Aventis CropScience presented yesterday to the Scientific Advisory Panel of the Environmental Protection Agency regarding the “Assessment of Scientific Information Concerning StarLink Corn.” Attached is a copy of a letter dated November 22, 2000 to the Environmental Protection Agency concerning updated information regarding the potential risk of allergenicity of Cry9C protein, the genetically modified material associated with StarLink corn. StarLink corn was originally developed to be resistant to an insect pest, the European corn borer. The Environmental Protection Agency has confirmed that the risk of an allergic reaction in people, to food containing StarLink corn, if any, is extremely low.

Aventis CropScience submitted this letter, along with an executive summary, in an effort to demonstrate that StarLink corn should be granted a time-limited food tolerance exemption by the Environmental Protection Agency, which would limit the potential disruption to the food chain from any StarLink corn prior to the voluntary withdrawal of the StarLink registration.

Since the discovery of cry9c DNA in taco shells in mid-September 2000, Aventis CropScience has taken unprecedented voluntary actions to successfully contain StarLink corn and corn commingled with StarLink and channel it to approved feed and industrial uses. We remain fully committed to the current StarLink grain management program regardless of the outcome of the Scientific Advisory Panel and the EPA deliberations.

Aventis November 22, 2000

Public Information and Records Integrity Branch Information Resources and Services Division (7502C) Office of Pesticide Programs (OPP) Environmental Protection Agency Rm. 119, CM #2, 1921 Jefferson Davis Highway Arlington, VA 22202

Attn.: Mr. Paul Lewis, Designated Federal Official,
Office of Science Coordination and Policy

RE: Docket Control Number OPP-00688

Comments from Aventis CropScience USA LP regarding the FIFRA SAP

Meeting on November 28, 2000 titled “Assessment of Scientific Information Concerning StarLink Corn”.

Dear Mr. Lewis:

On behalf of Aventis CropScience USA LP (Aventis), thank you for the opportunity to submit written comments for the November 28, 2000, Scientific Advisory Panel (SAP) meeting titled “Assessment of Scientific Information Concerning StarLink Corn”, docket control number OPP-00688. Following an overview of the background leading up to the upcoming SAP is an executive summary of Aventis’ recently submitted addenda to the food tolerance exemption petition, and specific comments for most of the questions that the EPA has asked the SAP to address.

Cry9C is an insecticidal protein that has been added to certain corn hybrids with the product name of StarLink(TM). Since the Cry9C protein represents a new class of Bt proteins for the market place, Aventis developed extensive data on the mammalian toxicity and potential for Cry9C to act as a food allergen. In November 1998 Aventis (formerly AgrEvo USA Company) submitted a petition of data to establish exemptions from the requirement of a tolerance for both food and feed uses for the plant-pesticide described above. These data have been submitted to and reviewed by the EPA. Most of these data are summarized in documents written by both Aventis (formally AgrEvo) (response letter to EPA background document dated December 14, 1999) and the EPA (“Cry9C Food Allergenicity Assessment Background Document”). The Cry9C protein was the subject of a SAP in February 2000, because the protein digests more slowly than other proteins currently on the market. The June 2000 SAP report from that meeting on the allergenic potential of the Cry9C protein was not conclusive.

In May 1998 the EPA granted an exemption from the requirement of a tolerance for animal feed uses of StarLink corn. Aventis, working with the EPA and the seed companies to which it licenses its technology, established a stewardship program to ensure compliance with the EPA’s limited approval. However, beginning in September 2000, StarLink corn DNA was found in taco shells. Promptly after verification of the first StarLink corn DNA finding in the US, Aventis took unprecedented, voluntary action and halted all future sales of StarLink corn and launched, a program to successfully contain StarLink corn grain on the farm and channel it, under USDA supervision, to approved feed and non-food industrial uses. StarLink corn is not a health issue. The EPA, in September, said the “health risk, if any, is extremely low.”

