22/11/2012 Aggregate exposure assessment: tiered ...cefic-lri.org/wp-content/uploads/uploads/Posters...22/11/2012 Aggregate exposure assessment: tiered approaches and illustration

22/11/2012

Aggregate exposure assessment: tiered approaches and illustration for indoor environments Rudi Torfs, VITO

22/11/2012 2 © 2012, VITO NV

CEFIC-LRI projects B4-CERTH & B5-THL (2010-2012)

22/11/2012 3 © 2012, VITO NV

AEA: an assessment of exposure to a single agent from all potential sources and pathways (the physical course taken by an agent as it moves from a source to a point of contact with a person) and the related exposure routes

22/11/2012 4 © 2012, VITO NV

Context

» ECETOC: Contribute to the development of a pragmatic, realistic, and science-based framework for the risk assessment of chemical mixtures.

» CEFIC-LRI: 21st Century Approaches to Risk Sciences

» Health impact of complex environments

» Exposure to mixtures, from multiple sources, indoor…

» Why? the need to have a better representation of exposure

» REACH (Biocides, food safety…)

» Moving towards integrated exposure science

(‘the exposome’)

22/11/2012 5 © 2012, VITO NV

Challenges

» Quantifying all possible sources, pathways and routes of exposure can become a very complex task in terms of data collection, data assessment, exposure modelling and – not least – verification.

» TAGS to provide a ‘decision structure’

» When to go to higher tiers

» Partial or incomplete tools to evaluate a full AEA

» ECETOC-TRA

» Full chain modelling tools (INTERA)

» Inconsistent ways to evaluate adequacy of models and data

» Verification strategy in TAGS

22/11/2012 6 © 2012, VITO NV

The Tiered Aggregate Approach (TAGs) - within Exposure Scenario

6

Tier 0

Tier 1

Tier 2

Define exposure scenario (single source)

Basis for

aggregation across

routes /

pathways?

dominant route /

pathway?

SEA – within exposure scenario

(Tier 1)


(Tier 2)

AEA – within exposure Scenario

(Tier 1)


(Tier 2)

No

Yes

Yes

No

22/11/2012 7 © 2012, VITO NV


7

Tier 0

Tier 1

Tier 2


Basis for

aggregation across

routes /

pathways?

dominant route /

pathway?


(Tier 1)


(Tier 2)


(Tier 1)


(Tier 2)

No

Yes

Yes

No

Identify all relevant routes of exposure (inhalation, dermal, ingestion) and the pathways for each exposure route.

Identify toxicological and/or health endpoints associated with each route and assess these for commonality.

22/11/2012 8 © 2012, VITO NV


8

Tier 0

Tier 1

Tier 2


Basis for

aggregation across

routes /

pathways?

dominant route /

pathway?


(Tier 1)


(Tier 2)


(Tier 1)


(Tier 2)

No

Yes

Yes

No

Identify if there is one dominant route and/or pathway of exposure compared to all other routes/pathways combined

22/11/2012 9 © 2012, VITO NV

Define relevant exposure scenario

(multiple source)

Basis for

aggregation across

exposure scenarios

(plausible)?

dominant plausible

exposure

scenarios?

No AEA across exposure scenarios AEA – across exposure scenario (Tier 1)

AEA – across exposure scenario (Tier 2)

No

Yes

No Yes

The Tiered Aggregate Approach (TAGs) - across Exposure Scenarios

22/11/2012 10 © 2012, VITO NV


(multiple source)

Basis for

aggregation across

exposure scenarios

(plausible)?

dominant plausible

exposure

scenarios?



No

Yes

No Yes


define the population groups of interest (e.g. consumers, workers, susceptible groups, geographical area, socio-economic status)

can the exposure from different scenarios lead to the same health endpoint or not

22/11/2012 11 © 2012, VITO NV


(multiple source)

Basis for

aggregation across

exposure scenarios

(plausible)?

dominant plausible

exposure

scenarios?



