Biotechnology Consultation Note to the File BNF No. 000128
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Biotechnology Consultation - Note to the File
Biotechnology Notification File BNF No. 000128
Date: January 30, 2012
Subject: Event 5307 Coleopteran insect-resistant corn expressing eCry3.1Ab
Keywords: Corn, maize, Zea mays L., Event 5307, ecry3.1Ab gene, phosphomannose isomerase (pmi) gene (or manA gene), eCry3.1Ab fusion protein, Coleopteran rootworm resistance, Bacillus thuringiensis, OECD Unique Identifier SYN-Ø53Ø7-1, Syngenta
This document summarizes our evaluation of biotechnology notification file (BNF) No. 000128 submitted by Syngenta Seeds, Inc. (Syngenta) on January 27, 2011. The consultation (or Syngenta’s submission) describes Syngenta’s safety and nutritional assessment of the bioengineered corn event 5307. Syngenta provided additional information in a submission dated April 15, 2011. FDA evaluated the information in Syngenta's submissions to ensure that human food and animal feed regulatory and safety issues regarding the food and feed derived from the new plant variety have been resolved prior to commercial distribution.
In our evaluation, we considered all information provided by the notifier as well as publicly available information and information in the agency’s files. Here we discuss the outcome of the consultation, but do not intend to restate the information provided in the final consultation in its entirety.
The intended effect of the modification in corn event 5307 is to confer resistance to certain Coleopteran insect pests of corn. To accomplish this objective, Syngenta introduced the ecry3.1Ab gene into immature embryos of a parental corn variety. The ecry3.1Ab gene encodes the eCry3.1Ab protein, which confers resistance to insects including western corn rootworm, northern corn rootworm, and Mexican corn rootworm. The eCry3.1Ab protein that is expressed in corn event 5307 is a fusion of modified Cry3A and Cry1Ab proteins derived from Bacillus thuringiensis. In the development of corn event 5307, Syngenta uses the pmi gene encoding phosphomannose isomerase (PMI) as a selectable marker.(1)
The Environmental Protection Agency (EPA) defines a plant-incorporated protectant (PIP) as "a pesticidal substance that is intended to be produced and used in a living plant, or the produce thereof, and the genetic material necessary for the production of such a pesticidal substance," including "any inert ingredient contained in the plant, or produce thereof (40 CFR 174.3). EPA regulates PIPs under the Federal Food, Drug, and Cosmetic Act and the Federal Insecticide, Fungicide, and Rodenticide Act. EPA reviews the PIP, including any inert ingredients, in corn event 5307.
Food & Feed Use
Corn (Zea mays L.) originated in Mexico and was grown as a food crop as early as 2700 B.C. Today, corn is grown worldwide for food, feed, and industrial uses. Corn is a significant source of nutritionally important amino acids and essential amino acids (except for lysine and tryptophan), carotenoids, and vitamin E. Corn grain is used in food primarily in the form of processed products, such as high fructose corn syrup, cereals, oil, meal, flour, starch, and grits. Corn oil is rich in polyunsaturated fatty acids and is used mainly as a salad and cooking oil and in margarine production.
Corn is also used in animal feed. Corn grain is fed to cattle, poultry, and swine either as intact or processed grain or as dry or wet milling byproducts. Corn silage is primarily fed to ruminants.
Scope of Analysis
Syngenta analyzed the composition of forage and grain from corn event 5307 and a nontransgenic, near-isogenic corn (hereafter referred to as the control). Syngenta stated that it used corn event 5307 hybrid plants and control hybrid plants in the analysis. Compositional analysis was conducted to identify any changes in key nutrients and anti-nutrients of the new corn variety compared with the control variety, and to assess whether these differences would raise any safety or nutritional concerns.
Syngenta provided data from compositional analysis on forage and grain from corn event 5307 and the control variety. The corn varieties were grown at six field sites across the United States during the 2008 growing season. Both corn varieties were grown using a randomized complete block design with three replicates per site. Syngenta assessed the data sets using a mixed model analysis of variance. Statistical analyses were conducted on data from each field site (individual-site) and on data aggregated from all six field sites (combined-site). Syngenta reported the compositional data by providing mean values, ranges, and P values for the components measured in corn event 5307 and control samples. Statistical significance was declared at 5% level (P ≤0.05). The analysis also included comparisons between mean levels and ranges of corn event 5307 components with the corresponding means and ranges reported for corn in the International Life Sciences Institute Crop Composition Database (ILSI-CCD).
