1. Safety assessment of dicamba mono-oxygenases that confer dicamba tolerance to various crops.
- Author
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Wang C, Glenn KC, Kessenich C, Bell E, Burzio LA, Koch MS, Li B, and Silvanovich A
- Subjects
- Administration, Oral, Amino Acid Sequence, Animals, Computational Biology, Consumer Product Safety, Crops, Agricultural enzymology, Crops, Agricultural genetics, Databases, Protein, Enzyme Stability, Female, Food Safety, Food, Genetically Modified parasitology, Gene Expression Regulation, Plant, Gossypium enzymology, Gossypium genetics, Humans, Male, Mice, Mixed Function Oxygenases administration & dosage, Mixed Function Oxygenases genetics, Mixed Function Oxygenases metabolism, Pancreatin metabolism, Pepsin A metabolism, Plants, Genetically Modified enzymology, Plants, Genetically Modified genetics, Protein Denaturation, Proteolysis, Recombinant Proteins genetics, Recombinant Proteins metabolism, Recombinant Proteins toxicity, Risk Assessment, Glycine max enzymology, Glycine max genetics, Stenotrophomonas maltophilia enzymology, Stenotrophomonas maltophilia genetics, Temperature, Toxicity Tests, Acute, Zea mays enzymology, Zea mays genetics, Crops, Agricultural toxicity, Dicamba pharmacology, Drug Resistance genetics, Food, Genetically Modified toxicity, Gossypium toxicity, Herbicides pharmacology, Mixed Function Oxygenases toxicity, Oxidoreductases, O-Demethylating toxicity, Plants, Genetically Modified toxicity, Glycine max toxicity, Zea mays toxicity
- Abstract
Dicamba tolerant (DT) soybean, cotton and maize were developed through constitutive expression of dicamba mono-oxygenase (DMO) in chloroplasts. DMO expressed in three DT crops exhibit 91.6-97.1% amino acid sequence identity to wild type DMO. All DMO forms maintain the characteristics of Rieske oxygenases that have a history of safe use. Additionally, they are all functionally similar in vivo since the three DT crops are all tolerant to dicamba treatment. None of these DMO sequences were found to have similarity to any known allergens or toxins. Herein, to further understand the safety of these DMO variants, a weight of evidence approach was employed. Each purified DMO protein was found to be completely deactivated in vitro by heating at temperatures 55 °C and above, and all were completely digested within 30 s or 5 min by pepsin and pancreatin, respectively. Mice orally dosed with each of these DMO proteins showed no adverse effects as evidenced by analysis of body weight gain, food consumption and clinical observations. Therefore, the weight of evidence from all these protein safety studies support the conclusion that the various forms of DMO proteins introduced into DT soybean, cotton and maize are safe for food and feed consumption, and the small amino acid sequence differences outside the active site of DMO do not raise any additional safety concerns., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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