On October 25, 2000, Aventis CropScience submitted an addendum to its original food tolerance exemption petition for StarLink corn. The addendum supports the establishment of a time-limited tolerance exemption for the Cry9C protein in food. The submission includes a new safety assessment prepared by Novigen Sciences, Inc. on behalf of Aventis. This focuses on the Cry9C protein since, according to previous findings of the EPA, cry9c DNA does not require a risk assessment or pose a health risk to humans as it has been determined to be “Generally Recognized As Safe”. While the presence of Cry9C protein has not been documented in foods to date, the Novigen work presents a worst case risk assessment based upon very conservative estimates of potential exposure to StarLink corn in food products. A revised safety assessment was submitted November 3, 2000 after discussions with the EPA. The revised approach parallels the way the EPA estimates dietary exposure to pesticide residues.

Aventis maintains that all the data it has developed, including the supportive exposure information, taken together provide a weight of evidence supporting a lack of food allergenic potential for the Cry9C protein. In particular, the low abundance of the Cry9C protein in grain and processed grain fractions is to be considered in light of the fact that known food allergens are present in high levels in foods. Taken together, this information collectively provides overwhelming support for the establishment of a time-limited exemption from the requirement of a tolerance for Cry9C protein and the DNA required for its expression in StarLink corn. This request is based on a “reasonable certainty of no harm” safety standard as defined by the Food Quality Protection Act.

Our comments to specific questions are provided beneath each question posed by the EPA to the members of the SAP. The above overview, and the attached executive summary and answers to questions summarize Aventis written comments for this important SAP meeting. Thank you for the opportunity to comment.


Sally Van Wert, Ph.D. Director, Regulatory Affairs-Biotechnology Aventis CropScience USA LP

Executive Summary

The Cry9C protein is a biological insecticidal protein that has been added to certain corn hybrids marketed under the product name of StarLink(TM). Aventis CropScience USA LP introduced StarLink corn into the market in 1998 following the granting of a registration and feed tolerance exemption by the EPA. The corresponding petition for a food tolerance exemption remains pending. In support of the aforementioned actions Aventis developed and submitted a comprehensive data package for the Cry9C protein which exceeds that stipulated by either EPA requirements or the requirements outlined in the ILSI-IFBC Decision Tree for the Assessment of Allergenicity of Food Produced by Genetic Modification (1996). The EPA and FDA have previously established that DNA is recognized as safe. The EPA has also determined that there are no general toxicity issues related to Cry9C protein. The weight of the scientific evidence presented by Aventis to the EPA supports the very low probability that the Cry9C protein in StarLink(TM) corn will pose a food allergenic potential, and that the inadvertent and temporary presence of Cry9C protein in food meets the “reasonable certainty of no harm” safety standard under the Food Quality Protection Act (FQPA).

Based on data previously submitted to the EPA by Aventis in support of petitions to establish exemptions for the requirement of a tolerance for both food and feed uses of the Cry9C protein and supported by new information recently submitted, it is clear that Cry9C protein has a very low potential of becoming a food allergen. The Cry9C protein does not match the physiochemical characteristics of known food allergens. Results from and oral, 30-day repeated dose study in mice demonstrated no immunological effects at any dose level (MRID #447343-03). The newly introduced protein in StarLink corn has been shown not to alter the endogenous levels of allergens in corn compared to traditional corn varieties (MRID #443844-05), and the Cry9C protein does not cross-react with sera from patients allergic to other major allergenic foods (MRID #452464-01). Furthermore, the Cry9C protein, though somewhat more stable than the other Bt Cry proteins, does digest under the conditions of the normal human stomach (pH 1.2- 1.5, fasting) within the normal gastric emptying time (30-60 minutes) (MRID #442581-08, 4473343-05, 451144-01, 451144-02).

Experts, such as Dr. Steve Taylor, state that in order for people to become allergic to a protein they must be exposed to it multiple times over an extended period until they become sensitized. The protein must also be present at a relatively high percentage of the total protein. Most allergenic proteins are present at levels of 1 to 40 percent. Cry9C protein, in contrast, is present in corn grain at levels of 0.0129 percent (12 ppm) (MRID # 450257-01).

Given that Aventis has agreed to halt all future sales of StarLink corn and has gone to extraordinary lengths to ensure that a minimal amount of the 2000 harvest of StarLink grain has the potential to enter the human food chain, the potential for exposure is minimal. Given these circumstances the greatest exposure, as it may be, exists today. As time progresses the exposure potential decreases, the opposite of normally evaluated risk scenarios in such safety assessments. Aventis concludes, therefore, that the time-limited tolerance exemption is an appropriate regulatory action.