Safety evaluation of an α-amylase enzyme preparation derived from the archaeal order Thermococcales as expressed in Pseudomonas fluorescens biovar I

• Published in: Regulatory toxicology and pharmacology Vol. 37; no. 1; pp. 149 - 168
• Main Authors: Landry, Timothy D, Chew, Lawrence, Davis, John W, Frawley, Nile, Foley, Holly H, Stelman, Steven J, Thomas, Johnson, Wolt, Jeffrey, Hanselman, David S
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2003
• Subjects: Administration, Oral; Alpha-Amylase; alpha-Amylases - chemistry; alpha-Amylases - toxicity; Animal Feed; Animals; Archaea; CAS 9000-90-2; EINECS 232-565-6; Enzyme; Enzyme Stability; Extremozyme; Eye - drug effects; Female; Food Additives - chemistry; Food Additives - toxicity; Hyperthermophile; IUB 3.2.1.1; Male; Mice; Mice, Inbred BALB C; Mutagenicity Tests; No-Observed-Adverse-Effect Level; Organ Size - drug effects; Pseudomonas fluorescens; Pseudomonas fluorescens - enzymology; Pseudomonas fluorescens - genetics; Pseudomonas fluorescens - pathogenicity; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Safety; Skin Irritancy Tests; Thermococcales - enzymology; Toxicity Tests, Chronic; CAS 9000-90-2; Hyperthermophile; EINECS 232-565-6; IUB 3.2.1.1; Enzyme; Archaea; Extremozyme; Pseudomonas fluorescens; Alpha-Amylase; Safety
• DOI: 10.1016/S0273-2300(03)00002-3
• ISSN: 0273-2300

BD5088 α-amylase derived from archaeal sources has characteristics of pH and temperature tolerance that are well suited to hydrolysis of starch in food processing applications. The production microorganism recipient strain, Pseudomonas fluorescens biovar I, strain MB101, was avirulent after oral administration to mice and does not represent an infectious threat to humans. Repeated dose gavage studies with BD5088 enzyme preparation, up to 13 weeks in duration, showed no systemic toxicity due to the oral route with an NOAEL of 890 mg/kg/day as Total Organic Solids. Some irritation occurred in the respiratory tract, which was considered to be a consequence of reflux and aspiration of test material that contained lipopolysaccharide from the Pseudomonas production strain. A 2-week dietary study (0 and 310 mg/kg/day) confirmed that there were no respiratory tract effects related to oral ingestion. There was no genotoxic activity based on Ames, mouse lymphoma, mouse micronucleus, and rat lymphocyte chromosomal aberration tests. There was no evidence of allergenic potential based on a comparison of the primary sequence of BD5088 with sequences in an allergen database. The enzyme was labile to pepsin digestion. Based on these data, BD5088 α-amylase preparation may be considered safe for use in food production such as corn wet milling.