# La crédibilité de l'expertise scientifique. Enjeux et recommandations

Pierre-Benoît Joly, Catherine Dargemont, Francine Behar-Cohen, Jean-Marc Bonmatin, Marion Desquilbet, Christian Ducrot, Alain Kaufmann, Emeline Lagrange

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Pierre-Benoît Joly, Catherine Dargemont, Francine Behar-Cohen, Jean-Marc Bonmatin, Marion Desquilbet, et al. La crédibilité de l'expertise scientifique. Enjeux et recommandations. ANSES. 2022. [hal-04308885](https://hal.science/hal-04308885v1)

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https://hal.science/hal-04308885v1

Submitted on 27 Nov 2023

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anses

Scientific Council of the French Food, Environment and Labour Safety Agency - Anses

Opinion on the report of the WG "Credibility of scientific expertise"
from the Scientific Council

In recent years, among the hundreds of opinions issued by the Anses, a few relating to regulated products have given rise to controversy and debate. In this context, the Agency's Scientific Council has mandated a working group (WG) to analyze the situation and make recommendations to strengthen the credibility of the Agency's expert opinions. It thus responds to the objective of permanent reflection stated by the Agency in its framework document on the methodology of collective expertise at Anses (June 2012) as well as to the objective of reinforcing scientific excellence, quality and independence of expertise (Anses Objective and Performance Contract 2018-2022).

The WG addressed the issue of the credibility of the expertise, i.e. the degree of trust it enjoys, based on a feedback approach on three case studies that have been the subject of controversy to varying degrees (glyphosate, SDHIs, neonicotinoids) and on an examination of the factors that determine the credibility of the expertise through a literature review and some 30 hearings. The data were examined along four lines: the discrepancy between the scientific knowledge available and that used for the three expert reports, the procedures, the discrepancy between the conclusions of the expert reports and the expectations of the stakeholders, and finally, the socio-economic impact of the implementation of risk management measures.

MAIN RESULTS: SCIENTIFIC EXPERTISE AT THE HEART OF THREE MAJOR TENSIONS

The results of this work shed light on three major tensions affecting scientific expertise in general.

Scientific expertise is subject to a first tension: on the one hand, the need to take into account the most advanced scientific knowledge and, at the same time, the need to rely on clear rules shared by all the actors concerned, so as to carry out a transparent, robust and reproducible risk assessment. This can lead to a discrepancy between scientific knowledge and the results of expert assessments, which is a source of public controversy.

The second tension refers, on the one hand, to the urgency of issuing certain opinions and, on the other, to the time needed to carry out a quality scientific expertise. The urgency may lead to adapting the usual codified rules of collective expertise to the time constraints
(plurality, capacity to analyze all available data, time for collective work, etc.). Their results
may be fragile and therefore subject to challenge.

A third tension runs through the expertise. On the one hand, it leads to the need to separate
risk assessment and risk management and, on the other hand, the need to put the results of
the assessment into perspective with regard to the feasibility of management measures. This
tension is

This is particularly true in situations of uncertainty, where, in application of the precautionary
principle, it is necessary to qualify the uncertainty and the level of risk, and to implement
proportionate measures. This requires, in particular, knowledge of the socio-economic
impacts of the measures and the possible alternatives. A lack of clarity in the separation of
assessment and management and a lack of transparency in the translation of advice into
management measures contribute to the erosion of the credibility of the expertise.

RECOMMENDATIONS

Concerning Anses, the Scientific Council emphasizes that procedural issues are already the
subject of constant attention and efforts by the agency (expert groups bringing together
scientists chosen for their expertise, subject to independence in the sector of activity
considered). The same applies to relations with research (own research capacities, funding
of programs supporting studies to fill knowledge gaps, coordination of the European
Partnership for Risk Assessment of Chemicals (PARC)). At the international level, the
agency is generally considered as one of the most advanced on these issues. Nevertheless,
the Anses is subject to the tensions of expertise.

The lessons and recommendations from the three case studies analyzed by the WG are
particularly relevant to situations in which there is high uncertainty and/or controversy among
experts.

In order to limit the risks of expertise being called into question, the Scientific Council has
formulated four groups of recommendations aimed at improving procedures, better informing
the decision-making process, intensifying interactions with stakeholders and strengthening
the separation of risk assessment and risk management within Anses.

1. IMPROVE PROCEDURES

1.1. Collectives of expertise

- Encourage scientific diversity (multidisciplinarity) as well as the dual presence of academic researchers and researchers familiar with the regulations

- Encourage the participation and renewal of experts

* Encourage employers (universities, research operators, health agencies, expertise institutes...) to recognize scientific expertise in the evaluation of researchers/teaching researchers and agents, to facilitate the exercise of expertise (partial availability, publication assistance...) and to make visible the major role that expertise plays in the relations between scientists and society

* Promote expert missions in the framework agreements between Anses and its partners, but also in the Research Alliances; develop new agreements if necessary

* Use auditions as much as necessary when a specific skill is required
* Ensure regular renewal of the pool of experts to avoid the accumulation of mandates over time

- Strengthen the application of the rules of collective expertise

* Clarify, for themselves and for the experts, the role of the expert group chairman, the expert coordinator and the Anses agents participating in these groups, in accordance with the new provisions of the internal regulations

* Reinforce the training/information of experts and Anses agents on the rules, rights and duties of collective expertise and on their protection against media exposure

* Ensure that discussions and minority opinions are recorded in the minutes of meetings

- Refine the treatment of links of interest, in particular by applying the guidelines for the analysis of intellectual links proposed by Anses

## 1.2. Referrals and self-referrals

- Systematize the possibility for expert groups to express their views on the formulation of questions and the timetable for dealing with them and, if necessary, plan discussions with the supervisory authorities to clarify the referral (subject, questions, deadlines and timetable for delivery, etc.)

- Informing expert groups of stakeholders' expectations expressed in Anses' dialogue structures

- To reserve the Emergency Collective Expertise Group (ECG) format exclusively for expertise that can be processed within a short timeframe, from the date of receipt of the referral

- Plan a long-term follow-up to ensure a continuous monitoring of knowledge on complex issues, where the health and/or media stakes are high

- Increase the use of self-referrals by the Agency in order to anticipate foreseeable problems

## 1.3. Scientific alerts

- Formalize the treatment of scientific alerts and promote exchanges with the scientists who formulate them
## 2. BETTER INFORMING THE DECISION THROUGH THE EXPERTISE PROCESS

- Systematically validate the selection of the literature taken into consideration with the groups of experts and develop a method for systematically screening for links of interest in the bibliographic journals used (conflicts of interest of authors and editors, funding of studies and scientific journals)

- Facilitate access to data contained in regulatory files

- Define a complete risk assessment grid, applicable in whole or in part depending on the situation, including risk assessment, qualification of the level of uncertainty (in accordance with the recommendations of the group "Accompanying the implementation of the Risk Assessment Methodology recommendations"), analysis of the economic and social impacts (CES "Socio-economic Analysis"), study of alternatives

- In the reports and opinions published by the Agency, systematically indicate: the level of uncertainty, scientific controversies (minority opinions, if any) and any discrepancies between the assessment carried out within the regulatory framework and the scientific knowledge produced outside the framework of the guidelines in force

- Use the recommendations resulting from the expert assessments in terms of knowledge improvement needs to prioritize funding for research projects (carried out by Anses laboratories or by external teams via research and development agreements or the National Environment-Health-Occupational Research Program), in particular to generate scientific data that will enable standards or assessment methods to evolve

- Collecting critiques and reservations from expert groups on regulatory frameworks for evaluation and increasing the Agency's role in the design of international guidelines (OECD, EU)

## 3. CONTINUE TO STRENGTHEN INTERACTIONS BETWEEN ANSES AND ITS STAKEHOLDERS

- Continue to report to stakeholders on how their expectations have been addressed by the Agency

- For management decisions under the responsibility of the Anses, ensure the same level of clarification as that required for risk assessment

- Strengthen the links between Anses and operators/research organizations

* Make research teams aware of the methodological prerequisites for taking their results into account in expert assessments

* Raise awareness among Anses agents and experts of the issues related to the interactions between expertise, politics and society

* Support an interagency initiative to analyze the mechanisms of ignorance production and their influences on regulatory frameworks

## 4. STRENGTHENING THE SEPARATION OF RISK ASSESSMENT AND MANAGEMENT AT ANSES

- Attach all specialized expert committees to the "Science for Expertise" cluster
- Improve the clarity of the missions of the different entities of the Agency, particularly with regard to regulated products

In conclusion, the implementation of the proposed recommendations requires support with adequate human and financial resources.
The credibility of scientific expertise

Issues and recommendations

REPORT
of the working group of
the Scientific Council of Anses

November 2022
**Suggested quote**

Joly, P.B., Dargemont, C., Béhar, F., Bonmatin, J.M., Desquilbet, M., Ducrot, C., Kaufmann, A., Lagrange, E. (2022). The credibility of scientific expertise. Enjeux et recommandations - Rapport du Groupe de travail du Conseil scientifique de l'Anses, Maisons-Alfort: Anses, 134 p.

**Key words**

Scientific expertise; credibility; procedures; regulatory science; risk communication; agnotology; socio-economic analysis; uncertainty; precautionary principle.
# Presentation of the speakers

## WORKING GROUP FROM THE ANSES SCIENTIFIC COUNCIL

### Chair of the WG

Mr. Pierre-Benoît JOLY - Research Director, President of the INRAE Occitanie center - Toulouse - Sociology of risk - Socio-economics of innovation - Biotechnologies - Seed industry - Science-society relations - Socio-ecological impacts of research

### Vice President

Mrs Catherine DARGEMONT - Research Director at the Centre national de la recherche scientifique (CNRS) - on leave - Genetics - Epigenetics - Cell biology - International scientific strategy - Evaluation - Research management

### Members

Mrs. Francine BÉHAR - University Professor at the University of Paris Descartes - Hospital practitioner in ophthalmology at the AP-HP - Neurosciences - Biology - Ophthalmology - Physical agents - Human health

M. Jean-Marc BONMATIN - Senior Research Fellow at the CNRS, Centre for Molecular Biophysics, Orléans - Chemistry - Toxicology

Mrs. Marion DESQUILBET - Senior Research Fellow at INRAE Toulouse and the Toulouse School of Economics - Economics, Interdisciplinarity - Environment - Food systems - Agricultural models - Socio-economic effects of GMOs

Mr. Christian DUCROT - Research Director, Deputy Head of the Animal Health Department at INRAE Montpellier - Epidemiology - Animal health - Antibiotics use - Infectious diseases - Interdisciplinarity

Mr. Alain KAUFMANN - Director of the ColLaboratory, a collaborative and participatory research unit of the University of Lausanne - Humanities and Social Sciences

Mrs Emmeline LAGRANGE - Hospital practitioner in neurology at the Grenoble Alpes University Hospital - Medicine - Neurology - Environment, Epidemiology - Neuromuscular diseases
ANSES SCIENTIFIC COUNCIL

**PREAMBLE:** The expert members of the Anses Scientific Advisory Board are all appointed in a personal capacity, intuitu personae, and do not represent their parent organization

The work, which is the subject of this report, has been monitored and adopted by the Anses Scientific Council.

- **Scientific Council** - [2020-2023]

**President**

Mrs. Isabelle MOMAS - University Professor, Public Health and Environment, University of Paris, Faculty of Pharmacy of Paris - Public health - Environmental health - Environmental epidemiology - Expology - Air pollution - Allergies

**Vice Presidents**

Mr. Alain BERGERET - Retired, Professor at the University of Lyon 1 - Hospital practitioner in occupational medicine and health at the Hospices Civils de Lyon - Occupational diseases - Occupational risks - Epidemiology - Cancer

Mr. Hein IMBERECHTS - Main function - Bacteriology (Escherichia coli and Salmonella) - Zoonoses - Antibiotic resistance - Molecular biology - Epidemiology - Risk assessment

**Members**

Mr. Robert BAROUKI - University Professor, Director of Research at the National Institute of Health and Medical Research (Inserm) - Biochemistry - Toxicology - Exposome

Mrs. Francine BÉHAR - University Professor at the University of Paris Descartes - Hospital practitioner in ophthalmology at the AP-HP - Neurosciences - Biology - Ophthalmology - Physical agents - Human health

Mr. Jean-Marc BONMATIN - Senior research fellow at the CNRS in Orléans - Chemistry - Toxicology

Mrs. Véronique COXAM - Research Director at INRAE Theix - Nutrition - Health - Nutritional prevention of chronic diseases

Mrs Catherine DARGEMONT - Research Director at CNRS Montpellier - on leave - Genetics - Epigenetics - Cell biology - International scientific strategy - Evaluation - Research management

Mrs. Marion DESQUILBET - Senior Research Fellow at INRAE Toulouse and the Toulouse School of Economics - Economics, Interdisciplinarity - Environment - Food systems - Agricultural models - Socio-economic effects of genetically modified organisms
Mrs. Pascale DUCHÉ - University Professor, Sciences and Techniques of Physical and Sports Activities, University of Toulon - Exercise Physiology

Mr. Christian DUCROT - Research Director, Deputy Head of the Animal Health Department at INRAE Montpellier - Epidemiology - Animal health - Antibiotic use - Infectious diseases - Interdisciplinarity

Mrs. Jeanne GARRIC - Director of research at INRAE Villeurbanne - Ecotoxicology - Ecological risk

Mr. Pierre-Benoît JOLY - Research Director, President of the INRAE Occitanie center - Toulouse - Sociology of risk - Socio-economics of innovation - Biotechnologies - Seed industry - Science-society relations - Socio-ecological impacts of research

Mr. Alain KAUFMANN - Director of the ColLaboratory, a collaborative and participatory research unit of the University of Lausanne - Humanities and Social Sciences

Mrs Emmeline LAGRANGE - Hospital practitioner in neurology at the Grenoble Alpes University Hospital - Medicine - Neurology - Environment, Epidemiology - Neuromuscular diseases

Mr. Bruno LINA - Professor at the University of Lyon - Practitioner in virology at the University Hospital of Lyon - Virology - Infectiology - Integrative approach to the characterization and control of influenza virus surveillance - Infectious diseases

Mr. Marc LUCOTTE - Professor at the Department of Earth and Atmospheric Sciences of the University of Quebec in Montreal - Environmental sciences - Aquatic systems - Agricultural soils - Heavy metals - Pesticides - Greenhouse gases - Dynamics of environmental systems

Mr. Francis MÉGRAUD - Professor emeritus at the University of Bordeaux - Attached practitioner at the University Hospital of Bordeaux - Helicobacter infections - Campylobacter infections and other digestive infections - Gastric cancer

Mrs Claire NEEMA - Professor in Plant Pathology, Montpellier Supagro - Plant health - Plant pathology - Plant epidemiology - Coevolution - Population genetics

Ms. Marie-Claude PAQUETTE - Specialized Scientific Advisor - Institutional Researcher at the Institut national de santé publique du Québec - Food environment - public policy - Food/nutrition - Processed foods - Taxation of sweetened beverages

Mr. Philippe QUÉNEL - Honorary Professor at the Ecole des hautes études en santé publique - Medicine - Epidemiology - Public Health

Mr. Marc SOULAT - Professor at the University of Toulouse 3 - Hospital practitioner in medicine and occupational health at the University Hospital of Toulouse - Occupational health - Occupational diseases - Environmental health - Phytopharmacovigilance - Agriculture agronomy - Exposomes
Mr. Noël TORDO - Head of the antiviral strategies unit at the Pasteur Institute of Paris and Director of the Pasteur Institute of Guinea - Virology - Antiviral strategies - Ebola - Animal health

Mrs. Florence VAL - Professor of Plant Pathology, Director of the Ecology Department, Agrocampus Ouest Rennes - Plant health - Genetics of resistance in plants

Mr. Xavier VAN HUFFEL - Former Director of the Directorate for Risk Assessment at the Belgian Federal Agency for the Safety of the Food Chain - Animal health - Epidemiology - Risk assessment - Food chain - Research - Emerging risks

## PARTICIPATION Anses

### Scientific and administrative coordination

Mrs. Fanny DEBIL - Coordinator of social science studies - Social Sciences, Economy and Society Department - Anses

### Administrative secretary

Mrs. Frieda Ngoue - Anses

## PERSONALITIES INTERVIEWED

*Three interviewees did not wish to be included in this list.*

*The quotes from the verbatims are anonymized and associated with generic categories, all of which are in the masculine form.*

### Anses

Mr. Thomas BAYEUX - Socioeconomic Analysis Officer - Social Sciences, Economy and Society Directorate - Anses

Mrs. Juliette BLOCH - Director of the Health Alerts and Vigilance Department - Anses

BOURDEAUX - Head of the Expertise Support Department - Anses

Mrs. Karine FIORE - Assistant to the Director of the Social Sciences, Economy and Society Directorate - Anses

Mr Roger GENET - Director General - Anses

Mrs. Sophie GUITTON - Assistant to the Director of Research Funding and Scientific Watch

Mr. Gérard LASFARGUES - Scientific advisor - Anses scientific integrity referent

Mr. Brice LAURENT - Director of the Social Sciences, Economy and Society Department - Anses
Mr. Gilles SALVAT - Deputy Director General of the Research and Reference Unit - Anses

## Research organizations, universities and national laboratories

Mr. Gérard ARNOLD - Emeritus Research Director - CNRS

M. Robert BAROUKI - University Professor, Director of Unit - Inserm Mme Judith

FAVIER - Research Director - Inserm

Mr. Christian GAUVRIT - Retired agronomist, INRAE, Vice-Chairman of the CES "Substances and phytopharmaceutical products, biocontrol".

Mrs Laurence HUC - Research Director - INRAE

Mr. Jean-Noël JOUZEL - Director of Research - CNRS/Centre de sociologie des organisations

Mrs. Laura MAXIM - Research Fellow - CNRS/Lisis

Mr. Rémy MAXIMILIEN - former scientific advisor - Commissariat à l'énergie atomique et aux énergies alternatives

Mr. Jean-Ulrich MULLOT - Chief Pharmacist, Army Health Service - LASEM

Mr. Pierre RUSTIN - Research Director - CNRS

Mr. Bernard SALLES - Professor emeritus of the universities, toxicologist - University Paul-Sabatier Toulouse III

## National Assembly

Mrs. Delphine BATHO - Member of Parliament

Mrs. Elisabeth TOUTUT-PICARD - Former Member of Parliament

Mr. Cédric VILLANI - Former Member of Parliament, Former President of the OPECST

## General Inspections

Mr. Benjamin FERRAS - Inspector General - IGAS Ms.