No

Yes

No Yes


For each combination of plausible exposure scenarios, determine if there are any scenarios that completely dominate the exposure from all other scenarios combined

22/11/2012 12 © 2012, VITO NV

Tiered approach : next steps

» Steps to go from TIER 0, via pre-TIER 1 to TIER 1 and further

TIER 1 – stage 1

TIER 1 INFORMATION

Default tier 1 model

- optional -

Module for input of

exposure estimates

from other tier 1

models

TIER 0 OUTPUT

· Quantification of uses/sources

· Toxicological criteria (by route, age,

duration)

· Physicochemical properties

· Levels in compartments

· Generates exposure (dose/concentration) for the

selected use/source and routes

· Generates exposure by predefined subpopulations

· Aggregates exposure across relevant routes for each

scenario

· RCR by route for each scenario

· Aggregate RCR across routes for each scenario

· Relative contribution of routes for each scenario

TIER 1 INFORMATION

· Plausible combinations of

scenarios

TIER 1 – stage 2

· Combines plausible combinations of scenarios to

describe hypothetical (sub)populations

· Aggregates exposure within (sub)populations (across

scenarios, across routes if relevant)

· RCR by route within (sub)population

· RCR by pathway, use/source within (sub)population

· Relative contribution of routes, pathways, uses, sources

TIER 1 – measured data

- optional -

Module for dose

calculations from levels

in compartments

· Default exposure

parameters

· Exposure by routes

and pathways

· Exposure by

predefined sub-

populations

· RCR by route

within

(sub)population

· RCR by pathway

within

(sub)population

· Relative

contribution of

routes, pathways

TIER 1 OUTPUT· Integrated evaluation

· Need for higher tier AEA

· Delineation of higher tier

Optional

pre-Tier 1

Select appropriate exposure scenario

Perform Tier 1 – stage 1 for every identified use/source

22/11/2012 13 © 2012, VITO NV

Tiered approach : next steps

TIER 1 – stage 1

TIER 1 INFORMATION

Default tier 1 model

- optional -

Module for input of

exposure estimates

from other tier 1

models

TIER 0 OUTPUT

· Quantification of uses/sources

· Toxicological criteria (by route, age,

duration)

· Physicochemical properties

· Levels in compartments

· Generates exposure (dose/concentration) for the

selected use/source and routes

· Generates exposure by predefined subpopulations

· Aggregates exposure across relevant routes for each

scenario

· RCR by route for each scenario

· Aggregate RCR across routes for each scenario

· Relative contribution of routes for each scenario

TIER 1 INFORMATION

· Plausible combinations of

scenarios

TIER 1 – stage 2

· Combines plausible combinations of scenarios to

describe hypothetical (sub)populations

· Aggregates exposure within (sub)populations (across

scenarios, across routes if relevant)

· RCR by route within (sub)population

· RCR by pathway, use/source within (sub)population

· Relative contribution of routes, pathways, uses, sources

TIER 1 – measured data

- optional -

Module for dose

calculations from levels

in compartments

· Default exposure

parameters

· Exposure by routes

and pathways

· Exposure by

predefined sub-

populations

· RCR by route

within

(sub)population

· RCR by pathway

within

(sub)population

· Relative

contribution of

routes, pathways

TIER 1 OUTPUT· Integrated evaluation

· Need for higher tier AEA

· Delineation of higher tier

Optional

pre-Tier 1

Select appropriate exposure scenario

Perform Tier 1 – stage 1 for every identified use/source

TIER 0 OUTPUT

Adequate biomonitoring

and associated health

criteria available?

Compare exposure

and heath criteria

Go to tier 1

assessment

Potential human

health risk?

No

Yes

StopNo

Yes

Go to tier 1 or

higher tier

assessment

Risk reduction

strategies

22/11/2012 14 © 2012, VITO NV

Tools for AEA

» The current, non-aggregated version of the ECETOC TRA tool forms a good basis for the further development of a Tier 1 tool for AEA.

» The structure and the current formulas and spreadsheets of the ECETOC TRA tool allow fairly easily the modifications to turn the tool into a more complete AEA tool.

» In TAGS we suggest modifications to account for:

» adult and children exposure separately in the consumer module ;

» adult and children exposure separately in the environment module ;

» aggregate exposure across routes (within scenario);

» aggregate exposure across scenarios (and across routes).

22/11/2012 15 © 2012, VITO NV

Verification strategy » To strengthen the plausibility of the assessment.

