WP2: Cumulative dietary exposure and hazard assessment Bernadette Ossendorp en Polly Boon

WP2: Cumulative dietary exposure and hazard assessment

Bernadette Ossendorp en Polly Boon

Kick-off meeting ACROPOLIS, 7-8 June 2010, Utrecht, The Netherlands 2

Contents

• What is probabilistic modeling

• Build upon previous work done for and by EFSA

• What need to be done in WP2- Exposure

- Effect modeling


consumptiondatabase

residuedatabase

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0.0 0.7 1.4 2.2 2.9 3.6-0.7-1.4-2.2-2.9-3.6

99, 99.9, and/or 99.99 percentile

RPF index

compound

Probabilistic modeling cumulative exposure


• Performed by RIKILT (RIVM), NFA, NIPH, CRD, AFSSA, INRAN, EVIRA

• Is probabilistic assessment possible and can it be used at the international level addressing both acute and chronic toxicity.

- actual exposure using monitoring results

- exposure using MRLs or STMRs

- acute toxicity corresponds with short-term exposure

- chronic toxicity corresponds with long-term exposure

EFSA contract probabilistic assessment


NLIT

SE

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UK

MCRA-software

E-platform of databases (food and residue)

CZ

FR


Short-term acute intake in different countries

CZ FR IT NL SEUK

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Exp

osur

e (u

g/kg

bw

/d)

Country

CZ FR IT NL SEUK

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Expo

sure

(ug/

kg b

w/d

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Country

Residue per country All residues pooled


Models and bimodal distributions

• No real cumulative model available

• Two alternative approaches were used

• Serious limitations


Other limitation in models for MRL setting

• BBN do not handle bimodal distributions properly

• Observed Individual Mean model as alternative

• Further model development will be done in WP5


Alternative model Observed Individual Mean

• OIM is conservative which is allowed in Risk Assessment

• Real cumulative models are not used


Main conclusions in EFSA opinion, RIKILT report

• Common Assessment Groups should be clear and the same over Europe

• Lot of work to solve compatibility issues and to organize data

• More understanding and model development regarding cumulative probabilistic modelling (EFSA works on opinion on probabilistic modeling)


Is MoE or level of protection adequate?

Is Margin of Exposure (or safety) acceptable

Hazard assessment(tiers)

Exposure assessment (tiers)


Tasks WP2

• Description of the work to be performed in WP2, including

- Deliverables

- Milestones

• Tasks are to be performed by all WP2 partners including AFSSA, unless stated otherwise

• Case studies


Task 2.1 Input data organisation• Food consumption and pesticide monitoring data for use in case studies:

- Organophosphates, conazoles, synthetic pyrethroids

• RPFs (NFA)

• Processing, variability factors and unit weights (CRD)

• All data will be linked in such to allow for cumulative assessments by M12 (ms. 2.2)

• Paper on availability and quality input data by M12 (del. 2.1)

NL ITSE

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UK

MCRA-software

CZ

FR


Task 2.2 Harmonising input data

• Link between foods consumed and products (RACs) analysed- Guidance document by M9 (del. 2.2) + training (RIVM)

- Conversion own food consumption data using national recipes by M15

• Pooling of food consumption data: vulnerable groups- Development of a methodology to merge different food surveys into a common database

(RIVM)

- Harmonisation food coding and compound coding

- M24

- Paper by M36, including uncertainties (del 2.5)


Task 2.3 Benchmark dose modeling, RPFs

• Summarise toxicological studies relevant for cumulative effects (NFA/UMIL +

EPA member advisory board) by M12 (ms 2.1)

• BMD modelling by M18 (NFA): needed for Task 2.4.

• What has been done:

- SAFE FOODS

- EFSA opinion

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log10-dose.mgkgbw

Tm

PA

H.C

i.m

OTA

E4: y = a*[c-(c-1)exp(-bx)]Proast23.8 v ar- 0.1513 a- 0.9628 b- 25.63 c 0.05854 loglik -24.68 conv : 1 sf .x : 1 dty pe : 10 selected : dur.mth 3 106 CES 0.05 BMD 0.002129


Task 2.4 Cumulative exposure and risk modelling (1)• Guidance document on (RIVM)

- Usage of the models developed in WP5

- Performance of cumulative exposure calculations 4 scenario’s• Acute and chronic exposure, actual (monitoring results)

• Acute and chronic exposure, MRL setting

• Use of model (exposure) by M18- Case studies

- Chlorpyrifos: results are input for quantitative link with biomarker measurements WP4 (ms 2.3)

- Vulnerable groups

- Scientific paper by M18 (del 2.3)


Task 2.4 Cumulative exposure and risk modelling (2)• After integration exposure with BMD modelling

- Estimating cumulative margin of exposure (MoE) using integrated model

- Uncertainty analyses

- User and reference guideline integrated model + uncertainty analysis by M30 (ms 5.5)

• Scientific paper by M36 (del. 2.4)

MoE


Task 2.5. Identification uncertainties

• Identification uncertainties expected to affect cumulative exposure and effect + qualitative importance (ms 5.1)

- M1-6

- Based on an approach developed in WP5

• Providing input (data + expert knowledge) for WP5 to develop models to assess most important uncertainties quantitatively

• Reviewing approaches developed in WP5

• Inclusion of uncertainties in cumulative assessments (Task 2.4)


Work to be done in coming months

• Discuss quality of data to be used

• Discuss data organisation based on previous work

• Both for exposure as for BMD modelling

Thanks

Bernadette Ossendorp en Polly Boon

Documents

WP2: Cumulative dietary exposure and hazard assessment Bernadette Ossendorp en Polly Boon