There is a dangerous gap in the safety assessment of pesticides. Neurotoxicity is not adequately investigated and this could contribute to damage to the brain development of children and the rapid development of diseases like Parkinson’s. In a letter to health commissioner Kyriakides, we have expressed our concerns and asked for urgent action. We also ask for solid action against the pesticide producers that withheld studies on neurotoxicity. This should lead to a hefty fine and withdrawal of the pesticide substances involved.
Damage to the brain is not a light matter. Pesticide-related neurological diseases are rising in the EU and specialists have raised alarms of an upcoming “Parkinson's epidemic” (1). Farmers are often the first victims. At the same time, scientific knowledge is evolving rapidly. Low-level pesticide exposures during pregnancy or childhood have been found to be associated with neurodevelopmental deficits such as lower IQ and disorders such as autism, attention deficit hyperactivity disorder, and pervasive developmental disorder. Therefore, it is completely unacceptable that people are not well protected from the negative effects of pesticides.
EU is too slow to act
Scientific evidence on the impact of neurotoxic insecticides on humans is steadily increasing: The new information from many studies should result in the implementation of sensitive neurodevelopmental toxicity tests in the frame of the pesticide risk assessment. An OECD test guideline exists (2) and should be included in EU regulation 284/2013 as mandatory, at least for insecticides. We do not see how the European Commission can justify to not yet having added this OECD guideline to the data requirements.
It has taken more than a decade for the EU to ban chlorpyrifos after the first evidence of its potential to cause developmental neurotoxicity. Considering the major impact it had on children's nervous system development, including the brain, we urge the EU not to repeat the same errors with neonicotinoids and other neurotoxic pesticides. Indeed, a strict implementation of the precautionary principle should lead to banning and deleting the maximum residue levels (MRLs) for all potential neurotoxic pesticides including neonicotinoids (and neonicotinoid-like) insecticides in European food.
Take action against industry withholding studies on neurotoxicity
Recently a study by the Swedish researchers Mie and Rudén disclosed that pesticide producers including Bayer and Syngenta had submitted neurotoxicity studies to US agencies but not to their European counterpart. (3) Professor Rudén from the Department of Environmental Science of Stockholm University said the cases of tobacco and PFAS – “forever chemicals” – were previous examples of where companies withheld knowledge about toxicity from the public.
The authors of the study notified EFSA and the Swedish national authorities (KEMI), and in 3 cases these originally undisclosed studies had regulatory consequences after they were requested and evaluated by the regulatory agencies (abamectin, ethoprophos, pymetrozine).
Four studies still have a potential effect on toxicological reference values or upcoming hazard classification (fenamidone, fluazinam, glyphosate-trimesium, pyridaben) and for one developmental neurotoxicity (DNT) study, the information available to assess the regulatory impact was insufficient.
Earlier misconduct by the pesticide industry
In 2018, following an analysis of the raw data of the DNT regulatory tests on chlorpyrifos and chlorpyrifos methyl from 20088, scientists identified that the pesticide industry had provided misleading conclusions on its studies, underreporting the adverse effects. This review resulted in the non-renewal of the authorisation of both substances in 2019, nevertheless with a 10 years of delay.
To our knowledge, in the EU, none of these 2 previous examples of misconduct have led to any kind of administrative or judicial procedure to suspend the EU approvals of these substances until the situation is clarified. There has been no penalty for infringement to the companies for non-compliance with the requirements of the EU law (article 72) and putting EU citizens in danger. For the pesticide industry, the signal is very clear: in case of failing to comply with the law, there are no legal or financial consequences on their business and staff.
This inaction on the side of European regulatory authorities is in sharp contrast with EU law. Article 44 from the pesticide regulation (EU) 1107/2009 obliges Member States to withdraw national authorisations of products if the applicant has not respected the requirements of the pesticide regulation. In the present case, the fact that the applicant did not respect Article 56 must lead to the immediate suspension of the authorisation of these products in all of the EU, and the issue of penalties for the companies that committed these infringements of the EU law.
An EFSA spokesperson explains that tougher EU rules on the notification of safety studies became applicable from March 2021, meaning companies now have to notify the authorities of all studies commissioned and cannot withhold studies even if they are considered to have found no adverse findings. However, Angeliki Lysimachou, our head of science and policy reacted in an article in The Guardian (4): “That means that all the pesticides already in the market won’t be examined until their reapproval comes up, which could take 10 or 15 years, sometimes more. In the meantime, the pesticides remain approved for use.”
