UNITED STATES ENVIRONMENT AL PROTECTION AGENCY 

WASHINGTON, D.C. 20460 

AUG 0 6 2015 

OFFICE OF CHEMICAL SAFETY 

ANO POLLUTION PREVENTION 

MEMORANDUM 

SUBJECT: 

FROM: 

THRU: 

EPA's Response to Comments Received on the January 13, 2014, Notice of Receipt for 

Experimental Use Permit 524-EUP-104 (Docket ID Number: EPA-HQ-OPP-2012-0780; 

FRL-9904-99) 

Shannon Borges, Lead Biologist ~ ~ ~ Microbial Pesticides Branch ~ '-~ Biopesticides and Pollution Prevention Division (751 lP) ~ 

Jeannine Kausch, Regulatory Action Leader 

Microbial Pesticides Branch 

Biopesticides and Pollution Preven · 

John L. Kough, Ph.D., Senior Scientist Gt: ~ , Microbial Pesticides Branch 

Biopesticides and Pollution Prevention ·vi on (751 IP) 

Chris A. Wozniak, Ph.D., Biotechnology Special Assistant If I -a I A');_ -_f'.. 

Biopesticides and Pollution Prevention Division (751 lP) VWM vu~ ,... 

Alan H. Reynolds, Lead Biologist / lJ /} 

Microbial Pesticides Branch lYL--V'----

Biopesticides and Pollution Prevention Division (75 11 P) 

TO: Kimberly Nesci, Chief 

Microbial Pesticides Branch 

Biopesticides and Pollution Prevention Division (7511 P) 

BACKGROUND 

On March 1, 2013, the U.S. Environmental Protection Agency (EPA) issued experimental use permit 

524-EUP-l 04 to Monsanto Company (Monsanto). The experimental use permit (EUP) allowed 

Monsanto to conduct testing with plant-incorporated protectant (PIP) corn seed containing a double-
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stranded RNA (dsRNA) suppression cassette in combination with several Bacillus thuringiensis (Bt) 

proteins (Cry1A.105, Cry2Ab2, Cry1F, Vip3Aa20, Cry3Bb1, Cry34Ab1, Cry35Ab1, and/or

eCry3.1Ab). The testing focused on seed development and increase for future testing (e.g., nursery 

observations of traits in various backgrounds) and product characterization work (e.g., efficacy and yield 

benefit evaluations), took place in several states and in the commonwealth of Puerto Rico, and was 

authorized until February 28, 2015. 

 

On October 17, 2013, EPA received an application from Monsanto to amend and extend 524-EUP-104.

EPA determined that this particular application “may be of regional or national significance” (40 CFR § 

172.11(a)); therefore, it published a Notice of Receipt in the Federal Register of January 13, 2014 (79 

FR 2169). In response to this publication, EPA received five public comments. The public comments 

and EPA’s response to these comments are presented below.

PUBLIC COMMENTS AND EPA’S RESPONSE

Public Comment #1

http://www.nationofchange.org/monsanto-s-bt-toxins-found-kill-human-embryo-cells-1390666070

BT corn safety needs to be reevaluated NOW! Because a Canadian study shows that it kills embryo cells 

in pregnant women!

EPA’s Response to Public Comment #1

An anonymous comment received cited a Nation of Change website that listed two articles to support 

the contention that Cry1Ab proteins enter the bloodstream, cause kidney damage, and kill human 

embryos. 

Aris and Leblanc (Reproductive Toxicology, 31:528–533, 2011), the first article, has some important 

design limitations that question the implications made in the paper about blood levels of Cry1Ab 

protein. There is no tracking of the actual diet of the subject women to trace the amount of genetically 

modified (GM) foods consumed, and the use of the enzyme-linked immunosorbent assay (ELISA)

detection method has serious flaws. The ELISA method is designed for use with plant tissue, not human 

serum, and detects both Cry1Ac and Cry1Ab. While the researchers did use a standard curve based on a 

purified Cry1Ab protein, the majority of values reported fall outside the range of the standards used to 

calibrate the ELISA method. There is no statement as to the critical level of detection or level of 

quantification for the ELISA method, and this is paramount to make any inference from the results 

reported considering that the majority of results above non-detectable are at or near the lowest standard 

(1 nanogram Cry1Ab/milliliter) from the calibration curve. More comments by Mueller and Gorst on the 

results of the Quebec study, which question its conclusions, are found at Reproductive Toxicology 

33:401–402 (2012).

