Assessment of genetically modified cotton MON 88913 for renewal authorisation under Regulation (EC) No 1829/2003 (dossier GMFF‐2023‐21234)

Abstract

Following the submission of dossier GMFF‐2023‐21234 under Regulation (EC) No 1829/2003 from Bayer CropScience LP, the Panel on genetically modified organisms of the European Food Safety Authority was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide‐tolerant genetically modified cotton MON 88913, for food and feed uses, excluding cultivation within the European Union. The data received in the context of this renewal application contained post‐market environmental monitoring reports, an evaluation of the literature retrieved by a scoping review, a search for additional studies performed by or on behalf of the applicant and updated bioinformatics analyses. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application. Under the assumption that the DNA sequence of the event in cotton MON 88913 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal dossier GMFF‐2023‐21234 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on cotton MON 88913.

SUMMARY

Following the submission of dossier GMFF-2023-21234 under Regulation (EC) No 1829/2003 from Bayer CropScience LP, the Panel on Genetically Modified Organisms of the European Food Safety Authority (GMO Panel) was asked to deliver a scientific risk assessment on the data submitted in the context of the renewal of authorisation application for the herbicide-tolerant genetically modified cotton MON 88913. The scope of the renewal dossier GMFF-2023-21234 is for the renewal of the placing on the market of cotton MON 88913 for food and feed uses, excluding cultivation within the European Union (EU).

In delivering its scientific opinion, the GMO Panel took into account dossier GMFF-2023-21234, additional information provided by the applicant, scientific comments submitted by the EU Member States and relevant scientific publications. The data received in the context of the renewal dossier GMFF-2023-21234 contained: post-market environmental monitoring reports, an evaluation of the literature retrieved by a scoping review, a search for additional studies performed by or on behalf of the applicant and updated bioinformatics analyses. The GMO Panel assessed these data for possible new hazards, modified exposure or new scientific uncertainties identified during the authorisation period and not previously assessed in the context of the original application.

Under the assumption that the DNA sequence of the event in cotton MON 88913 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal dossier GMFF-2023-21234 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on cotton MON 88913 (EFSA GMO Panel, 2013).

INTRODUCTION

Background

On 5 March 2024, the European Food Safety Authority (EFSA) received from the European Commission dossier GMFF-2023-21234 for the renewal of the authorisation of cotton MON 88913 (Unique Identifier MON-88913-8), submitted by Bayer CropScience LP (hereafter referred to as ‘the applicant’) according to Regulation (EC) No 1829/2003.¹

Following receipt of dossier GMFF-2023-21234, EFSA informed the Member States (MS) and made the summary of the application available to the public on the Open EFSA portal.²

EFSA checked the dossier for compliance with the relevant requirements of Regulation (EC) No 1829/2003 and Regulation (EU) No 503/2013³ and, when needed, asked the applicant to supplement the initial application. On 24 June 2024, EFSA declared the application valid and made the valid application available to the MS and the European Commission.

Following the submission of applications EFSA-GMO-UK-2007-41 and the publication of the EFSA scientific opinion (EFSA GMO Panel, 2013), the placing on the market of cotton MON 88913 for (a) foods and food ingredients containing, consisting of or produced from this GM cotton; (b) feed containing, consisting of or produced from this GM cotton; and (c) products containing this GM cotton or consisting of it for any other use than (a) and (b), excluding cultivation in the EU, was authorised by Commission Implementing Decision EU 2015/688.⁴ A copy of this authorisation was provided by the applicant.⁵

From the validity date, EFSA and its scientific Panel on Genetically Modified Organisms (hereafter referred to as ‘the GMO Panel’) endeavoured to respect a time limit of 6 months to issue a scientific opinion on dossier GMFF-2023-21234. This time limit was extended whenever EFSA and/or its GMO Panel requested supplementary information to the applicant. According to Regulation (EC) No 1829/2003, any supplementary information provided by the applicant during the risk assessment was made available to the MS and European Commission (for further details, see the Section 5).

In accordance with Regulation (EC) No 1829/2003, EFSA consulted the nominated risk assessment bodies of the MS, including national Competent Authorities within the meaning of Directive 2001/18/EC.⁶

The MS had 3 months to make their opinion known on dossier GMFF-2023-21234 as of date of validity.

Terms of Reference as provided by the requestor

EFSA and its GMO Panel were requested to carry out a scientific risk assessment of cotton MON 88913 for the renewal of authorisation, according to Articles 11 and 23 of Regulation (EC) No 1829/2003.