We have therefore asked health commissioner Kyriakides to suspend the approval of the 5 remaining authorised substances, to make sure that all national authorisations will be withdrawn, and to impose a stiff fine on the companies involved.
- The Parkinson Pandemic, a call to action, E Ray Dorsey, Bastiaan R Bloem
- OECD guidelines for the testing of Chemicals, section 4
- Non-disclosure of developmental neurotoxicity studies obstructs the safety assessment of pesticides in the European Union, Axel Mie and Christina Rudén
- Pesticide firms withheld brain toxicity studies from EU regulators, study finds, Guardian June 1, 2023
Key points from the Mie and Rudén study
"Of the 35 identified DNT studies, 26 (74%) were included in the most recent corresponding EU summary dossier, while 9 (26%) were not. In none of these 9 cases could we find a justification for the non-inclusion. Products containing 4 of the compounds were approved in Sweden at the time the DNT study report was issued. In none of these cases, the sponsor informed the Swedish Chemicals Agency of the DNT study or its results. For the 9 compounds, the results from the DNT study, the EU regulatory history, and the potential for regulatory impact of the DNT study are summarised."
Abamectin- 01/04/2023 - 31/03/2038, DNT study (2005/2007) not submitted in 2016, but Austria requested it. DNT study should result in Reprotox1B, but the classification hasn’t changed- because of overall toxicity it was approved (under restriction) in greenhouses
Buprofezin – authorised 01/02/2011 - 31/01/2024, DNT (2002) they informed EFSA and said it will take it into account but there is no info on the study
Ethoprophos- 01/10/2007 - 21/03/2019 non-approval, the DNT study from 2004 was missing (was not available in the previous approval assessment, before 2007 nor the recent one), they informed EFSA and asked for the study, which played a role in the non-renewal of the substance (there were also areas of concern for genotoxicity)
Fenamidone – 01/10/2003 - 14/08/2018 non-approval, area of concern on genotoxicity identified, DNT study (2005 ) was not submitted and was not part of the non-renewal. It could have changed classification (right now there is no classification). They anyways notified EFSA about the study in 2020. A 2-generation study showed effects on brain weight of Sprague Dawley rats, EPA asked Bayer to perform a DNT study on the same strain of rats but Bayer submitted one on Wistar rats. EPA requested again additional data on Sprague Dawley strain, but there is no information if this has been done.
Fenamiphos – 01/08/2007 - 23/09/2020 non-renewal based on other concerns (risk for consumers not finalised as genotoxicity of metabolites is missing, concerns for drinking water contamination), DNT study (2004) not included in the dossier, EFSA was informed in 2018 and the study was included, but had no impact
Fluazinam – authorised 01/03/2009 - 29/02/2024, DNT (2005) was missing from the dossier in 2016 and identifies adverse effects in offspring, they informed EFSA and they said they have included it in the current assessment
Glyphosate (trimesium salt) - 16/12/2017 - 15/12/2023 - The DNT study (2011) was missing from the dossier (2021), however this form of glyphosate salt is not sold anymore therefore the adverse effects were excluded by ECHA. EFSA has been informed too.
Pymetrozine- nonrenewal 2018, DNT study 2003/2005 adverse effects reported, not included in application dossier in 2012. Non- renewal for other reasons: for groundwater and ED effects but ECHA changed the classification to Reprotox2 because of DNT
Pyridaben – 01/05/2011 - 31/07/2026 approved, DNT study (2007) not included in 2020 application dossier, EFSA has been notified about DNT study, which will be included in the ongoing assessment
Regulatory impact
According to the article:
- For one compound (abamectin), EFSA has based the safety exposure levels based on the DNT study.
- For four compounds (fluazinam, glyphosate, pymetrozine, pyridaben), the results from the DNT study could potentially affect the exposure safety values, because the DNT No-Observed-Adverse-Exposure-Level was equal to or lower than the point of departure currently used for deriving these reference values.
