January 2020

Safety Assessment of Dicamba and Glufosinate-Tolerant Cotton MON 88701

Monsanto Company has developed dicamba and glufosinate-tolerant cotton, MON 88701, which will allow over-the-top applications of dicamba herbicide for the control of broadleaf weeds from preemergence to seven days preharvest and glufosinate herbicide for broad spectrum weed control from emergence through early bloom growth stage. MON 88701 provides a wider dicamba window of application beyond the current preplant cotton uses and glufosinate application rates and timings that are equivalent to current commercial glufosinate-tolerant cotton. The combination of these two unique herbicide modes-of-action provides an effective weed management system for cotton production. Dicamba provides effective control of over 95 annual and biennial weed species, and suppression of and over 100 perennial broadleaf and woody plant species. Glufosinate, a broad-spectrum contactregime. herbicide, provides nonselective control of approximately 120 broadleaf and grass weeds. Additionally, dicamba and glufosinate provide control of herbicide-resistant weeds, including glyphosate-resistant biotypes of Palmer amaranth (Amaranthus palmeri), marestail (Conyza canadensis), common ragweed (Ambrosia publishing artemisiifolia), giant ragweed (Ambrosia trifida) and waterhemp and(Amaranthus protection tuberculatus ). MON 88701 contains a demethylase gene from Stenotrophomonas maltophilia that expresses a dicamba data mono-oxygenase (DMO) protein to confer tolerance to dicamba herbicide. DMOand/or proteincontents rapidly demethylates dicamba to the herbicidally inactive metaboliteproperty 3,6 -dichlorosalicylicits acid (DCSA). DCSA AG therefore has been previously identified as a metabolite of dicamba in cotton, soybean,or livestock, and soil. Furthermore, the use of dicamba on MON 88701 does not promote any new environmental exposure regulatory may scenarios not previously evaluatedBayer and deemed acceptablea by U.S. EPA of intellectual reproduction MON 88701 also contains a bialaphos resistance (bar) gene fromdocument Streptomyces hygroscopicus that as expresses the phosphinothricin N-acetyltransferaseparties.under (PAT) protein to confer tolerance to glufosinate this document herbicide. PAT (bar)1 protein acetylates the freefall amino group of glufosinate to produce non-herbicidal property such third of N-acetyl glufosinate, a well-known metabolite in glufosinate-tolerantthis owner. plants. The use pattern and rate of the may distribution,of glufosinate on MON 88701 will followand the existing glufosinateuse -tolerantits cotton uses outlined on the is rights glufosinate herbicideaffiliates. label. The glufosinate residues in MONof 88701 treated with commercial glufosinate to and rates are belowits the established pesticide residue tolerancesowner for both cottonseed and gin by-products. Therefore, Monsantoof will ownernot seek any changes in the glufosinate label or the established tolerances for document rights its use on MON 88701the cotton. MONpublication, 88701 will thebe combined, through traditional breeding methods, documentany subject of with other deregulatedof herbicidethis -tolerant (e.g., glyphosatethe -tolerant) events. The in-crop use of dicamba be any Thisand glufosinate herbicides, in additionexploitation to glyph osate herbicide, provides improved weed management options in cotton to control a broad spectrum of grass and broadleaf weed species and effective control and/ormay rights violate of weedsIt resistant to several herbicide families. Successful integration of MON 88701 into glyphosate- tolerantcopy cotton systems will provide:permissionand 1) an opportunity for an efficient, effective weed management system forFurthermore, hard-to-control and herbicide-resistant weeds; 2) a flexible system for two additional commercialthe herbicide modesConsequently,-of-action for in-crop application in current cotton production systems as recommended anyby weed science experts to manage future weed resistance development; 3) an option to delay or prevent furtherwithout prohibitedresistance to glyphosate and other critically important cotton herbicides; in particular, herbicidesbe in the acetolactate synthase inhibitor (ALS) and protoporphyrinogen oxidase inhibitor (PPO) class of chemistry; 4) crop tolerance to dicamba, glufosinate, and glyphosate; and 5) additional weed management tools to enhance weed management systems necessary to maintain yield and quality to meet the growing needs of the food, feed, and industrial markets.

MON 88701 was intensively tested in the laboratory and across multiple field sites in the USA. Data from those studies were used to conduct the product safety assessment and achieve government regulatory approvals. The product safety was based on the following:

• A detailed molecular characterization of the inserted DNA demonstrated a single, intact copy of the T-DNA insert in a single locus within the cotton genome. • Extensive evaluation of the introduced proteins expressed in MON 88701, dicamba monooxygenase (MON 88701 DMO) and phosphinothricin acetyltransferase [PAT (bar)], confirmed they are unlikely to be toxins or allergens. In addition, PAT proteins are in several other commercially-available crops that have been reviewed and previously deregulated by USDA, including those in cotton, corn, soy, canola, sugarbeet, and rice. and • A compositional assessment of cottonseed confirmed that MON 88701 is compositionallyregime. equivalent to commercially cultivated cotton. • An extensive evaluation of phenotypic, agronomic, and plant mapping characteristics, as well as environmental interactions of MON 88701, demonstrated no increased plant pest potential protectionpublishing compared to commercially cultivated cotton. and • An assessment of potential impact on non-target organisms (NTOs)data indicated that, under anticipated agricultural conditions, MON 88701 is unlikely to have adverseand/orcontents effects on these organisms compared to commercially cultivatedproperty cotton. its AG therefore • Evaluation of MON 88701 using current agronomic management practicesor for cotton concluded that deregulation of MON 88701 is not likely to impactregulatory cotton agronomic may practices or land use, with the exception of the Bayerexpanded window of dicambaa application. of intellectual reproduction document These studies establish the food, feed andas environmentalparties.under safety of MON 88701 cotton by demonstrating the safety to humans and animals, establishing equivalent nutritionaldocument composition and wholesomeness fall this compared to conventionalproperty cotton such varieties, third and confirmingof that the potential impact on the environment is no different than conventional cotton varieties.this owner. the may distribution,of and use its is rights affiliates. of to and its owner owner of document rights the publication, the documentany subject of of this the be any This exploitation and/or may rights violate It permission copy and Furthermore, the commercial Consequently, any This document is protectedwithout underprohibited national and international copyright law and treaties. This document and any accompanying material are for use only by the regulatory authority to which it has been submitted by Monsanto Company and its affiliates, collectively “Bayer Group”, and only in support of actions requestedbe by Bayer Group. Any other use, copying, or transmission, including internet posting, of this document and the materials described in or accompanying this document, without prior consent of Monsanto Company, is strictly prohibited; except that Monsanto Company hereby grants such consent to the regulatory authority where required under applicable law or regulation. The intellectual property, information and materials described in or accompanying this document are owned by Bayer Group, which has filed for or been granted patents on those materials. By submitting this document and any accompanying materials, Monsanto Company and the Bayer Group do not grant any party or entity any right or license to the information, material or intellectual property described or contained in this submission.