Comments on the Assessment of Scientific Information
Concerning StarLink Corn (Cry9C Bt Corn Plant-Pesticide)
EPA Docket Number OPP-00688
Consumers Union* thanks the EPA for the opportunity to comment on Aventis’ petition for a temporary exemption from the requirement of a tolerance for the genetically engineered plant-pesticide materials (Cry9C protein and the genetic material necessary for the production of this protein) in StarLink. Although Aventis has narrowed the scope of their petition from asking for an exemption covering both the Cry9C DNA and Cry 9C protein in all food commodities to one asking for an exemption only for food products made from StarLink corn, and only for a limited time of four years, we firmly believe that the EPA should not grant Aventis petition, for both scientific and legal reasons.
As explained below, we believe Aventis has shown neither
that the Cry9C protein is not an allergen nor that StarLink corn could
meet the "reasonable certainty of no harm" safety standard
under the Food Quality Protection Act (FQPA). Furthermore, we have
a number of criticisms of the methodology Aventis uses to estimate
human exposure to the Cry9C protein. Indeed, we believe it is an open
question whether the Cry9C protein is an allergen, especially an inhalant
allergen and feel that more research is needed in this area.
On a policy level, we think it would be very dangerous for EPA to grant Aventis request and feel that the agency’s credibility is on the line. We note that the EPA Science Advisory Panel was asked earlier this year (February 2000) whether Cry9C was an allergen and was unable to give a positive or negative answer. Instead, they called for more research.
What has changed between February 2000 and the present?
As EPA notes in its Federal Register Notice, Aventis has asked that
the exemption be granted for a limited time of four years, which time,
Aventis contends, is necessary to allow all processed foods potentially
made from StarLink corn grown in 1999 or 2000 to pass through channels
of trade (65 FR 65248). When EPA first granted approval for StarLink
corn in 1998, Aventis agreed to a restricted registration for animal
feed (and industrial uses) and vowed that they could ensure through
a number of mechanisms (such as restrictive farmer contracts, use
of 660 foot buffer zones, etc.) that none of the StarLink corn would
make it into the human food chain or into export channels. From 1998
until September 2000, EPA did virtually nothing to ensure that Aventis
was following the rules they had agreed to, and it appears that Aventis
did not abide by the rules. Instead, an environmental organization–Friends
of the Earth– tested products and was able to demonstrate that StarLink
was in the human food chain. Furthermore, since the story broke in
late September, further testing by citizen groups, as well as by industry
and the FDA, has shown that the contamination was not restricted to
the one batch of taco shells, but was more widespread than initially
believed. Testing by a consumer group in Japan revealed that corn
products contaminated with StarLink had been exported from the U.S.
in clear violation of StarLink’s limited registration (Strom, 2000).
Other stories in the press have revealed that some farmers appear
not to have been told that StarLink corn could not go into the human
food chain, or that corn in the buffer zone (within 660 feet of the
edge of StarLink fields) could not be sold for human food use, nor
required to sign contracts stipulating all the restrictions (Eichenwald,
2000; Feder, 2000). Even though Aventis (1998, Agro Evo) had agreed
to these restrictions as a condition for partial registration of StarLink
it is now clear that they have not abided by these restrictions. Rather
than face the consequences of their failure to adhere to these restrictions,
Aventis, instead, is functionally asking the EPA to bail them out
by granting their temporary exemption from a tolerance for Cry9C DNA
and protein. EPA should not reward Aventis for their failure to follow
It should be pointed out that the world is watching
what action the EPA will take. Indeed, EPA’s decision could have effects
overseas. While citizen organizations were testing corn products in
September 2000 and revealing the presence of StarLink corn, Aventis,
in the same month, was applying for approval to grow StarLink corn
in South Africa. According to a story a couple of week ago in a South
African newspaper, Department of Agriculture spokesperson Magriet
Engelbrecht says the Aventis application to bring StarLink to South
Africa is being reviewed by an advisory committee. "’What happens in other countries is going to be taken into account by the committee,’ Engelbrecht adds, ‘The experience in the U.S. will play a role.’" (Maclead, 2000: 7). The article also points out that Aventis "says it has new data to demonstrate that fears about allergies are unfounded and has asked for temporary approval of the maize from the U.S. authorities" (Maclead,
Thus, if EPA does grant Aventis request, the end result may be the approval to grow StarLink in South Africa, possibly without any restrictions, and perhaps approvals elsewhere. We could then potentially see Starlink in imported corn products, perhaps indefinitely.