Cécilia BERTHAUD - Inspector General - IGF
Journalists

Mr. Stéphane FOUCART - Journalist - Le Monde

Mr. Fabrice NICOLINO - Journalist - Charlie Hebdo

Companies

Mrs. Eugénia POMMARET - Public Affairs Manager - Crop Science Division - Bayer (General Manager of the Union des Industries de la Protection des Plantes until January 2022)

ACKNOWLEDGEMENTS

Adèle Canus-Lacoste, Lawyer

Christine Noiville, Research Director, CNRS
# Contents

<table><tr><td>Presentation of the speakers</td><td>3</td></tr><tr><td>Contents</td><td>9</td></tr><tr><td>Acronyms and abbreviations</td><td>13</td></tr><tr><td>List of tables</td><td>15</td></tr><tr><td>List of figures</td><td>16</td></tr><tr><td>List of boxes</td><td>17</td></tr><tr><td>Summary of the case and recommendations</td><td>18</td></tr><tr><td>Synthesis</td><td>18</td></tr><tr><td>WG Terms of Reference</td><td>18</td></tr><tr><td>Method</td><td>18</td></tr><tr><td>Results</td><td>20</td></tr><tr><td>Recommendations</td><td>21</td></tr><tr><td>Regulatory framework and new science</td><td>22</td></tr><tr><td>Procedures</td><td>23</td></tr><tr><td>Interactions of the Anses with its stakeholders</td><td>25</td></tr><tr><td>Precautionary principle and the evaluation/management link</td><td>25</td></tr><tr><td>Organization of the Anses</td><td>25</td></tr><tr><td>Cross-cutting recommendation</td><td>26</td></tr><tr><td>1. Context, purpose and methods of carrying out the expertise</td><td>27</td></tr><tr><td>1.1 Context</td><td>27</td></tr><tr><td>1.2 Subject of the referral</td><td>27</td></tr><tr><td>1.2.1 Processing methods: means implemented and organization</td><td>27</td></tr><tr><td>1.3 Preventing the risk of conflicts of interest</td><td>27</td></tr><tr><td>2. Heuristic framework and methodology of the WG</td><td>29</td></tr><tr><td>2.1. Issue</td><td>29</td></tr><tr><td>2.1.1. Complex factors and environment to consider when assessing the credibility of scientific expertise</td><td>29</td></tr><tr><td>2.1.2. Specific questions posed by regulatory science</td><td>30</td></tr><tr><td>2.2. Theses retained by the WG</td><td>32</td></tr><tr><td>2.2.1. Thesis 1. Credibility is a matter of reducing the gap between scientific knowledge and expertise</td><td>33</td></tr><tr><td>2.2.2. Thesis 2. Credibility is a matter of procedure</td><td>33</td></tr><tr><td>2.2.3. Thesis 3. Credibility is a matter of reducing the gap between the expertise and the expectations of the concerned</td><td>33</td></tr></table>
2.3. Survey techniques ..................................................................................................................35

2.4. A few points of reference on the expertise activities of Anses ........................................36

3. Presentation of the case studies ................................................................................................39

3.1. Neonicotinoids....................................................................................................................39

3.1.1. A coalition of stakeholders emphasizes the importance of knowledge not considered in the regulatory framework ....................................................................................................................39

3.1.2. Europe takes over ................................................................................................................40

3.1.3. The specific contribution of the Anses as evaluator and manager ................................41

3.1.4. Reflection on the integration of new knowledge................................................................43

3.1.5. Lessons from the case concerning the credibility of scientific expertise....................43

3.2. Glyphosate............................................................................................................................44

3.2.1. The context ....................................................................................................................44

3.2.2. Opinion of the Anses........................................................................................................47

3.2.3. The lessons of the glyphosate case concerning the credibility of scientific expertise
51

3.3. SDHI .................................................................................................................................51

3.3.1. Case Summary ................................................................................................................52

3.3.2. Lessons from the case concerning the credibility of scientific expertise....................58

4. Thesis 1. Integration of the evolution of scientific knowledge in a science framed by regulations ....................................................................................................................59

4.1. Regulatory science and structuring of knowledge mobilized in scientific expertise......
60

4.1.1. The documentary base mobilized in the expertise....................................................60

4.1.2. Links of interest in the affiliations of the authors of the articles or their funding ............61

4.1.3. Consideration of emerging scientific hypotheses and recent data ................................63

4.1.4. Consideration of academic scientific results obtained outside of GLP guidelines and standards, including when analyzing the risks of regulated products ........................................64

4.1.5. Access to the details of regulatory data ........................................................................67

4.1.6. Time to analyze the collected data in detail ........................................................................68

4.1.7. Ability to return to literature reviews with different lexical queries as the expertise......
68

4.1.8. Work carried out in Anses laboratories or in academic laboratories and funded by Anses ....................................................................................................................................................
4.2. Role of Anses in establishing guidelines..................................................................................69

5. Thesis 2. Procedural issues................................................................................................................71

5.1. Preparation of the referral........................................................................................................72

5.2. Composition of committees and selection of experts................................................................74

5.2.1. A panel of quality, multidisciplinary experts from different professional backgrounds
74

5.2.2. The pool of experts: difficulties in recruitment, attractiveness, commitment..................76

5.2.3. Dealing with conflicts and links of interest ........................................................................78

5.3. The GECU: an inappropriate forum for assessing uncertain and controversial issues ..
80

5.4. Implementing expertise: working together ................................................................................82

5.4.1. Animation and coordination of expert groups ........................................................................82

5.4.2. The contradictory opinion within the group or the minority opinion: a statutory obligation of the agency to be trivialized ....................................................................................................................84

5.5. The need to formalize the handling of alerts........................................................................85

6. Thesis 3. The gap between the expertise and the expectations of the concerned
audiences..................................................................................................................................................89

6.1. The credibility paradox: trust in science but mistrust in the role of public authorities...
89

6.2. Recognition of the agency's work to build trust........................................................................91

6.2.1. Various interlocutors underline a discrepancy between the quality of the work of the Anses and the criticisms addressed to it....................................................................................91

6.2.2. Stakeholder dialogue structures - an internal communication problem?....................92

6.2.3. Two obstacles: media coverage of controversies and totemic subjects....................93

6.2.4. How to improve risk assessment communication? ........................................................95

6.3. Too narrow a scope of expertise ................................................................................................98

6.3.1. A critique of case-by-case evaluation................................................................................99

6.3.2. Too much influence of the regulatory framework on risk assessment ....................100

6.3.3. The influence of industry groups on regulatory frameworks ............................................101

7. Thesis 4. Socio-economic impact of the implementation of risk management
measures....................................................................................................................................................103

7.1. Socio-economic issues mentioned in the case studies.................................................................103

7.2. Views on the positioning of the Anses in the conflict over pesticide issues....................105
Acronyms and abbreviations

<table><tr><td>AFSSA</td><td>:</td><td>French Food Safety Agency</td></tr><tr><td>AGG</td><td>:</td><td>Assessment group on glyphosate</td></tr><tr><td>AMM</td><td>:</td><td>Marketing authorization</td></tr><tr><td>APR-EST</td><td>:</td><td>Call for research projects - environment-health-work</td></tr><tr><td>ANMV</td><td>:</td><td>National Agency for Veterinary Medicines (Anses)</td></tr><tr><td>BfR</td><td>:</td><td>Bundesinstitut für Risikobewertung, German Federal Institute for Risk Assessment</td></tr><tr><td>GLP</td><td>:</td><td>Good laboratory practice</td></tr><tr><td>CDPCI</td><td>:</td><td>Ethics and Conflict of Interest Committee of the Anses</td></tr><tr><td>CE</td><td>:</td><td>European Commission</td></tr><tr><td>CES</td><td>:</td><td>Specialized expert committee</td></tr><tr><td>IARC</td><td>:</td><td>International Agency for Research on Cancer</td></tr><tr><td>COP</td><td>:</td><td>Contract of objectives and performance</td></tr><tr><td>COT</td><td>:</td><td>Thematic Steering Committee</td></tr><tr><td>CLP</td><td>:</td><td>Regulation No. 1272/2008 of the European Parliament on classification, labelling and packaging of chemicals and mixtures</td></tr><tr><td>cnDAspe</td><td>:</td><td>National Commission on Ethics and Alerts in Public Health and the Environment</td></tr><tr><td>DAMM</td><td>:</td><td>Directorate of Marketing Authorizations (Anses)</td></tr><tr><td>DAVS</td><td>:</td><td>Direction des alertes et des vigilances sanitaires (Anses)</td></tr><tr><td>DER</td><td>:</td><td>Risk Assessment Department (Anses)</td></tr><tr><td>DEPR</td><td>:</td><td>Directorate for the Evaluation of Regulated Products (Anses)</td></tr><tr><td>DiSSES</td><td>:</td><td>Social Sciences, Economy and Society Directorate (Anses)</td></tr><tr><td>ECHA</td><td>:</td><td>European Chemicals Agency</td></tr><tr><td>EFSA</td><td>:</td><td>European Food Safety Authority</td></tr><tr><td>GECU</td><td>:</td><td>Emergency Collective Expertise Group</td></tr><tr><td>GT</td><td>:</td><td>Working Group</td></tr><tr><td>INRAE</td><td>:</td><td>National Research Institute for Agriculture, Food and Nutrition the environment</td></tr></table>
Inserm : National Institute of Health and Medical Research

PARK : European Partnership for Risk Assessment of Chemicals

OECD : Organization for Economic Cooperation and Development

OFB : French Office for Biodiversity

GMO : Genetically modified organisms

NGO : Non-governmental organization

OPECST : Office parliamentary d'évaluation of choices scientific and technological choices

NRP-EST : National environment-health-work research program

REACH : Regulation n° 1907/2006 of the European Parliament and of the Council on the registration, evaluation, authorization and restriction of chemicals

EU : European Union
List of tables

Table 1. Overview of scientific expertise modes and productions at Anses
List of figures

Figure 1: Anses organization chart as of June 1, 2022

Figure 2: Chronology of the SDHI case

Figure 3: A general lack of confidence in the ability of public authorities to protect people
(Source: IRSN 2021 p.34).
List of boxes

Box 1. Key lessons from the case studies
# Synthesis of the argument and recommendations

## Synthesis

### WG Terms of Reference

In recent years, the expert reports produced by the Anses (and in some cases the experts who contributed to them) have been contested and even violently attacked, directly or through the media. This situation, if not carefully managed, could threaten the credibility of the agency, particularly for the management of pesticide dossiers and for the planned transfer of the evaluation of genetically modified organisms (GMOs), another very sensitive dossier. In this context, the Working Group (WG) set up by the Anses Scientific Council was tasked with diagnosing past events, analyzing the various cause-and-effect relationships, and making proposals on the various possible ways to improve the situation.

By addressing these issues from a feedback approach and by mobilizing scientific knowledge on scientific expertise, this working group intends to contribute to the institutional reflexivity of the Agency and to strengthen its credibility. It thus meets the objective of permanent reflection stated by the Agency in its framework document on the methodology of collective expertise at Anses (June 2012) as well as the objective of reinforcing scientific excellence, quality and independence of expertise (Anses Objective and Performance Contract (COP) 2018-2022)

## Method

The credibility of expertise can be defined as the degree of confidence in it. Credibility is the result of a set of factors that manage to convince people of the accuracy of the expertise within a defined framework. As sociology and the history of science show, the credibility of expertise depends on many factors: institutional, social, procedural... but first of all on the rigor, impartiality and transparency with which it is conducted. In order to identify these different factors, the approach was conducted at two levels:

* The core of the analysis is the realization of case studies on the glyphosate, SDHI and neonicotinoid dossiers, allowing for feedback. These studies are based on a detailed analysis of the processes aimed at identifying the role of factors related to the conduct of the process;

* A more general approach, based on a literature review and interviews with agency managers and stakeholders, is also used. It aims to understand the factors related to (i) organizational reputation and (ii) stakeholder expectations. This general approach makes it possible to supplement or even extrapolate the case studies, in order to identify cross-cutting findings and recommendations.
The three case studies

The choice of three cases (glyphosate, SDHI, neonicotinoids) was guided by the repeated
criticism of the opinions issued and the intensity of the controversies and polemics generated
by the glyphosate and SDHI assessments in different arenas (media, Parliament, non-
governmental organizations (NGOs), administrations, etc.), which have damaged the
agency's reputation - in contrast to the case of neonicotinoids, for which criticism of the
agency's assessments has, on the contrary, been limited. These cases, which are rare but
relevant for an in-depth analysis of the scientific credibility of the Anses, are not
representative of the hundreds of opinions issued each year by the agency. Nevertheless,
the analysis of such cases is timely and necessary when one is interested in the credibility of
scientific expertise. Moreover, the intensity of the controversies and polemics makes it
possible to collect a very rich material, which is essential for such an analysis.

In a transversal way, a heuristic framework was also mobilized. It includes four working
theses:

* Thesis 1. Credibility is a matter of discrepancy between scientific knowledge and expertise

- Thesis 2. Credibility is a matter of procedures

* Thesis 3. Credibility is about the gap between expertise and the expectations of the concerned audiences

* Thesis 4. Credibility is about the socio-economic impact of implementing risk management measures

For each of the three cases, descriptive sheets were produced based on the collection of all
available literature. This documentary phase was extended beyond the cases to cross-cutting
themes by collecting a variety of sources. About thirty interviews were conducted with
researchers (13), Anses officials (11) and various stakeholders (8). These interviews were
processed in two phases:

- A double-coding of all interviews according to the four theses of the heuristic framework

* An analysis of the different hypotheses for each case (transversal elements, specific elements) based on the verbatim
# Results

## Neonicotinoids

In the case of neonicotinoids, criticism of the Anses' expertise remained limited in the media and focused on the authorization of sulfoxaflor. The decision of the Nice court and the non-appeal of the Anses have extinguished the controversy. The absence of questioning of scientific credibility in this case is due to the integration of new scientific knowledge in the regulatory framework, even if the time required for the investigation is undeniably too long and the process is still incomplete. This integration tends to reduce the distance between the answers provided by the agency and the expectations of the various stakeholders. The weight of economic interests limits the integration process, both at the European level (little integration of knowledge in the guidelines) and at the French level (derogation granted to the beet industry). The content and lack of transparency of these decisions undermine the credibility of the expertise. Concerning the role of procedures, the mobilization of expertise predates the creation of the agency. The history of this case shows the procedural progress linked to the creation of the Anses compared to what prevailed before. Witnesses cite in particular the independence of the expertise and the scientific referencing of arguments. The possibility of self-referral, which is essential to investigate complex and uncertain issues, was also mentioned. It is therefore essential that the principles of impartiality and adversarial nature of the collegial expertise be strictly respected.

## Glyphosate

The Anses has faced significant criticism concerning the expert assessments it has conducted on glyphosate. These criticisms are part of a context in which the regulatory evaluation of glyphosate has crystallized criticisms and strong expectations from civil society, but also from actors in the scientific and political worlds, and has become an emblem of expected changes, on a better consideration of the dangers and risks of pesticides, more broadly as regards agricultural production methods. The procedures play an essential role here with the restriction of the questions asked to the experts in the referrals, the modalities of functioning of an expertise in the form of Groups of collective expertise in urgency (GECU), the literature taken into account, the reading of the precautionary principle, the non finalization of a mandate entrusted to a group of experts. The gap between science and expertise also plays an important role, with the whole issue of the gap between the evaluations of the International Agency for Research on Cancer (IARC) and EFSA (European Food Safety Authority), strong criticism of the European regulatory expertise on glyphosate. They affect the Anses via the collectives of experts mobilized but also via the agency's activity, whether it is the legal ban on Roundup Pro 360 or the criticisms addressed to the Assessment Group on Glyphosate (AGG) consortium, in charge of the re-evaluation of the authorization of glyphosate. Finally, because of the importance of glyphosate's uses and the difficulties of doing without this active substance, the weight of economic interests appears to be an obstacle to the consideration of independent expertise.

## SDHI

The Anses' management of the scientists' alert on SDHI was strongly criticized for the procedures implemented, both for the initial exchanges with the group of scientists and for various limitations related to the choice of a GECU format for the initial investigation of the alert (limited in duration, number of experts involved and their field of expertise, consideration of scientific literature). The gap between science and expertise also plays an essential role, since the alert concerns a gap between scientific knowledge on known toxicity mechanisms (mitotoxicity) and the regulatory framework for the evaluation of pesticides, which does not take these mechanisms into account. A strong involvement of different stakeholders from civil society, the political world and the scientific community, testifies to the discrepancy between the expectations of a broad assessment of the dangers and risks of pesticides and the narrow framework of regulatory expertise, which is also a source of erosion of credibility. Finally, the high economic stakes surrounding the use of SDHI in the agricultural sector appear to be a brake on the societal and political demand for a reduction in the use of pesticides.

**Box 1. Key lessons from the case studies**
## Main results: scientific expertise at the heart of three major tensions

The results of this work shed light on three major tensions affecting scientific expertise in general.

Scientific expertise is subject to a first tension: the need to take into account the most advanced scientific knowledge while relying on clear rules shared by all the actors concerned, for the conduct of a transparent, robust and reproducible risk assessment. This can result in a discrepancy between scientific knowledge and the results of expert assessments, which is a source of public controversy.

The second tension refers, on the one hand, to the urgency of issuing certain opinions and, on the other, to the time needed to produce a quality scientific assessment. The urgency can lead to work that does not respect all the usual and codified rules of collective expertise (diversity of experts, access to all available documentation, time for collective work, etc.). Their results can be weakened and thus be the subject of contestation.

Finally, a third tension runs through the expertise. On the one hand, it leads to the need to separate risk assessment and risk management and, on the other hand, the need to put the results of the assessment into perspective with regard to the feasibility of management measures. This tension is particularly strong in situations of uncertainty, where, in application of the precautionary principle, it is necessary to qualify the uncertainty and the level of risk, and to implement proportionate measures. This requires, in particular, knowledge of the socio-economic impacts of the measures and the possible alternatives. A lack of clarity concerning the modalities for separating assessment and management and a lack of transparency concerning the translation of opinions into management measures are another source of erosion of the credibility of expertise.

## Recommendations

As far as the Anses is concerned, procedural issues are already the subject of constant attention and efforts by the agency (expert groups bringing together scientists chosen for their competence, subject to independence in the sector of activity concerned). The same applies to relations with research (own research capacities, funding of programs supporting studies to fill knowledge gaps, coordination of the European Partnership for Risk Assessment of Chemicals (PARC)). At the international level, the agency is generally considered as one of the most advanced on these issues.

However, the Anses is subject to the tensions of expertise. In particular, the gap between science and expertise is one of the most important factors in the erosion of credibility, and the Anses does not always succeed in reducing this tension. In particular, in the fields studied, compliance with a European regulatory framework does not allow for the rapid integration of new scientific knowledge, which is nonetheless relevant for risk assessment. In addition, expert reports from Emergency Collective Expertise Groups (GECU) have been challenged.
The lessons learned from the three case studies analyzed by the WG are particularly relevant to situations in which there are high uncertainties and/or controversies between experts. The WG's recommendations are in line with the continuous improvement of scientific excellence, quality and independence of expertise at Anses (Anses COP, 2018-2022). Some of these recommendations do not fall within the scope of the Anses' competences or means, but the WG considers that they should be implemented, as they refer to the Anses' direct environment, which must be considered.

## Regulatory framework and new scientific knowledge

The credibility of an expert scientific opinion (or of a decision based on an opinion) is all the stronger if the opinion is based on criteria deemed to be in line with the state of the art of scientific knowledge on the subject. Nevertheless, the risk assessment of regulated products imposes guidelines and standards. This can result in a gap between scientific knowledge and expertise, which is a source of public controversy and criticism of expert opinions. Limiting this discrepancy makes it possible to better inform the decision-making process and to limit the risks of challenges to the expertise.

