EFSA s perspective on risk assessment of chemical mixtures

Transcription

1 EFSA s perspective on risk assessment of chemical mixtures Christer Hogstrand King s College London Jean-Lou Dorne European Food Safety Authority, Scientific Committee

2 Past Activities on Chemical Mixtures in EFSA

3 Future Mixture RA EFSA EFSA MIXTURE METHODS: HUMAN RISK ASSESSMENT: HUMAN RISK ASSESSMENT EFSA PPR (2008) Suitability of existing methodologies assessing cumulative and synergistic risks from pesticides to human health to set MRLs (Regulation (EC) 396/2005). EFSA Journal 704, EFSA PPR (2009) Assessment of cumulative human health effects of Triazole fungicides. EFSA Journal; 7 (9); 1167 [187 pp.]. EFSA PPR (2013) Identification of pesticides to be included in cumulative assessment groups on the basis of their toxicological profile. EFSA Journal 11(7):3293 [131 pp.]. EFSA PPR (2013) Relevance of dissimilar mode of action and its appropriate application for cumulative risk assessment of pesticides residues in food. EFSA Journal 11(12):3472 [40 pp.]. 5

4 Future Mixture RA EFSA EFSA MIXTURE METHODS: ECOLOGICAL RISK ASSESSMENT EFSA PPR (2012) Science behind the development of a risk assessment of Plant Protection Products on bees (Apis mellifera, Bombus spp. and solitary bees). EFSA Journal 10(5):2668 [275 pp.]. o Methodologies to deal with mixture toxicity/synergistic effects of pesticides in honey bees, bumble bees and solitary bees o Key Recommendations: Need dose responses: lethal/sub-lethal effects in adults/larvae to predict magnitude of interactions for honey bees, solitary bees and bumble bees- Lab work performed on 6 compounds and 6 mixtures for 3 species. Include multiple stressors in risk assessment (e.g chemicals and bee diseases): MUST-BEE project on-going

5 Main title EFSA PPR DEFINITION OF CAG FOR PESTICIDES Groups are formed by identifying pesticides that produce similar toxic effects in a specific organ or system. The methodology consists of four stages: Hazard identification: Identifying specific and unambiguous toxic effects that adversely affect an organ or system (e.g. imbalance of the thyroid system). Hazard characterisation: describing the precise nature of this adverse effect to specific organs or systems (e.g. identifying the most appropriate indicator for the specific effect, for instance, a hormone). Data collection: Gathering data on the indicators (e.g. changes in hormone levels at the dose where the advesre effect occurs) that point to a specific toxic effect in an organ/system (e.g. imbalance of the thyroid system). Grouping of pesticides that exhibit a similar toxicological effect into cumulative assessment groups by organ or system (e.g. thyroid). 8

6 Main title EFSA PPR DEFINITION OF CAG FOR PESTICIDES The following groups were proposed for the 68 pesticides identified as having specific effects on the nervous system: Acute exposure (47) Motor division (45) Sensory division (20) Autonomic division (29) Chronic exposure (64) Motor division (53) Sensory division (21) Autonomic division (24) Neuropathological changes (19) EFSA Journal 2013;11(7):3293 9

7 Main title REVIEW OF FRAMEWORKS FOR MIXTURES RA 10

8 Future Mixture RA EFSA REVIEW OF FRAMEWORKS FOR MIXTURES RA: RECOMMENDATIONS (I) Harmonised Terminology Harmonisation of terminology between EFSA and others Harmonisation of terminology between HRA and ERA Harmonised Methodologies For HRA, between regulated compounds and contaminants Between animal health RA and ERA Future Methods for risk assessment of multiple chemicals in combination with biological and biophysical stressors Optimise process of problem formulation to identify chemicals of priority (exposure- and hazard-based) prior to embark on risk assessments of multiple chemicals Integration of Exposure and Hazard-based problem formulation (Risk driven) Provide guidance taking into account differences in legal frameworks 11

