Media coverage concerning the approval of pesticides in the EU and Switzerland

Various media last week accused several agrochemical companies – including Bayer – of withholding neurotoxicity development studies when approving crop protection products in the European Union. Bayer clearly rejects these accusations. We submitted the necessary studies at all times, as required by the regulations at the time. The media coverage is tendentious and suggests that we are not honest in regulatory matters – this is wrong and undermines the reputation of the entire industry. Enclosed we have compiled the most important facts:

What exactly is Bayer accused of? 
Bayer is accused of failing to submit several DNT studies – including for the active ingredients ethoprophos, fenamiphos and fenamidone – to European regulators in the early 2000s, even though the same studies had been submitted to U.S. regulators.

Are the allegations substantiated?
No. We have always submitted the necessary studies that were required by the EU regulations at the time. Since the regulatory processes have developed over the years, similar re-approval processes can now require studies that were not required 15 years ago, for example. The following applies to all three active ingredients: the studies that were mentioned would not have changed the risk assessment of the authorities. The risk assessment could therefore be carried out reliably in any case. I'll go into more detail on that below. In general, we have carried out very extensive DNT studies for a large number of active ingredients and have also submitted these accordingly to the regulatory authorities. 

How are crop protection products regulated?
The crop protection industry is one of the most heavily regulated in the world. Products undergo extensive evaluation before they are approved for registration and sale. They must meet local regulatory standards, be safe to use and have no negative impact on the environment or the crops they are intended to protect.

What is Bayer doing to ensure that our products are safe?
We are committed to scientifically based assessments that takes into account the risks of a product under realistic conditions of use. Before crop protection products can be approved, it must be demonstrated that they are harmless to humans when used correctly and that the environment is not exposed to an unacceptable risk. The official approval is regulated by numerous international and national laws and regulations. Our chemical and biological crop protection products are screened in the early development phase thoroughly regarding their mode of action, their toxicological properties and the extent of possible residues in plants and in the environment, so that we only develop products with the best safety profiles.

Regulatory studies for the approval of crop protection products are based on the strict international guidelines of the Organization for Economic Cooperation and Development (OECD). We evaluate the possible health and environmental risks of a product along the entire value chain: from research and development through production, marketing and use by the customer to disposal. The basis for this is compliance with legal regulations and internal standards that go even beyond.

What are DNT studies?  
DNT stands for Developmental Neurotoxicity. The aim of such studies is to investigate whether and how certain substances affect the brain development of children and unborn babies in the womb. For ethical reasons, these studies are conducted in rodents. The transferability of the study results to humans is not always clear, which is why the usefulness of DNT studies is also controversial for animal welfare reasons.

Details of the allegations concerning the three individual active ingredients: 

Ethoprophos:
Bayer's submission to the Rapporteur Member State (in this case the United Kingdom) was made on January 19, 2004, in accordance with Directive 91/414/EEC at the time and its equivalent data requirements. Study MRID 4627801 and a recent multiple-dose DNT screening study were already part of the submission. In addition, the rapporteur Member State was informed that a further study was planned and not yet completed at the time of submission and the expert meetings regarding the evaluation of the data package. Therefore, study MRID 46636401 was not considered in the approval process. Nevertheless, the risk assessment could be carried out reliably because it was carried out with the corresponding lowest toxicological endpoints from the available studies and the reference values derived from them. The MRID 46636401 study, which the authorities were aware of, would therefore not have changed the risk assessment, since the endpoints considered in the EU process were already lower. Both studies were passed on to AMVAC when the active ingredient was divested in 2010.

Fenamiphos:
In 2002, Bayer, along with other companies, submitted an active ingredient dossier in accordance with Directive 91/414/, which was into force at the time. EEC and related data requirements. The evaluation of the dossier began in the months that followed. The mentioned DNT study was carried out in parallel and completed only in 2004. The risk assessment could be carried out reliably, since the endpoints used in the EU from the studies submitted were lower than the endpoints of the study addressed. These endpoints were confirmed in the later evaluation (as can be seen from the EFSA Conclusion 2019), which also took into account the DNT study. The implementation of the study was therefore transparent for the authorities and its results therefore had no impact on the risk assessment when submitted later. Bayer divested the active ingredient to AMVAC in 2010.

Fenamidone:
The study was not submitted because it was not required under the data requirements of Regulation EU 1107/2009 which was into force at that time. According to the "List of End Points" from the EFSA Conclusion from 2016, p. 43, a DNT study was not necessary. A DNT study would have been necessary if the drug had a mode of action that would suggest DNT effects. But there were no indications of that. The endpoints of the study were so high that they would not have changed the risk assessment. In the end, the active ingredient was not re-approved for other reasons and Bayer did not pursue re-approval after that. The active ingredient was divested to Gowan in 2019.