title: Corn rootworm-active RNA DvSnf7: Repeat dose oral toxicology assessment in support of human and mammalian safety.
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.
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, Creve Coeur, MO 63167, USA. Electronic address: jay.s.petrick@monsanto.com.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Petrick
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, Creve Coeur, MO 63167, USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Frierdich
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, Creve Coeur, MO 63167, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Carleton
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, Creve Coeur, MO 63167, USA.
authors.forename: Colton R
authors.initials: CR
authors.lastname: Kessenich
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, Creve Coeur, MO 63167, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Silvanovich
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, Creve Coeur, MO 63167, USA.
authors.forename: Yuanji
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Monsanto Company, 800 North Lindbergh Boulevard, Creve Coeur, MO 63167, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Koch
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D001517:Coleoptera / Q000235:genetics* / Q000472:pathogenicity; D019295:Computational Biology; D018556:Crops, Agricultural / Q000235:genetics / Q000469:parasitology / Q000633:toxicity*; D004435:Eating; D005260:Female; D059022:Food Safety; D030841:Food, Genetically Modified / Q000469:parasitology / Q000633:toxicity*; D018506:Gene Expression Regulation, Plant; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size; D010572:Pest Control, Biological / Q000379:methods*; D030821:Plants, Genetically Modified / Q000235:genetics / Q000469:parasitology / Q000633:toxicity*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000633:toxicity*; D018570:Risk Assessment; D013045:Species Specificity; D013997:Time Factors; D023382:Toxicity Tests, Acute; D003313:Zea mays / Q000235:genetics / Q000469:parasitology / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D012330:RNA, Double-Stranded
keywords: Biotech crop; GM crop; Gene suppression; Genetically modified crop; Plant incorporated protectant; RNAi; dsRNA