**RECOMMENDATION 1** Systematically validate the selection of the literature taken into consideration with the expert groups and ensure that new scientific knowledge is taken into account

**RECOMMENDATION 2** Develop a method for systematically screening for links of interest in the bibliographic journals used (conflicts of interest of authors and editors, funding of studies and scientific journals) and define criteria for taking them into account

**RECOMMENDATION 3** Facilitate access to data in regulatory files

**RECOMMENDATION 4** Do not limit the risk assessment of products subject to regulatory constraints to expertise restricted to the regulatory framework (knowledge produced in accordance with regulatory frameworks and/or in laboratories governed by good practices (GLP), etc.), and provide for the possibility for expert groups to express criticisms and reservations about the regulatory frameworks of the assessment

**RECOMMENDATION 5** In cases where the referral requires the use of only knowledge generated according to existing guidelines, incorporate out-of-framework knowledge into a specific part of the body of the report and opinion

**RECOMMENDATION 6** Use the recommendations resulting from the expert assessments in terms of knowledge improvement needs to prioritize funding for research projects (carried out by Anses laboratories or by external teams via research and development agreements or the National Environment-Health-Work Research Program (PNR-EST)), in particular to generate the scientific data required to develop standards or assessment methods
**RECOMMENDATION 7** Increase the Agency's role in the design of transnational guidelines (Organisation for Economic Co-operation and Development (OECD), European Union (EU)) and dedicate additional resources to this mission

## Procedures

The credibility of scientific expertise is all the stronger when the expertise procedure has followed the golden rules (impartiality, transparency, plurality and adversarial process). Since its creation, the Anses has been committed to continuously improving its procedures, in particular through the creation of specifically dedicated WGs (WG Risk Assessment Methodology (WG RAM), WG Accompanying the implementation of RAM recommendations (WG ACCMER)). Our recommendations are fully in line with this continuous improvement process.

## Referrals and self-referrals

**RECOMMENDATION 8** Systematize the possibility for expert groups to express their views on the formulation of questions and the timetable for dealing with them and/or to supplement the expertise corresponding to the referral with additional elements in order to better inform the decision and, if necessary, provide for discussions between the expert groups and the supervisory authorities to clarify the referral (purpose, questions, deadlines and timetable for delivery, etc.).

**RECOMMENDATION 9** Increase the use of self-referrals by the Agency to anticipate foreseeable problems

**RECOMMENDATION 10** Provide for long-term monitoring to ensure continuous knowledge surveillance of complex issues with significant health and/or media implications.

## Collectives of expertise

**RECOMMENDATION 11** Foster scientific diversity

* Promote a balance between academic researchers and researchers familiar with the regulations

* Encourage multidisciplinarity and, in particular, when relevant, the involvement of experts in the human and social sciences

**RECOMMENDATION 12** Encourage the participation and renewal of experts

* Encourage employers (universities, research operators, health agencies, expertise institutes...) to recognize scientific expertise in the evaluation of researchers/teaching researchers and agents, to facilitate the exercise of expertise (partial availability, publication assistance...) and to publicize the major role that expertise plays in the relations between scientists and society

* Include expert missions in the framework agreements between Anses and its partners; develop new agreements if necessary
* Develop interactions between Anses and research alliances (Allenvi, Aviesan) to raise the awareness of scientific communities to the expertise mission

* Protect and train experts from media exposure

* Make more systematic use of the audition format when a specific skill is required

**RECOMMENDATION 13** Refining the treatment of conflicts and links of interest

* Apply the guidelines for the analysis of intellectual connections

* Building the capacity to control IPR

**RECOMMENDATION 14** Strengthen the application of the rules of collective expertise

* Clarify the role of the expertise coordinator and of the Anses agents present in the expertise groups (provision of scientific information, coordination support, etc.)

* Set up internal training for expertise coordinators

* Clarify and strengthen the role of the collective chairman in ensuring compliance with the rules of collective expertise, including the role of Anses agents in the experts' discussions

* Establish a quorum for each collective meeting, not just for the adoption of the work

* Ensure that discussions and minority opinions are recorded in the minutes of meetings and facilitate the use of minority opinions throughout the expertise

**RECOMMENDATION 15** Reserve the GECU format exclusively for expert reports that can be processed within a short period of time (typically less than one month from the date of receipt of the referral)

* Prefer a "classic" WG format (except for emergencies) for controversial subjects and/or subjects of scientific alert (with, therefore, a public call for experts)

## Scientific alerts

**RECOMMENDATION 16** Formalize the handling of scientific alerts

* Report in a precise and argued way on the treatment of a scientific alert

* Adopt a scientific alert analysis grid that identifies potential gaps in current guidelines and ways to improve them

**RECOMMENDATION 17** Consider scientists carefully when they issue warnings

* Facilitate their access to data and knowledge exchange

* Integrate them as early as possible in the expertise process (in groups/at hearings)
## Interactions of the Anses with its stakeholders

Concerning interactions with stakeholders, the comparison with other agencies, especially internationally, is generally advantageous for Anses, which has taken many initiatives to open up to society (Thematic Steering Committees (TSC), Dialogue Committees, etc.). The WG encourages the continuation of this approach.

**RECOMMENDATION 18** Inform, internally and in expert groups, of the expectations of stakeholders expressed in Anses' dialogue structures (dialogue committees, COT, inter-COT, phyto platform)

**RECOMMENDATION 19** Continue to report to stakeholders on how their expectations have been addressed by the Agency

**RECOMMENDATION 20** In the reports and opinions published by the Agency, systematically indicate: the level of uncertainty, the scientific controversies (minority opinions if any) and any discrepancies between the assessment carried out within the regulatory framework and the scientific knowledge produced outside the framework of the guidelines in force

**RECOMMENDATION 21** Support an interagency initiative to analyze the mechanisms of ignorance production and their influence on regulatory frameworks

## Precautionary principle and the evaluation/management link

Scientific expertise provides the decision-maker with the necessary arguments to act in a proportionate manner, which requires a necessary qualification of the level of uncertainty, which can be improved in the current procedures of the Anses, and an integration of the socio-economic analysis in order to evaluate the effects of the proposed measures.

**RECOMMENDATION 22** Define a complete risk assessment grid applicable in whole or in part depending on the situation, including risk assessment, qualification of the level of uncertainty (in accordance with the recommendations of the group "Accompanying the implementation of the recommendations of the Risk Assessment Methodology"), analysis of the economic and social impacts (CES "Socio-economic Analysis"), reversibility of damage, analysis and study of alternatives

**RECOMMENDATION 23** For management decisions under the responsibility of the Anses, ensure the same level of explicitness as that required for risk assessment

## Organization of the Anses

Anses carries out risk assessment and, in some cases, risk management missions in a range of fields and for a range of products governed by national, European or international regulations. The organization of the Anses into divisions, effective in 2017, and in particular the structuring of risk assessment and management missions for regulated products, and risk assessment for non-regulated products, is still perfectible. The separation between assessment and management is not clear to some stakeholders.
RECOMMENDATION 24 Attach all ESCs to the "Sciences for Expertise" cluster

RECOMMENDATION 25 Improve the internal and external readability of the missions of the Agency's various entities, particularly with regard to regulated products

RECOMMENDATION 26 Strengthen links between the Agency and operators/research organizations

* Make research teams aware of the methodological prerequisites for taking their results into account in expert assessments likely to lead to changes in regulatory standards

* Raise awareness among Anses agents and experts of the issues related to the interactions between expertise, politics and society

**Cross-cutting recommendation**

RECOMMENDATION 27 In conclusion, the implementation of the proposed recommendations requires support with adequate human and financial resources.
# 1. Context, purpose and modalities of the expertise

## 1.1 Context

In recent years, some of the expert reports produced by the Anses (and sometimes the experts who contributed to them) have been contested, or even violently attacked, directly or through the media. Although the cases that pose a problem are numerically marginal, it is feared that their impact on the agency's reputation may weaken its credibility and the scope of its opinions.

## 1.2 Purpose of the referral

This study aims to provide a better understanding of the factors that condition the credibility of expertise and its challenge, in order to identify predictable factors and provide avenues for improvement.

By addressing these questions from a feedback approach and by mobilizing scientific knowledge on scientific expertise, this working group intends to contribute to the institutional reflexivity of the agency and to the reinforcement of its credibility.

### 1.2.1 Processing methods: means implemented and organization

In this context, the Scientific Council (SC) of Anses has created a working group on the credibility of scientific expertise. The mandate of this WG is to "analyze the different factors and scope of the destabilization of the credibility of the scientific expertise produced by the Agency based on three case studies in the field of plant protection products: SDHI, glyphosate and neonicotinoids".

The work of this WG was regularly presented and discussed in the SC. The report takes into account the observations and additional elements transmitted by the members of the SC.

This work is the result of an interdisciplinary group of researchers with complementary skills.

## 1.3 Prevention of the risk of conflicts of interest

The Anses analyses the links of interest declared by the experts before their appointment and throughout the work, in order to avoid the risk of conflicts of interest with regard to the points dealt with in the expertise.

The declarations of interest of the experts are published on the website https://dpi.sante.gouv.fr/.
The Anses identified a major link of interest in Mr. Bonmatin's declaration of interest concerning the specific case of neonicotinoids. In view of the manageable nature of this major link, a deferral measure was adopted: Mr. Bonmatin did not participate in the writing of the neonicotinoids case.
## 2. Heuristic framework and methodology of the WG

### 2.1. Issue

#### 2.1.1. Complex factors and environment to be considered to understand the credibility of scientific expertise

In the terms of reference of this WG, credibility of expertise is defined as the degree of confidence in it. Credibility is the result of a set of factors that convince people of the accuracy of the expertise within a defined framework. As sociology and the history of science show, the credibility of expertise depends on many factors: institutional, social, procedural... It depends first of all on the rigor, impartiality and transparency with which it is conducted. Nevertheless, the basic axiom of our work is that the credibility of a scientific statement is not equivalent to its validity. Of course, the two are generally linked, but there are many situations where one believes statements that are false or where one does not believe statements that are true<fnref n="1" />.

As Shapin (1995) points out, the factors that influence scientific credibility (not scientific expertise) are numerous and there is no exhaustive list of them. Among the factors most frequently mentioned in the literature, he cites (Shapin 1995: 260):

* the plausibility of the claim

* the reputation (reliability) of the procedure used to produce the result

* the importance and multiplicity of witnesses

* accessibility and replicability of the phenomenon

* the ability to impute bias to the researcher making the claim

* the reputation of the researcher and his/her institution

* the reputation of the researcher's allies

* the estimated costs of the implications of the claim

* a set of characteristics of the researcher (class, gender, age, race, religion, nationality...)

* the level of expertise (competence) of the researcher, taking into account also the means by which this expertise is known and recognized

* the researcher's behaviour and the way in which he or she communicates the claim

* the details of the lives of those evaluating the claim and their knowledge of the lives of those making the claim

* (...)

Shapin's argument concerns the credibility of scientific statements. The difference with the credibility of expertise is that, while for scientific statements the main part is played in the scientific field, for expertise, the arenas of credibility are much more diverse, starting with the traditional media, social networks, politics,

<footnote n="1">¹ In science, and even more so in scientific expertise, the question of truth and falsehood is obviously not so simple and clear-cut. This does not detract from this statement.</footnote>
In addition, the historical dimension of expertise and the multiple arenas in which it is
inscribed must be considered.

To put it another way, thinking about the credibility of scientific expertise, in this case
that of the Anses, cannot be done without analyzing the Agency's place in :

a) a historical trajectory and context

b) an environment, with its multiple actors, spaces and levels - an environment with
which Anses interacts, by which it is influenced, which it influences in return.

2.1.2. Specific questions posed by regulatory science

Scientific expertise is subject to a strong tension between, on the one hand, the need to take into account the most advanced scientific knowledge and, on the other hand, the need to rely on clear rules that are known to all the actors concerned, in order to carry out a transparent, robust and reproducible risk assessment. Regulatory science" is at the heart of this tension. It is therefore necessary to define the concept and to clarify its relationship to so-called academic science. Indeed, regulatory science is more or less institutionalized depending on the country and is not subject to a stabilized definition. We propose to provide an overview based on a synthesis of social science research (notably : Boubal and Jouzel 2019, Camadro et al. 2018, Joly 2016, Borraz and Demortain 2015).

Boubal and Jouzel (2019) define regulatory science as the specific form of recourse to expertise practiced by the agencies in charge of controlling the risks of industrial products and activities. They specify that, for academic researchers, it refers to the coexistence of scientific and political considerations in the work of agencies in charge of risk assessment. For Camadro et al. (2018), the term covers all scientific activities that produce the knowledge used to develop, support, or adapt public health and environmental regulations. According to Borraz and Demortain (2015), regulatory science is a set of scientific assessment activities that participate in the taking of legal measures to frame industrial activities and products (authorization, withdrawal, setting of presence or exposure thresholds, labeling of drugs, cosmetics, certain foods or chemicals, etc.).

Different regulatory bodies around the world use the concept of regulatory science, giving it
different meanings (Camadro et al. 2018). For the Japanese Medical Device and
Pharmaceutical Agency, regulatory science is an estimation science, which aims to estimate
the social impact of scientific and technological advances, regulate and adjust them, and
functions as a bridge between science and society by providing patients with new scientific
knowledge. In the United States, the Food and Drug Administration defines it as the science
that develops new tools, standards and approaches to evaluate the safety, efficacy, quality
and performance of all products regulated by this agency. The European Medicines Agency
considers it to be the range of disciplines applied to the assessment of the quality, safety and
efficacy of medicines, informing regulatory decision making throughout the life cycle of a
medicine: it encompasses medical science (basic and
and social sciences, and contributes to the development of standards and regulatory tools.

The modalities of articulation between agencies and the academic world vary throughout the world and according to the subject. Boubal and Jouzel (2019) describe, in broad strokes, a professionalization of regulatory scientists in the United States, with the scientific community encouraging the development of research in regulatory science, whereas in Europe recourse to academic expertise remains more ad hoc for the purposes of assessing and managing risks induced by industrial development - the modalities of articulation between agencies and the academic world may present different subtleties depending on the precise context (see also July 2016 on these differences).

Irwin et al (1997) propose a framework for analysis by introducing the concept of the "regulatory pentangle". This framework is composed of five categories that indicate the various activities included in regulatory science, which can be carried out by scientists, public experts or industrial actors:

* Academic research on topics that may have regulatory relevance;

* Development and validation of regulatory tests so that products can be analyzed for potential hazards and risks;

* Regulatory compliance testing by industry, often in collaboration with various scientific departments, as required by regulatory authorities;

* Further investigation of test results showing non-compliance with regulations, to identify if the results are false positives, or if there are special circumstances that suggest the result is not relevant to the risk assessment;

* Compiling the regulatory assessment package for review.

While regulatory science is practiced within institutions that make public and discuss the knowledge produced, it is largely based on data that remain private, which limits public expertise. Thus, a significant part of the data produced by firms is not made public. Moreover, under the pretext of protecting intellectual property rights and business secrecy, precise elements of the composition or manufacture of products may not be disclosed, making analysis of the data produced limited.

Moreover, regulatory science requires a large upstream infrastructure that is largely private (Borraz and Demortain 2015):

* The production and interpretation of data are governed by guidelines developed in expert committees;

* Good Laboratory Practice (GLP) codes, which dictate quality assurance requirements for regulatory testing provided by private companies, condition the knowledge generated;

* The development, performance and interpretation of the tests are based on experience that is essential for toxicologists and scientists.
The development and maintenance of this infrastructure is transnational, invisible, dominated by private interests and controlled by relatively closed collectives. The rules and norms that frame regulatory assessment are defined in "invisible colleges" of scientific experts working in regulatory agencies, research organizations or companies. These invisible colleges are built both by the professional circulation of scientists interested in regulatory issues, their activities as scientific advisors or consultants for private actors, and their participation in various organizations bringing together experts from different backgrounds (professional associations, learned societies, intergovernmental bodies ...) (Demortain 2011). Among these organizations, one can note the particular role of science lobbying organizations, which decline the usual techniques of lobbying in the world of science and scientific experts. One example is the International Life Science Institute, a nonprofit organization funded by large agribusiness, agrochemical, chemical, and petroleum companies, whose activities include promoting regulatory science methods that benefit industry (Demortain 2020).

In order to change the guidelines and standards, some academic laboratories carry out studies using innovative techniques and methods, with exposure times and methods not constrained by regulatory texts, on models that are relevant but not recognized or validated by certain stakeholders involved in the regulatory approach. This work, even if it is deemed relevant by peers (peer review) and published, is not easily taken into account either in hazard and risk assessments or in the revision of limit values, either because exposure data are insufficiently described for the regulator, or because the number of repetitions of the experiments is deemed arbitrarily low (note that GLP does not stipulate any explicit obligation of reproducibility, cf. decree 2006-1523 of 4 December 2006).

In addition, international recommendations, aimed at researchers, indicating the methodological prerequisites for the inclusion of studies in expert assessments and institutions that evolve standards, are advocated and are beginning to be published (Ågerstrand et al 2017, Ågerstrand et al 2018). Similar steps are being taken to conduct non-regulatory preclinical studies for highly innovative therapies (Vestergaard et al 2013). In addition, groups of researchers are publishing strategies for assessing endocrine disruptor toxicity (Lupu et al 2020). A documented publication shows that the application of regulatory values such as GLP can defeat regulatory agencies (Myers et al 2009).

## 2.2. Theses retained by the WG

Given the wide variety of factors affecting the credibility of scientific expertise, it is proposed here to rely on four theses inspired by the Anses colloquium on the credibility of scientific expertise<fnref n="2" /> and the bibliography. The focus on these four theses does not exclude the factors mentioned above. However, it allows us to build a heuristic framework necessary to study the three selected cases (glyphosate, neonicotinoids, SDHI).

<footnote n="2">² International online symposium "Credibility of scientific expertise and public decision making", 20 January - 9 February 2021, Anses.</footnote>
### 2.2.1. Thesis 1. Credibility is a matter of reducing the gap between scientific knowledge and expertise

**Main statement:** The credibility of an expert opinion (or of a decision based on an opinion) is all the stronger when the expertise procedure has allowed to take into account all relevant scientific knowledge, including recent knowledge. Discrepancies are a source of controversy between scientists and of criticism of expert opinions by the various stakeholders.

**Sources in the literature:** various analyses of the differences and relationships between "academic science" and "regulatory science" (see above).

**Examples:** See the examples given in the General Inspectorate report on environmental health (Lavarde et al. 2020).

**Levers for action:** evolution of the guidelines for expertise, evaluation grid of the scientific references taken into account in the expertise, possibility for expert groups to express criticisms and reservations on the regulatory frameworks.

**Derived statements:**

* Expertise loses credibility if it is perceived as limited to a regulatory framework that ignores important academic knowledge

* An expert opinion loses credibility if it indiscriminately cites articles written by employees of firms or financed by firms that have an interest in influencing the regulation of their products in their favor

### 2.2.2. Thesis 2. Credibility is a matter of procedures

**Main statement:** The credibility of an expert opinion (or of a decision based on an opinion) is all the stronger if the expertise procedure has followed the golden rules (impartiality, transparency, plurality and contradictory)

**Sources in the literature:** theories of legitimacy, procedural approaches to expertise, analyses on judicial expertise.<fnref n="3" />

**Examples:** founding documents of European expertise, dominant culture in the agencies, separation between risk assessment and risk management.

