The 90-day MON 863 rat feeding study was conducted at an independent toxicology facility, Covance Laboratories, Inc. This laboratory is internationally recognized and routinely inspected by government regulatory authorities for compliance with Good Laboratory Practice standards. The study design followed internationally recognized (OECD) toxicology testing guidelines developed by a diverse group of experts using a science-based approach to ensure wide acceptability of these studies for regulatory purposes. The study conduct also adhered to OECD Good Laboratory Practice Regulations, thereby assuring data quality and accuracy.

The identity of MON 863, parental control, and reference maize grain was preserved by following Good Field Production Practices. In addition, PCR analysis was also used to confirm the identity of the test grain and its absence in parental control grain. Diets containing MON 863, parental control and reference grain were prepared by Purina Mills Inc. and nutritionally balanced to meet Purina specifications for certified diets. Purina Mills manufactures high quality animal diets for toxicology and research laboratories around the world.

The study included 400 rats divided into 10 groups of 20 male and female animals/group fed diets containing either MON 863 or control grain. During the course of the study, more than 900 statistical comparisons were made between test and control animals for the parameters that were measured. Based on chance alone, several statistically significant differences were expected that were not biologically meaningful. The results were reviewed by toxicology experts at Covance, the German RKI (rapporteur country), the Member States, EFSA, and independent toxicology experts from New Zealand, Italy, Germany, and England. All of these experts concluded that the statistical differences resulted from normal fluctuations that occur in rat studies, were not clinically related, and thus not biologically meaningful. Questions regarding the biological relevance of a few kidney pathology findings observed in male rats were independently reviewed a second time by expert pathologists who confirmed the conclusions of the Covance pathologist and EFSA that the findings were normal for rats and not related to MON 863.

In summary, the 90-day rat feeding study with MON 863 followed a harmonized, scientifically-based experimental design as specified in OECD guidelines as well as Good Laboratory Practices to insure the quality of the data. Independent scientists in Europe have concluded the study was appropriately conducted according to internationally accepted methods, and found no evidence of harmful effects of MON 863 maize. After a thorough analysis of study methodology and results, European regulatory authorities have concluded that MON 863 will have “no adverse effects on human or animal health.” The safety of MON 863 grain has also been confirmed by other regulatory authorities in the US, Canada, Japan, Korea, Taiwan, the Philippines, Russia, Australia/New Zealand and Mexico.

Background: The rootworm issue
Corn rootworm is one of the most pernicious pests affecting maize crops around the world. Corn rootworm larvae damage maize by feeding on the roots, reducing the ability of the plant to absorb water and nutrients from soil and causing harvesting difficulties due to plant lodging. The US Department of Agriculture estimates that this pest causes $1 billion in lost revenue annually to the US maize crop. An estimated 5.7 million hectares of maize in the US are treated annually with chemical insecticides to control this pest.

What is MON 863 YieldGard® Rootworm maize?
As an alternative to chemical insecticides, YieldGard® Rootworm contains a protein from Bacillus thuringiensis (Bt), a common soil microbe that specifically targets corn rootworm larvae, allowing the corn plant to naturally protect its roots against the damaging corn rootworm.

The use of biological insect control is more environmentally sustainable than the use of pesticides. Bt proteins have been used for pest control for more than 40 years by farmers worldwide, including organic farmers.

MON863 YieldGard® Rootworm has been grown commercially in the United States and Canada since 2003, and has been approved for import and food use in many countries around the world, including Japan, Korea, Taiwan, the Philippines, Russia and Mexico.

Details on MON 863 maize can be found at http://www.essentialbiosafety.info/main.php.

Regulatory status of MON 863 maize in the EU Regulatory approval for the import and use of biotech crops in the EU requires a number of steps involving review by more than one hundred independent scientists acting on behalf of the European Commission and Member States' governments. The regulatory steps that MON 863 has undergone in the EU are described below.

In July 2002, Monsanto submitted an application for import of MON 863 maize (excluding cultivation) under Directive 90/220/EEC to Germany, the country acting as Rapporteur for this file. This submission, which contained the Rat 90-day Subchronic Dietary Feeding Study conducted by a third party (1), was then updated to fulfill the new 2001/18/EC requirements. Germany issued a positive Initial Assessment Report (2), which was forwarded to the EU Member States for review in April 2003.