9 Future Mixture RA EFSA REVIEW OF FRAMEWORKS FOR MIXTURES RA: RECOMMENDATIONS (II) Exposure assessment Generate means for cross-agency occurrence data collection for multiple priority chemicals in food samples Develop case studies and training data sets comparing deterministic vs. probabilistic methods of exposure assessment Develop methods for aggregate exposure assessment Hazard assessment Support harmonisation of methodologies with regards to hazard assessment Develop methods for whole mixture approach Design a scientific basis for setting Assessment Groups Facilitate data collection on TK/TD using systematic review Risk characterisation and uncertainty analysis Support harmonisation of methodologies for risk characterisation and uncertainty analysis Provide guidance document for hazard assessment/risk characterisation 12

10 Scientific Basis of Uncertainty Factors Collection of data and generation of tools 13

11 Main title DATA COLLECTION PROCUREMENT 1(2) Metabolic interactions and synergistic effects of chemical mixtures for human risk assessment using systematic review 14

12 Main title PROCUREMENTS TO COLLECT DATA 2(2) Combined toxicity of multiple chemicals: evidence-based approach for animal health and ecological risk assessment using systematic review 15

13 Future Mixture RA EFSA TK AND MULTIPLE CHEMICALS : TOOLS AND MODELS Procurement call on the integration of TK tools in chemical risk assessment applied to human health, animal health and the environment aiming to develop models for single and multiple chemicals Objective 1: Review models and tools in human, animal and environmental risk assessment Objective 2: Collect physiological/biological parameters - Develop TK tools and models for single compounds (from simple tools to generic PB-PK models). - Case studies 10 compounds relevant to food and feed safety combining TK and TD Objective 3: Develop TK tools and models for multiple chemicals (from simple tools to generic PB-PK models). - Case studies 10 compounds relevant to food/feed safety 16

14 Future Mixture RA EFSA DYNAMIC ENERGY BUDGET (DEB) MODELS Procurement on modelling population dynamics of aquatic and terrestrial organisms using Dynamic Energy Budget Models aiming to develop models for the risk assessment of single and multiple chemicals Objective 1: Review DEB models (Dec 2015) Objective 2: Collect physiological/ biological parameterscalibration of models single compounds incl DEB (Jan Apr 2017) - Develop generic/specific models for aquatic and terrestrial organisms for single compounds-endocrine case study Objective 3: Develop tools and models for multiple chemicals (Jan Jan 2018). All tools in R and as Open sources on EFSA website 17

15 Harmonisation of Human and Ecological Risk Assessment of multiple Chemicals 19

16 Main title SCIENTIFIC COLLOQUIUM IN SEPTEMBER

17 Future Mixture RA EFSA TERMS OF REFERENCE 1(2) The WG should review available tools for different risk assessment contexts and develop a harmonised framework for human and ecological risk assessment of combined exposure to multiple chemicals using tiered approaches. The tiered approaches should start from first scientific principles for all relevant steps i.e. Problem formulation Hazard identification and characterisation Exposure assessment Risk characterisation and Uncertainty analysis. For each step, tiered approaches for harmonisation of methodologies should be developed where feasible, depending on purpose of the assessment, data availability, resources, and include explicit description of assumptions. 21

18 Future Mixture RA EFSA TERMS OF REFERENCE 2(2) Circumstances under which harmonisation between human and ecological risk assessment may not be possible or relevant should also be discussed. In developing the guidance, work should start from and build on European and international methods and frameworks, to ensure inter-agency cooperation, consistency and avoid duplication of the work. Case studies should be annexed in the GD to explore the feasibility and spectrum of applications of the proposed methods and approaches for human health and ecological risk assessment. In line with EFSA s initiative on Transparency and Engagement in Risk Assessment (TERA), the draft GD will be subject to public consultation. The published GD will be presented and discussed at an international event. 22

19 Main title TOR SUBJECTED TO PUBLIC CONSULTATION 23

20 Future Mixture RA EFSA TIMELINE February 2016: Nomination of WG by the Scientific Committee June 2016: First WG meeting November 2016: Launch Public Consultation of the ToR March 2017: Draft technical report on outcome of the Public Consultation December 2017: Two technical reports on tiered approaches for ecological and human risk assessment of combined exposure to multiple chemicals June 2018: Draft guidance document prepared by WG June 2018: Public Consultation of draft Guidance December 2018: Adoption of the draft guidance document Spring 2019: International workshop to present the SC guidance documents 24

21 Future Mixture RA EFSA THANK YOU FOR YOUR ATTENTION Ecological Human 25