Mesnage et al. (Journal of Applied Toxicology 33:695–699, 2013), the second article, reports effects on 

cell cultures of human embryonic kidney after exposure to Cry1Ab and Cry1Ac toxins and a 

commercial preparation of Roundup GT Plus. The effects noted relate to changes in the activity of three 

enzymes in the Cry1Ab protein and Roundup treatments, and none resulted in cell death. Typically, 

cytotoxicity is monitored by the viability of the treated cell cultures. The succinate dehydrogenase 

enzymatic activity effects due to the Cry toxins do not show a dose-response effect over a six order of 

magnitude range in the dose administered. The lack of a dose-response indicates a lack of toxicity. The 

paper also cites references for previous reports of Cry toxin activity on cell cultures. In examining these 
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cited reports, the results show cytotoxic effects on human cancer cells but not normal cells. In addition, 

the authors of the cited studies are clear that the Bt toxins tested have no insecticidal activity so are 

probably not related to the insecticidal Cry toxins used in the Mesnage study. While depressed 

enzymatic activity may be a significant effect, they do not show cytotoxicity or mortality. Since there 

are feeding and toxicity studies that show a lack of whole animal effects to the Cry1Ab and Cry1Ac 

toxins, it is not clear what to infer from these cell culture studies with marginal effects on enzymatic 

activity. 

Public Comment #2

No

http://www.nature.com/news/genetically-modified-crops-pass-benefits-to-weeds-1.13517

 

EPA’s Response to Public Comment #2

Since this anonymous comment does make a scientific point or query and references a website that 

discusses genetically engineered rice (re: gene flow), EPA did not consider this comment in making a 

decision on 524-EUP-104, an EUP that involves corn PIPs only. 

Public Comments #3, #4, and #5

• We need to stop allowing businesses to produce these chemicals. There is no safe level for pollution. 

As a business consultant and engineer, I believe that we can have a MUCH healthier economy if we 

make the polluter pay. Monsanto is CREATING the pollution. You as a resugulator [sic] are 

approving the pollution. Please stop. Please take a stand.

Terra from Boston

• No, EPA, we the people of the United States of America do not support any form of corporate 

control of our food supply, national food safety standards, or publicly subsidized land, water, and 

resources for experimental use of pesticides and GMOs. The corporate model as applied to the fair 

supply of basic human needs has proven time and time again to have devastating effects on the 

health of communities local, regional, national and international. Why should we trust companies 

that produce and use GMO products when they refuse to label their own product?

And now the companies that buy, sell and use 100 tons of Roundup in Kauai'i County alone - not to 

mention the 22 tons a year of unregulated, untested, NON-FDA-APPROVED EXPERIMENTAL 

CHEMICALS that are being sprayed within 500 feet of our schools, parks and hospitals - are suing 

our county for the right to continue and expand these operations. They can afford to wage this legal 

war on us because they profit in the hundreds of billions per year at the expense of our water, soil 

and personal and community health. 

I urge you to SUMMARILY block Monsanto, who already control 90% of the GMO seed on the 

planet, from further advancing their inhumane plan of monopolizing the food supply, patenting seed 

and suing farmers out of their land for trying to grow food organically. I promise you, you have the 

support of the hundreds of millions around the world who have been made aware of the extreme 

danger of food and chemical corporations governing state and federal law.
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• Monsanto is wrecking [sic] havoc on the environment with their dangerous genetically engineered 

crops which are failing as we speak! Please deny this permit! e [sic] plant-incorporated protectants 

(PIPs) corn event MON 87411 in combination with single and combined traits against lepidoptera 

and corn rootworm.

EPA’s Response to Public Comments #3, #4, and #5

These three comments, two that are anonymous and one from a private citizen, generally expressed 

opposition to pesticides, pollution, biotechnology, corporations, and/or EPA’s approval of the 

amendment and extension for 524-EUP-104. EPA conducted risk and other assessments on the testing 

program proposed and the PIP active ingredients to be tested. Based upon these scientific assessments,

which are available as “Supporting Documents” in this docket (EPA-HQ-OPP-2012-0780), EPA 

concluded that the active ingredients to be tested are not expected to cause unreasonable adverse effects 

to human health or the environment and that the applicant’s limited testing was needed to accumulate 

information for a Federal, Insecticide, Fungicide, and Rodenticide Act (FIFRA) registration. Pursuant to 

its authority under FIFRA and without further consideration of these comments, EPA therefore 

proceeded forward with amending and extending 524-EUP-104.