Results of Analyses
Compositional analysis of corn forage
Syngenta reports the results of compositional analysis for nine components in corn forage: proximates (moisture, crude protein, crude fat, ash, and carbohydrates (by calculation)), acid detergent fiber (ADF), neutral detergent fiber (NDF), calcium, and phosphorus. In the combined site analysis, Syngenta reports that no statistically significant differences were observed in the mean levels of all measured components between corn event 5307 and the control.
In the individual-site analysis, Syngenta reports that statistically significant differences were observed in the mean levels of moisture, crude protein, calcium, and phosphorus between corn event 5307 forage and the control. However, for each of these components, the statistically significant differences occurred only at one of six locations, and the mean levels of all nine components fell within the range of natural variation for corn reported in the ILSI-CCD. Thus, Syngenta reports that any statistically significant differences in the levels of all components measured in forage are not biologically meaningful.
Compositional analyses of corn grain
Syngenta reports the results of compositional analysis of 59 components in grain: proximates, ADF, NDF, starch, 10 minerals, 18 amino acids, 4 secondary metabolites, 7 vitamins, 8 fatty acids (C16-C22), and 3 anti-nutrients (phytic acid, raffinose, and trypsin inhibitor). For the combined-site analysis, no statistically significant differences were observed in mean levels of 52 of 59 components between corn event 5307 and the control. Statistically significant differences between corn event 5307 and the control were observed in the mean levels of vitamins A, B6, and B9, and four fatty acids (palmitic, stearic, linolenic, and eicosenoic acids). Syngenta notes that these differences were small and that the mean level of each of these components, except for linolenic acid, was within the ranges obtained for grain harvested from the nontransgenic control. Syngenta also notes that mean levels of all these components fell within the natural variation of corn reported in the ILSI-CCD. Thus, Syngenta concludes that the statistically significant differences in the levels of these seven components are not biologically meaningful.
For the individual-site analysis, Syngenta reports that statistically significant differences were observed for corn event 5307 compared with the control in mean levels of crude protein, magnesium, phosphorus, zinc, vitamins A and B6, aspartate, threonine, glutamate, glycine, alanine, valine, leucine, histidine, and stearic acid. However, Syngenta states that these differences were not consistent among locations and fell within the range of natural variation reported for corn in the ILSI-CCD, except for the levels of starch and vitamin B2 in the control corn at one location, which exceeded the levels reported by ILSI.
Broiler Chicken Feeding Study
Syngenta provided the results of a 49-day broiler chicken study in which chickens (90 males and 90 females) were fed diets prepared with (1) corn event 5307 grain, (2) near-isogenic hybrid grain, or (3) a commercially available maize grain. Starter and grower diets were formulated with corn content ranging from 55% to 63% by weight, depending on the type of diet. The parameters that were assessed in the study included mortality, feed consumption, and growth (e.g., overall mean body weight, overall carcass yield, and yield of various carcass portions). Syngenta reports some statistically significant decreases in the carcass yields (as a percentage of total body weight) of broiler chickens that received corn event 5307 diets.(2) However, Syngenta states that these decreases were most likely due to the numerical differences in body weight of broiler chickens that were randomly selected for processing from each group. Syngenta states that for the other parameters that were assessed, no statistically significant differences were observed between birds that received diets prepared with corn event 5307 grain and those that received diets prepared with the near-isogenic hybrid grain or the commercially available grain. Syngenta concluded that there were no adverse dietary effects on broiler chickens that consumed diets prepared with corn event 5307 grain, either as a direct effect of the transgenic proteins in the diet or as a result of any unintended compositional changes in the grain that may have altered its nutritional value.
Syngenta has concluded that, with the exception of the intended modifications (expression of the eCry3.1Ab and PMI proteins),(3) corn event 5307 and the foods and feeds derived from it are not materially different in composition, safety, or any other relevant parameter from other corn varieties now grown, marketed, and consumed in the U.S. At this time, based on data and information provided by Syngenta, the agency considers Syngenta’s consultation on corn event 5307 to be complete.
Shayla West-Barnette, Ph.D.
(1)Syngenta submitted its evaluation of the potential for allergenicity and toxicity of the PMI protein, which FDA designated as New Protein Consultation No. NPC 000002 under FDA's Guidance to Industry: "Recommendations for the Early Food Safety Evaluation of New Non-Pesticidal Proteins Produced by New Plant Varieties Intended for Food Use." FDA responded that it had no questions regarding Syngenta's conclusions that the PMI protein is neither toxic nor allergenic.
(2)FDA notes, however, that the magnitude of these percentage decreases was small (<1%).
(3)Under the purview of EPA.