According to Regulation (EC) No 1829/2003, this scientific opinion is to be seen as the report requested under Articles 6(6) and 18(6) of that Regulation including the opinions of the nominated risk assessment bodies of the MS.⁷

In addition to the present scientific opinion on cotton MON 88913, EFSA and its GMO Panel were also asked to report on the particulars listed under Articles 6(5) and 18(5) of Regulation (EC) No 1829/2003. The relevant information is made available in the OpenEFSA portal,⁸ including the information required under Annex II to the Cartagena Protocol, a labelling proposal, a post-market environmental monitoring (PMEM) plan as provided by the applicant; the method(s), validated by the Community reference laboratory, for detection, including sampling, identification of the transformation event in the food-feed and/or foods-feeds produced from it and the appropriate reference materials.

DATA AND METHODOLOGIES

Data

The applicant has submitted a confidential and a non-confidential version of the dossier GMFF-2023-21234 following the EFSA requirements as detailed in EFSA GMO Panel (2015) and EFSA (2021).

In accordance with Art. 38 of the Regulation (EC) No 178/2002 and taking into account the protection of confidential information and of personal data in accordance with Articles 39 to 39e of the same Regulation, the non-confidential version of the dossier has been published on OpenEFSA.⁹ According to Art. 32c(2) of Regulation (EC) No 178/2002¹⁰ and to the Decision of EFSA's Executive Director laying down the practical arrangements on pre-submission phase and public consultations,¹¹ EFSA carried out a public consultation on the non-confidential version of the dossier from 6 December to 27 December 2024 for which no comments were received.

The GMO Panel based its scientific assessment of cotton MON 88913 on the valid dossier GMFF-2023-21234, additional information provided by the applicant during the risk assessment, relevant scientific comments submitted by EU MS and peer-reviewed scientific publications.

In the frame of the contracts OC/EFSA/GMO/2021/06 and OC/EFSA/MESE/2022/03-01-SC17, the contractor performed preparatory work and delivered reports on the methods applied by the applicant in performing updated bioinformatics analyses and literature search, respectively.

Post-market monitoring and post-market environmental monitoring reports¹²

Based on the outcome of the initial food and feed risk assessment, a post-market monitoring plan for monitoring of GM food and feed was not required by the authorisation decision. The implementation of a PMEM plan, consisting of a general surveillance plan to check for any adverse effects on the environment arising from cotton MON 88913, was a condition for the authorisation. As no potential adverse environmental effects were identified in the environmental risk assessment of cotton MON 88913 (EFSA GMO Panel, 2013), case-specific monitoring was not considered necessary by the GMO Panel.

The applicant provided nine annual PMEM reports covering a reporting period from April 2015 to June 2023. The annual PMEM plans submitted by the applicant included (1) commodity crop (GM and non GM) imports into the EU by country of origin and destination; (2) the description of a centralised system established by EuropaBio¹³ for the collection of information recorded by various operators (federations involved in cotton import and processing) on any observed adverse effect(s) on human health and the environment arising from handling of cotton possibly containing cotton MON 88913; (3) the reports of the surveillance activities conducted by such operators; and (4) the review of relevant scientific peer-reviewed studies retrieved from literature searches.

Systematic search and evaluation of literature¹⁴

In addition to the separate searches provided as part of the annual PMEM reports, the applicant performed scoping reviews covering the period from January 2014 to February 2025, in accordance with the recommendations on literature search outlined (EFSA, 2010, 2019).

Searches in electronic bibliographic databases and in websites of relevant organisations were performed to identify relevant publications. After applying the eligibility/inclusion criteria defined a priori by the applicant, two peer-reviewed publications and one non-peer-reviewed publications were identified as relevant for food and feed safety assessment. The relevant publications are listed in Appendix A.

Updated bioinformatics¹⁵

At the time of submission of the renewal dossier, the applicant provided a complete bioinformatics data set for cotton MON 88913 including an analysis of the insert and flanking sequences, an analysis of the potential similarity to allergens and toxins of the newly expressed CP4 EPSPS protein and of all possible open reading frames (ORFs) within the insert and spanning the junction sites, an analysis of possible horizontal gene transfer (EFSA, 2017) and a safety assessment of the newly expressed CP4 EPSPS protein regarding its potential capacity to trigger coeliac disease symptoms (EFSA GMO Panel, 2017). The outcome of the updated bioinformatics analyses is presented in Section 3.3.

