National human biomonitoring programme in France: selection of substances and prioritization of biomarkers

Transcription

1 National human biomonitoring programme in France: selection of substances and prioritization of biomarkers Coordination of the working group: Clémence Fillol and Stéphanie Vandentorren Members belonging to the Department of Environmental Health at the French Institute for Public Health Surveillance (InVS): Philippe Bretin, Anne Etchevers, Nadine Fréry, Laurence Guldner, Agnès Lefranc, Joëlle Le Moal, Amivi Oleko and Georges Salines Members of Scientific Council Céline Boudet, Robert Garnier, Isabelle Momas, Jean-Ulrich Mullot

2 Context A French national biomonitoring programme: to estimate the exposure of the French population to chemicals in food and environment to better understand the determinants of chemical exposures Two studies in this programme A cross-sectional survey in the French continental population aged 6-74 years (Esteban) A survey in mothers included in the ELFE cohort (Longitudinal Study from Childhood)

3 First step: creating the list of priority biomarkers Selection of a first set of compounds that should be considered for assessment in the Esteban study ( ) : Working group included members belonging: to the Department of Health and Environment in InVS to ministries (health, ecology and labour) to other public health agencies Obtention of a list of chemicals based on: feasibility criteria (foreign and French experiences: ENNS study) relevance according to key information on the toxicity (IARC, endocrine disruptors ) Existing regulation (in air, water or food, law, priorities)

4 First step: creating the list of priority biomarkers Compounds finally grouped by biomarkers sets based on chemical properties, toxicity analytical techniques, Leading to a list of 50 groups validated by members of the Scientific Council In order to reach a final list of biomarkers to be analyzed in both Elfe and Esteban, we then developed a method of prioritization.

5 Second step: prioritization method Principle : use of a Delphi method to obtain a consensus list of prioritized biomarkers or groups of biomarkers according to agreed selection criteria a formalized approach Two groups of experts consulted French-speaking : 11 experts 8 toxicologists or epidemiologists including a Belgian and a Canadian experts 2 from NGOs 1 from industry Experts in human biomonitoring from Europe and Canada Three phases prioritization process, ending by a meeting to finalize the list of biomarkers (BM)

6 Prioritization of biomarkers: First phase on criteria A short postal questionnaire Same 8 criteria submitted to each expert Each criterion had to be given a mark (score from 0 to 10) according to its relevance for biomarkers ranking (0 = not relevant ; 10 = very relevant) Experts could justify the score given and add comments or suggest additional criteria

7 CRITERIA Hazard identification Toxicity of substances and severity of effects, known or potential: carcinogenicity, reproductive toxicity (possible impact on several generations...), mutagenicity and other (neurotoxicity, immunotoxicity,...) Score 0 to 10 Exposure characteristics Contamination sources (anthropogenic and natural), dispersive or not (exposure of consumers and the public versus workers only), multimedia exposure, human exposure known, susceptible population exposure Social perception Level of public concern (exposure and potential effects) Biomarker characteristics reflect current, cumulated past exposure, or biologically effective dose, sensibility, specificity, intra and inter individual variability

8 CRITERIA Results interpretation Existence of information for results interpretation: distribution in reference populations, known relationship between level and risk (dose-response relationship...), PBPK model known, health risk assessment available Logistic and analytic feasibility invasiveness of the sampling, volume required, conditions for collection (transport...), analytical (validated assay method): sufficiency information (LOD...), cost analysis Feasibility of the prevention European legislation, national regulations, toxicity reference value (TRV), support a public health policy, reductions techno-economic and social of exposure feasible ) Score 0 to 10 Contribution in terms of new knowledge (particularly in France) Gaps or no knowledge at national, international level, French specificities (exposure, behavior, susceptibility...), Harmonization and national, European and international comparisons

9 Prioritization of biomarkers: First phase on criteria Compilation of the results of the first questionnaire: for each criterion, calculation of the median of scores given by the experts (W1-8) Synthesis sent to the experts included in a 2 nd questionnaire Each expert could comment on his score and eventually change it CRITERIA Median Your answer Your new answer Hazard identification 4 - Your answer: 2 - Do you keep your answer? YES Social perception 0 - Your answer: Do you keep your answer? NO Compilation of the results of the first phase: for each criterion, calculation of the median of scores given by the experts

10 Delphi Results: final results on weight of each criterion (French-speaking experts) A B C D E F G H I J K Hazards 8, Exposure Social perception BM characteristics Interpretation Analytic feasability Prevention 8, , New knowledges ((Foreign experts) L M N O P Q R S T U V Med. Hazards Exposure Social perception BM characteristics Interpretation Analytic feasability Prevention New knowledges Med. W1-8

11 Prioritization of biomarkers: second phase For each expert : a score for each biomarker or group of biomarkers (50 groups), according to each criterion (8 criteria) For each biomarker or group of biomarkers (j) and for each criterion (i) 4 possible answers (Cij) totally yes: score 0.8 rather yes: 0.6 rather no: 0.4 totally no: 0.2 Calculation of mean Cij accross experts Global rating for each group of biomarkers Σ [ median weight Wi X mean score of Cij ] Rate for the biomarker j: BMj = (W1 x C1i) + (W2 x C2i) + + prioritized list, sorted according to each group ranking

12 Example: urinary arsenic (ias+mma+dma), answer from an expert X Criteria Answer score Hazard identification: "Is Arsenic toxic?" Totally yes 0.8 Importance of exposure: "Is the exposed population to arsenic rather large?" rather yes 0.6 Social Perception: "Is Arsenic a matter of public concern? " rather yes 0.6 Characteristics of the biomarker: " Is the measure of urinary ias and its metabolites a good indicator of exposure to As?" Feasibility of results interpretation: " Is there enough information (eg dose-response) to interpret the As levels?" Logistic and analytic feasibility: "Does any validated analytic method exist?" Feasibility of prevention: "Is it possible to reduce As exposures?" Contribution expected in terms of new knowledge: "Will As levels provide new knowledge? Could French As levels be compared with other countries? rather yes 0.6 rather yes 0.6 rather yes 0.6 rather no 0.4 rather yes 0.6

13 Biomarker or biomarkers group Example: urinary arsenic and bisphenol A 3 experts: A, B, C Hazard, toxicity (X 10 (W1)) Criteria Exposure Importance (x 8 (W2)) Social perception (x 5 (W3)) Total Experts A B C Total A B C Total A B C Total Total score iarsenic and metabolites (MMA+DMA) 0.8 Cij Bisphenol A

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15 Prioritization of biomarkers: third phase: a meeting A final meeting To finalize the definition of relevant criteria and submit to the experts the prioritized list of biomarkers obtained Production of a consensual, prioritized, list of biomarkers to be included in the French national biomonitoring program.

16 Conclusion A formalized approach for prioritization of biomarkers - long and sometimes arduous (discrepancies in the understanding of criteria definition) - but useful in terms of tracability of the final selection of biomarkers included in the HBM programme Results obtained from French-speaking experts Unfortunately, not enough participation of foreign experts to compare results obtained The final list contains both historical and emerging substances Final results presented to the different stakeholders Perspectives: French HBM programme: - Elfe: publications report in Esteban : analysis of BM in

17 Thank you for your attention