ABSTRACT
Xylanase 50316 enzyme (also known as VR007) can be added to the diets of monogastric animals to hydrolyze the glycosidic linkages of xylans that are found in these animal feeds. This enzyme was produced from a Pseudomonas fluorescens (P. fluorescens) production strain and was tested in acute, subchronic, and genotoxicity studies. Dosages of the test article preparation ranged from 5000 µg/plate for in vitro toxicity studies to 2000â¯mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo (NOAEL of 2000â¯mg/kg/day) resulted in a safety margin of 7226 based on TOS and a conservative estimate of total poultry consumption at the highest inclusion rate. There was no toxicity reported in any of the studies conducted. A review of the public literature indicated that P. fluorescens fulfilled the recognized safety criteria pertinent to microbial production strains used in the manufacture of food/feed enzyme preparations. The results of the toxicity studies presented herein attest to the safety of the xylanase 50316 enzyme for its intended use.
Subject(s)
Animal Feed/analysis , Endo-1,4-beta Xylanases/metabolism , Pseudomonas fluorescens/enzymology , Animals , Endo-1,4-beta Xylanases/administration & dosage , Endo-1,4-beta Xylanases/biosynthesis , Female , Male , Rats , Rats, Sprague-DawleyABSTRACT
Phytase 50104 enzyme (also known as VR003) can be added to swine and poultry diets to catalyze the hydrolysis of phosphate from phytic acid, thereby increasing phosphorus bioavailability in these animals. This enzyme was produced from a Pseudomonas fluorescens (P. fluorescens) production strain and was tested in acute, subchronic and genotoxicity studies. Dosages of the test article preparation ranged from 5000µg/plate for in vitro toxicity studies to 2000mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo (NOAEL of 2000mg/kg/day) resulted in a safety margin of 5870 based on TOS and a conservative estimate of total poultry consumption at the highest inclusion rate. There was no toxicity reported for any of these studies or in the following additional safety studies: eye irritation, dermal irritation, and delayed hypersensitivity studies. A review of the public literature indicated that P. fluorescens fulfilled the recognized safety criteria pertinent to microbial production strains used in the manufacture of food/feed enzyme preparations. The results of the toxicity studies presented herein attest to the safety of phytase 50104 enzyme for its intended use.
Subject(s)
6-Phytase/adverse effects , Digestion/drug effects , Pseudomonas fluorescens/metabolism , Adult , Animal Feed/adverse effects , Animals , Cells, Cultured , Dietary Supplements/adverse effects , Dose-Response Relationship, Drug , Female , Humans , Mice , Mice, Inbred ICR , Phytic Acid/adverse effects , Rats , Rats, Sprague-Dawley , SafetyABSTRACT
The lipase enzyme, BD29241 Palmitase, can be used as a processing aid for removing palmitic acid from triacylglycerol in the production of refined oil. This enzyme was produced from a Pseudomonas fluorescens (P. fluorescens) production strain and was tested in acute, inhalation, and subchronic toxicity studies. In addition, this enzyme was also tested for its potential to induce genotoxicity. Dosages of the test article preparation ranged from 5000µg/plate for in vitro toxicity studies to 2000mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo (NOAEL of 2000mg/kg/day) resulted in a safety margin of 2.442×10(3) based on a conservative estimate of the total human consumption of BD29241 Palmitase of 0.819mg/kg/day. There was no toxicity reported for any of these studies including additional safety studies. A review of the literature indicates that P. fluorescens fulfills recognized safety criteria pertinent to microbial production strains used in the manufacture of food enzyme preparations. The results of the toxicity studies presented herein attest to the safety of BD29241 Palmitase for its above-stated intended use.
Subject(s)
Carboxylic Ester Hydrolases/toxicity , Plant Oils/toxicity , Pseudomonas fluorescens/enzymology , Triglycerides/metabolism , Animals , Carboxylic Ester Hydrolases/metabolism , Chromosome Aberrations/chemically induced , Dermatitis, Allergic Contact/etiology , Dermatitis, Allergic Contact/immunology , Dermatitis, Allergic Contact/pathology , Dose-Response Relationship, Drug , Eye Diseases/chemically induced , Eye Diseases/pathology , Guinea Pigs , Humans , Inhalation Exposure , Lethal Dose 50 , Lymphocytes/drug effects , Lymphocytes/pathology , Mice , Micronuclei, Chromosome-Defective/chemically induced , Mutagens/metabolism , Mutagens/toxicity , No-Observed-Adverse-Effect Level , Plant Oils/metabolism , Rabbits , Rats , Rats, Sprague-Dawley , Risk Assessment , Safety , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Toxicity TestsABSTRACT
BD16449 lipase is the product of a phospholipid-specific lipase gene expressed in the yeast Pichia pastoris strain DVSA-PLC-004. This type C phospholipid lipase (EC 3.1.4.3) is intended for use in the degumming of edible vegetable oil. BD16449 lipase was tested as a refined test article preparation (DV16449) for its effects on genotoxicity and in acute, inhalation, and subchronic toxicity studies. Dosages ranged from 5000 microg/plate for in vitro toxicity studies to 2000 mg/kg/day for in vivo toxicity studies. The highest oral dose tested in vivo (NOAEL of 2000 mg/kg/day) resulted in a safety margin of 133,000 based on the conservative estimate of the total human consumption of BD16449 lipase of 0.015 mg/kg/day. When adjusted for total organic solids (TOS), the highest oral dose tested in vivo (NOAEL of 1680 mg TOS/kg/day) resulted in a safety margin of 18,300 based on the conservative estimate of the total human consumption of BD16449 lipase of 0.092 mg TOS/kg/day [corrected] There was no toxicity reported for any of these studies including additional safety studies. A review of the literature indicates that P. pastoris fulfills recognized safety criteria pertinent to microbial production strains used in the manufacture of food enzyme preparations. The results of the toxicity studies presented herein attest to the safety of BD16449 lipase for use in the degumming of edible vegetable oil.
Subject(s)
Lipase/toxicity , Pichia/enzymology , Plant Oils/standards , Recombinant Proteins/toxicity , Animals , Cells, Cultured , Chromosome Aberrations/chemically induced , Female , Humans , Lethal Dose 50 , Lipase/biosynthesis , Lymphocytes/drug effects , Lymphocytes/metabolism , Mice , Micronucleus Tests , No-Observed-Adverse-Effect Level , Rats , Recombinant Proteins/biosynthesis , Safety , Toxicity Tests, Acute , Toxicity Tests, ChronicABSTRACT
BD006 phytase is the product of the Escherichia coli B app A gene expressed in Schizosaccharomyces pombe strain ASP595-1. This enzyme preparation is intended for use in animal feed applications where it improves the bioavailability of phosphate for monogastric animals. BD006 phytase was tested as an unrefined (DV006U) and a refined (DV006R) preparation for its effects on genotoxicity and in acute, inhalation and subchronic toxicity studies. Dosages ranged from 5000 microg/plate for in vitro toxicity studies to a high of 2000X for oral in vivo toxicity studies. The highest oral dose tested (2000X) is 2000 times the highest expected consumption of product by poultry or swine (X=50 units of phytase per kg bwt/day). There was no genotoxicity or any in vivo toxicity reported which could be directly related to systemic effects of the product. Other additional safety studies conducted were devoid of any relevant toxicity. The historic safety profile of the production organism S. pombe, and the results of the toxicity studies presented herein, attest to the safety of BD006 phytase for use in animal feed applications.
