but also in all control female rats. These findings can be considered to be due to the high fat content of the diets, and are not related to the treatment with KPNO. Based on these findings a No Observable Adverse Effect Level (NOAEL) of 15% has been established for KPNO. This NOAEL corresponded to a mean of 8866 and 10,242 mg KPNO/kg bw/day for males and females, respectively. This dose level was the highest achievable oral dose for KPNO in rats. The in vitro reverse mutation test (Ames test), showed no significant dose-related increase in the number of revertants in two independently repeated mutation assays. The negative and strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly. Based on these results it has been concluded that KPNO is not mutagenic in the Escherichia coli and Salmonella typhimurium reverse mutation assays. In conclusion, KPNO can be considered to be non-genotoxic in the AMES test. A NOAEL of 8866 and 10,242 mg KPNO/kg bw/day has been established for male and female rats, respectively. For both sexes, the NOAEL was achieved at the highest dose tested.