Risk assessment of Commercial release of genetically modified soy (MON 87751 x MON 87708 x MON87701 x MON 89788) insect resistant and tolerant to herbicides - Thecnical Report 5832/2018

all proteins expressed in soy have already been approved in Brazil, Cry1Ac, Cry1A.105, Cry2Ab2, CP4 EPSPS and DMO, show that they have no effect on the environment and on human and animal health. The studies that evaluated the events that originated this Soy concluded that they are as safe as conventional soy; the biosafety assessment of the events present in Combined Soy was based on the information generated on the levels of expression of exogenous proteins in plant tissues, their modes of action, the places of biological activity and the histories of safe use of the approved events. The staked events were launched in 1999 and no reports of adverse effects were reported

So far, there are no examples of interactive effects between Cry proteins with insecticidal activity and CP4 EPSPS and DMO proteins that confer tolerance to glyphosate and dicamba herbicides, respectively. The absence of interaction between these proteins of very different and specific natures is evidenced by the knowledge available on the safety of all of them, by the well-described and distinct modes of action, by the low levels of expression of these proteins in the plant and by their history of use and insurance exposure. The levels of expression of proteins in different tissues of individual events are comparable to the levels of expression of these same proteins in tissues of Combined Soy. These are data that show that the cry1Ac, cry1A.105, cry2Ab2, cp4 epsps and dmo genes do not interact with each other in Combined Soy, since the levels of expression found in individual events and in Combined Soy are comparable. For all the aspects presented above, the proteins Cry1Ac, Cry1A.105, Cry2Ab2, CP4 EPSPS and DMO present in Combined Soy can be evaluated independently, and the studies of each one in the individual events are valid to demonstrate the safety of these proteins in that product combined by classical genetic improvement. This principle of independent assessment has been used for many years for microbial risk assessments by the United States Environmental Protection Agency and applied in Brazil as well.

Considering that the proteins Cry1Ac, Cry1A.105 and Cry2Ab2 that confer resistance to insects and the proteins CP4 EPSPS and DMO that confer tolerance to the herbicides glyphosate and dicamba, respectively, are expressed in several events of different agricultural cultures already submitted to the evaluation of risk and approved for commercial use, the conclusions on the biological safety of the present genetic transformation (event) took into account the biology of the culture, the genetic characteristics introduced, the receiving environment, the familiarity with the culture in the different areas of Brazil with aptitude for the planting of soybeans, the available literature and the integration between these factors that underlie the comparative risk assessment.
The spectrum of protein activity, the low levels of protein expression in the soybean, the absence of interaction between the biochemical pathways of the proteins and the absence of adverse activity in representative indicator organisms were also considered. In addition, field trials were conducted in which they indicated that there was no difference between conventional soybeans and combined soybeans.

The proteins Cry1Ac, Cry1A.105, Cry2Ab2, CP4 EPSPS and DMO were evaluated for their potential for toxicity to humans and animals according to international recommendations (Codex, 2003; Codex 2009). These proteins have a history of safe use, have no structural similarity to known toxins or biologically active proteins that cause effects in mammals, do not cause acute oral toxicity in mice, and constitute a very small portion of the total protein present in soybean-derived food and foods. MON87751 x MON87708 x MON87701 x MON89788. In laboratory animal studies, the NOAEL for the Cry1A.105 protein was 2,072 mg / kg body weight, the highest dose tested. For the Cry2Ab2 protein, NOAEL was 2,198 mg / kg of body weight, the highest dose tested. For the CP4 EPSPS protein the NOAEL of the mouse study was 572 mg / kg of body weight, the highest dose tested. For the DMO protein the NOEL was 140 mg / kg of body weight, the highest dose tested. For the Cry1Ac protein, NOAEL was 1,292 mg / kg of body weight, the highest dose tested. These data, taken together, allowed the applicant to conclude that it is highly unlikely and unexpected that the proteins Cry1Ac, Cry1A.105, Cry2Ab2, CP4 EPSPS and DMO cause any toxic effect on humans and animals.

the data presented from field and laboratory tests allow us to conclude that the event Soy MON 87751 x MON 87708 x MON87701 x MON 89788 does not present risks different from conventional soybeans to the environment.

there are no indications that justify special attention to crosses between genetically modified plants with respect to genetic stability, expression of new genes and new interactions in the resulting genetically modified plant. However, this does not exclude the possibility of considering the assessment case by case if there is any reason based on scientific data that may require more information or data on the combined product, which would be in line with the approach advocated by bodies such as FAO / WHO, OECD and EFSA. In this case, several studies were carried out with the combined event, confirming the premise of the absence of harmful interactions between the inserted transgenes

a Soybean MON 87751 x MON 87708 x MON87701 x MON 89788 does not present risks distinct from conventional soy to the environment

Molecular tradicional method