**Levers of action:** definition and implementation of procedures, quality management.

**Derived statements:**

* The participation of stakeholders upstream of the expertise contributes positively to its credibility because it allows witnesses to be brought on board to ensure that it is carried out properly

* A committee made up of experts with relevant skills, without major conflicts of interest and with a variety of views on the subject of the expertise contributes positively to the credibility of the opinion given by the committee

* The reputation of the body contributes positively to the credibility of scientific expertise (Carpenter 2010)

<footnote n="3">³ See the work of O. Renn on risk governance.</footnote>
### 2.2.3. Thesis 3. Credibility is a matter of reducing the gap between the expertise and the expectations of the concerned audiences

**Main statement:** The credibility of an expert opinion (or a decision based on an opinion) is stronger the more it corresponds to the expectations of the different audiences involved. There are two very different interpretations of this thesis:

* Some consider that it is a matter of cognitive bias or confirmation bias: credibility would then be all the weaker if the expertise goes against the spontaneous beliefs of the population. Conversely, an opinion would be all the more credible if it confirms these beliefs. In the age of the Internet and social networks, this phenomenon would explain the cognitive bubbles and the propagation of "infoxes". Attitudes towards vaccination and vaccines are often taken as an example.

* The other interpretation, more generous to the publics and stakeholders, suggests that the credibility of an opinion is stronger the more the framing of the problems corresponds to their concerns; in other words, that the opinion considers the problem in the way the publics and stakeholders see it, and answers the questions they have.

Various scientific works support one or the other of the two interpretations. It is not a question of settling this controversy or taking sides. The investigation will be attentive to both positions without necessarily opposing them because each one can shed some light on phenomena whose complexity must be understood.

The fact remains that, depending on the interpretation, the levers are different:

* In the first case, it is generally considered that adequate communication and better education on scientific issues are likely to solve the problem by orienting beliefs and expectations.

* In the second case, it is considered necessary to set up broad debates upstream of the expertise, to encourage participation and consultation with the stakeholders in the definition of the questions. We pay attention to the plurality of views in the expert committees. Citizen science and participatory research approaches may be implemented (Houllier et al. 2017) in order to involve the people and territories concerned in the production of knowledge in risk assessment.

### 2.2.4. Thesis 4. Credibility is about the socio-economic impact of implementing risk management measures

**Main statement:** Expert advice (or a decision based on advice) is more debated the higher the estimated impact of implementing management measures, or conversely, the higher the health impact of not implementing them appears to stakeholders.

**Sources in the literature:** regulatory capture theory, organizational denial, agnotology
**Examples:** Numerous examples in the analyses of Dedieu and Jouzel, but also in the report *Late Lessons from early warning* of the European Environment Agency which highlights that in many cases, proven scientific knowledge has not been implemented given the socio-economic impact

**Levers for action:** Better highlight the costs of the *status quo*; accelerate research on alternatives

**Derived statements:**

* The socio-economic analysis allows us to objectify the economic stakes and the obstacles that need to be removed

* Alternative development is an essential function for good risk governance

These four theses have been added to during the course of the investigation. Initially, the two versions of thesis 3 were the subject of two separate theses; the current thesis 4 was added at the very beginning of the survey. Apart from these changes, the analysis conducted by the WG did not lead to the addition of new theses. Rather, it led to the development of specific reflections on the precautionary principle and the structure of the Anses regarding regulated products.

## 2.3. Survey techniques

The originality of this report lies in the collective investigation method that was implemented with the support of the Anses. The working group is composed of eight scientists from different disciplinary backgrounds (cell biology, chemistry, ophthalmology, neurobiology, veterinary science, sociology, economics) who themselves have diverse experiences of the practice of collective scientific expertise, at the Anses or in other organizations. The group has co-constructed the heuristic framework presented above.

The members of the group conducted about thirty interviews which constituted the core of the survey work. For each case, the interviews were preceded by the preparation of descriptive sheets based on the collection of all available literature: secondary and primary sources (agency opinions, press articles, main scientific articles, court decisions). This documentary phase was extended, beyond the cases, to cross-cutting themes by collecting a variety of sources: reports from parliamentary or administrative bodies, expert reports, internal Agency documentation on expert procedures, reports from the Agency's Committee on Ethics and the Prevention of Conflicts of Interest (CDPI)...

The interviews were conducted using the semi-structured interview method. The group used an interview guide consisting of three parts: one part on the interviewee's experience with the subject matter of the work, one part focused on the case(s), and one free-form part addressing the broader issue of scientific credibility. As is customary with this method, the interview guides listed the topics to be addressed and included follow-up questions used only when necessary. At the end of the interview, the group gave the interviewee the opportunity to add points about scientific credibility that had not been addressed and to make suggestions for improvement.
The interviews were systematically conducted by videoconference. They lasted between 1h30 and 2h00 and were systematically recorded and transcribed. Three or four members of the WG usually took part, which made it possible to conduct the interviews with a diversity of views and skills. The interviews were then double coded, taking up the four theses of the heuristic framework in order to carry out the transversal analysis.

The panel of interviewees includes external scientists who have participated in the Agency's collective expertise (members or presidents of CES, WG or GECU), Agency staff and stakeholders (politicians, journalists, industrial representatives, whistleblowers, etc.). These people were selected on the basis of:

* their participation in the expert work on the three cases studied

* their transversal knowledge, relative to these three cases and/or to the different issues of scientific expertise

* their involvement in the public or political problematisation of these three cases

We began the interviews with the people who had worked directly on the selected cases. Then, a "snowball" logic was used to identify other people to interview.

## 2.4. A few points of reference on the expertise activities of Anses

For a proper understanding of this report, a preliminary presentation of the main expert assessment activities carried out at Anses is necessary. They are listed in Table 1, which distinguishes between risk assessment exercises or more general approaches and external referrals or self-referrals, and whether these activities concern regulated or unregulated products. As will be seen, an important distinction is made between products for which the Anses has both an assessment and management mission and those for which, given the strict application of the principle of separation of assessment and management, it only has an assessment mission.
<table><caption>Table 1. Overview of scientific expertise modes and productions at Anses</caption><thead><tr><th>Objects</th><th>Time frame</th><th>Institutional format/frames work</th><th>Coordination</th><th>Realization</th><th>Productions (public)</th></tr></thead><tbody><tr><td rowspan="2">Health risk assessment (HRA)</td><td>Non-emergency</td><td>Referral, self-referral</td><td>Risk Assessment Directorate (RAD), Regulated Products Evaluation Directorate (RPED), National Veterinary Drugs Agency (NVDA)</td><td>Specialized expert committee(s) Group Working Group (WG)<sup>4</sup></td><td>Notice<br>Report<sup>4</sup></td></tr><tr><td>In emergency</td><td></td><td></td><td>Emergency Collective Expertise Group Expertise Group (GECU)</td><td>Notice<br>Report</td></tr><tr><td rowspan="3">ERS</td><td rowspan="3">Regulatory deadlines</td><td>Authorization of setting on the market, approvals</td><td>DER</td><td>CES<br>GT<sup>4</sup></td><td>Notice</td></tr><tr><td>Implementation of REACH regulations</td><td>DER</td><td>CES</td><td>Notice<br>European report</td></tr><tr><td>Implementation of regulations / inputs / plant inputs, biocides</td><td>DEPR</td><td>CES</td><td>European report<br>Notice<sup>1</sup></td></tr><tr><td>Other expertises outside of ERS</td><td>Non-emergency</td><td>Referral, Self-referral</td><td>DER<br>DEPR<br>ANMV<br>Laboratories<br>Direction des alertes et des vigilances sanitaires (DAVS)<br>DiSSES (Direction sciences sociales, économie et société)</td><td>Anses teams</td><td>Notice<br>Report<sup>4</sup></td></tr><tr><td>Scientific and technical support (AST)</td><td>Non-emergency</td><td>Studies, development of tools...</td><td>All entities</td><td>Anses teams<br>CES if the AST accompanies a HRA</td><td>Note, synthesis, base of data...<sup>5</sup></td></tr></tbody></table>

<footnote n="4">⁴ Possible but not necessary.</footnote>
<footnote n="5">⁵ Published unless otherwise specified in the framework.</footnote>
Depending on these situations, the constraints on these activities are very different. These are important elements that will also condition the credibility of the expertise.

Table 1 also indicates that, depending on the case, three different types of committees are in charge of collective expertise: the ESCs, the WGs and the GECUs. These committees have different compositions and operating rules. We will come back to this later.

To complete these points of reference, it should be added that the institutional affiliation of the committees may also vary (see Figure 1). The ESCs are generally attached to the Risk Assessment Department (DER) of the Science for Expertise Pole, which corresponds to the need for strong interactions between science and expertise. Nevertheless, two ESCs are exceptions:

"Plant protection substances and products, biocontrol" and "Biocidal substances and products".

We will see that these characteristics, which are not necessarily legible even for the scientists involved in the expertise, also have an influence on the conditions of realization of the expertise.

<figure><img src="image_3.png" /><figcaption>Figure 1: Anses organization chart as of June 1, 2022</figcaption></figure>
# 3. Presentation of the case studies

The three cases analyzed (neonicotinoids, glyphosate, SDHI) were chosen for different reasons, notably because the opinions of the Anses have been intensely discussed and, sometimes, strongly criticized. They are therefore not at all representative of the hundreds of opinions issued each year by the agency. Nevertheless, the analysis of such cases is timely and necessary when one is interested in the credibility of scientific expertise. On the one hand, the intensity of the controversies and polemics makes it possible to collect very rich material, which is indispensable for such an analysis. On the other hand, in public arenas (media, parliament, mobilization of associations, general inspection reports, etc.) reference to the Anses is very often linked to these cases. Thus, even if they are rare, they have an effect on the public image of the agency.

In this section, we present the three case studies. The narratives of these cases are based on a processual analysis conducted using secondary sources and a set of focused interviews.

## 3.1. Neonicotinoids

### 3.1.1. A coalition of stakeholders emphasizes the importance of knowledge not considered in the regulatory framework

In 1994, French beekeepers observed and reported sudden and alarming signals in the behavior of honeybees, ranging from failure to return to the hives to mortality observed in front of and in the hives, and this particularly in the vicinity of sunflower fields.

These troubles coincide with the introduction of a new insecticide, Gaucho®, marketed by the firm Bayer from 1991 and used in France since 1993. This insecticide, whose active substance is imidacloprid, is not used for spraying but for coating sunflower seeds. The alert of the beekeepers and the financial impact on the beekeeping production and the essential role for the pollination of many crops oblige the public authorities to launch studies in 1997-1998 (Steering Committee "Gaucho" of the Ministry of Agriculture, in consultation with Bayer). These studies do not allow any conclusion but they raise serious suspicions supported by scientific knowledge. As a result, the Gaucho® treatment was suspended for the first time in 1999 for all sunflower crops, in the name of the precautionary principle. In addition, the beekeeping unions raised awareness and encouraged public research to take up these issues in order to conduct more in-depth exposure and toxicology studies.

Over time, the progression of scientific knowledge in three complementary fields has challenged the risk assessment as it had been carried out until then:

* Demonstration of the importance of chronic low-dose exposures (Suchail et al. 2001)

* High exposure levels compared to previous results (Bonmatin et al. 2003)
* The need to take into account the synergies between molecules and between biotic and abiotic agents in the toxicological analysis (CST report of the Ministry of Agriculture 2003).

In view of this new knowledge, the Ministry of Agriculture suspended the Gaucho treatment for maize in 2004, while the fipronil-based Regent® treatment (a phenylpyrazole also a systemic insecticide) was suspended for all crops at the end of 2004. The Ministry issues new marketing authorizations (MA), in particular for the Cruiser® treatment based on another neonicotinoid (thiamethoxam) for rapeseed (2008). These authorizations will also be withdrawn.

The accumulation of scientific knowledge used by stakeholders, the increasing judicialization, the constitution of coalitions (environmental associations and beekeepers, researchers, elected officials, but also agricultural unions, seed companies, agrochemical industries and even the Ministry of Agriculture at certain times), accompanied by intense media coverage, have highlighted the need to rethink the risk assessment and management system. The scientific method underlying the regulatory assessment of risks to bees must be improved, in particular the development of new eco-toxicological tests, the treatment of multi-causality, the quality criteria of studies, the consideration of multiple exposures at low doses, and all this in the dimension of a family of products, in this case neonicotinoids. Indeed, until now, when a product was banned, it was generally replaced by another of the same family or with the same modes of action, which only shifted the problem.

### 3.1.2. Europe takes over

As Arnold (2018) reminds us, in 2011, the European Commission (EC) asked the European Food Safety Authority (EFSA) to assess, before any marketing, the quality of the evaluations on the risks that pesticides represent for bees. In particular, it asked to assess the environmental assessment system, which was then based on the recommendations of the *International Commission for Plant-Bee Relationships*, an organization close to the plant protection companies.

Following this request, an EFSA working group drafted a scientific opinion in 2012 noting that the toxicity of pesticides placed on the market had not been properly assessed. Several key aspects had not been taken into account: toxicity on larvae, long-term effects on colonies, chronic toxicity on adults, sublethal toxicity (the fact that bees may become disoriented after exposure to an insecticide, not returning to their hive and dying quickly) (EFSA 2012).

Since the late 1990s, the effects of these products on bees have thus not been properly assessed before they were placed on the market. A new guide for the assessment of these risks to honeybees and wild bees was published by EFSA in 2013 (EFSA 2013)<fnref n="6" />. Nearly ten years after its publication, this guide is still not adopted at the European level. According to the representation of the producers of the pesticides concerned, the tests

<footnote n="6">⁶ https://efsa.onlinelibrary.wiley.com/doi/pdfdirect/10.2903/j.efsa.2013.3295
This EFSA report proposes guidelines for the assessment of risks to bees. But these have not been implemented by the Member States (interview with an expert, 10 June 2021).</footnote>
proposed would not be robust and reproducible enough. Presumably, the economic pressure
is strong. Under the influence of industrialists considering that the implementation of these
guidelines would lead to the removal of a large number of authorized substances, several
countries voted against the adoption of this guide and have reportedly asked EFSA to make
the guidelines more flexible (OPECST 2019).

Specifically concerning neonicotinoids, EFSA concludes unambiguously that insecticides of this family are dangerous to the health of bees. It suspends the use of three of the six molecules on the market for honey crops. Fipronil is also suspended. In 2018, the member states of the European Union extend the ban on the three neonicotinoids and fipronil for all outdoor crops; treatments are now only allowed under closed greenhouses. Moreover, scientific findings extend the deleterious impacts of neonicotinoids to many other species, invertebrates (e.g. beneficial insects), vertebrates (e.g. birds) and even humans.

3.1.3. The contribution specific of the Anses as evaluator and manager

The Agency has played an important role in building the knowledge base needed to better
assess the complex effects of insecticides on bee health<fnref n="7" />:

* Between 2012 and 2015: Expertise on the effects of co-exposure of bees to different stressors and their respective roles in the phenomena of weakening, collapse or mortality of bee colonies.

* 2015: Expertise on the prioritization of bee diseases.

* 2016: Expertise on the risks posed by insecticides based on substances in the neonicotinoid family.

* 2018: Recommendations to strengthen national provisions imposing restrictions on the use of plant protection products during periods when crops are attractive to these insects.

* 2019 : Recommendations for strengthening risk assessment methods for plant protection product marketing authorization applications.

On this basis, and in consideration of the decree of 20 November 2021 on the protection of
bees and other pollinating insects, the Anses has implemented a more comprehensive risk
assessment than required by current European regulations, with additional toxicity tests in
laboratories, "flight back" tests, and tunnel tests (Anses, undated information note ).<fnref n="8" />

Since 2015, the Anses has also been in charge of the management of plant protection
products, and therefore in charge of issuing MAs. In France, the ban on all neonicotinoids
was enacted in 2016 by the law for the reconquest of biodiversity, taking effect in September
2018 and without possible derogation after 2020. An amendment of 2018 (EGAlim law) had
also been added to ban in France any molecule with the same mode

<footnote n="7">⁷ https://www.anses.fr/fr/content/santé-des-abeilles</footnote>

<footnote n="8">⁸ https://www.anses.fr/fr/content/note-d-information-on-risk-assessment-for-bees-and-other-insects</footnote>
action than the five neonicotinoids targeted by the 2016 law. The Anses was then asked to study alternatives to neonicotinoids and the agency submitted a report, which was voluminous and well argued, in 2018.

In 2017, the Anses issued a MA to the insecticides "Transform" and "Closer" based on sulfoxaflor. This decision may be surprising because, according to the Agency, this active substance, although related to neonicotinoids, is registered by the European Commission. These MAs will be cancelled by the Court of Nice by a decision of November 2019. The Court will consider that the risk assessment by the Anses is not consistent with the precautionary principle :

"It follows from the precautionary principle enshrined in these provisions that, where there is uncertainty as to the existence or extent of risks, protective measures may be taken without having to wait for the reality and seriousness of these risks to be fully demonstrated" (...)

"The conclusions of the evaluation on the marketing authorization application published by Anses on June 26, 2017, state the dangerousness of the products "Transform" and "Closer" for auxiliary fauna and pollinating insects when used under cover. In addition, the European Food Safety Authority noted high risks to bees and bumblebees when using sulfoxaflor in its reports published on March 11, 2015 and February 26, 2019. While Anses and Dow Agrosciences argue that the use of the insecticide is accompanied by risk mitigation measures, such as the absence of application of the product during the flowering period, these measures cannot be considered sufficient since they are general in scope and are not accompanied by any obligation for users of the product. Under these conditions, the existence of a risk for pollinators must be considered as a sufficiently plausible hypothesis in the state of scientific knowledge.

(Decision of the Court of Nice of 29/11/2019)

As the government has decided to ban the use of sulfoxaflor and flupyradifurone, two plant protection substances with the same mode of action as neonicotinoids, in application of the EGALim law, the Anses will not appeal the judgment of the Nice court<fnref n="9" />.

Following the pressing demand of the sugar beet industry, which experienced production losses in 2020, the government proposed and passed an order, in early 2021, which again authorizes the treatment of beet seeds with the neonicotinoids imidacloprid or thiamethoxam. The authorization is renewable for three years, while research proposes alternatives for this crop. There was a lot of media and legal controversy about this derogation for sugar beet, but no scientific controversy. The socio-economic impact will have been the reason for a scientific expertise and stabilized and concordant national and European regulatory procedures. Nevertheless, such derogations concern several countries of the European Union (EU). The Anses report submitted in June 2021 identifies some 20 alternatives to neonicotinoids for this particular crop, of which four or five are considered operational<fnref n="10" />. The government has therefore proceeded with this authorization

<footnote n="9">⁹ https://www.anses.fr/fr/content/jugement-du-tribunal-administratif-de-nice-l%E2%80%99anses-retire-put-on-permissions-0</footnote>

<footnote n="10">¹⁰ https://www.anses.fr/fr/content/des-solutions-alternatives-aux-n-C3%A9onicotino-C3%AFdes-to-fight-yaunice-in-themselves</footnote>
without waiting for the Anses evaluation, which suggests that political and economic considerations prevail.