Problems with Aventis Submission
Data on Commercial Bt Sprays Do Not Support Safety
Aventis argues that Cry9C is not an allergen based in part on our experience with commercial Bt sprays. Although there have been no commercially available Bt microbial sprays which contain the Cry9C protein, Aventis notes that there are microbial sprays (Agree, Xen Tari) with the Cry9B protein, which is highly homologous with the Cry9C protein (Aventis Submission, pg. 14). Aventis then argues that after more than 30 years of commercial use of Bt sprays containing a variety of Cry proteins, including proteins from the Cry9 class, no allergy has been attributed to Cry proteins. While true in a narrow sense, this could be the result of not looking for such data. In fact, data exist which suggests that some Cry proteins may be allergenic–particularly when inhaled.
According to a paper published last year, "potential allergic reactions associated with the use of Bt have not been considered" (Bernstein et al., 1999: 575). That article noted, "In 1992 the use of Bt in an Asian gypsy moth control program was associated with classical allergic rhinitis symptoms, exacerbations of asthma, and skin reactions among exposed individuals reporting possible health effects after the spraying operation. Unfortunately, there was no follow-up to determine whether these events were Bt-induced hypersensitivity or toxic reactions or merely due to common aeroallergens coincidental to the season during which the spraying occurred. Similar findings occurred during another Bt spraying in the spring of 1994" (Bernstein et al., 1999: 575). In other words, even though there was suggestive evidence that Bt sprays may be aeroallergens, no one bothered to follow-up on such evidence at the time.
To address this question, researchers carried out a health survey of farm-workers before and after exposure to Bt pesticide sprays. The study found that a number of farm workers reacted positively to skin prick tests involving Bt spore extracts, with the number of positive skin tests being significantly higher in farm workers with high exposure to Bt sprays compared to those with low or medium exposure (Bernstein et al. 1999). Furthermore, the presence of IgE antibodies against the Bt sprays was more prevalent in the high Bt exposure workers compared to low-or moderate Bt exposure workers.
In an attempt to find out which proteins of the Bt sprays were causing the IgE and hypersensitivity (e.g. positive skin prick test), four different types of BtK spore extracts were tested, along with two vegetative extracts. One of the four BtK spore extracts, labeled J-PROTOX, consisted of the pro-delta-endotoxin, derived from a BtK product called Javelin, which was the main product used during the growing season during which the study took place. Two workers had a positive skin prick test to J-PROTOX. Molecular identification, using polymerase chain reaction (PCR) technology, demonstrated the presence of Cry1Ab and Cry1Ac genes in the Javelin product. Thus, the purified pro-delta-endotoxin in J-PROTOX probably consists of Cry1Ab and Cry1Ac.
The authors concluded that "the fact that skin and serologic tests of immediate hypersensitivity developed in some workers indicates that adverse IgE mediated health effects could develop if repetitive exposure continues in some of these workers"(Bernstein et al., 1999: 581). Although clinical disease was not seen in the farm workers studied, the authors note that such results "should be interpreted with caution because of the healthy worker effect, which might be more prevalent among migrant farm workers who, upon associating clinical symptoms with a particular crop or farm job, would likely seek employment in a different agricultural area" (Bernstein et al., 1999: 580).
