Chapter 3
Role of Composition and Animal Feeding Studies in the Safety Assessment of Biotech Crops William P. Ridley, Gary F. Hartnell, and Bruce G. Hammond Downloaded by COLUMBIA UNIV on September 7, 2012 | http://pubs.acs.org Publication Date: November 23, 2004 | doi: 10.1021/bk-2005-0892.ch003
Product Safety Center, Monsanto Company, 800 North Lindbergh Boulevard, St. Louis, MO 63167
The safety assessment of biotech crops is a multidisciplinary process that involves investigations of the gene, the gene product (protein), and the whole crop. Composition analyses of nutrients, anti-nutrients, and secondary metabolites in crop tissues plus the measurement of performance, carcass yield, and meat composition in broiler chickens and the measurement of growth and numerous pathology parameters in a 13 week rat safety study were conducted to investigate the safety of the whole crop for Roundup Ready® maize event NK603. The results of these studies demonstrate that NK603 is as safe and nutritious as conventional, commercial maize (Zea mays L.) currently in the marketplace.
28
© 2005 American Chemical Society In New Discoveries in Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.
Downloaded by COLUMBIA UNIV on September 7, 2012 | http://pubs.acs.org Publication Date: November 23, 2004 | doi: 10.1021/bk-2005-0892.ch003
29 The development of transformed plants during the 1980's and the product efficacy and safety testing that followed set the stage for the introduction of herbicide-tolerant soybeans and insect-protected maize during 1995-1996 (1). The increase in productivity and the decrease in the impact of agricultural practices that these new biotechnology products provided the producer led to their rapid adoption. The acreage planted with seed derived through biotechnology continues to increase and in 2003 the global area of biotech crops was 167 million acres, representing an increase of 15 percent or 22 million acres over 2002 (2). The development of new crops containing specific agronomic traits in food and animal feed required careful evaluation to make sure there are no safety concerns. The scheme for assessing the food and feed safety of biotech products has been described previously (3, 4). Briefly, this process involves the safety evaluation of the gene and gene product (protein) responsible for the agronomical advantageous trait and a comparison of the biotechnology plant with its conventional counterpart. The comparative process using the whole plant and tissues derived from it such as forage and grain has been referred to as the evaluation of "substantial equivalence" (5, 6, 7). An essential part of the substantial equivalence process has been the analysis of composition including nutrients, anti-nutrients, and secondary metabolites, since these materials are responsible for the nutritional properties that support normal growth and development in humans and animals. Furthermore, the assessment of the equivalence of biotechnology crops compared to conventional commercial cultivars for providing nutrients to livestock and the assessment of safety in rodent feeding studies have emerged as additional studies that provide important information to support the equivalence evaluation (8,9). In 2001 Roundup Ready® maize event NK603 was approved for production in the United States and Canada. This product provided farmers an effective weed control option in maize since event NK603 was tolerant to glyphosate, the active ingredient in the Roundup® family of agricultural herbicides. Glyphosate acts by the inhibition of a key enzyme, 5-enoylpyruvylshikimate-3-phosphate synthase (EPSPS) in the shikimate pathway in plants, some bacteria and fimgi, but not in mammals, birds, or fish (10). The introduction of a glyphosate tolerant enzyme, CP4 EPSPS, into maize event NK603 plants conferred tolerance to the herbicide. Prior to the introduction of Roundup Ready maize event NK603, extensive evaluation of composition, livestock performance, and rat performance were conducted to assess the safety of the product compared to its conventional counterpart and for evaluating any unintended effects. This report will describe the results of representative studies conducted for the assessment of plants containing Roundup Ready maize event NK603. ® Roundup and Roundup Ready are registered trademarks of Monsanto Technology LLC.
In New Discoveries in Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2004.
30
Downloaded by COLUMBIA UNIV on September 7, 2012 | http://pubs.acs.org Publication Date: November 23, 2004 | doi: 10.1021/bk-2005-0892.ch003
Materials and Methods The assessment of compositional equivalence, livestock nutritional performance, and safety in rodent feeding studies share many common features. All these studies involve test, control, and reference groups, a specified experimental design that involves randomization and replication, followed by data collection (measurements) and lastly, evaluation (statistics). The study plan for the compositional analysis of maize has been described in detail previously (11) and is summarized in Table 1. The maize test line (event NK603), the control line (a near isogenic parental hybrid), and reference lines (19 conventional, non-transgenic commercial hybrids) obtained from controlled field trials were included in the study. Field sites were located in two different geographic areas, the United States (U.S.) and the European Union (E.U.), over Table 1. Study Plan for Compositional Analysis of Maize Event NK603 Study Items Variables Test Line Control Line Reference Lines Groups Field Sites U.S. -1998 Field Sites E.U.-1999 Design Replication Randomization Measurements Forage Grain
Evaluation Within sites and combination of all sites Biological relevance
Description
Maize Event NK603 Near isogenic hybrid (LH82 χ B73) 19 commercial hybrids Seven non-replicated, two replicated Four replicated Non-replicated, four replications Randomized complete block Protein, fat, ash, moisture, fiber, carbohydrate by calculation Protein, fat, ash, moisture, fiber, carbohydrate by calc, amino acid profile, fatty acid profile, minerals, vitamin E, trypsin inhibitor, ferulic and p-coumaric acids, raffinose, 2-fiiraldeyde Mixed model analysis of variance, significance: ρ