- For one compound (pymetrozine), the DNT study contributed to a classification as “Toxic to reproduction Category 2” according to CLP. For four compounds (abamectin, ethoprophos, fenamidone, fluazinam), offspring DNT effects were observed at dose levels not causing overt maternal toxicity; therefore, these studies could potentially contribute to a classification according to the CLP.
- For one compound (ethoprophos), DNT effects contributed to the non-renewal decision [48].
In summary, according to the investigation "three undisclosed DNT studies have already had regulatory consequences after they had been requested and evaluated by regulatory agencies (abamectin, ethoprophos, pymetrozine). Four DNT studies have a potential effect on toxicological reference values or hazard classification (fenamidone, fluazinam, glyphosate-trimesium, pyridaben). One DNT study had no regulatory consequences (fenamiphos). For one study (buprofezin), insufficient information was available for assessing a potential regulatory impact".
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Relevant pieces of EU Legislation
Transparency Regulation updating the General Food Law (for application starting in March 2021):
Article 32b: Notification of studies
1. The Authority shall establish and manage a database of studies commissioned or carried out by business operators to support an application or notification in relation to which Union law contains provisions for the Authority to provide a scientific output, including a scientific opinion.
2. For the purposes of paragraph 1, business operators shall, without delay, notify the Authority of the title and the scope of any study commissioned or carried out by them to support an application or a notification, as well as the laboratory or testing facility carrying out that study, and its starting and planned completion dates.
Article 61a: Fact-finding missions
Commission experts shall perform fact-finding missions in Member States to assess the application, by laboratories and by other testing facilities, of the relevant standards for carrying out tests and studies submitted to the Authority as part of an application, as well as compliance with the notification obligation set out in Article 32b(3), by 28 March 2025.
Pesticide EU Law Reg (EC) 1107/2009
Article 8. Dossiers
1. The summary dossier (submitted by the applicant/company) shall include the following: (b) for each point of the data requirements for the active substance, the summaries and results of tests and studies, the name of their owner and of the person or institute that has carried out the tests and studies;
Whereas:
Regulation on data requirements for active substances (No 283/2013)
Annex I: Information to be submitted, its generation and its presentation
1. The information submitted shall meet the following requirements.
1.1. The information shall be sufficient to evaluate the foreseeable risks, whether immediate or delayed, which the active substance may entail for humans, including vulnerable groups, animals and the environment and contain at least the information and results of the studies referred to in this Annex.
1.2. Any information on potentially harmful effects of the active substance, its metabolites and impurities on human and animal health or on groundwater shall be included. Commission Communication in the framework of the implementation of Commission Regulation (EU) No 283/2013 of 1 March 2013 setting out the data requirements for active substances, in accordance with Regulation (EC) No 1107/2009
Development Neurotoxicity (DNT) study is included in the data requirements under section 5
5. TOXICOLOGICAL AND METABOLISM STUDIES
5.6. Reproductive toxicity
5.6.2. Developmental toxicity studies
Method B.31 Prenatal developmental toxicity study (Annex to Regulation (EC) No 440/2008).
OECD Test Guideline 414: Prenatal developmental toxicity study.
OECD Test Guideline 426: Developmental neurotoxicity study.
Pesticide EU Law Reg (EC) 1107/2009
Article 56. Information on potentially harmful or unacceptable effects
1.The holder of an authorisation for a plant protection product shall immediately notify the MemberStates that granted an authorisation of any new information concerning that plant protection product, the active substance, its metabolites, a safener, synergist or co-formulant contained in the plant protection product, which suggests that the plant protection product no longer complies with the criteria set out in Articles 29 and 4 respectively. In particular, potentially harmful effects of that plant protection product, or of residues of an active substance, its metabolites, a safener, synergist or co-formulant contained in it, on human or animal health or on groundwater, or their potentially unacceptable effects on plants or plant products or the environment shall be notified. To this end the authorisation holder shall record and report all suspected adverse reactions in humans, in animals and the environment related to the use of the plant protection product. The obligation to notify shall include relevant information on decisions or assessments by international organisations or by public bodies which authorise plant protection products or active substances in third countries
Article 72. Penalties
The Member States shall lay down the rules on penalties applicable to infringements of this Regulation and shall take the measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate and dissuasive. The Member States shall notify those rules and any subsequent amendment to the Commission without delay.