Additional documents or studies performed by or on behalf of the applicant¹⁶

In line with the renewal guidance requirements (EFSA, 2021; EFSA GMO Panel, 2015), the applicant provided an overview on the worldwide approvals of cotton MON 88913 and searched for any available full reports of studies performed by or on behalf of the applicant over the course of the authorisation period and not previously submitted to the EU.

The relevance of the listed studies for molecular characterisation, human and animal safety and the environment was assessed by the applicant.

Overall assessment¹⁷

The applicant provided an overall assessment concluding that information provided in the application for renewal of authorisation of cotton MON 88913 for food and feed uses in the EU does not change the outcome of the original risk assessment (EFSA GMO Panel, 2013).

Monitoring plan and proposal for improving the conditions of the original authorisation¹⁸

The applicant indicated in the dossier that the environmental post-market monitoring plan is appropriate and does not need any changes.

Methodologies

The GMO Panel assessed the application for renewal of the authorisation of cotton MON 88913 for food and feed uses in accordance with Articles 11 and 23 of Regulation (EC) No 1829/2003. The GMO Panel took into account the requirements described in its guideline for the risk assessment of renewal applications of GM food and feed authorised under Regulation (EC) No 1829/2003 (EFSA GMO Panel, 2015). The opinions raised by the nominated risk assessment bodies of EU Member States were taken into consideration during the scientific risk assessment.

ASSESSMENT

Evaluation of the post-market monitoring and post-market environmental monitoring reports

The GMO Panel assessed the nine PMEM reports submitted by the applicant. During the general surveillance activities covering the authorisation period of cotton MON 88913, no adverse effects were reported by the applicant. This was confirmed by the evaluation of the results of the annual literature searches and the annual communications by the operators collating reports of adverse effects from their member organisations and companies. No safety concerns were identified by the GMO Panel.

Evaluation of the systematic search and evaluation of literature

The GMO Panel assessed the applicant's literature searches on cotton MON 88913 and the newly expressed protein CP4 EPSPS. The overall quality of the performed literature searches is acceptable.

The GMO Panel reviewed the publications identified as relevant by the applicant. No new information raising safety concerns for human and animal health and the environment which would change the original risk assessment conclusions on cotton MON 88913 was identified (EFSA GMO Panel, 2013).

Evaluation of the updated bioinformatics analyses

Updated bioinformatics analyses to assess the potential interruption of cotton endogenous genes confirm previous results indicating that no endogenous genes were interrupted (EFSA GMO Panel, 2013, 2014, 2016). Recent data suggest that a transgene insertion in that region may affect the expression of the endogenous gene pkiwi501 with possible effects on chlorophyll content, leaf area and plant biomass (Wang et al., 2023). However, no relevant differences which would raise safety concerns were identified in the agronomic, phenotypic and compositional characteristics of cotton MON 88913 compared with its conventional counterpart and non-genetically modified reference varieties (EFSA GMO Panel, 2013; Horak et al., 2007). Therefore, in case that the insert in MON 88913 affects the expression of the pkiwi501 gene, the agronomic phenotypic and compositional analyses of MON 88913 suggest that this does not translate in differences that would raise safety concerns.

The updated analyses of the amino acid sequence of the newly expressed CP4 EPSPS protein confirm no significant similarities to toxins, allergens or immunogenic gluten-related epitopes. Moreover, the updated bioinformatics analyses of the newly created ORFs within the insert and spanning the junctions between the insert and genomic DNA confirm previous results which did not indicate sequence similarities to toxins or allergens in cotton MON 88913 (EFSA GMO Panel, 2013, 2014, 2016).

While previous bioinformatics analysis for event MON 88913 did not reveal relevant identity to sequences of microbial origin that could support horizontal transfer to microorganisms (EFSA GMO Panel, 2013, 2016), the updated one revealed two sequences displaying sufficient length and identity with Paracoccus salsus. This would result in the transfer of the plant codon optimised cp4 epsps by double homologous recombination. Given that the recombinant DNA in cotton MON 88913 does not confer a selective advantage to microorganisms, the GMO Panel identified no safety concern linked to an unlikely but theoretically possible HGT (EFSA GMO Panel, 2013, 2016).

