Preclinical safety evaluation of Lipase OF from Candida cylindracea

• Published in: Journal of applied toxicology 2023-04, Vol.43 (4), p.517-533
• Main Authors: Matten, Kevin J., Hashikawa, Shinnosuke, Harada, Kazunori
• Format: Article
• Language: English
• Subjects: Aberration; Animals; Beverages; Body Weight; Candida; Candida cylindracea; Chromosome Aberrations; Chromosomes; enzyme; Female; Food; Food processing; Food production; Humans; In vitro methods and tests; Lipase; Lipase OF; Male; Metabolic activation; Metabolic rate; Mutation; No-Observed-Adverse-Effect Level; NOAEL; processing aid; Prothrombin; Rats; safety; Toxicity; Trace levels; Triglycerides
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.4403

Triacylglycerol lipases are enzymes commonly used to process foods and beverages such as oils, wines, and cheeses through catalyzation of long‐chain triglyceride hydrolysis. Lipase OF derived from Candida cylindracea (strain MS‐5‐OF) is only intended for use as a processing aid in food production applications; however, it may be present at trace levels in some products. As such, the safety of Lipase OF was evaluated in this study that included a bacterial reverse mutation assay, an in vitro chromosome aberration test, and a 90‐day subchronic toxicity study in rats. In the in vitro bacterial reverse mutation and chromosome aberration assays, Lipase OF was not observed to be mutagenic at concentrations up to 5000 μg/plate and 50 μg/ml, respectively, in the presence or absence of metabolic activation. Results from the 90‐day subchronic toxicity study indicated only minimal adverse effects (i.e., increased platelet count and prothrombin time) in male rats from the high‐dose group following administration of Lipase OF via the diet at levels of 0, 1.0, 2.5, and 5.0 w/w%. The no‐observed‐adverse‐effect level (NOAEL) for Lipase OF was therefore considered 2.5 w/w% (1597.6 mg/kg body weight/day [1027.3 mg TOS/kg body weight/day]) in males and 5.0 w/w% (3700.4 mg/kg body weight/day [2379.4 mg TOS/kg body weight/day]) in females under the test conditions. Thus, the evidence presented within this study supports the safe use of Lipase OF as a processing aid in various food production applications for human consumption. Lipases derived from microorganisms can provide functional value during the manufacture of foods. The safety of Lipase OF derived from Candida cylindracea (strain MS‐5‐OF) for use as a processing aid was evaluated via two in vitro genotoxicity studies and a 90‐day subchronic toxicity study in rats. No evidence of genotoxicity was observed and a no‐observed‐adverse‐effect level of 1597.6 mg/kg body weight/day in males was identified, which supports the safe use of Lipase OF as a processing aid in foods.