1. Committed since 2002
to ensuring that Europe’s food is safe
PPR Panel’s Work on
Cumulative Risk Assessment of Pesticides
ECPA – IBMA- EFSA Workshop
Parma, 26th April 2012

2. • Over the last decades – growing concern in Europe on
combination or cumulative effects of chemical
substances
• Ever growing number of EU and Member State
reports, publications and studies on the issue:
“Chemical cocktails – a serious matter of concern”
published 10 February 2012
http://www.norden.org/en/publications/publikationer/2
012-711

3. Legislative background for CRA
Regulation EC 396/2005 on maximum residue levels (MRLs)
Art 14 (Decision on applications concerning MRLs)
“ …account shall be taken of… the possible presence of pesticide residues arising
from sources other than current plant protection uses of active substances,
and their known cumulative and synergistic effects, when the methods to
assess such effects are available…”
Whereas (6)
“It is also important to carry out further work to develop a methodology to take
into account cumulative and synergistic effects. In view of human exposure to
combinations of active substances and their possible aggregate and synergistic
effects on human health, MRLs should be set after consultation of the
European Food Safety Authority…”

4. 7th EFSA Scientific Colloquium,
28 - 29 November 2006, Parma, Italy
• 2007 The EFSA's 7th Scientific Colloquium Report –
Cumulative Risk Assessment of pesticides to human health:
The Way Forward
http://www.efsa.europa.eu/en/supporting/pub/117e.htm
Participation from experts from EU member states and
Accession Countries

5. 7th EFSA Scientific Colloquium,
28 - 29 November 2006, Parma
Conclusions/Recommendations:
• Develop a methodology for assessment of cumulative hazards
preferably on bases of existing approaches
• Develop criteria for grouping substances
• Consider also dissimilar mode of action
• Develop guidance for probabilistic exposure modeling
• Prioritise compounds (organophosphates, carbamates, triazoles,
pyrethroids, dithiocarbamates)
• PPR Panel to prepare an opinion based on the outcome of the
colloquium

6. PPR Scientific Opinions on CRA
• 2008 PPR Scientific Opinion to evaluate the suitability of
existing methodologies and, if appropriate, the identification
of new approaches to assess cumulative and synergistic risks
from pesticides to human health with a view to set MRLs for
those pesticides in the frame of Regulation (EC) 396/2005
http://www.efsa.europa.eu/en/efsajournal/pub/705.htm

7. PPR Scientific Opinions on CRA
Principles established :
• Dose addition (similar action)
response addition (dissimilar action) and interaction not
considered
• Criteria grouping of substances for CRA
• Tiered approach for hazard assessment
• Tiered approach for exposure assessment

8. PPR Scientific Opinions on CRA
• 2009 PPR Scientific Opinion for a selected group of pesticides
from the triazole group to test possible methodologies to assess
cumulative effects from exposure through food from these
pesticides on human health
http://www.efsa.europa.eu/en/efsajournal/pub/1167.htm

9. PPR Scientific Opinions on CRA
11 Triazole pesticides (fungicides)
Structure (diniconazole)
• Target organism: inhibition of ergosterol synthesis
(inhibition of CYP51)
• Laboratory rodent (rat):
– Acute: Cranial malformations (inhibition of CYP26 in
embryo)
– Chronic: Liver toxity (inhibition/induction of CYPs)

10. Current PPR/PRAS activities on CRA
Completion of PPR work on cumulative risk
assessment - similar MoA (dose addition)
• Article 36. grant on Identification of cumulative
assessment groups of pesticides
- initial deadline of December 2010 delayed to October 2011

11. Current PPR/PRAS activities on CRA
Completion of PPR work on cumulative risk
assessment - similar MoA (dose addition)
• PPR Scientific Opinion on the identification of
pesticides to be included in cumulative assessment
groups on the basis of their toxicological profile
• Groups for all active substances approved in EU
• Criteria for addition of new groups/substances
• Grouping essentially based on common effects + mode of action
• Adoption foreseen for June 2013

12. Current PPR/PRAS activities on CRA
Cumulative risk assessment - dissimilar MoA
(response addition):
• Procurement on Investigation of the state of the science on
combined actions of chemicals in food through dissimilar
modes of action and proposal for science-based approach for
performing related cumulative risk assessment
- published January 2012
http://www.efsa.europa.eu/en/supporting/pub/232e.htm

13. Current PPR/PRAS activities on CRA
Cumulative risk assessment - dissimilar MoA
(response addition):
• PPR Scientific opinion on the relevance of
dissimilar mode of action (response addition) and
its appropriate application for cumulative risk
assessment of pesticides in food
- activities to commence last trimester 2012
- deadline December 2013

14. Current PPR/PRAS activities on CRA
• PPR guidance on the use of probabilistic
methodology for modelling dietary exposure to
pesticide residues
- deadline for adoption: September 2012
Currently posted for second public consultation in
order to get the views of EU Member State
Authorities and other stakeholders:
http://www.efsa.europa.eu/en/consultations/call/120125.htm

15. Timeline for activities on cumulative risk
assessment for pesticide residues in the diet
2 0 0 7 2 0 0 8 2 0 0 9 2 0 1 0 2 0 1 1 2 0 1 2 2 0 1 3
PPR opinion - methodology for
CRA
PPR opinion – CRA triazoles
Project - CAGs similar MoA
PPR opinion – CAGs similar MoA*
Project - CRA dissimilar MoA
PPR opinion – CRA dissimilar MoA*
PPR guidance - probabilistic modelling for dietary exposures to pesticides

16. “Non-dietary” CRA– Legislative background
Regulation (EC) No 1107/2009 concerning the placing of plant
protection products on the market
“A plant protection product, consequent on application consistent
with good plant protection practice and having regard to realistic
conditions of use, shall meet the following requirements: it shall
have no immediate or delayed harmful effect on human
health,…, or consequences in the workplace or through other
indirect effects, taking into account known cumulative and
synergistic effects where the scientific methods accepted by the
Authority to assess such effects are available;….”

17. “Non-dietary” CRA – PPR/PRAS activities
• Procurement contract for collection and assessment of data
relevant for non-dietary cumulative exposure to pesticides and
proposal for conceptual approaches for non-dietary cumulative
exposure assessment
- deadline June 2012
- Collection of data from application and use of pesticides (e.g. arable,
vineyards, greenhouses, orchards, amateur uses) – involving 9
organisations in different EU countries

18. “Non-dietary” CRA – PPR/PRAS activities
• PPR Scientific Opinion on non-dietary
cumulative risk assessment of pesticides
- Development of a methodology
- Start of activities foreseen for end of 2012

19. Thank you for your attention!