In vitro and in vivo safety evaluation of Nephure™.
Nephure™ is a proprietary oxalate decarboxylase (OxDC) enzyme being developed as a food ingredient. In this study, the safety of Nephure™ was evaluated in a bacterial mutagenicity assay and in a sub-chronic (13-week) oral toxicity study in rats. Nephure™ did not show any mutagenic properties in the mutagenicity assay. In the 13-week sub-chronic oral toxicity study in which 10 Sprague Dawley rats per sex were administered 0, 118, 235 and 475 mg/kg bw/day (8260, 16450 and 33,250 Units/kg bw/day, respectively) of Nephure™ by gavage, male and female rats did not show any test article-related clinical observations or effects on body weight, body weight gain, food consumption, food efficiency, ophthalmology, functional observational battery parameters or motor activity. Furthermore, there were no changes in coagulation, clinical chemistry, urinalysis or hematology parameters, macroscopic/microscopic findings or organ weights that could be attributed to the test article. Based on these results, Nephure™ was not mutagenic and the no-adverse-effect level (NOAEL) in the 13-week study was determined to be 475 mg/kg bw/day (33,250 Units/kg bw/day). Evaluation of the estimated consumption of Nephure™, generation of the metabolite formate, and the current safety studies resulted in a conclusion of a tolerable upper limit of 3450 Units of OxDC activity/day (57.5 Units activity/kg bw/day), when Nephure™ is added to food to decrease dietary oxalate.
Captozyme Inc., 1622 NW 55th Place Gainesville FL 32653, United States.
Helena
H
Cowley
Captozyme Inc., 1622 NW 55th Place Gainesville FL 32653, United States.
Qin
Q
Yan
Product Safety Laboratories, 2394 Highway 130, Dayton, NJ 08810, United States.
Lee
L
Koetzner
Burdock Group, 859 Outer Road, Orlando FL 32801, United States.
Laurie
L
Dolan
Captozyme Inc., 1622 NW 55th Place Gainesville FL 32653, United States.
Erik
E
Nordwald
Captozyme Inc., 1622 NW 55th Place Gainesville FL 32653, United States. Electronic address: aaron.cowley@captozyme.com.
Aaron B
AB
Cowley
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D008297:Male; D009152:Mutagenicity Tests; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D059550:Toxicity Tests, Subchronic
Mutagenicity; Oxalate decarboxylase; Rat; Subchronic; Toxicity