### 3.1.4. Reflection on the integration of new knowledge

The case of neonicotinoids is considered rich in lessons regarding the integration of new knowledge into the existing regulatory framework, even if this integration is very slow (Maxim, van der Sluijs 2013, Arnold 2018) and remains fragile. This is essential because the gap between scientific knowledge and the regulatory framework is one of the main sources of criticism of expertise for regulatory purposes.

If we follow David Demortain's analysis, this rather singular case has more to do with extrinsic characteristics than with elements directly under the control of the Anses:

> "The singularity of the restrictions applied to neonicotinoid products in France is that they were decided by actors who were not the usual and designated risk assessors or managers in the regulatory space. Existing bureaucracies, in this case, were placed at the center of a space that was completely reconfigured by the rise of an advocacy coalition demanding a ban on neonics.
> (...) The knowledge resulting from the research did not only circulate among the usual actors in the regulatory space. It was produced in relation to this broader mobilization, which was deployed over time and took as its object the successive chemicals of the neonicotinoid class. The coordinated restrictions of all neonicotinoids thus result from a reversal of the routine and closed functioning of the regulatory space and the production of a standard regulatory science that structurally ignores low-dose, chronic, and sub-lethal problems. A fragile, and in fact reversible, outcome of the politics of knowledge that is at the heart of environmental policy."

(Demortain 2021, our translation)

### 3.1.5. Lessons from the case concerning the credibility of scientific expertise

Criticism of the Anses' expertise has been limited in the case of neonicotinoids. They focused on the authorization of sulfoxaflor. The decision of the Nice court and the non-appeal of the Anses have extinguished the controversy.

We hypothesize that these limited criticisms can be explained by the ability to integrate new scientific knowledge into the regulatory framework (Thesis 1), although, as various observers note (Maxim, van der Sluijs 2013, Arnold 2018), the time frames are unquestionably too long and the process remains unfinished.

This integration tends to reduce the distance between the responses provided by the agency and the expectations of the various stakeholders (Thesis 3). The strong investment in the study of the effects of co-exposures allows the production of relevant systemic knowledge to understand and anticipate the problems affecting pollinators. The weight of economic interests (Thesis 4) limits the integration process, both at the European level (non-integration of knowledge in the guidelines) and at the French level (derogation granted to the beet industry). The content of these decisions and the lack of transparency undermine the credibility of the expertise.
It is therefore thesis 1 that plays an essential role here. Concerning the role of procedures (Thesis 2), the mobilization of expertise predates the creation of the agency. The history of this case thus shows the procedural progress linked to the creation of the Anses. The witnesses cite in particular the independence of the expertise and the scientific referencing of the arguments put forward. The possibility of self-referral, which is essential to investigate complex and uncertain issues, is also mentioned. It is therefore essential that the principles of independence and adversarial process be strictly respected.

## 3.2. Glyphosate

Glyphosate is a non-selective herbicide (it kills most plants to which it is applied at an effective dose). It was first marketed in 1974 by the company Monsanto and became publicly available in 2000. It is currently one of the main pesticides sold in the world, with an annual global market estimated at more than 4 billion euros, and a very wide use, mainly in North and South America, to eliminate weeds, after harvesting crops and on crops of genetically modified plants tolerant to glyphosate. In France, the use of alternatives to glyphosate can lead to significant additional costs in certain situations. In the European Union, a classification of glyphosate as a suspected carcinogen (class 1B of the CLP regulation, relating to the classification, labelling and packaging of chemical substances and mixtures) would have significant economic repercussions, since it would lead, according to European regulations, to a ban on this active substance.

The evaluation of the dangers and the conditions of the authorization of glyphosate have crystallized strong tensions. They have been the subject of strong mobilizations in the scientific, political, media and civil society spheres. This background is first recalled. It allows us to contextualize the opinions of the Anses on this active substance, which are then presented, before providing information on the reactions they have provoked.

### 3.2.1. The context

The reflections on the active substance glyphosate are born in a particular context on the political level (file of deputies, empty National Assembly during votes, phone calls to or by experts on Monsanto / Bayer in session ECHA (European Chemicals Agency) or EFSA (European Food Safety Authority)), societal (nucleation of social networks, aggressive practices of the firm to place favorable content in the press and on the Internet, false advertising, false petitions ...) with discrimination of authors and scientists considered as opponents - including those of the IARC (International Agency for Research on Cancer, agency of the World Health Organization) like Christopher Portier or Christopher Paul Wilde on social networks.

Concerns about the product were reported as early as 2000 by associations that filed a complaint for false advertising on the labeling of products formulated with glyphosate. A 2012 Anses scientific watch note calls for verification in other studies and on other models of knowledge regarding the possible endocrine disrupting effects of glyphosate (Crettaz 2012).
While in 2015, the IARC declared glyphosate genotoxic, carcinogenic to animals and probably carcinogenic to humans (Group 2A) (IARC 2015), the German agency BfR, in charge of examining the dossier for the renewal of the authorization of glyphosate for Germany, the reporting Member State, concluded that there was no sufficient evidence of carcinogenicity to humans. The BfR does not propose a classification of glyphosate in terms of carcinogenicity or mutagenicity. However, it identifies a concern about the toxicity of glyphosate-based preparations, particularly with regard to genotoxicity. On this basis and on the proposal of EFSA, the Commission renews the authorization of glyphosate, but only for a period of five years, until 2022.

As early as 2015 an alert was launched by Christopher Portier and several scientists (Portier 2015) on the evaluation of glyphosate conducted by the BfR, and an open letter was sent in 2017 to the President of the European Commission (Portier 2017). In the same year, an expert report commissioned by the NGO Global 2000 (Weber 2017), which was widely reported in the press, showed that long passages of the BfR's glyphosate assessment report were identical to the application for renewal of glyphosate registration sent to the European authorities by Monsanto.

Also in 2017, glyphosate was at the center of the "Monsanto Papers" affair, revealed in France by the newspaper *Le Monde* following access to internal documents of the firm made public by the American justice system in the context of trials (Foucart, 2017; Foucart, 2018; Horel and Foucart 2017b and 2017c). This case shows the strategies deployed by Monsanto to denigrate the IARC's work on the carcinogenicity of glyphosate. It also highlights the firm's practice of "ghostwriting", which consists of having scientists sign scientific articles, written by employees of the firm, agreeing to put their names to them in exchange for payment. Some articles later known to be

"It also shows older strategies within Monsanto to minimize the risks of glyphosate: a scientist paid in the 1980s to review data considered problematic by the EPA; a scientist paid in the 1990s to review data considered problematic by the EPA; a scientist paid in the 1990s to review data considered problematic by the IARC. It also shows older strategies within Monsanto to minimize the risks associated with glyphosate: a scientist paid in the 1980s to re-examine data considered problematic by the EPA; another scientist carrying out a consultancy in the late 1990s that concluded against glyphosate, and was not taken into account by the firm that had commissioned it. These various elements are taken up in the 2019 report of the Parliamentary Office for the Evaluation of Scientific and Technological Choices (OPECST), which recommends improving the transparency of evaluation work by the agencies by making available to the public all of the data contained in the files submitted to the evaluation agencies in order to allow for a citizen's counter-expertise, by making the links of interest transparent and by controlling the links of interest declared within the framework of strong ethical obligations weighing on the agencies' personnel and experts (OPECST 2019).

Another attack on the European evaluation of glyphosate is taking place in 2020. The NGO PAN Europe reveals that a German laboratory implicated in fraud conducted numerous tests of the 2017 glyphosate reauthorization dossier (PAN Europe 2020).

At the same time, four ministerial departments (risk prevention, health, labor, research and innovation) and the Ministry of Agriculture and Food) commissioned Inserm for a collective expertise report on pesticides and health to be published in July 2021 (Inserm 2021). The Inserm Collective Expertise Pole attached to the Thematic Institute
Public Health is coordinating this work. This work is based on more than 5,300 documents, mainly from the scientific literature available in the first quarter of 2020. The expert opinion concludes that there is an increased risk of non-Hodgkin's lymphoma with a medium presumption of a link, and evokes an increased risk of multiple myeloma and leukemia with a low presumption. It considers that mutagenicity tests on glyphosate are rather negative, while genotoxicity tests are rather positive, which is consistent with the induction of oxidative stress. Experimental carcinogenesis studies in rodents show excess cases, but are not convergent. It mentions other mechanisms of toxicity (intergenerational effects, disruption of the microbiota, etc.) that it would be interesting to consider in the evaluation procedures. The report concludes by stressing the importance of periodically re-evaluating knowledge in the field of pesticides and health, and the need to further study and integrate the indirect effects of certain pesticides on human health through effects on ecosystems and social and economic aspects, in order to inform decision-making when developing public policies.

Anses is participating in the re-evaluation process of glyphosate<fnref n="11" />, whose current authorization expires at the end of 2022, in a consortium of four reporting Member States (France, Hungary, the Netherlands, Sweden), the Assessment Group on Glyphosate (AGG). The draft assessment report on glyphosate delivered by this consortium in June 2021 considers that glyphosate does not meet any of the criteria for a ban (including carcinogenicity). The large number of comments received during the public consultation on this draft report led to a delay in the European assessment, which is expected to be concluded in June 2023 (EFSA 2022a). Among the many comments received during the public consultation, several were from Inserm following its 2021 assessment and contradicting some of the conclusions of the assessment report of the consortium of Member State rapporteurs (Foucart 2022).

In 2021, two reports by two toxicology researchers for the NGO SumOfUs asserted the unreliability of the vast majority of genotoxicity studies relied upon by BfR, EFSA, and ECHA experts during the last evaluation of glyphosate in 2017 and during the ongoing authorization renewal process (Knasmueller and Nersesyan 2021; Nersesyan and Knasmueller 2021). These reports were made possible by two rulings of the Court of Justice of the European Union on March 7, 2019, which, when seized by Members of the European Parliament and a toxicology consultant for NGOs, ordered EFSA to provide access to industry-derived files on the genotoxicity of glyphosate, which had previously been placed under the seal of industrial secrecy (CJEU 2019a and 2019b). According to these reports, the industry-derived data did not comply with the OECD guidelines that are supposed to frame regulatory testing. According to cnDAspe (Commission nationale de la déontologie et des alertes en matière de santé publique et d'environnement), "this conclusion is likely to mislead the public serious doubts about the impartiality of the experts from the agencies that gave their opinion on this dossier. Far from responding to these concerns, EFSA refused to publish the names of the experts from the Member States involved in this scientific evaluation and their statements of interest" (cnDAspe 2022a).

In the same year, the cnDAspe recommended harmonizing the conflict of interest management systems within the agencies responsible for risk assessment in the context of the review

<footnote n="11">¹¹ Reassessment process still underway as this report is adopted (November 2022).</footnote>
of pesticide registration applications by recommending the development of a set of common minimum rules (cnDAspe 2022b). A new front is opening up in the controversy surrounding the European reauthorization procedure for glyphosate, with scientists pointing out that a 2001 industrial study showing neurotoxic effects of a glyphosate salt was not communicated to European authorities, contrary to regulatory requirements (Mie, Rudén 2022). These scientists suggest a retrospective check of the lists of studies performed by testing laboratories against studies submitted to regulatory authorities to examine the completeness of data submitted to authorities. They also suggest that future toxicity studies be commissioned by the authorities rather than by companies, to improve the authorities' oversight of existing data and to avoid economic conflicts of interest affecting the reporting of study results and conclusions.

### 3.2.2. Opinion of the Anses

#### 3.2.2.1. 2015 GECU and 2016 Anses opinion on the comparison of IARC and BfR opinions on the carcinogenicity of glyphosate

In March 2015, the Anses was asked to clarify the discrepancy between the IARC and EFSA opinions on the carcinogenicity of glyphosate. It created a GECU of four experts, attached to the CES "Plant Protection Substances and Products, Biocontrol"<fnref n="12" />, and assigned it two missions (Anses 2016a):

* "Identify whether the elements presented by IARC and BfR are such as to support a proposal to modify the classification of glyphosate for carcinogenic properties, to inform the position of Anses during the upcoming public consultation in the framework of the classification procedure by ECHA" (report requested for December 16, 2015);

* "Identify whether the results of the genotoxicity studies in the BfR assessment projects are sufficiently robust, and whether these results should lead to additional studies on formulants and/or glyphosate-based formulations" (report requested by March 22, 2016).

For the first part of the referral, the GECU met twice. Its report mentions that "Given the time frame for responding to the request, GECU was unable to consult the reports of regulatory studies and/or all published articles that were used by the BfR and IARC to support their conclusions. This report identifies important differences in the bodies of studies considered by the two agencies:

* IARC relies on articles published in the open literature (peer review) with a critical analysis of the quality and validity of the methods and results presented;

* The European evaluation procedure is based on regulatory studies generally conducted according to the principles of good laboratory practice (GLP) and subject to OECD guidelines. These studies are rarely published in peer-reviewed journals.

<footnote n="12">¹² Here named CES Phyto.</footnote>
Thus, it notes:

* The large body of regulatory data is not considered by IARC, except for those that have been published;

* A high number of published studies are not considered by the BfR (lack of precision on the material used, non-conformity of the protocol with experimental standards, lack of raw data...)

* Given the format of the available glyphosate database, the BfR assessment is based on a broad spectrum of validated studies rather than a key study for each item;

* The lack of sufficient qualitative and quantitative data on impurities in the batches of glyphosate tested, either in a publication or in a regulatory study, generally calls into question the acceptability of the results and the proposed conclusions.

The GECU will conclude along the lines of the European expertise (Anses 2016a): "In conclusion, taking into account, on the one hand, the time limits for the investigation and, on the other hand, the very large number of

In view of the large number of studies and publications available, the working group's analysis was based exclusively on the reports of the European and IARC evaluations and not directly on the reports of studies conducted according to the guidelines, which incorporate raw data, as well as on the published scientific literature. Consequently, it is not in a position to give an opinion on a classification in category 2 or on the absence of classification within the meaning of Regulation (EC) No 1272/2006. On the other hand, the working group considers that the analysis conducted shows that the level of evidence of carcinogenicity in animals can be considered as relatively limited and does not allow, within the meaning of Regulation (EC) No 1272/2008, to classify glyphosate (active substance) as a category 1B carcinogen.

. In its opinion of February 9, 2016, the Anses repeated this conclusion.

### 3.2.2.2. Lack of advice on the second part of the 2015 GECU mandate on glyphosate-based formulations

The second question put to the GECU experts, concerning glyphosate-based formulants and preparations, will not result in an opinion or a decision by the CES Phyto, thus justifying the abandonment of the draft report, which will be denounced in an article in Le Monde (Foucart 2021a). However, the 2016 Anses opinion indicated that the agency was continuing its work by setting up a working group on the risks associated with co-formulants present in all plant protection products, with priority given to glyphosate-based products and the re-evaluation of products combining glyphosate and tallowamine, products for which compliance with the requirements set out in Article 29 of Regulation (EC) No. 1107/2009 is a major issue. In July 2016, the Anses proceeded to withdraw 132 marketing authorizations for glyphosate-based products following the identification of concerns regarding the co-formulant POE-Tallowamine (Anses 2016b). In contrast, the second GECU report, on glyphosate-based formulations, will never be published. This will lead Le Monde to consider that the Anses has buried a report on glyphosate (Foucart 2021a). In a message addressed to the members of its boards (Board of Directors, Scientific Council, Ethics Committee), the Agency's DG will state: "This additional expertise, announced in the February 2016 opinion and mentioned in CES in September 2016, was not finalized in this form due to the
consideration of the question posed in other scientific and regulatory frameworks. While there
was no scientific deliverable duly finalized and endorsed by a group of experts in accordance with
Anses expertise procedures - which could explain why the experts contacted by Le Monde were
unable to respond to the journalist's request - I would like to emphasize that this subject, on
which we have remained very vigilant, has

> well taken up and educated through other channels."

### 3.2.2.3. Roundup Pro 360 herbicide approved in 2017, overturned in court in 2019

After its 2016 opinion, the Anses continues to authorize commercial glyphosate-based herbicides. On March 6, 2017, it authorized the marketing of Roundup Pro 360. This decision was annulled by the Administrative Court of Lyon in 2019 "in application of the precautionary principle defined by Article 5 of the Charter of the Environment", on the grounds of "suspected carcinogenic potential" and the Anses was called into question for "error of assessment with regard to the precautionary principle" (Administrative Court of Lyon 2019). The opinion of the Anses of 2016 is mentioned in the judgment. This decision will be confirmed by the Administrative Court of Appeal of Lyon in 2021, according to which "[a] plant protection product that disregards the requirements of the precautionary principle cannot benefit from a marketing authorization" (Administrative Court of Appeal of Lyon 2021).

### 3.2.2.4. 2018 GECU and 2019 Anses opinion on the terms of reference for a study on the carcinogenicity of glyphosate

Following the controversies over the carcinogenic classification of glyphosate, the Anses received a referral in March 2018 from the Ministers of Ecological and Solidarity Transition, Solidarity and Health, and Agriculture and Food, to establish the specifications for a study on the carcinogenicity of glyphosate (Anses 2019a). The referral letter mentions that the glyphosate hazard study will follow a study protocol "based on European or international guidelines."

The Agency is setting up a GECU made up of five members, including two Europeans outside France, to work on these specifications. It met three times, from September to December 2018, and presented its report in February 2019 to the CES Phyto. A hearing of Roger Genet at the National Assembly reports that "[t]he quality of some of the studies in the assessment was deemed to be improvable and an approach to distinguish both epigenetic and genotoxic effects was proposed." The report is finalized in March 2019 and the Anses opinion published in July 2019. It may be noted that the report cites without comment an article then known to be "ghostwritten" by Monsanto, without questioning whether its content may be favorable to that firm's interests (Brusick et al. 2016), to support the assertion that one test (the in vitro comet assay) is considered to have low weight in a weight-of-evidence approach.

To meet these specifications, the agency is launching an international call for applications during the summer of 2019, closing on October 15, 2019. The agency will receive only two proposals (Anses 2020a) and will select one, that of a consortium coordinated by the Pasteur Institute of Lille, while offering to fund part of the project proposed by IARC with the unsuccessful consortium.
The selection of a consortium coordinated by the president of the GECU and including two of the four other members of the GECU will lead to a written question on the ethics and independence of the procedure by the deputy Mrs. Delphine Batho on June 9, 2020 (National Assembly 2020). The reproaches formulated are nourished:

* The specifications were written by a GECU expert, who applies for and wins the tender, which is contrary to ethical principles and the rules of public procurement;

* This same expert participated in the CES Phyto which deliberated on the GECU report

* He was also one of the experts on the 2015 GECU on the comparison of IARC and BfR opinions on the carcinogenicity of glyphosate, which presented the risk of a lack of impartiality.

This initiative is relayed by an article in Le Monde (Horel, Foucart 2020) which also argues that the specifications of the Anses on the carcinogenicity of glyphosate would favor the candidacy of the members of the GECU, and would include scientifically unjustified and questionable requirements:

* The requirement of GLP conditions for the *in vivo* genotoxicity test would favor the laboratory of the GECU president. It is presented in the Le Monde article as the only public laboratory approved in France for this purpose; in reality it is a private foundation. The list of test facilities controlled by Cofrac in accordance with the principles of Good Laboratory Practice (GLP)¹³ confirms that only private laboratories are GLP certified for toxicity and mutagenicity studies and that only the Institut Pasteur Lille laboratory works in the framework of public expertise.

