Safety assessment of dicamba mono-oxygenases that confer dicamba tolerance to various crops

Regul Toxicol Pharmacol. 2016 Nov:81:171-182. doi: 10.1016/j.yrtph.2016.08.014. Epub 2016 Aug 27.

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.

Keywords: Dicamba; Dicamba mono-oxygenase; Domain structure; Functionality; Safety assessment.

MeSH terms

  • Administration, Oral
  • Amino Acid Sequence
  • Animals
  • Computational Biology
  • Consumer Product Safety
  • Crops, Agricultural / enzymology
  • Crops, Agricultural / genetics
  • Crops, Agricultural / toxicity*
  • Databases, Protein
  • Dicamba / pharmacology*
  • Drug Resistance* / genetics
  • Enzyme Stability
  • Female
  • Food Safety
  • Food, Genetically Modified / parasitology
  • Food, Genetically Modified / toxicity*
  • Gene Expression Regulation, Plant
  • Glycine max / enzymology
  • Glycine max / genetics
  • Glycine max / toxicity*
  • Gossypium / enzymology
  • Gossypium / genetics
  • Gossypium / toxicity*
  • Herbicides / pharmacology*
  • Humans
  • Male
  • Mice
  • Mixed Function Oxygenases / administration & dosage
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism
  • Mixed Function Oxygenases / toxicity*
  • Oxidoreductases, O-Demethylating / toxicity*
  • Pancreatin / metabolism
  • Pepsin A / metabolism
  • Plants, Genetically Modified / enzymology
  • Plants, Genetically Modified / genetics
  • Plants, Genetically Modified / toxicity*
  • Protein Denaturation
  • Proteolysis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / toxicity
  • Risk Assessment
  • Stenotrophomonas maltophilia / enzymology
  • Stenotrophomonas maltophilia / genetics
  • Temperature
  • Toxicity Tests, Acute
  • Zea mays / enzymology
  • Zea mays / genetics
  • Zea mays / toxicity*

Substances

  • Herbicides
  • Recombinant Proteins
  • Pancreatin
  • Mixed Function Oxygenases
  • Oxidoreductases, O-Demethylating
  • dicamba O-demethylase
  • Pepsin A
  • Dicamba