Evaluation of the additional documents or studies performed by or on behalf of the applicant

Taking into account (i) the relevance for molecular characterisation, human and animal safety and the environment; and (ii) the scope of this renewal application, the applicant declared that there were no available unpublished (EFSA GMO Panel, 2016) studies produced, controlled or sponsored by the applicant or provided to the applicant by a third party and not previously submitted to the EU since cotton MON 88913 was authorised.

Evaluation of the overall assessment

The GMO Panel evaluated the overall assessment provided by the applicant and confirms that there is no evidence in renewal dossier GMFF-2023-21234 indicating new hazards, relevant changes in exposure or scientific uncertainties that would change previous conclusions on cotton MON 88913.

Evaluation of the monitoring plan and proposal for improving the conditions of the original authorisation

The PMEM plan covers general surveillance of imported GM plant material, including cotton MON 88913. This general surveillance is coordinated by CropLife Europe and implemented by selected operators (federations involved in cotton seeds import and processing). In addition, the applicant reviews relevant scientific publications retrieved from literature searches on an annual basis. The GMO Panel is of the opinion that the scope of the plan provided by the applicant is consistent with the scope of dossier GMFF-2023-21234 but reminds that the final adoption and implementation of the PMEM plan falls outside the mandate of EFSA.

CONCLUSIONS

Under the assumption that the DNA sequence of the event in GMFF-2023-21234 considered for renewal is identical to the sequence of the originally assessed event, the GMO Panel concludes that there is no evidence in renewal dossier GMFF-2023-21234 for new hazards, modified exposure or scientific uncertainties that would change the conclusions of the original risk assessment on cotton MON 88913 (EFSA GMO Panel, 2013).

DOCUMENTATION AS PROVIDED TO EFSA

• Letter from the European Commission to EFSA received on 5 March 2024 for the continued marketing of genetically modified cotton MON 88913 submitted in accordance with Articles 11 and 23 of Regulation (EC) No 1829/2003 by Bayer CropScience LP (GMFF-2023-21234).
• The application was made valid on 24 June 2024.
• Additional Information (Clock 1) was requested on 2 September 2024.
• Additional Information (Clock 1) was received on 15 November 2024.
• Additional Information (Clock 2) was requested on 20 December 2024.
• Additional Information (Clock 2) was received on 7 February 2025.
• Additional Information (Clock 3) was requested on 17 February 2025.
• Additional Information (Clock 3) was received on 19 February 2025.

ABBREVIATIONS

• GM
• genetically modified
• GMO
• genetically modified organism
• GMO Panel
• EFSA Panel on Genetically Modified Organisms
• HGT
• horizontal gene transfer
• ORFs
• open reading frames
• PMEM
• post-market environmental monitoring

ACKNOWLEDGEMENTS

The Panel wishes to thank the members of its standing Working Groups on Molecular Characterization, Food/Feed and Environmental Risk Assessment for the preparatory work on this scientific opinion, and the EFSA staff member Andrea Gennaro for the support provided to this scientific opinion.

REQUESTOR

European Commission (DG SANTE)

QUESTION NUMBER

EFSA-Q-2024-00131

COPYRIGHT FOR NON-EFSA CONTENT

EFSA may include images or other content for which it does not hold copyright. In such cases, EFSA indicates the copyrightholder and users should seek permission to reproduce the content from the original source.

PANEL MEMBERS

Josep Casacuberta, Francisco Barro, Albert Braeuning, Ruud de Maagd, Michelle M. Epstein, Thomas Frenzel, Jean-Luc Gallois, Frits Koning, Antoine Messéan, F. Javier Moreno, Fabien Nogué, Giovanni Savoini, Alan H. Schulman, Christoph Tebbe and Eve Veromann.

Appendix

APPENDIX A - List of relevant publications identified by the applicant through literature searches (January 2014 to February 2025)

References

Gampala, S. S., Fast, B. J., Richey, K. A., Gao, Z., Hill, R., Wulfkuhle, B., Shan, G., Bradfisch, G. A., & Hermann, R. A. (2017). Single-event transgene product levels predict levels in genetically modified breeding stacks. Journal of Agricultural and Food Chemistry, 65(36), 7885–7892.

Shahid, A. A., Haider, T., Samiullah, T. R., Ali, M. A., Bajwa, K. S., Rao, A. Q., Salisu, I. B., & Husnain, T. (2019) Risk assessment of transgenic cotton harboring Bt and glyphosate resistance gene on fish (Labeo rohita). Journal of Animal and Plant Sciences, 29(6), 1761–1769.