* The DNA breakage methods required in the specification would favor the candidacy of some GECU members. It can be noted that in the specifications, their description is supported by the citation of two publications of which two GECU members are co-authors.

* The Cell Transformation Assay required in the specification would favor the application of a GECU member and would be scientifically questionable as probably not sensitive for a low dose pesticide. It can be noted that eleven publications cited in the section describing the Cell Transformation Assay requirements have a GECU member as a co-author.

* Two cell lines required in the specification are linked to GECU member laboratories and would not allow for the study of lymphomas and blood cancers highlighted in epidemiological studies of farmers in relation to glyphosate.

An article published by Libération in July 2020 questioned various links of interest of the GECU president during his career with pesticide industrialists (Massiot 2020). The Anses, quoted in the article, indicates that it has taken into account and analyzed the links of interest included in the declaration of interest of this expert according to the Agency's analysis grid for links of interest, which is public and validated by its ethics committee, and has qualified these links as minor.

<footnote>13https://www.cofrac.fr/fileadmin/user_upload/cofrac/Liste_des_installations_d_essais_controlees_par_le_Cofrac_2022-05-31.pdf</footnote>
This challenge led to the withdrawal of the consortium in July 2020 (Anses 2020b). The IARC in turn withdrew in October 2020, which was covered in an article in Le Monde questioning the requests of the Anses, which the IARC considered unacceptable ("glyphosate will have to be supplied by the Glyphosate Renewal Group and the protocol transmitted to the latter") (Foucart 2021b). In the end, no study will be launched.

### 3.2.2.5. Anses participation in the European re-evaluation of glyphosate

In June 2021 the four member states of the EU Glyphosate Assessment Group (AGG) (France, Hungary, the Netherlands, and Sweden) deliver their assessment report, which proposes no new classification for glyphosate, whose marketing authorization expires on December 15, 2022. The four Member States present an 11,000-page evaluation report and conclude that no further classification as a carcinogen is warranted. Their work is now in the hands of the European Food Safety Authority (EFSA) and the European Chemicals Agency (ECHA) who will have to finalize the risk assessment. Their conclusions, expected at the end of 2022, have been postponed to mid-2023 and will serve as a basis for the European Commission to propose, or not, the renewal of the herbicide to the EU Member States (EFSA 2022a; EFSA 2022b). The assessment group proposes that the active substance be classified as H318 ("Causes serious eye damage"), and H411 ("Toxic to aquatic organisms, causing long-term adverse effects").

### 3.2.3. The lessons of the glyphosate case concerning the credibility of scientific expertise

The Anses has faced significant criticism concerning the expert assessments it has conducted on glyphosate. These criticisms are part of a context in which the regulatory evaluation of glyphosate has crystallized criticisms and strong expectations from civil society, but also from actors in the scientific and political worlds, and has become an emblem of the changes expected more broadly on a better consideration of the dangers and risks of pesticides (Thesis 3).

Thesis 2 plays an essential role here with the restriction of the questions asked of the experts in the referral, the modalities of operation of an expertise in the form of a GECU, the questions concerning the literature taken into account, the positioning in relation to the precautionary principle and the non-finalization of a mandate given to a group of experts. Thesis 1 on the role of procedures also plays an important role; fueled by the discrepancy between the IARC and EFSA evaluations, the European regulatory expertise on glyphosate is strongly criticized. Criticism affects the Anses via the groups of experts mobilized, but also via the agency's own activities, whether it be the legal ban on Roundup Pro 360 or criticism of the AGG consortium in charge of re-evaluating the authorization of glyphosate.

Finally, because of the importance of glyphosate uses and the economic costs of alternatives to the use of this herbicide, thesis 4 on the influence of economic issues is also quite relevant.

## 3.3. SDHI
### 3.3.1. Summary of the case

In October 2017, Pierre Rustin, research director at the CNRS and specialist in mitochondrial diseases related to SDH (succinate dehydrogenase, complex II of the mitochondrial respiratory chain) dysfunction, contacted the Anses by email after having fortuitously discovered with various colleagues the existence of a family of fungicides, SDHIs (succinate dehydrogenase inhibitors), which act on target fungi by blocking their SDH. Genetic mutations that cause partial blockage of SDH are the cause of human diseases such as encephalopathies and cancers. The group of scientists wonders how the scientific knowledge on SDH was taken into account when these pesticides were authorized.

Although the scientists did not have this information when they contacted Anses, it turns out that SDHIs represent an important commercial and agronomic issue, in a context where some fungicidal active substances are losing their effectiveness due to the development of resistance in pathogen populations, and where other active substances are banned.

Exchanges took place with the Anses, which notably transmitted certain dossiers on authorized SDHI active substances to the group of scientists and encouraged them to apply for the Anses' Call for Environment Health and Work projects (APR-EST). However, a real dialogue did not take place during these first exchanges. The Anses representatives consider that the elements on genetic diseases related to a deficit of SDH activity do not provide evidence of toxicity under conditions of exposure to SDHI that are punctual, partial and fluctuating over time. Scientists are unfamiliar with the regulatory assessment framework for pesticides and note in regulatory dossiers that SDHI toxicity to mitochondria is not tested during approval procedures. Moreover, their letter of intent to the RPA EST Anses is rejected. They contacted their research organizations (CNRS, INSERM, INRAE) to inform them of their alert, but these institutions did not support their approach. They published a *preprint* in March 2018 (Bénit et al. 2018). They then decide to make a public alert through an op-ed published in *Libération* on April 15, 2018. In addition to the known effects of SDH blockage due to genetic mutations, the op-ed also exposes that cellular respiration and the SDH enzyme function in the same way in all living species, and questions how SDHI pesticides could have been put on the market with the assurance of having no impact on human health and ecosystems.

Three days later, the Anses announced the constitution of a GECU. In the weeks and months that followed, environmental NGOs took up the case, with a dossier from Générations Futures<fnref n="14" /> and a petition from Pollinis<fnref n="15" />. The scientists were heard at the National Assembly by the parliamentary commission of inquiry on industrial food¹⁶. The opinion of the Anses, following the work of the GECU, published on January 15, 2019, concludes that the information and scientific hypotheses given by the whistleblowers do not provide evidence in favor of a health alert that would lead to the withdrawal of authorizations for

<footnote n="14">¹⁴ https://www.generations-futures.fr/actualites/boscalid-sdhi/</footnote>

<footnote n="15">¹⁵ https://www.pollinis.org/publications/pollinis-demande-le-retrait-immediat-des-fongicides-sdhi-en-waiting-for-their-evaluation/
16 https://www.assemblee-nationale.fr/dyn/15/comptes-reports/cealimindu/l15cealimindu1718005_report#</footnote>
marketing of plant protection products containing SDHI (Anses 2019b). It recommends that knowledge of the hazards of SDHIs, exposure to these products and the risks that may arise from such exposure, and the strengthening of regulatory risk assessment mechanisms be further developed. It notes that these issues will be shared at the European level.

The group of scientists regretted various limitations of the GECU report in a letter addressed to Anses and later made public on a website created at the initiative of two scientists of this group, Pierre Rustin and Paule Bénit<fnref n="17" />. He argues that data on the use and presence of SDHI residues are incomplete and insufficiently questioned, that the importance of mitochondrial diseases in public health is not taken into account, and that epidemiological and biomonitoring data are lacking despite worrying signals. He questions the composition of the group of experts, which does not include any specialist in mitochondrial physiology, diseases associated with mitochondrial function impairment or cancer pathology. Finally, he regrets that the knowledge of the mode of action of SDHI, of their capacity to inhibit the human enzyme as well as that of other living organisms, and of the pathologies linked to the blocking of SDH in humans, does not lead to the application of the precautionary principle.

In June and July 2019, while the NGO Pollinis is preparing a petition for the European Commission, MEPs, and EU member states, research funding is granted for work on SDHI. Two are granted by the Anses on a project to characterize the toxicity mechanisms of SDHi fungicides and on a project to explore the data of the national registry of hereditary paraganglioma linked to a mutation of SDH, to specify the evolution of the incidence of this pathology and to carry out a case control study The other one is granted by the French Office of Biodiversity (OFB) in the framework of the Ecophyto 2 plan.

The fall of 2019 is marked by the release of a book by journalist Fabrice Nicolino, opening a campaign on SDHIs by the movement "We want poppies," a movement of which he is the president and which calls for a ban on all synthetic pesticides in France (Nicolino 2019). In his book, the journalist describes in particular the tense meeting of the group of scientists with the GECU and other members of the Anses in June 2018, and also questions the links of interest of a member of the GECU with actors in the agricultural and agrochemical world.

Also in the fall of 2019, the SDHI alert appears for the first time in the European review procedure for an application for authorization of a fungicide in this family, pydiflumetofen. The EFSA peer-review document on this active substance cites the alerters' preprint (EFSA 2019). The issue of diseases that may be linked to SDH inhibition is presented in general terms by France, the rapporteur Member State on this dossier. The experts note that a concern and a relevance for humans cannot be excluded. But the assessment of these issues is considered inconclusive, due to lack of data and validated methodology to address the issue.

<footnote n="17">¹⁷ http://endsdhi.com</footnote>
The preprint of the collective of scientists leads shortly after to a publication in the journal PLOS One (Bénit et al. 2019). This will be the subject of a communication by the CNRS<fnref n="18" /> but also of a counter-analysis video by the Union des Industries de la Protection des Plantes (UIPP) in January 2021¹⁹ and of a counter-publication by authors from BASF in February 2021 (Kamp et al. 2021).

The cnDAspe is issuing an opinion in November 2019 following a report on possible risks related to SDHI fungicides (cnDAspe 2019). It considers that the situation constitutes an alert due to the dangers not taken into account in the European regulation on pesticides and calls for dedicated funding due to the substantial uncertainties remaining on the risks that would be induced in humans. It also considers that the Anses has treated the report communicated to it by the research team in a reactive and thorough manner. Anses officials are the subject of a (non-public) hearing by the National Assembly's environmental health study group in November 2019.

In January 2020, the daily newspaper *Le Monde* published an article by 450 scientists, supported by ten scientists specializing in mitochondrial diseases, deploring the denial of scientific data and calling for a halt to the use of SDHIs in open environments. A hearing on SDHI took place a few days later at the OPECST. In its conclusions, the OPECST considers that the work of the group of researchers raises interesting points, some of which need to be validated and deepened, but do not seem sufficient to legitimize a health alert commensurate with the fears expressed in the press. He recommends that the toxicologists responsible for establishing guidelines at the international level take up the potential mitotoxic effects of phytopharmaceutical substances (OPECST 2020).

In January 2020, three associations, the movement "We want poppies", Générations Futures and France Nature Environnement, asked the Anses to cancel the marketing authorizations of three SDHI-based fungicides. They announce a legal action if the agency does not respond within two months. Also on the judicial front, a ruling was made on Voxan, a fungicide containing three active substances including an SDHI (fluxapyroxad). It follows a lawsuit filed by a beekeeper who had rented his hives to pollinate a farmer's rapeseed field and whose bees had suffered a high mortality attributed to the treatment of a neighboring field with this fungicide. The judgment rendered in June 2020 was in favor of the beekeeper. In February 2021, the BASF firm was dismissed from a lawsuit seeking to overturn this earlier judgment. In the meantime, Voxan has lost its registration, following the withdrawal of marketing authorizations in France for another active substance contained in the product, epoxiconazole. Part of the media coverage of this bee loss and the subsequent ruling referred to the SDHI scare<fnref n="20" />.

In February 2020, Anses launched a call for applications for a WG on SDHI, which began work in October 2020 and is expected to publish its work by the end of 2022. In October 2020, two new projects are funded by the ANR and the Foundation for

<footnote n="18">¹⁸ https://www.cnrs.fr/fr/les-fongicides-sdhi-sont-toxiques-pour-les-cellules-humaines</footnote>

<footnote n="19">¹⁹ https://www.youtube.com/watch?v=BQL9da6qENw</footnote>

<footnote n="20">²⁰ For example: https://france3-regions.francetvinfo.fr/occitanie/ariege/foix/ariege-victoire-apiculteur-justice-recognized-poisoning-his-millions-bees-1842402.html
https://www.leparisien.fr/environnement/pesticides-un-apiculteur-obtient-la-reconnaissance-de-l-intoxication-of-his-bees-18-06-2020-8337723.php</footnote>
Medical Research and are in addition to projects previously funded by the OFB and Anses.
They fund a consortium of French researchers in chemistry, toxicology, ecotoxicology,
epidemiology, medicine, agronomy, economics, sociology and history, which aims at an
integrated assessment of the toxicity and ecotoxicity of mitochondrial toxic pesticides and
their regulation<fnref n="21" />.

In December 2020, the report of the parliamentary commission of inquiry on the evaluation of public environmental health policies recommended, with regard to the Anses and based on the example of SDHI, that the evaluation of hazards and risks be entrusted to scientists who meet the standards of the scientific method, so as to impose regulatory frameworks that are truly protective of the health of living beings and of the environment (Toutut-Picard, Josso 2020)

On June 30, 2021, the Inserm expertise on pesticides and health addresses the case of SDHI and devotes a chapter to it (Inserm 2021). It describes the lack of epidemiological data and the potential endocrine disrupting effect shown in some animal models. She discusses the regulatory basis for considering tumors observed in rodent tests as irrelevant to humans and concludes that research is needed to improve the assessment of the carcinogenic potential of SDHIs, and more generally of non-genotoxic active substances.

In november 2021, following its 2019 opinion on SDHI reporting, the cnDAspe will issue an opinion on "alert management of chemical risk" (cnDAspe 2021) on the basis of a report that it had commissioned from a group of experts. The opinion includes various recommendations on the methods of questioning or monitoring the scientific expertise of the competent agency, a clarification of the criteria leading the agency to update or not the risk assessment, transparency on the data taken into account in the updating of the risk assessment, publication of the recommendations addressed to the government, and a new procedure for the examination by the European competent authority of a recourse to safeguard clauses by a Member State, as well as an improvement in the quality of the public debate on chemical risk through the training of professional actors.

In June 2022, Pollinis' petition was submitted to the European Commission. Also in June 2022, EFSA publishes a peer review of the SDHI active substance isoflucypram (EFSA et al. 2022). It notes that the active substance could be tested in vitro for its potential to inhibit SDH but does not require it and considers that the toxicological assessment conducted by the petitioning company corresponds to the current regulatory requirements.

Some SDHI fungicides were marketed as early as the 1960s (Pesticide Property Database, Lewis 2016), but SDHIs have mostly entered the crop protection market since the early 2000s, with a "SDHI wave" of new active substances (Leadbeater 2015; Phillips 2020) intentionally developed to achieve greater biological efficacy (Rheinheimer 2019; Coqueron et al. 2019). Currently 27 SDHI active substances (23 fungicides, one fungicide and nematicide, and three acaricides) are identified by the Fungicide and Insecticide Resistance Action Committees (FRAC 2022)

IRAC 2022). In the European Union, four of them have been banned since 2002, two have been banned in 2021 and 2022 respectively, eleven are authorized and four are in

<footnote n="21">²¹ Holimitox Scientific Network, https://holimitox.fr/</footnote>
The last six have not yet entered the EU authorisation procedure (EU Pesticides Database 2022). SDHIs represent a significant share of the pesticide active substances under review for EU authorization (a total of 64 active substances, many of which are biocontrol products). The value share of SDHIs in the global fungicide market increased from 2% in 2004 (Krämer et al. 2007) to 8% in 2015 (Jeschke et al. 2019).

SDHIs are therefore of great interest to the agricultural world, where they are often used in products or crop management programs that combine active substances from several families, particularly to limit the development of resistance. In addition, production methods that rely more on natural regulations and less on synthetic inputs allow a reduction in the use of fungicides, but do not necessarily exclude them.

It can also be noted that strobilurins, an even more important family of fungicides (20% of the market in 2015, Jeschke et al. 2019) are also substances with mitochondrial toxicity, which in turn target complex I of the respiratory chain. The question of mitochondrial toxicity posed by the group of scientists thus concerns a broader field than just SDHIs.
<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /><figcaption>Figure 2: Chronology of the SDHI case</figcaption></figure>
### 3.3.2. Lessons from the case concerning the credibility of scientific expertise

The management of the SDHI scientists' alert was strongly criticized under thesis 2 (procedures), both for the initial exchanges with the group of scientists and for various limitations related to the choice of a GECU format for the initial instruction of the alert (limitations in the duration, the number of experts involved and their field of expertise, the consideration of the scientific literature).

Thesis 1 (mismatch between academic knowledge and regulatory expertise) also plays an essential role, since the alert concerns a mismatch between scientific knowledge on known mechanisms of toxicity (mitotoxicity) and the regulatory framework for evaluating pesticides, which does not take these mechanisms into account.

The strong involvement of different stakeholders from civil society, politics and science testifies to the relevance of thesis 3 with strong expectations for a better assessment of the hazards and risks of pesticides.

Finally, thesis 4 (on the impact of economic issues) is also illustrated by this case, given the increasing use of SDHI as a fungicide, which is in conflict with social and political demands to reduce pesticide use.
# 4. Thesis 1. Integration of the evolution of scientific knowledge in a science framed by regulations

The hearings have consistently shown that, compared to other European agencies, the Anses has a certain advantage in terms of its links with the academic world and the mobilization of scientific data. It also benefits from the framework of the health expertise charter on the management of experts' links of interest and from ethical rules that allow a better distance with the bearers of interest than in other European agencies. However, as is also the case in other European agencies, some of the agency's work may be criticised: it is perceived as insufficiently integrating the state of scientific knowledge, or as being too favourable to the interests of private companies, or as being too subject to political pressure.

The Agency is obliged to comply with national, European and international regulatory frameworks when it examines applications for marketing authorizations for regulated products for which it is responsible for risk management at the French level, or when it participates in European evaluations of marketing authorizations managed at this level. However, on a certain number of subjects within the scope of Anses' missions, the regulatory framework is increasingly questioned as being out of step with the state of the art of scientific knowledge. The Anses is not exempt from criticism when some stakeholders consider that the assessments comply with regulatory frameworks that are too narrow. This situation is encountered in our case studies, for example, with the legal cancellations of the MAs that the agency had granted to Roundup Pro or sulfoxaflor. It is also found in the current evaluation of the renewal of the European authorization for glyphosate, for which the Anses is participating in the consortium of rapporteur Member States, and which was the subject of numerous comments during the public consultation phase.

As for its risk assessment mission outside of these national or European authorization procedures, the Anses is not obliged to comply with regulatory frameworks; it may have the latitude - sometimes limited by the scope and timeframe of the referrals - to broaden the spectrum of scientific opinions issued, including by integrating elements that may go against regulations and/or suggest regulatory changes. Anses has also been criticized for its risk assessment mission, for example when it dealt with the alert on SDHI, or following the non-finalization of the second part of the mandate given to a GECU on glyphosate in 2015, concerning glyphosate-based formulations. In this case, it is the agency's capacity to use methodological references that deviate from the regulatory frameworks that is called into question, and its independence in relation to a political order.