This study clearly suggests that the Cry1Ab and/or Cry1Ac proteins are inhalant allergens. Although this study did not address the question of whether the Cry9C protein is an inhalant allergen, the authors pointed out that the workers had been exposed in the previous year to the Bt product Agree, which contain Bacillus thuringiensis awazi, or Bta. As Aventis pointed out in their submission Agree does contain the Cry9B protein which is highly homologous with the Cry9C protein. Furthermore, the authors of the farm worker study note that Bta (found in Agree and Xentari) is among the most commonly used strains of Bt.
Thus, we suggest that a farm worker study, similar to the one conducted by Bernstein et al. (1999), should be carried out on farm workers exposed to Bta to determine if these workers have positive skin prick tests and IgE antibodies to the Cry9B protein. If the answer is yes, one could probably assume that such workers would also exhibit similar reactions to the Cry9C protein. Such a study would be far more accurate way to determine if the Cry9C protein is an allergen, compared to relying on a comparison of the physiochemical properties of the Cry9C protein to those of known food allergens.
We are particularly concerned about mill workers and other workers such as those who work in grain elevators who are exposed to high levels of corn dust in their job. This would particularly be the case for such workers in the areas, such as parts of Iowa, with, the largest acreage of StarLink corn.
As an alternative to the farm worker test suggested above, one could develop an antibody test for the Cry9C protein either by getting purified samples of the Cry9C protein from Aventis, or isolating it from Bacillus thuringiensis tolworthi.. One could then use such a test on mill workers or grain elevator workers in those areas where the plantings of StarLink have been the highest. Such workers may have been exposed to StarLink corn dust since 1998, when it was first approved. Furthermore, Aventis points out in their submission that the 1999 corn crop will not be cleared from the bins/elevators until October, 2001 (pg. 4 of Aventis submission). Thus, the 2000 corn crop will not be cleared from the bin until October 2002. Thus, mill workers and grain elevator workers in some regions of Iowa, may be exposed to StarLink dust for five years (1998-2002). Mill workers, especially, may be exposed to corn dust year round, while farm workers are usually exposed to Bt sprays only during the growing season. Such mill workers may be at an increased risk, due to continuous exposure over a long time period (up to five years) and so may develop IgE mediated disease.
Cross Reactivity Study
Among the "new" studies submitted to EPA by Aventis, was one which involved using sera from individuals allergic to the common food allergens wheat, rice, buckwheat, soy, peanut, milk, eggs and shrimp and seeing if it cross reacts with the Cry9C protein. Using the technique known as RAST (radioallergosorbent test), they demonstrated a lack of cross-reactivity of these sera to the Cry9C, concluding that such a study "provides additional evidence of the low probability that Cry9C is a food allergen"(pg.25, Aventis Submission). We disagree; such a study provides only weak evidence at best.
Protein Abundance and Potential Allergenicity
Aventis argues that proteins must be present at particularly high levels in a food before they can trigger an allergic response. They note that induction (i.e., becoming sensitized) of an IgE response is dose-related, with a larger dose needed to induce a response in a naive person compared to the dose that elicits a response in an already sensitized person.
Aventis refers to a study involving "highly peanut allergic patients" that were exposed to peanut protein levels between 10 micrograms to 50 milligrams to determine the threshold of response. The lowest level of peanut protein that elicited a response albeit one with mild short-lived reactions was 100 micrograms (Hourihane et al., 1997). Aventis then calculates that the highest possible level of exposure to Cry9C in the human diet is 8.6 micrograms for 2000 and then maintains that this is much lower than the dose that results in mild, subjective symptoms in highly peanut allergic patients.
There are a number of flaws with this analysis. First, Aventis ignores the fact that much lower doses of an allergen, either food or inhalant, can elicit an allergic response in already sensitized people. As pointed out in the report of EPA’s Scientific Advisory Panel, (SAP) that met last February, and which discussed scientific issues related to the potential allergenicity of the Cry9C protein/endotoxin, "it is known that nanogram levels of house dust mites are capable of causing dust mite allergy symptoms. With peanut allergies, ingestion of nanogram quantities can cause anaphylaxis" (pg.6, http://www.epa.gov/scipoly/sap/2000/february/foodal.pdf). Clearly, according to EPAs own SAP, very low levels of peanut allergens can cause a fairly serious reaction–anaphylaxis. Yet Aventis argues, based on the Hourihane et al. (1997) study that 100,000 nanograms of peanut allergen only elicits mild, subjective symptoms in highly peanut allergic patients. Clearly, the Hourihane study is not as definitive as Aventis would lead one to believe.