A. verification of the applicability domain of substances and spatial and temporal resolution;

B. verification of the conceptual model;

C. verification of the applicability domain of databases and parameters;

D. verification of model software implementation;

E. verification of model predictions (assessment verification):

» E1. verification of intermediate steps along the source to receptor chain, and

» E2. verification of by means of biomonitoring data.

validity of conceptual

model

validity of

implementation

availability of existing

data for verification

verification data supporting

asssessment

assessment A major source missing

assessment B OK not OK - -

assessment C OK OK - -

assessment D OK OK limited data

data inappropriate for

verification

assessment E OK OK OK

limited support due to

inappriate data

assessment E OK OK OK

verification data support

assessment

22/11/2012 16 © 2012, VITO NV

Illustration of Tiered Aggregate exposure: TAGS BDE 209 case study

» TIER 0 : need for aggregation? » Yes : systemic health effects: neurodevelopmental, liver, thyroid and possible contribution

from different pathways and routes

» Pre-TIER 1: Indication of low risk, however: » data for children; lower brominated congeners

» TIER 1: » ECETOC TRA v2 overconservative

» Assessment based on measured levels:

» Highly exposed subpopulations

» Lacks direct contact with articles

» Generation of lower brominated congeners

not accounted for

» TIER 2: » Low to no health risk

» Need to account for children in all tiers

» Evaluate EFSA dietary methodology and data versus ECETOC TRA dietary data

0

5

10

15

20

25

30

35

40

45

50

1975 1980 1985 1990 1995 2000 2005 2010 2015

ng

/g li

pid

Austria Belgium Denmark Faroer France Greece

Luxemburg Norway Spain Sweden the Netherlands United Kingdom

0

50

100

150

200

250

300

350

2002 2003 2004 2005 2006

ng

/g li

pid

Luxemburg the Netherlands United Kingdom

Adult serum levels

22/11/2012 17 © 2012, VITO NV

Summary

» The TAGS project developed a tiered approach to (non-occupational) aggregate exposure assessment, distinguishing three tiers with increasing levels of data needs and complexity.

» A methodology and process for verification of aggregate exposure assessments is available.

» A tiered approach guiding the user towards the relevant aspects of aggregation helps to optimize and reduce efforts.

» Suggestions to improve the ECETOC TRA with TAGS findings

» Full chain modelling tool has been developed for indoor exposures =INTERA

22/11/2012 18 © 2012, VITO NV

Integrated Exposure for Risk Assessment in Indoor Environments (INTERA)

» The INTERA project (http://www.intera-home.eu/) developed and applied a full chain mechanistic modelling approach that includes:

» The relations among the sources of contamination (outdoor and indoor), and the levels of indoor contamination.

» The modelling of actual exposure to indoor contamination, from source to dose, including internal dose modelling (Physiology Based ToxicoKinetic (PBTK) modeling)

» Available at http://www.intera.cperi.certh.gr

» As part of INTERA a Knowledge Management System has been developed: » Incorporating appropriate databases of quality assured source data;

» Making available and applying suitable models and statistical methodologies for the characterization and treatment of such data;

» With the ability to display exposure predictions in a number of formats.

» Available at http://en.opasnet.org/w/Intera

http://www.intera-home.eu/



http://www.intera.cperi.certh.gr/

http://en.opasnet.org/w/Intera

22/11/2012 19 © 2012, VITO NV

Client side (browser)

Server side

Computational platform

Visualization platform

(PHP data processing) 1 2

3

Results database

22/11/2012 20 © 2012, VITO NV

To conclude and continue

» Better and more integrated tools for tiered aggregate exposure assessment are needed to overcome the current difficulties when using different models for part of the aggregate exposure modelling.

» More data is needed in many cases, for instance for model parameterization and verifying the aggregate exposure assessment.

» Try developing research to differentiate the exposure assessment between children and adults.

» In the longer term all knowledge and tools, including aggregate exposure tools, should be integrated in an overall framework to characterize the exposome.

22/11/2012 21 © 2012, VITO NV

Thank you

Arja Asikainen, Katleen DeBrouwere, Emma Doust, Karen Galea, Alberto Gotti, Einari Happonen, Araceli Sanchez Jimenez, Anastasios Karabelas, Spyros Karakitsios, Periklis Kontoroupis, Eelco Kuipers, Elias

Mplatsis, Spyridoula Nikolaki, Denis Sarigiannis, Sean Semple, Arnout Standaert, Rudi Torfs, Matti Jantunen, Martie van Tongeren, John Cherrie, Christa Cornelis, Carole Garden, Sally Spankie

created for Cool Risk.com by Michael Mittag

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22/11/2012 Aggregate exposure assessment: tiered ...cefic-lri.org/wp-content/uploads/uploads/Posters...22/11/2012 Aggregate exposure assessment: tiered approaches and illustration