Finally, the Anses has a role to play in discussions and working groups on the evolution of regulatory frameworks and guidelines at the European and international levels. Regulations evolve according to scientific knowledge, but with a time lag that is sometimes very significant (several decades) and that can cause sometimes irreversible damage to the health of individuals and the environment. This time lag is difficult to reduce because there are evaluation methods
The regulatory framework and the normative values associated with it are European and depend on international guidelines, notably those established by the OECD. This discrepancy is not only temporal, but also conceptual, and raises questions about the level of certainty that scientific data must provide in order for the guidelines to evolve. Bringing the regulations closer to the state of knowledge therefore requires a continuous evolution of standardized evaluation methods and standards at the European or international level, which requires a significant and long investment in the bodies concerned, with no guarantee of success. Even if significant efforts are made (see in particular the role of Anses in the European PARC program), the Agency's investment in the evolution of international and European regulatory frameworks can sometimes be considered insufficient, as illustrated by the case study on SDHI.

# 4.1. Regulatory science and structuring of knowledge mobilized in scientific expertise

This section shows both the importance, and the difficulty, of striking the right balance between academic and regulatory science at all levels of expertise, and of paying attention to the implications of possible biases in the scientific knowledge mobilized in the expertise.

## 4.1.1. The documentary base mobilized in the expertises

The literature base used in the scientific assessments is a central point that emerges from the case studies.

The methodological framework for the mobilization of bibliographic sources in expert assessments has developed considerably in recent years at the Anses. The "Risk Assessment Methodology" WG (MER WG) attached to the Agency's Scientific Council has made various proposals to structure the evaluation of the weight of evidence and the analysis of uncertainty in the agency's expert assessments (Anses 2016c, 2017a and 2017b). The WG

The successor group "Accompanying the implementation of the recommendations of the MER WG" (ACCMER WG), which also reports to the Anses Scientific Council, has developed an internal methodological guide for the planning of expert assessments, uncertainty analysis, literature review, and evaluation of the weight of evidence (Anses 2022, forthcoming) based on this work. In particular, this work establishes a reference method for literature review in expert assessments. It corresponds to a systematic review of the literature on the most important data in the realization of the expertise, i.e. those whose impact on the result of the expertise is significant. The assessment of the importance of the data is left to the unit and the group in charge of the expertise. The flow chart of the method and its different steps are detailed in the report of the ACCMER WG (Anses 2022, forthcoming) and in various internal Anses documents.

The expert assessments at Anses are carried out using the data available at a given date (scientific literature, data from surveys, reports from other agencies, results from experiments carried out in the context of registration dossiers, etc.), which are identified, selected, evaluated and summarized by Anses experts and agents as part of the first stage of the assessment.
This methodology, well detailed in the reports of these WGs, is not repeated here, the objective being rather to present the problems identified during the analysis of the cases that it does not cover. Indeed, the case studies highlight several blind spots in this approach, which can impact the quality of the expertise.

### 4.1.2. Links of interest in the affiliations of the authors of the articles or their funding

As mentioned above in the presentation of the glyphosate case study, an article then known to be "ghostwritten" by Monsanto employees (Brusick et al. 2016) was cited in the 2019 GECU report, without specific comment. Beyond this particularly emblematic case, the same report cited several publications with authors affiliated with private companies (industry or private testing and contract research firms, including in several cases a signatory of the previous publication

"The report was also published in a publication funded by the Glyphosate Task Force (an industry platform for producers of glyphosate-based herbicides).

These remarks on this report illustrate a more general problem: the Anses does not currently have a methodology or recommendations for analyzing the links of interest in the literature and contextualizing a publication financed by a firm with an interest in a regulation that is favorable to it, or co-authored by employees of this firm. However, industrialists can influence the scientific literature mobilized for the constitution of guidelines or, further downstream, for the work of internal experts or groups of experts in the agencies, as analyzed in the scientific and journalistic work on the merchants of doubt. The extent of this phenomenon is difficult to document precisely, apart from cases where company archives are made public during legal proceedings.

This influence can take the form of private funding of research whose methodologies aim to underestimate the risks of the products of the companies concerned, or to put forward alternative causalities to the risks of these products, in order to artificially maintain open controversies (Oreskes and Conway, 2010; Proctor, 2012). It also involves the creation of scientific journals, an example of which is the journal *Regulatory Toxicology and Pharmacology*, an official publication of an association dominated by scientists who work for industrial trade groups and consulting firms (Michaels, 2008). For example, Velicer et al. (2017) document this journal's ties to the tobacco industry and their consequences, arguing that "*[t]he significant representation other industries with an interest in regulatory science (chemical, pharmaceutical, food, as well as lawyers representing industry) on the editorial board raises similar concerns for research of broad interest range of other industries*". This influence can also come through the underwriting of scientific papers by employees of private companies that are signed by other scientists, or ghostwriting, as documented in the Monsanto Papers (Horel and Foucart, 2017c).

Transparency on conflicts of interest in the scientific literature has improved, with more and more scientific journals requiring the declaration of conflicts of interest in author affiliations or study funding. This gives the possibility to exercise more vigilance on this type of influence in the expertise. But this is not the case for all
journals, nor for older scientific articles, and this obviously does not allow the detection of
ghostwriting.

On the other hand, in various fields, the situation of industrialists is sufficiently favourable for
the production and interpretation of knowledge to converge with their interests without them
having to deploy strategic intervention. This is what is analyzed in the work on "undone
science," which focuses on the nonexistence of certain knowledge resulting from an unequal
distribution of power in society (Hess, 2016). From another perspective, work on the
institutionalized production of ignorance emphasizes that the institutions in charge of risk
assessment are dependent on the forms of knowledge that are most compatible with their
modes of action, which induces selection effects of the available knowledge, and leads to the
ignoring of some (Jouzel, 2019). Finally, Boullier and Henry (2021) show situations where
expertise depends on unpublished industrial data. More generally, they analyze the structural
forms of influence of private actors on the knowledge mobilized in public expertise, which the
current problematization in terms of the management of conflicts of interest of experts tends
to make invisible.

Vigilance on the funding or authorship of studies was recommended in a 2016 opinion of the
Anses Ethics Committee on the exploitation of scientific literature (CDPCI Anses 2016). In
particular, the following extracts can be cited:

"Several researches, in various fields, have shown that full or partial funding of the study by industry or service sector actors influences the published results. A statistical analysis of the studies shows a significant overrepresentation of results favorable to industry when the research received funding from them."<fnref n="22" />

(CDPCI Anses 2016, p.4)

"The efforts made by the Anses to prevent the risk of conflicts of interest have mainly focused on the appointment of experts and the conditions of their participation in expert assessments. However, the use of bibliographic tools for expertise purposes (bibliographic files and databases, criteria for the thematic selection of publications, choice of journals, etc.) also constitutes a major risk of exposure to conflicts of interest, which is not mentioned in the Agency's normative documents on the

<footnote n="22">²² The CDPCI report cites the following publications: CAMPBELL E. G. et al. 2007. Institutional Academic-Industry Relationships, JAMA, 298(15):1779; CAMPBELL E. G et al., 2007. A National Survey of Physician-Industry Relationships. NEJM, 356(17):1742; LESSER L. I. et al. 2007. Relationship between Funding Source and Conclusion among Nutrition-Related Scientific Articles. PLOS Medicine, 4(1):e5 - 0041; KRIMSKY S. 2010. Combating the Funding Effect in Science: What's Beyond Transparency? Stanford Law and Policy Review (21)1:101; MAXIM L. and ARNOLD G. 2012. How conflicts of interest can influence research and expertise. Hermes. 64:48-59; BAS- RASTROLLO M. et al. 2013. Financial Conflicts of Interest and Reporting Bias Regarding the Association between Sugar-Sweetened Beverages and Weight Gain: A systematic Review of Systematic Reviews. PLOS Medicine.10(12); DIELS J. et al. 2011. Association of financial or professional conflict of interest to research outcomes on health risks or nutritional assessment studies of genetically modified products. Food Policy. 36:197-203; Union of concerned scientists. 2012. Heads They Win, Tails We Lose - How Corporations Corrupt Science at the Public's Expense. Feb.</footnote>
ethics of expertise<fnref n="23" />. This risk, which has only recently been understood, concerns both the status of authors of publications, peer review arrangements, and the source of funding for journals, as previously reported."

(CDPCI Anses 2016 p.12)

In this report, the Anses CDPCI recommended the creation of a WG on "Evaluation and methodology for processing bibliographic sources" attached to the Anses Scientific Council and to the Technical Committee on Referrals, whose mission would be to "develop an analysis method on the quality of bibliographic sources, the detection of practices the mechanisms of institutional regulation, the relevant period for taking into account publications (how far back?), in order to encourage the Agency's experts to be more vigilant in the constitution and selection of bibliographies"

(CDPCI Anses p.13). It called for the development of methodological guides on the minimum conditions that must be met by a study to be retained in the framework of an expertise, including the consideration of links of interest in the articles, and encouraged "the identification of obstacles and biases encountered by experts in the development of bibliographies in support of expertise in order to build a memory of these incidents, accessible to subsequent practitioners" and a "monitoring function on the development and the growing potential of data collection, processing and analysis tools (knowledge of the state of the art in science, controversies, modes of perception of weak signals...), detection of influences" (ibid.).

In addition to the work of the MER WG (which the ACCMER WG followed), this CPDCI Anses report called for international standards relating to ethics and good practices in the field of publications to be taken into account, in particular the principles established by the Committee on Publication Ethics<fnref n="24" />.

The analysis of the case studies shows that these recommendations are still relevant. In addition to the inclusion of links of interest in articles, this can be added to the need to do so for journals. As an example, the *Regulatory Toxicology and Pharmacology* journal mentioned above, for which industry influence is documented in academic work, is cited without specific comment in the reports of the two glyphosate GECUs (Olson et al. 2000 in Anses 2016a; Annys et al. 2014 in Anses 2019a).

### 4.1.3. Consideration of emerging scientific hypotheses and recent data

In essence, very new scientific data are generally not yet replicated by other groups when the question arises as to whether they should be considered for risk assessment. However, they should not be discarded because they can

<footnote n="23">²³ The CDPCI Anses (2016) report cited these documents: Code of Ethics for Expertise (Nov. 2012), Fundamental Principles and Key Points of Collective Expertise (Nov. 2012), Note de cadrage sur la méthodologie de l'expertise collective (Feb. 2012), Quality Management Manual (version b of Aug. 25, 2014). The risk of exposure to conflicts of interest through the use of bibliographic instruments for expertise purposes is also not included in the current versions of these documents.</footnote>

<footnote n="24">²⁴ https://publicationethics.org/files/Code_of_conduct_for_journal_editors_Mar11.pdf</footnote>
constitute warning signals. On this subject, the CDPCI Anses recalled the principles of impartiality, transparency, plurality and adversarial nature of health expertise set out in Article L.1452-1 of the Public Health Code and formulated the following recommendations in the aforementioned 2016 opinion:

> [It is essential to look for any studies that contradict the dominant results. Identifying minority or emerging scientific hypotheses and taking them into account in the assessment is a necessary condition for drawing up an inventory that reflects as accurately as possible the state of knowledge at the time of the assessment and, if necessary, inviting more in-depth studies to be carried out.](CDPCI Anses 2016 p.15)

> "Care must be taken to ensure that the selection criteria...are not so rigorous as to exclude any study that does not conform to mainstream thinking.](CDPCI Anses 2016 p.12)

Such recommendations are still valid. When quantitatively assessing the level of evidence provided by the various documents included in the literature base, they call for the inclusion of articles whose level of evidence may remain low due to their novelty, as long as the methodology used to produce the results is well described.

The CDPCI (Anses 2016) recommendations can be extended to studies that are consistent with mainstream thinking but critical of regulatory approaches. Again using the example of the 2019 GECU report on glyphosate as an illustration, it shows that the choices in the specification were not situated with respect to the academic literature about the controversy over the carcinogenicity of glyphosate following the classification discrepancy between IARC and EFSA. Thus, for example, the publication by Portier et al. (2016) on the comparison of IARC and EFSA assessments of glyphosate carcinogenicity, signed by 96 mostly academic authors, was not cited. It is important that critical knowledge on regulatory assessments be taken into account in Anses' expert assessments.

It is also essential to have the ability to incorporate important recent knowledge, even published after the initial literature search. An example is the publication by Simon-Delso et al. (2018), showing chronic toxicity effects of an SDHI substance on bees that are not considered in regulatory procedures. Released near the beginning of the SDHI ECWG work, it is not cited in their report.

### 4.1.4. Consideration of academic scientific results obtained outside of GLP guidelines and standards, including when analyzing the risks of regulated products

For risk assessment evaluations, whether they are carried out in the context of a marketing authorisation or outside such a framework, the interviews highlight the need to allow experts to explore the literature without any a priori restrictions, and in particular
not to be limited to publications and studies that comply with good laboratory practices and guidelines, which are the most usable in a regulatory framework.

"In terms of regulatory science and academic science, I think that's the crux of the problem. This is something that should be better explained to policymakers. Again, there is confusion, including in the scientific community. That's what's terrible. I realized in working on these glyphosate stories that for the broader scientific community or the medical community, a regulatory opinion is a scientific opinion. It's an opinion in which we've implemented a strategy of exploring the literature looking for what might explain what we're seeing in the real world or these kinds of things. That's a scientific approach. It's obviously not and it's so shocking."

(journalist)

"Everything that is a scientific study that can be looked at within the framework of a specific expertise, including regulated products, must be for me. Afterwards, if it is not retained for this or that reason, it must be said, traced and made transparent. But, in my opinion, one cannot say: "I exclude this study" without giving precise and valid reasons. When the BfR at the time, in the first glyphosate expert report that I re-read, rejected the epidemiological studies because they did not respect the Klimisch criteria, I had serious doubts. For an epidemiological study, by definition, the Klimisch criteria do not apply, even if we can try to transform them. There are published methodological references that can be used in these circumstances. For me, it is clear that if there are studies, other than GLP studies or industrial studies, that are useful, that could be useful in a regulatory assessment, they should be used."

(Anses manager)

The scientists involved in the collective expertise must remain free to choose the references to be considered and must remain independent in their reasoning, questions, observations and analyses, without interfering with the regulatory issues. When the questions put to the experts are limited to the regulatory framework in force, a proposal emerged from several interviews: to allow the experts to give complementary points of view outside these regulatory frameworks as long as they are supported by solid scientific arguments. These additional points of view could be given separately in the opinion, in addition to the response limited to the strict scope of the referral:

"Secondly, when we are a state agency, we are always free to have prerogatives with a scientific dimension. We are always able to provide an answer to the question that the government asks. Then, it is possible to add an additional chapter saying that we have been questioned on certain data and to present our answer. On the other hand, it is also possible to say that one should be careful because other data are not based on the framework mentioned. It is possible to say that this data is about this and that. It is quite possible, not to go outside the framework, but in the response given to the government, to draw their attention to the fact that another view of the situation exists, from a strict scientific point of view, than the framework that the government has set."

(political leader)

This proposal is also consistent with the following recommendation from the Anses Ethics Committee in 2021:
"This disjunction between regulatory and academic science - always temporary but often long-lasting - is recognized as one of the causes of public distrust. In the name of transparency on the one hand, and contradictory science on the other, the addition of certain results of academic science, convergent although not yet totally validated, should be mentioned as a track to follow and at least serve as an alert to deepen the subject within a time limit to be fixed."

(CDPCI Anses 2021 p.6)

For risk assessments carried out in the context of marketing authorizations, we can thus recall this excerpt from a judgment of the European Court of Justice (CJEU, 2018): "On the other hand, this does not does not mean that the relevant scientific literature should not be taken into account in the context of a review under Article 21 of Regulation 1107/2009. [Unless otherwise specified, the decisions that the Commission is called upon to take under this Regulation must always take into account the latest scientific and technical knowledge more recent". The practical implementation of this recommendation within the framework of MA procedures continues to be debated.

The long excerpt from the interview reproduced below illustrates the topicality of the criticism of the practice of excluding articles from the academic literature in the context of the European review procedure for the authorization of glyphosate.

"Now that I've been fortunate or unfortunate enough to be interested in these issues for a while, I sometimes spot a paper in the literature. Sometimes there are critical papers. We know they are very important papers. I wonder how they will take this paper into account in the next European re-evaluation. There is one example that I find very amusing. It's a paper that came out in 2019 or 2020 by Swiss researchers. They did an experiment on humans to find out how much glyphosate we were actually exposed to. Strangely enough, it's an open question that we don't really have an answer to. We can measure what comes out in the urine. Then we do a bit of a messy calculation to see what that corresponds to in terms of oral exposure. We come up with a result. The basis for these calculations are regulatory studies done on rats. So researchers did the experiment on humans to see if it was the same in rats as in humans. That was published. Unfortunately, they didn't find the same result at all. There is a difference of a factor of 20 on average, and as much as 50. We take in on average 20 times more glyphosate than the regulatory agencies think. We can take it any way we want, but it's a subject. So I had fun looking through the thousands of pages of the glyphosate renewal report to see how we took that study into account.... The study in question is crossed out with a stroke of the pen, saying, "We didn't look at everything that came out in all the excreta of the people who were sampled. That's not reliable. So we're not going to take that into account. I was interested in how biomonitoring experts talk about this study in their own work, because this study has been cited a lot since it was published. Indeed, the experiment had never been done. It was replicated by Swedes who found the same result. There is not even the objection that they are the only ones to have done this study. They were the first to do it, but it has been replicated by other teams who find a result that matches. Explicitly in the scholarly literature, there is a whole paragraph in the latest journal on population exposure to glyphosate in which the researchers say, "We finally have a human toxicokinetic and impregnation study of glyphosate. That's great. This should definitely be considered in the next re-evaluation." The
> The result is a line in a table. When we object to the regulators that they don't take the scientific literature into account, they immediately say, "Oh, but we don't. We have taken everything into account. We have taken everything into account. You have to see how poorly the work is dismissed out of hand. You are the best people to know that all studies have their limits. As soon as there is the slightest limitation, the study is dismissed without further ado, even if you have 50 papers that point in the same direction. That's a huge problem."

(journalist)

It can also be noted that the Anses staff of the Regulated Products Unit do not make much use of the Anses service for scientific resources. We have not found the explanation for this surprisingly low use. This is certainly an avenue that needs to be explored.

### 4.1.5. Access to the details of the regulatory data

It also seems necessary for experts to have access to the details of the regulatory data that they consider useful for their analysis (including studies presenting the raw data) and to have the time and means to analyze them.

