14-Day Repeat-Dose Oral Toxicity Evaluation of Oxazyme in Rats and Dogs
Tóm tắt
Oxazyme (OC4) is an orally administered formulation that has as an active component a recombinant mutant form of Bacillus subtilis oxalate decarboxylase (OxDC) enzyme C383S, designed to degrade dietary oxalate in the stomach. Fourteen-day repeat-dose studies were conducted in rats and dogs to evaluate toxicity and determine a no observed adverse effect level (NOAEL). Animals were administered OC4 by oral gavage twice daily for 14 consecutive days. Reversibility, progression, and delayed appearance of any observed changes were evaluated in a subset of animals that underwent a recovery of 7 days following 14 days of control or test-article. There were no test-article-related adverse effects or deaths in either species. Results indicate that the NOAEL under the conditions used in the studies was 720.8 mg/kg/d in rats and 187.2 mg/kg/d in dogs, the high dose tested in each species.
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Tài liệu tham khảo
Hesse A, 1999, J Am Soc Nephrol, 10, S329
US FDA, 1979, Federal Register 21 CFR Part 58, June 20, 1979 and all subsequent amendments
OECD, 1981, ENV/MC/CHEM(98)17, 1981, and all subsequent amendments
US-FDA, 2003, Redbook 2000. Toxicological Principles for the Safety Assessment of Food Ingredients: Office of Food Additive Safety
OECD, 1995, Guideline for the Testing of Chemicals 407: Repeated Dose 28-Day Oral Toxicity Study in Rodents
US-FDA, Federal Register 9 CFR Part 1, August 31, 1989 and all subsequent amendments
US-USDA. Animal Welfare Act. 7 USC 2131. August 24, 1966 and all subsequent amendments. Washington, DC: US Department of Agriculture; 1966.
National Research Council, 1996, Guide for the Care and Use of Laboratory Animals
Moser VC, 1996, US EPA/AIHC training video and reference manual for a functional observational battery
Meyer OA, 1979, Neurobehav Toxicol, 1, 233
International Conference on Harmonisation
Levene H, 1960, Contributions to Probability and Statistics: Essays in Honor of Harold Hotelling, 78
Tukey JW, 1977, Exploratory Data Analysis
McMartin KE, 1977, J Pharmacol Exp Ther, 201, 564
Malorny G, 1969, Z Ernaehrungswiss, 9, 443