EU Methods for Pesticide Data Requirements: An Update

These updates could have a strong impact on regulatory dossier preparation

The approval of active substances and plant protection products in the EU is a complex process that largely consists of generating data to assess the risks for human health and the environment caused by pesticide use, and then demonstrating the adequate management of those risks. 

You would think it would be a straightforward process, but unfortunately that isn’t always the case. At one time, the focus of these tests were largely in vivo experiments, but with mounting evidence around the value of in silico methodologies and in vitro tests Applicants and contract research organizations need additional guidance. 

So it is not surprise, perhaps, that just two months after clarifying the methods of microorganisms in plant protection products, the Standing Committee on Plants, Animals, Food and Feed (SCoPAFF) is close to endorsing a revision of the test methods and guidance documents that should be used for chemicals. Of note, the update on chemicals might have a strong impact on regulatory dossier preparation since it lists the test methods and guidance relevant for the harmonized implementation of the data requirements laid down in the Annexes of Regulation (EU) No 283/2013 and Regulation (EU) No 284/2013.

Still, since their first publication in 2013 the EU has not offered up any updates to better implement methods for testing with the latest scientific developments. This gap in the legislation caused delays in procedures and unnecessary testing, especially when vertebrates were involved. 

What can you expect from the pesticide update? 

Although there are no draft documents circulated yet, one can get a feel of what’s coming by reviewing the current EU Commission communications for microbial active substances and plant protection products.  Yet while the use of alternative methods, such as in silico and in vitro studies, have been explicitly promoted in Europe, especially for industrial chemicals under REACH Regulation (EC) 1907/2006, as an option to meet data requirements in the evaluation of pesticides, there is still room to grow. It is therefore expected that the update on chemicals will open the door to more alternatives to animal testing. 

Consider skin sensitization tests. Although a full animal-free testing strategy has been available for identifying skin sensitizers at Charles River for quite some time, based on the OECD Guideline No. 497 on the defined approaches to be used for skin sensitization assessment, Regulation (EU) 283/2013 still states that a skin sensitization study shall be performed preferably with mice or guinea pigs. It is promising that this OECD Guideline promoting animal-free testing strategies has been suggested for microbial-based pesticides since it could hopefully pave the way for a change in this direction also for chemical active substances and products.

Another expected development is increased openness on the part of regulators toward the combination of repeated dose toxicity studies and genotoxicity testing to minimize animal use. At Charles River we already provide tailored studies aimed at investigating, simultaneously, general toxicity and genotoxicity. It is expected that along with in vivo genotoxity tests like the comet and micronucleus  assays, we might also see wider use of the Pig-a gene mutation assay, an alternative to transgenic rodent models that are more complex in terms of resources and data interpretation and can’t be complemented with other toxicity studies. 

Lastly, given the importance of endocrine disrupting (ED) properties in risk assessments, the update is expected to provide more clarity on the conduct of high-tier (eco-)toxicological studies, contributing to the ED assessment. For instance, the Extended One-Generation Reproductive Toxicity (EOGRT) study currently is designed to include different cohorts of animals depending on the need for specific investigations. It will be interesting to see whether the EU’s Commission communications on chemicals will provide specific study design indications that might help Applicants meet the data requirements before starting this study. Nor now, clarity is only given at the conclusion of the EU’s evaluation process.

Charles River can support you!

Given the complex nature of the Plant Protection Product legislation, complying with regulations and their amendments can be puzzling and not always straight-forward. It can be difficult, therefore, to come to the right decisions. In this legislative maze, our regulatory experts are available to discuss the impact of these expected upcoming changes on your testing strategy and your dossier compilation. Feel free to reach out if you have questions about agrochemical and industrial regulations.

Andrea Pelizzari and Hester van der Woude are principal regulatory toxicologists at Charles River Laboratories.