Furthermore at the October 20 meeting of EPA’s SAP, the Aventis representative made the basic argument that fairly high levels of an allergenic protein were needed to sensitize individuals and that such levels were far higher than the level of Cry9C protein in StarLink corn. One scientist on the SAPoDr. Rick Helm, a scientist who’s specialty is peanut allergies– pointed out that in some severely peanut allergic children , even the odor of peanuts can elicit asthma symptoms. Dr. Helm further noted that in such individuals, we have no idea how small a dose of peanut allergen is needed to sensitize a person. In essence, Dr. Helm said that we don’t know enough even about peanut allergies to be able to talk with any confidence about what a safe level might be.
Second, there are problems with Aventis calculation of 8.5 micrograms as the maximum level of Cry9C protein in the diet of certain sub-populations in the U.S. But even if we accept Aventis’ calculation, 8.5 micrograms equals 8,500 nanograms. Compare that level to the SAP finding that "ingestion of nanogram quantities [of peanut allergen] can cause anaphylaxis." Thus, according to Aventis own calculation, the level of Cry9C protein in the diet of a segment of the Hispanic population may be orders of magnitude higher than the level of peanut protein needed to cause anaphylaxis, according to EPA’s own SAP.
Finally, the February 29, 2000 meeting of EPA’s SAP mentions the need to look at allergenicity via both inhalation and ingestion and concludes that more research is needed: "The exposure and/or monitoring of Cry9C as an inhalant or potential food allergen source in the population has not taken into consideration the exposed population demographics, the exposure concentrations or the exposure time in hours, days or subsequent seasonal exposures. In essence, well designed scientific studies are not available to critically assess Cry9C as a potential food allergen" (pg. 9 http://www.epa.gov/scipoly/sap/2000/february/foodal.pdf). We wholeheartedly agree with this conclusion and do not think that the "new" data submitted by Aventis constitutes "well designed scientific studies." Indeed, we think the Aventis argument provides very weak evidence.
In sum, the data presented in Aventis’ submission are not strong enough for them to conclude that there is reasonable certainty that Cry9C protein is not and will not become an allergen (pg.23, Aventis Submission). Until such time as Aventis can supply the type of well designed scientific studies that EPA’s SAP says are needed to critically assess this question, EPA should not grant Aventis present request.
*Consumers Union is a nonprofit membership organization chartered in 1936 under the laws of the State of New York to provide consumers with information, education and counsel about goods, services, health, and personal finances; and to initiate and cooperate with individual and group efforts to maintain and enhance the quality of life for consumers. Consumers Union’s income is derived solely from the sale of Consumer Reports, its other publications and from noncommercial contributions, grants and fees. In addition to reports on Consumers Union’s own product testing, Consumer Reports, with approximately 4.5 million paid circulation, regularly carries articles on health, product safety, marketplace economics and legislative, judicial and regulatory actions which affect consumer welfare. Consumers Union’s publications carry no advertising and receive no commercial support.
Bernstein, IL, Bernstein, JA, Miller, M, Tierzieva,S., Bernstein, DI, Lummus, Z, Selgrade, MK, Doerfler, DL and VL Seligy. 1999. Immune responses in farm workers after exposure to Bacillus thuringiensis pesticides, Environmental Health Perspectives, 107(7): 575-582.
Eichenwald, K. 2000. New concerns rise on keeping track of modified corn. New York Times, October 14.
Feder, B.J. 2000. Farmers cite scarce data in corn mixing. New York Times, October 17.
Macleod, F. 2000. Bid to grow harmful GM crop in SA. Mail and Guardian, November 10-16,pg 7