In parallel, the application was opened for public review and comment on 05 May 2003.

Monsanto submitted an application under the novel food and novel food ingredients Regulation (EC) N° 258/97, also to Germany as lead Member State, in July 2002. Germany issued an Initial Assessment Report, which was forwarded to the EU Member States for review in June 2003. Answers to additional questions, comments and reasoned objections from some Member States were submitted to all Member States in September 2003.

In order to provide further independent assessment, Monsanto commissioned a formal Study and Pathology, Peer review (7). This was a voluntary activity on behalf of Monsanto in which two highly experienced independent veterinary pathologists, one having particular expertise in relation to renal histopathology, conducted a Peer Review of this study to arrive at a scientific consensus on whether there were any toxicologically significant findings in this study. After detailed review and discussion, the experts concluded, consistent with the original report, "that dietary administration of MON 863 corn did not induce toxic effects in the kidneys of rats".

The European Foods Standards Authority (EFSA) evaluated the complete dossier and adopted a positive scientific opinion on 02 April 2004, concluding, "the placing on the market of MON 863 is unlikely to have an adverse effect on human and animal health or the environment in the context of its proposed use." (http://www.efsa.eu.int/) (3).

Regulators at some Member States raised questions about the studies submitted as part of Monsanto's applications, and this is a normal part of the regulatory process. Monsanto has addressed these questions and performed additional scientific analysis as necessary. As a result, European competent authorities now concur that MON 863 YieldGard Rootworm maize is as safe as conventional maize for human and animal health and the environment.

The next stage in the process is a vote on MON 863 by EU Member States.

References

(1) 13 week Dietary Subchronic Comparison Study with MON 863 Corn in Rats Preceded by a 1 - Week Baseline Food Consumption Determination with PMI Certified Rodent Diet #5002. (OECD Protocol 408) Covance Study No. 6l03-293, issued 17th December 2002

(2) Assessment Report of the Robert Koch Institut in Accordance with Directive 2001/18/EC, Insect -Resistant Maize MON 863 and MON 863 x MON 810, 8th April 2003 (draft translation); http://gmoinfo.jrc.it/gmc_browse.asp Assessment Report PDF file

(3) Opinion of the Scientific Panel on Genetically Modified Organisms on a request from the Commission related to the safety of foods and food ingredients derived from insect-protected genetically modified maize MON 863 and MON 863 x MON 810, for which a request for placing on the market was submitted under Article 4 of the Novel Food Regulation (EC) No 258/97 by Monsanto (Question No EFSA - Q - 2003 - 121) Opinion Adopted on 2nd April 2004

(3a) Opinion of the Scientific Panel on Genetically Modified Organisms on a request from the Commission related to the Notification (Reference C/DE/02/9) for the placing on the market of insect-protected genetically modified maize MON 863 and MON 863 x MON 810, for import and processing, under Part C of Directive 2001/18/EC from Monsanto (Question No EFSA-Q-2003-089) Opinion Adopted on 2nd April 2004

(4) AFSSA (French Food Safety Agency) Opinion dated 2nd December 2003 http://www.afssa.fr/Object.asp?IdObj=-4&Pge=0&search=MON%20863&cwSID=E95C8119B0E544B8A64296D770CA52B5&AID=0

(5) CGB (Commission du Genie Biomoleculaire) Opinion dated 28th October 2003 … http://ogm.agriculture.gouv.fr/mise_marche/avis_scientifiques/avis_scientifique_2003.htm

(6) Supplemental Analysis of Selected Findings on the Rat 90-day Feeding Study with MON 863 Maize, Report MSL - 18175; Hammond, B.G. and Ward, D.P., Monsanto Co., USA, 24th May 2004

(7) Retrospective Evaluation of Renal Tissues and data from Monsanto Co. Study CV - 2000 - 260 (MSL 18175): a 13 week Rat Feeding Study with MON 863 Corn, (Covance Laboratories Study No 6103-293)