To give an example, during the GECU work on the comparison of IARC and EFSA opinions on the carcinogenicity of glyphosate (Anses 2016a), a letter to EFSA from about 100 scientists detailed various criticisms of the assessment conducted by EFSA and BfR (Portier et al. 2015, which later led to the publication Portier et al. 2016). One example is the unpublished study by Sugimoto (2017), whose observed trends in tumor incidence were rejected by the BfR on the grounds that the maximum observed response was within the range of historical control data. This study was challenged by Portier et al. (2015) because of the use of historical controls from a different mouse line than the mice tested. In contrast, it was cited without comment in the 2016 GECU report. When asked about this, one expert responded:

> "You're putting words in my mouth. It doesn't tell me anything, but I can tell you something else. If we had access to the raw file, we would have seen it. I remember that I criticized an active ingredient in this way. There were two cancer studies, and they had used the controls from one study to make the calculations for the other. At the time, we were defending the files at the EU, I went to York and I told the British: "I don't agree with this amalgam of data". They told me: "You are looking in the corners and we did not notice it". So you have to look precisely. It's possible that they misused the historical controls, because there are rules for using them. These are the historical witnesses from the same lab, which cover a period of less than five years. Invoking historical witnesses is not enough, and is inadmissible if the batch of witnesses covers a period that extends beyond five years. You have to dig to see all this.

(expert)

As another example, the question of access to data also arises for the second part of the mandate of this expert group, on glyphosate-based formulations, which did not result in the publication of an opinion:

> "The GECU had begun to answer the second question, looking at what method could be used and what tests could be done very easily. However, I had stressed that in order to interpret the data, it seemed to me essential to have the compositions of the formulations and not only the representative formulation. And then if we want to say something useful, it is
> In particular, to look at the composition of the formulations on the market, to be able to say if it is valid or not, or if we should rather test for this one or that one, depending on what we know about the co-formulants. The answer is simple: we never have access to the co-formulants. I have never seen them. So we asked for details but they were not available. I was puzzled by this lack of information, and it seemed unnecessary to continue to answer this kind of question. If the compositions are not accessible why ask such a question?"

(expert)

Anses agents provide valuable assistance to expert groups for literature reviews. Anses' support could be strengthened to facilitate access to the data in the regulatory dossiers requested by the experts, or to clearly explain the reasons why these data could not be provided.

### 4.1.6. Time to analyze the collected data in detail

Mobilizing and analyzing the literature in detail requires time, which is not always available, due to constraints often experienced by the agency. On this subject of the need for time for a detailed analysis of studies, feedback from experience may be interesting to mobilize (for example, the case of an expertise outside the Anses with a public sponsor, for which the group of experts had negotiated two two-year post-docs). Another idea that emerged from the interviews is to anticipate subjects that we know will be sensitive, in order to arrive with a background if a somewhat urgent request arrives. In particular, having time is not possible in GECUs, so the analysis may remain on the surface on some points.

### 4.1.7. Ability to return to literature reviews with different lexical queries as the expertise progresses

Like the questions asked in the referrals, the subjects taken into account and explored in the framework of the expertise may change as the expertise progresses. Limiting the questions to those that are too narrow exposes us to the risk of overlooking important fields of knowledge for a relevant risk assessment.

### 4.1.8 Work carried out in Anses laboratories or in academic laboratories and funded by Anses

Another important subject is the consideration of the recommendations of the expert assessments, in terms of the need to advance knowledge, in order to prioritize either research funding by the Anses (through research and development agreements or within the framework of the PNR-EST), or research in the Anses laboratories. One point in particular is the interest in generating scientific data to develop standards or assessment methods.

Anses does not appear to have been proactive in conducting work in its laboratories to clarify the appropriateness of the regulatory assessment mode for SDHIs, even though the SDHI GECU had made numerous recommendations on this topic (Anses, 2019b).

> "On very specific and particular issues, the Anses laboratories eventually need to have a little more money and flexibility to approach the subject. Let me give you an example. One of the Anses laboratories is working in 2022 on
Paraquat. Paraquat has been banned since 1969 in Switzerland and in France since a certain date. We still have laboratories of the Anses working on paraquat. It is money badly used. The Anses laboratory that works on paraquat should work on SDHI. We asked very concrete and direct questions about SDHI. We brought answers. We could relocate people to a research topic".

(scientist)

The question also arises as to the means available to Anses for such work. The Anses has the possibility of launching studies conducted by mutual agreement with research teams, notably in the form of research and development agreements. However, it does so with limited means, which can be an obstacle. In 2021, the Ethics Committee of the Anses recommended increasing the resources of the Anses to finance such complementary studies:

"Part of the difficulties encountered by the agencies comes from public doubts about the reliability or completeness of the data. However, constrained by the regulations, the Agency can only act on the margins by refusing a marketing authorization or by requesting confirmation studies from manufacturers each time the data seem to be fragile or incomplete, which it already does. But it would also be appropriate to finance additional independent research when the petitioners' results are not in line with the results of academic research. The concerns of civil society about current agricultural production methods, relayed by several parliamentary reports, should make it possible to justify to the legislator an increase in the resources of the Agency, whose competencies are constantly being expanded. It is essential, from a deontological point of view, that the Agency be able to finance such complementary studies and that its staff work in optimal conditions.

(CDPCI Anses 2021 p.5)

## 4.2. Role of Anses in establishing guidelines

The case studies highlight the inadequacy of current guidelines for assessing the toxicity of pesticides on bees (neonicotinoids), the failure to take into account the effects of mitochondrial toxicity in the regulatory assessment of pesticides (SDHI), as well as various alerts on the conditions of marketing authorizations for pesticides, For example, in the glyphosate case study, the existence of fraud in a laboratory that is GLP-accredited (PAN Europe 2020), or the failure of a company to comply with its obligation to submit all known data on the toxicity of its product (Mie, Rudén 2022).

Several hearings emphasized that France should lead efforts at the European and international levels to change the European regulatory framework and reduce the differences with scientific knowledge; in particular by investing in the construction of guidelines at the OECD. Among the other French actors that could have an impact on this issue, the Anses could play a more proactive role in changing regulatory methods.

"We had made a proposal on the mobilization of European and OECD levers under the aegis of the General Secretariat for European Affairs. I don't remember who said it earlier, but in France, the experts didn't seem to us
have a great deal of appetite to position themselves on everything that is done
at the OECD level or in the implementation of methods at the European level.
This is something we regret. On the OECD side, we tried to see a little more
clearly, but it was a real black box. We were not able to find out who was sitting
in the different bodies and how they worked. But we realize that some of the
methods of expertise are derived from the discussions at the OECD. (...) I believe
that for the credibility of the expertise, there is a real need to go upstream, to
invest more in everything that concerns methods, guidelines, definition of
good laboratory practices at the OECD and that people sit on the committee. I
understand that this is very long, that potentially seven years of working groups
have to be done and that it is not necessarily very gratifying, including in
professional terms. I don't know how it should be organized, but for me, the
Anses would have an essential role to play, to contribute to the animation of the
pool of experts who will sit in all these method definition bodies."

(Inspector General)

This is what is proposed in the General Inspections' report of 2020 "Health-Environment: research, expertise and public decision making", under proposal 27, of high priority: "Establish, under the aegis of the SGAE [General Secretariat for European Affairs], a roadmap for mobilizing European (and OECD) levers that is shared between the various administrations, the organizations concerned (in particular the Anses), the Permanent Representation to the European Union, and the ministers' offices concerned" (Lavarde et al. 2020, p. 4).

A more proactive involvement in the European and international bodies that develop
guidelines and regulatory frameworks, and greater transparency in the functioning of these
bodies, appear to be central. The Anses could play an important role in this process, not only
to better take into account scientific knowledge on the toxicity and ecotoxicity of products, but
also to improve the current limitations of the European authorization procedure (possible
fraud in GLP-accredited laboratories, subtraction of data on the toxicity of their products by
the companies, etc.)
# 5. Thesis 2. Procedural issues

Since the end of the 1990s, scientific expertise has been the subject of a series of reforms aimed at increasing its quality and restoring confidence, with, in particular, in France, the Law of 1 July 1998 on health security. This law defines the main lines of the reform: implementation of the separation between expertise and management, delegation of expertise to specialized agencies -independent authorities, several of which were created by the 1998 law, others will follow- which rely mainly on external expertise, obligation of transparency and communication with the public and stakeholders. These reforms therefore establish several "fundamental principles" that constitute the foundations of expertise: competence, independence and transparency.

The production of procedures is part of this framework. It can be identified by a series of texts. Without attempting to be exhaustive and limiting ourselves to France, we can give a few points of reference. The AFNOR NF X 50-110 standard of May 2003 "Quality in expertise - General competence requirements for expertise" aims to "improve the control of points having an impact on the product of expertise and to allow, if necessary, a recognition of the capacity to conduct expertise". It defines expertise as "the set of activities whose purpose is to provide a client, in response to a question, with an interpretation, an opinion or a recommendation that is as objectively founded as possible, based on available knowledge and demonstrations accompanied by professional judgment. This standard indicates in particular that: "The quality of an expertise depends on the competence, independence and probity of the experts, and on the expertise process itself, the transparency and justification of which are increasingly required." The standard is supplemented by several fascicles detailing recommendations for its application (FD X 50-046: 2010, FD X 50-046: 2011).

Anses is firmly committed to this movement and actively contributes to the development of the doctrine, its implementation and its continuous improvement. The Anses expertise process is under quality assurance, with an ISO 9001 certification, including

* The fundamental principles of the agency's expertise

* The regulatory requirements of the decree on health expertise (decree 2013-413)

* The normative requirements of the NFX 50-110 standard

The internal corollary is that various stages of the process are documented or framed by documents attached to the realization process. The work on procedures is therefore quite considerable and aims at a continuous improvement of expertise.
## 5.1. Preparation of the referral

A referral is a request for expertise leading to an opinion from the Anses, issued by an authority or an authorized legal entity, on clearly identified points within the Agency's fields of competence.

The applicant may or may not be one of its supervisory ministries, public establishments of the State, associations approved at the national level in the fields of environmental protection, quality of health and care of patients, consumer protection, as well as associations providing assistance to victims of work or occupational diseases represented in the Asbestos Victims' Compensation Fund, trade unions, professional and interprofessional organizations. The Agency also has the power to refer cases to itself.

To respond to the referral, the agency mobilizes a collective scientific expertise that meets the principles of impartiality, transparency, plurality and adversarial debate, as defined by article L. 1452-1 of the Public Health Code. It is part of "all the activities having to provide a client, in response to a question, with an interpretation, opinion or recommendation, as objectively based as possible, developed from available knowledge and demonstrations supported by professional judgment". (NF X50-110 standard).

The referral must therefore allow the full expression of scientific knowledge: "Science is the basis for public decision-making by producing reliable benchmarks that allow the various options available to the decision-maker to be evaluated" (Benoit Vallet, Chairman of the Board of Directors of the Anses)

The drafting and the outlines of the referral are mentioned in some interviews as a fundamental step that conditions the quality of the whole process. The question posed by the referral must not only enlighten the client in his decision making but also have a certain "value" for the experts and the stakeholders of the company. It is this value that generates motivation and commitment to the agency, from the moment the experts are called for. However,

"Sometimes the questions that, for example, guardianship wants answered are not necessarily the questions that society or society's stakeholders are asking."

(Anses manager)

"Several people contacted me and said they would no longer participate in the working group because they felt they were not being used."

(expert)

Or again, in the case of the glyphosate carcinogenicity referral, where the framework and deadlines were very restrictive:

"I would never have gone there."

(expert)

The wording of the question must therefore be clear and unambiguous to allow the experts to produce relevant scientific benchmarks.
"It is very clear that the principal sometimes plays on ambiguity to give himself the means to get around it"

(political leader)

"Sometimes the questions appeared ambiguous or too general. One of the suggestions we made to the Agency was to be able to discuss the text of the referral beforehand to better target the possible response.

(expert)

The clarity of the referral makes it possible to better decide on the knowledge that can be mobilized to see to what extent the knowledge that corresponds to the regulatory framework must be supplemented by academic knowledge.

The need to go beyond the question posed in the referral was frequently mentioned. For several interviewees, the committees must be able to complete a referral that they consider restrictive, both in terms of the state of the art of scientific knowledge and the regulatory and methodological framework.

"There is nothing to prevent us from saying: 'In connection with your answer, without it being directly the question asked, we take the liberty of pointing out this or that'"

(political leader)

"Not addressing certain aspects can be abusive in relation to the mandate of the expertise. Experts also have their autonomy. This is also good. A compromise is bound to take place somewhere between the sponsor and the experts."

(expert)

A poorly formulated referral with too narrow a scope may be perceived by the experts as an injunction or an intention to restrict the expertise intellectually and interpreted a *posteriori* by certain observers as a desire to influence the expertise and the risk assessment.

"The department will therefore be tempted to direct its referral in a direction that suits it for reasons that are not necessarily scientific."

(political leader)

In some cases, referrals can be a wait-and-see or problem-avoidance strategy, which can undermine the agency's credibility.

"There are obviously many ways for the opinion seeker to influence. They can change the scope of the question. We see cases where the answer comes in and you can say in hindsight that it was the wrong question. At the time it was formulated, no one was moved by it."

(political leader)

The drafting of referrals in a negotiated partnership between the client, the agency and, as far as possible, the expertise groups seems to us to be necessary in order to *ultimately* produce an expertise that is useful to the client and scientifically founded.
> The "scoping paper" (...) defines the perimeter of the question, saying what is included and what is excluded, to avoid embarrassment. There must first be a dialogue between the agency and the client so that it is not just an order received, but a dialogue is established until there is agreement that the question makes sense and is good."

(political leader)

> "In our group, we really had latitude. It wasn't total. That's okay, but it was important and it allowed us to rephrase questions that we thought were relevant or not relevant to get our heads around the issue. I think the agency really respected that."

(expert)

It thus appears, for all the interlocutors, that the drafting of the referral is the first element that conditions the future credibility of the expertise produced. It must be the subject of increased attention, involving the experts as much as possible, which is not a problem for ESC referrals.

Self-referrals are described as a comfortable way of exercising, a facilitating anticipation of debates, both by the experts of the CES, WG, GECU and the managers of the agency. Thus, the Anses has used its capacity to take on certain questions on its own initiative, to evaluate the co-exposure of bees to stress factors, playing its role of prospective intelligence, monitoring and scientific development.

> "On the one hand, the working group formed was multidisciplinary and balanced; on the other hand, the material conditions (means, support and duration) were adapted to the questions asked. Finally, from the beginning, the questions could be broadened by the experts as much as needed to provide answers and recommendations relevant to all stakeholders."

(expert)

> "It's to integrate the agency into its role, much more in a normal life, anticipating issues, rather than grabbing it like a firefighter."

(stakeholder)

## 5.2. Composition of committees and selection of experts

### 5.2.1. A panel of quality, multidisciplinary experts from different professional backgrounds

The evaluation groups, whether they are CES, WG or GECU, are made up of experts appointed by Anses according to specific procedures. The NFX50-110 standard defines an expert as "a person whose competence, independence and probity are such that he/she is formally recognized as suitable to carry out expert assessment work".

The appointment of experts for the ESCs and WGs follows a call for applications published on the Anses website, advertised and managed by the Agency's expertise support department, in conjunction with the scientific coordinator of the group of experts and the head of the Anses unit concerned, according to
procedures that allow the traceability and transparency of the selection methods. It should be
noted that the applications of experts for the ESC are also presented, discussed and
validated by the Scientific Council. The selection criteria are traditional - competence,
scientific excellence, complementarity, practice of expertise (a prerequisite that is not
indispensable but often taken into consideration), independence (analysis of the Public
Declaration of Interest, see below).

On the other hand, the appointment of GECU experts is carried out without a call for tenders. The Anses may call upon experts already appointed to Anses evaluation bodies, or from the list of competent persons (persons who have applied for calls for tenders but have not been selected but whose competence in a given field has been identified), or from any other scientific personality. The emergency nature of the GECUs has sometimes justified the appointment of experts whose competence in the subject matter may have been questioned after the fact, thereby undermining the credibility of the expertise produced.

"We were also challenged by who these rapporteurs were, who had worked on this topic and the fact that no one had expertise in mitochondrial diseases. The report had been looked at in terms of the value and use of these pesticides."

(expert)

The disciplinary diversity of the experts in the teams is a guarantee of the credibility of the expertise and is the subject of constant attention by the Anses departments. While the need for complementary scientific skills is obvious to all, the representation of human and social sciences (sociology, epistemology, economics, law, etc.), which are able to detect and decipher rhetorical and socio-economic phenomena, particularly in difficult contexts (heated scientific debate, high economic stakes, etc.), must not remain marginal.

"By this I mean that I have not made a complete examination of all the forms and modalities covered by this notion of expertise meeting the AFNOR quality standard, but it seems to me that it is very heterogeneous. It is very heterogeneous in terms of ambition, in the number of experts and in the diversity of disciplines, between an emergency expertise between four toxicologists and a very multidisciplinary expertise like the one I participated in on the exposure of agricultural workers to pesticides. There was history, epidemiology, ergonomics, sociology and toxicology."

(expert)

"From my perspective, the people who have best understood what has happened on the neonicotinoid issue, for example, and who have described the socio-economic phenomena at work, are often people from the humanities and social sciences. They are often historians of science. These are people who were used to seeing this kind of rhetoric coming into the public debate and this kind of intervention on literature and research to muddy the waters, to find alternative causalities and fund what is interesting to fund rather than research on toxins, varroa mites, parasites and viruses."

(journalist)

In addition, the balance between academic experts with strong expertise in their scientific field and researchers who are better trained in regulatory constraints and collegial expertise practices is a real difficulty, starting with the Anses staff in charge of
the composition of the committees. Ensuring this balance is indeed essential in order to articulate in a fruitful way the necessary knowledge of the formal and even regulatory procedures of expertise and the possibility of integrating the most recent knowledge when it is relevant.

A third, well-known tension is between the requirement of competence and the requirement of independence of experts.

"I came to this kind of expertise very late, but I was always told that if we don't have any contact with the industry, we don't know how it works, especially in the drug industry. So we would be bad experts. If we refuse to take on independent groups the people who know the pharmaceutical industry well, as soon as they declare their interests, we will have no experts. I am now involved in the Anses expertise and then in others, but it is a job. It is not the job of a researcher. It's another job. I didn't know that."

(expert)

Finally, it is important to ensure that the pool of experts is regularly renewed in order to avoid relying on a population that is too narrow and made up of researchers who are no longer active on the science fronts. The agency is particularly active in identifying new experts and helping them learn the practices of collegial expertise. This is a real challenge. It is all the more important because the competence specific to collective expertise activities is acquired through learning by experience in different roles in committees.

"Then, the scarcity, the involvement, as an expert, you have a hunger that is inexhaustible. You get involved, you get involved, and afterwards, I've won other collectives. I always talk about collectives."

(expert)

### 5.2.2. The pool of experts: difficulties in recruitment, attractiveness, commitment

The multidisciplinary nature of expert committees and the establishment of a fruitful dialogue based on mutual trust between experts are the basis of collective expertise, provided, however, that the commitment of each is similar. However, the regular presence of experts within the collectives is not systematic. This lack of commitment can not only harm the quality of the debates, but can also lead to significant biases in the expertise due to a lack of competence in a given field or, on the contrary, favour a minority position and thus give an angle of attack to opponents. The attendance and commitment of experts are absolutely essential in small groups, such as the GECUs, which work under time constraints.

"I discovered this world where most of the experts in the group did not work much, it must be said. It was finally a chance, because those who wanted to work (4 or 5 people) could work on scientific bases ... One of the negative aspects was that some people did not come much. So there was an overload of work for the others. This is always a problem. I would like to say one thing: You have to exclude the people who don't come."

(expert)