ECETOC Human Health Exposure TF

1. ECETOC Human Health Exposure TF Identified priorities and work topics

2. Task Force members • Sarah Tozer (PG) • Tanya Dudzina (EM) • Oliver Henschel (BASF) • Gerald Bachler (PFA b/o Wacker) • Chris Money (Cynara Consulting) • Rosemary Zaleski (ECETPC SC/EM) • Wouter ter Burg (RIVM) • Peter Fantke (DTU) • Carlos Rodriguez (ECETOC SC/PG) • Tim Meijster (Shell/ Chair)

3. Introduction • In 2014 ECETOC Task Force on Human Exposure was initiated Guidance for Effective Use of Human Exposure Data in Risk Assessment of Chemicals • Identified aggregate consumer exposure assessment as priority across regulations • Identified overall paucity of accessible data, but differ needs between regulations • Workshop with experts identified need to address uncertainty and create a framework for read-across of exposure data • Output: • Human Exposure Assessment Tools Database (ECETOCheatdb). • ECETOC TR126 on aggregate consumer exposure assessment

4. Introduction • 2018 HHE scoping meeting broad support for more strategic program on exposure science • Two focus areas identified for exposure science • Innovation of exposure assessment abilities (methods, tools, etc) • Stronger integration of exposure in innovative testing strategies • The ECETOC HHE TF was reinstated • Agree in priority needs for exposure science to address • Define activities needed to meet those needs (project proposals, workshops) • Identify opportunities from other programs (exposome, human biomonitoring) • Regulatory focus but agreement this is cross-discipline (e.g. link with OSH)

5. Current activities • Identify topics to propose for CEFIC LRI projects or ECETOC activities • Based on 2018 HH scoping meeting outcome • Input from TF members and ECETOC SC • Current topics and scope: • Optimising the Benefits of REACH Worker Exposure Models: Focus on Tier-2 models (LRI) • Biomonitoring: Update Guidance for the Interpretation of Biomonitoring Data (new ECETOC TF) • Aggregate exposure assessment (ECETOC HE TF) • Exposure assessment of UVCB’s and mixtures (LRI) • Advancing personal exposure monitoring (innovation) (scoping) • An Integrated Approach for Precision based Risk Assessment in the 21st Century (provide input) • Extension of B19: Extrapolation of human exposure data (LRI)

6. Optimising the Benefits of REACH Worker Exposure Models • Increasing recognition that REACH processes for worker EA/CSA need to better integrate available data and offer meaningful risk communication via ext-SDS • assessment needed of the relationship between the exposure models used to support REACH CSAs and the ability of their outputs to be communicated and understood by users • Tier2 worker models need further refinement to meet requests for more representative and reliable exposure assessment. • Tools lack REACH terminology • Gaps in assessment capabilities exist (dermal exposure, certain substances) • REACH exposure tools must be fit for purpose in terms of their abilities to deliver meaningful outputs (in terms of OCs and RMMs) that can be suitably communicated, as well as being understood by users in the workplace. • Impacts to DUs of any future refinements/changes to exposure models is not clear • TF to initiate discussion with stakeholders (CEFIC, ENES, DUCC) to outline way forward and activities to overcome above issues • (Further) development of models will be a second step • Workshop with various stakeholders may be needed

7. Aggregate human exposure assessment • Large difference exist between regulatory domains in use of aggregate exposure assessment in risk assessment • Used commonly in sectors like food, cosmetics and personal care products • Not common in most other sectors (e.g. REACH/industrial chemicals) • Clear increase in requests from regulators to determine if aggregate exposure assessment is needed and if so apply it reliably • No clear guidance/approach to assess on when needed (e.g. REACH) • Data availability varies per sector in many sectors lack of data prevents realistic assessment of aggregate exposure (e.g. only very conservative additive method) • In some sectors conservatism of approach is questioned (e.g. regulators enfoce use of conservative point estimates for specific parameters) • TF to identify opportunities to progress industries ability to evaluate need for aggregate exposure assessment and if needed perform in a sensible way. • Building on previous TF activities • Look at activities that provide benefit across sectors • Framework to assess where aggregate exposure assessment adds value to risk assessment • Increase understanding of need/possibility/impact of using probabilistic and realistic worst case estimates for specific parameters in assessments (both tier 1 and higher tiers) • Linkage with TF program and REACH worker exposure topic

8. Human exposure assessment of UVCB’s and mixtures • In EU increased regulatory scrutiny of (polymer) mixture risk assessments • Some specific characteristics should be taken into account for reliable risk assessment • Understanding and accountability of the “cocktail” effect • “matrix effect” has been observed for mixtures (incl UVCB’s) which may reduce bioavailability of constituent • Could these interactions be modelled/predicted (UNIFAC method) • Current assessment methods primarily focus on single chemical exposures • Simple additive application of such methods to mixtures may lead to considerable risk overestimation • To what extend can current models/tools be used to assess exposure and risk of mixtures (petrorisk, consexpo, skinperm, TRA, etc) • GAP assessment is needed to identify improvements needed • What mechanisms and refinements to include and how • Run a series of case studies following a predetermined format • Concawe has an interest in this topic and may be willing to collaborate/co-fund in an LRI project

9. Advancing personal exposure monitoring (innovation) • (technology) innovations provide opportunities to advance the exposure assessment capabilities • More (detailed) collection of exposure data • Collection of more contextual information to improve quality of collected data • Many innovation parties and little view on landscape • Limited oversight of development and industry input on needs • Little collaborative industry effort, contrary to innovation in hazard assessment • Map existing and emerging technologies and define how they could be used for exposure assessment • What gaps can be filled, what purpose • Task Force to connect with ongoing research initiatives to explore potential industry benefits/contributions (e.g. exposome studies, HBM ) • Pilot studies, advisory roles, co-development

10. An Integrated Approach for Precision based Risk Assessment in the 21st Century • Transformational program refers to Task Force to articulate needed development and related activities • Reliable and representative human exposure input is key to precision based risk assessment • Aggregate and cumulative exposure assessment are identified as a priority topic for more reliable risk assessment including criteria for when to do aggregate/cumulative • Conflict between classification and risk assessment needs to be addressed • Exposure also has to inform testing strategies thus should come first – the new paradigm should rather be ‘Exposure-informed risk assessment’ • Develop revised hazard categorization based on predicted human safe dose (true exposure) • Collaborate with “potency in classification TF” • Other remarks?

11. Other topics on the radar • Biomonitoring: Update Guidance for the Interpretation of Biomonitoring Data (new ECETOC TF) • May need to include some innovative methods that are currently being developed • Extrapolation of human exposure data • B19 extension, focus on stakeholder support and extensive proof of usefulness (case studies) • Advancing modelling of External – Internal exposure (e.g. specific exposure patterns PBPK) • Allow modelling of more complex/realistic exposure patterns (peak exposures, multiple routes, repetitive low exposures • Person-oriented exposure assessment framework (link to exposome) • Complex topic with increasing attention, articulate role of industry, track developments, identify opportunities to contribute to or use outcome of development (e.g. linked to innovation topic) • Assessment of low exposures • The ECETOC TF on exposure based waiving is expected to look at this. Tanya is part of both TF’s and will be able to monitor if there are any further needs for this TF to work the topic • After initial scoping TF will develop TOR on topics that will be worked