CFIA (Canadian Food Inspection Agency). (2017). DD2005-56: Determination of the Safety of Monsanto Canada Inc.'s Roundup Ready® Flex Cotton (Gossypium hirsutum L.) Line MON 88913.

References

EFSA (European Food Safety Authority). (2010). Application of systematic review methodology to food and feed safety assessments to support decision making. EFSA Journal, 8(6), 1637. https://doi.org/10.2903/j.efsa.2010.1637

EFSA (European Food Safety Authority), Gennaro, A., Gomes, A., Herman, L., Nogué, F., Papadopoulou, N., & Tebbe, C. (2017). Technical report on the explanatory note on DNA sequence similarity searches in the context of the assessment of horizontal gene transfer from plants to microorganisms. EFSA Supporting Publications, EN‐1273. https://doi.org/10.2903/sp.efsa.2017.EN‐1273

EFSA (European Food Safety Authority), Devos, Y., Guajardo, I. M., Álvarez, F., & Glanville, J. (2019). Explanatory note on literature searching conducted in the context of GMO applications for (renewed) market authorisation and annual post‐market environmental monitoring reports on GMOs authorised in the EU market ‐ note on literature searching to GMO risk assessment guidance. EFSA Journal, EN‐1614. https://doi.org/10.2903/sp.efsa.2019.EN‐1614

EFSA (European Food Safety Authority). (2021). Administrative guidance for the preparation of renewal applications on genetically modified food and feed. EFSA Supporting Publications, EN‐647. https://doi.org/10.2903/sp.efsa.2021.EN‐6474

EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms). (2013). Scientific Opinion on application EFSA‐GMO‐UK‐2007‐41 for the placing on the market of herbicide‐tolerant genetically modified cotton MON 88913 for food and feed uses, import and processing under Regulation (EC) No 1829/2003 from Monsanto. EFSA Journal, 11(7), 3311. https://doi.org/10.2903/j.efsa.2013.3311

EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms). (2014). Statement complementing the EFSA opinion on application EFSA GMO UK 2007 41 (cotton MON 88913 for food and feed uses, import and processing) taking into consideration updated bioinformatics analyses. EFSA Journal, 12(3), 3591. https://doi.org/10.2903/j.efsa.2014.3591

EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms). (2015). Guidance for renewal applications of genetically modified food and feed authorised under Regulation (EC) No 1829/2003. EFSA Journal, 13(6), 4129. https://doi.org/10.2903/j.efsa.2015.4129

EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms). (2016). Scientific Opinion on an application by Dow Agrosciences LLC (EFSA‐GMO‐NL‐2009‐68) for placing on the market of cotton 281‐24‐236 × 3006‐210‐23 × MON 88913 for food and feed uses, import and processing under Regulation (EC) No 1829/2003. EFSA Journal, 14(4) e04430. https://doi.org/10.2903/j.efsa.2016.4430

EFSA GMO Panel (EFSA Panel on Genetically Modified Organisms), Naegeli, H., Birch, A. N., Casacuberta, J., De Schrijver, A., Gralak, M. A., Guerche, P., Jones, H., Manachini, B., Messéan, A., Nielsen, E. E., Nogué, F., Robaglia, C., Rostoks, N., Sweet, J., Tebbe, C., Visioli, F., Wal, J.‐M., Eigenmann, P., … Fernandez Dumont, A. (2017). Guidance on allergenicity assessment of genetically modified plants. EFSA Journal, 15(6), 4862. https://doi.org/10.2903/j.efsa.2017.4862

Horak, M. J., Rosenbaum, E. W., Woodrum, C. L., Martens, A. B., Mery, R. F., Cothren, J. T., Burns, J. A., Nickson, T. E., Pester, T. A., Jiang, C., Hart, J. L., & Sammons, B. (2007). Characterization of roundup ready flex cotton, ‘MON 88913’, for use in ecological risk assessment: Evaluation of seed germination, vegetative and reproductive growth, and ecological interactions. Crop Science, 47(1), 268–277. https://doi.org/10.2135/cropsci2006.02.0063

Wang, W. R., Cao, Y. F., Sheng, K., Chen, J. H., Zhu, S. J., & Zhao, T. L. (2023). GhFP positively regulates chlorophyll content and seedling biomass in upland cotton. Industrial Crops and Products, 204, 117388. https://doi.org/10.1016/j.indcrop.2023.117388