Corn rootworm-active RNA DvSnf7: Repeat dose oral toxicology assessment in support of human and mammalian safety

Regul Toxicol Pharmacol. 2016 Nov:81:57-68. doi: 10.1016/j.yrtph.2016.07.009. Epub 2016 Jul 18.

Abstract

Genetically modified (GM) crops have been developed and commercialized that utilize double stranded RNAs (dsRNA) to suppress a target gene(s), producing virus resistance, nutritional and quality traits. MON 87411 is a GM maize variety that leverages dsRNAs to selectively control corn rootworm through production of a 240 base pair (bp) dsRNA fragment targeting for suppression the western corn rootworm (Diabrotica virgifera virgifera) Snf7 gene (DvSnf7). A bioinformatics assessment found that endogenous corn small RNAs matched ∼450 to 2300 unique RNA transcripts that likely code for proteins in rat, mouse, and human, demonstrating safe dsRNA consumption by mammals. Mice were administered DvSnf7 RNA (968 nucleotides, including the 240 bp DvSnf7 dsRNA) at 1, 10, or 100 mg/kg by oral gavage in a 28-day repeat dose toxicity study. No treatment-related effects were observed in body weights, food consumption, clinical observations, clinical chemistry, hematology, gross pathology, or histopathology endpoints. Therefore, the No Observed Adverse Effect Level (NOAEL) for DvSnf7 RNA was 100 mg/kg, the highest dose tested. These results demonstrate that dsRNA for insect control does not produce adverse health effects in mammals at oral doses millions to billions of times higher than anticipated human exposures and therefore poses negligible risk to mammals.

Keywords: Biotech crop; GM crop; Gene suppression; Genetically modified crop; Plant incorporated protectant; RNAi; dsRNA.

MeSH terms

  • Administration, Oral
  • Animals
  • Biomarkers / blood
  • Body Weight
  • Coleoptera / genetics*
  • Coleoptera / pathogenicity
  • Computational Biology
  • Crops, Agricultural / genetics
  • Crops, Agricultural / parasitology
  • Crops, Agricultural / toxicity*
  • Eating
  • Female
  • Food Safety*
  • Food, Genetically Modified / parasitology
  • Food, Genetically Modified / toxicity*
  • Gene Expression Regulation, Plant
  • Host-Pathogen Interactions
  • Humans
  • Male
  • Mice
  • No-Observed-Adverse-Effect Level
  • Organ Size
  • Pest Control, Biological / methods*
  • Plants, Genetically Modified / genetics
  • Plants, Genetically Modified / parasitology
  • Plants, Genetically Modified / toxicity*
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / toxicity*
  • Risk Assessment
  • Species Specificity
  • Time Factors
  • Toxicity Tests, Acute
  • Zea mays / genetics
  • Zea mays / parasitology
  • Zea mays / toxicity*

Substances

  • Biomarkers
  • RNA, Double-Stranded