Biotechnology Consultation Note to the File BNF No. 000136
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Biotechnology Consultation - Note to the File
Biotechnology Notification File BNF No. 000136
Date: March 20, 2013
Subject: Event 4114 insect-resistant, herbicide-tolerant corn
Keywords: Corn; maize, Zea mays L., Event 4114, Cry1F, Cry34Ab1, and Cry35Ab1, Lepidopteran and Coleopteran pest resistance, Bacillus thuringiensis, phosphinothricin N-acetyltransferase, PAT, herbicide tolerant, glufosinate-ammonium tolerant, OECD Unique Identifier DP-004114-3, Pioneer
This document summarizes our evaluation of biotechnology notification file (BNF) No. 000136. In a submission dated December 22, 2011, Pioneer Hi-Bred (Pioneer) submitted to the Food and Drug Administration (FDA) a safety and nutritional assessment of bioengineered corn event 4114 (referred to as event 4114 corn in this document). Pioneer provided additional information on June 12, 2012. FDA evaluated the information in Pioneer’s submissions to ensure that regulatory and safety issues regarding human food and animal feed from the new plant variety have been resolved prior to commercial distribution.
In our evaluation of BNF 000136, we considered all of the information provided by Pioneer 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 technical effects of the modification in event 4114 corn are to confer resistance to certain Lepidopteran and Coleopteran corn pests and to confer tolerance to glufosinate-ammonium. To accomplish this objective, Pioneer introduced the cry1F, cry34Ab1, cry35Ab1, and pat genes, which encode the proteins Cry1F, Cry34Ab1, Cry35Ab1 and phosphinothricin acetyltransferase (PAT), through Agrobacterium-mediated transformation. The Cry1F, Cry34Ab1, and Cry 35Ab1 proteins confer resistance to Lepidopteran and Coleopteran corn pests, including European corn borer and Western corn rootworm. The PAT protein confers tolerance to glufosinate-ammonium.
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 event 4114 corn. Under EPA regulations, in event 4114 corn, the cry1F, cry34Ab1, and cry35Ab1 genes and resulting expression products are considered pesticidal substances and the pat gene and its expression product are considered inert ingredients.
Inheritance and Stability
Pioneer confirmed the genomic stability of the inserted DNA and its single-locus inheritance pattern through five generations. Pioneer expects that event 4114 corn will be used in a breeding program that would incorporate additional traits.
Food & Feed Use
Pioneer states that corn is the largest crop grown in the U.S. in terms of acreage and value. Corn is typically milled, though either dry or wet methods, to yield a wide variety of food and feed products. Foods and ingredients from corn include flour, meal, oil (cooking oil, margarine), starch and starch-derived sweeteners, gluten, grits, and beverage alcohol (from fermentation). Feed uses of corn include whole or ground corn grain, ground corn ears, and the whole corn plant (silage), as well as co-products derived from corn milling used as ingredients in animal feeds, such as corn gluten meal and distillers grains with solubles.
Scope of Analysis
Pioneer reports data on sixty-nine components, including key nutrients, anti-nutrients, and secondary metabolites in grain and forage derived from a hybrid corn containing event 4114 corn and compares them to a non-transgenic, near-isogenic corn hybrid line (control). Pioneer also compares the composition of event 4114 corn with eight commercial hybrid corn varieties (reference varieties). Pioneer grew the corn at sites managed to be relatively weed-free and thus did not use glufosinate-ammonium herbicide during these studies.
Study Design - Compositional Analyses
Pioneer states that grain and forage were obtained from corn grown at six field locations in North America during the 2010 growing season. Each field site utilized a randomized block design with four replicates of event 4114 corn and control planted in two row plots. Grain samples (composite of five ears) and forage samples (composite of three whole plants) were collected from each of four blocks. Pioneer analyzed the data using analysis of variance methods comparing compositional data combined across all field sites on event 4114 corn and control grain and forage.(1) Statistical differences in composition were considered significant at the P < 0.05 level after applying a statistical method intended to minimize the rate of false discovery.(2) Pioneer also compared compositional data from event 4114 corn and control to reference varieties grown in North America during the 2003 and 2007 growing seasons. These reference varieties were used to establish a 99% tolerance interval that would serve as a comparator for data from event 4114 corn and the control. Pioneer also cited composition information on corn from the published scientific literature in its discussion for comparison.
Results of analyses
Compositional Analysis of Corn Forage
Pioneer reports the results of compositional analysis for nine components in corn forage (crude protein, crude fat, crude fiber, acid detergent fiber (ADF), and neutral detergent fiber (NDF), ash, carbohydrates by calculation, calcium and phosphorus). Pioneer reports that no statistically significant differences were observed in the mean values for each of the measured components from event 4114 corn forage and control forage. Pioneer concludes that this analysis supports the conclusion that forage from event 4114 corn is compositionally equivalent to conventional corn forage.
Compositional Analysis of Corn Grain
Pioneer reports results of compositional analyses for 60 components in corn grain.(3) Pioneer analyzed grain for proximates (crude protein, crude fat, crude fiber, ash, carbohydrates by calculation), ADF, NDF, fatty acids, amino acids, B-vitamins, vitamin E , β-carotene, minerals, anti-nutrients (phytic acid, raffinose, and trypsin inhibitor) and secondary metabolites (p-coumaric, furfural, and ferulic acid). Pioneer reports statistically significant differences in ash, phosphorus, potassium, and eicosenoic acid (C20:1) levels in event 4114 corn compared with control corn.
Pioneer notes that where statistical differences were detected, the mean values for all nutrients were within the tolerance interval established for the reference varieties and within published literature ranges for corn. Pioneer thus concludes that these differences are not biologically meaningful to food and feed safety.
Summary of Compositional Analyses
Pioneer concludes that the compositional analyses indicate that event 4114 corn is compositionally equivalent to conventional corn varieties. Pioneer concludes that statistical differences in components between event 4114 corn and control were within the ranges for the reference varieties and within published literature ranges for corn. Pioneer states that differences observed in grain components were not biologically meaningful to food and feed safety.
FDA evaluated Pioneer’s submission to determine whether event 4114 corn raises any safety or regulatory issues with respect to the intended modifications or with respect to the food and feed itself. Based on the information provided by Pioneer and other information available to the agency, FDA did not identify any safety or regulatory issues under the FD&C Act that would require further evaluation at this time.
Pioneer has concluded that, with the exception of the intended modifications (expression of the Cry1F, Cry34Ab1, Cry35Ab1 and PAT proteins),(4) event 4114 corn and 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 Pioneer’s data and information, the agency considers Pioneer’s consultation on event 4114 corn to be complete.
Richard E. Bonnette
(1) Results of statistical analysis of moisture content data for forage and grain samples were not provided in the submission, but the data for each of the components, with the exception of fatty acids, were expressed on a dry matter basis. Fatty acids were expressed as percentage of fatty acids.
(2) Benjamini Y, Hochberg Y (1995). Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society. 57: 289-300.
(3) Based on the OECD Consensus Document on Compositional Considerations for New Varieties of Maize (Zea mays): Key Food and Feed Nutrients, Anti-Nutrients and Secondary Plant Metabolites (2002).
(4) Under the purview of EPA.