Overview of the MERLIN-Expo tool
A number of fate and exposure problems can be addressed by the MERLIN-Expo tool with bespoke scenarios easily constructed thanks to its flexible, modular format. Other features such as uncertainty and sensitivity analysis as well as the consideration of pharmacokinetics put this tool at the forefront of regulatory science.
Use of this tool will enable robust, regulatory-relevant environmental fate and exposure assessments to be performed with ease and transparency.
A substantial package of online training material will support the use of the tool and a training programme is planned for 2015 (including several workshops and a summer school) to bring this new tool to the environmental and human health risk assessment community.
- Integrated multimedia and PBPK models,
- Coverage of the total exposure assessment chain,
- Estimation of internal exposures for different human populations,
- Functionality for uncertainty and sensitivity analysis (from screening methods to variance-based approaches), in line with the tiered approach recommended by the WHO,
- Ability to perform both deterministic and probabilistic simulations,
- Consideration of multiple exposure pathways for multiple chemicals to estimate combined exposure of humans and biota,
- Ability to perform steady-state as well as time-varying simulations,
- A modular structure allowing the easy construction of complex scenarios,
- A robust, transparent (‘difficult-to-abuse’) platform which is amenable to further development,
- Quality assured and standardised documentation (developed in collaboration with CEN),
- A comprehensive package of on-line training material.
Drivers for development
Currently, exposure assessment is often recognised as a weak point in ecological and human health risk assessment due to:
- a lack of integrated approaches for combined stressors (mixtures),
- the widespread use of over-conservative ‘worst-case’ scenarios,
- estimation of external exposures and not of internal exposures,
- a lack of uncertainty and sensitivity analysis for the identification of key exposure drivers.
Consideration of pharmacokinetics is crucial considering the current development of ‘Equivalent Biomonitoring Reference Doses’, and uncertainty and sensitivity analysis has already been identified as essential in current health risk assessment guidelines (e.g. WHO 2008, Uncertainty and data Quality in Exposure Assessment).
In response, the successive European projects 2FUN (FP6) and 4FUN (FP7) developed the MERLIN-Expo software which contains a library of models for exposure assessment coupling environmental multimedia and pharmacokinetic (PBPK) models.
MERLIN-Expo tool description
The MERLIN acronym derives from this description of the tool:
Modelling Exposure to chemicals for Risk assessment: a comprehensive Library of multimedia and PBPK models for Integration, Prediction, uNcertainty and Sensitivity analysis.
Modelling Exposure to chemicals…
- ‘Exposure models’ generally refer to the rate of intake of contaminants from media such as air, water, dust and food via ingestion, inhalation and direct contact.
- But, the actual targets of interest in terms of chemical toxicity are the internal tissues where toxic effects arise.
- In the MERLIN-Expo tool, the exposure concept is extended from the environment to the internal tissues of the human body so that the full exposure chain can be considered in a comprehensive health effects evaluation.
- Exposure assessment can focus on biota (for environmental risk assessment) or humans (for human health risk assessment).
- In general, Environmental Exposure Assessment (EEA) and Human Exposure Assessment (HEA) tend to rely on separately developed data, methods, scenarios and models. They are usually performed parallel and often with a poor connection between them.
- While EEA and HEA protection goals are different, EEA and HEA are clearly linked:
- Fate models used in EEA and HEA for predicting the distribution of chemicals among physical and biological media are essentially dictated by the intrinsic properties of the chemical substances in question,
- Species that are assessed in the frame of EEA can also form part of the human food chain (g. fish),
- EEA and HEA are both face common challenges, in particular with regard to increasing scientific complexity and resourcing.
- In the MERLIN-Expo tool, the exposure concept covers both EEA and HEA in order to enable consistent evaluations for several environmental and human targets.
… for Risk assessment …
- The MERLIN-Expo tool provides results that can be relevant for Environmental and for Human Health Risk Assessments (ERA and HHRA respectively).
- In particular, the incorporation of pharmacokinetic considerations in exposure assessment will become crucial with the development of ‘Equivalent Biomonitoring Reference Doses’ that provide concentration thresholds of contaminants in human tissues (instead of thresholds in environmental media only).
- The MERLIN-Expo tool anticipates such evolution and will enable a comparison between contaminant levels in human tissues with ‘Equivalent Biomonitoring’ thresholds.
- The MERLIN-Expo tool allows lifetime risk assessments (rather than just simple daily intakes) for different human populations (general population, children at different ages, pregnant women…) including exposure through multiple pathways.
… a comprehensive Library of multimedia and PBPK models …
- The MERLIN-Expo tool is based on a library of models simulating the fate of chemicals (organic substances and metals) in the main environmental systems and in the human body.
- The MERLIN-Expo library currently contains models for: atmosphere, rivers, lakes, soils (natural, agricultural and industrial soil), vegetables (tubers, leaf vegetables, root vegetables, fruits, cereals, grass), animal food (beef meat, milk, mammals) and the aquatic food-web (phytoplankton, zooplankton, fish). It is planned to extend the library for new substances (nanomaterials) and for other systems (groundwater, terrestrial animals).
… for Integration, Prediction …
- The MERLIN-Expo tool provides an integrated approach for ERA and HHRA which allows consistent use of information, with information generated for HEA able to be applied to EEA and vice-versa.
- To enable the software to be used by a wide range of end-users (SMEs, industry, regulators, policy makers, academics), it was designed to allow flexible construction of exposure scenarios by linking the models available in the library.
- The format of the tool is such that it is
- easy to use,
- easy to understand,
- robust and transparent (difficult to abuse).
- In conjunction with CEN (European Committee for Standardisation) a standard framework for documentation has been developed with the aim of ensuring:
- the rigorous formulation of exposure models,
- comparability between the different exposure models,
- transparency and ease of understanding for the tool’s users.
- All models within MERLIN-Expo are implemented on the same platform (Ecolego – see www.facilia.se) in order to facilitate integrated full-chain assessments for combined exposures.
- One of the main features of Ecolego is the simple creation and linkage of models to form an exposure scenario that can be easily visualized, as it might be when conceptualized ‘on paper’.
- Alerts are included in the tool to prevent irrelevant or nonsensical calculations (‘difficult-to-abuse’ criteria).
… uNcertainty and Sensitivity analysis…
- Uncertainty and sensitivity are issues that are now systematically identified as essential in all the guidelines referring to environmental and health risk assessment.
- It is indeed stressed that more attention should be drawn to the nature and extent of scientific uncertainty associated to risk assessments and that uncertainty should be taken into account in the decision-making process.
- The MERLIN-Expo tool contains a set of functionalities for uncertainty/sensitivity analysis that are in line with the tiered approach recommended by WHO (i.e. from screening semi-quantitative to quantitative variance-based methods).
- In addition, all the uncertain parameters are informed by default (justified) Probability Density Functions, that end-users can eventually change according to their own scenario.
- MERLIN-Expo can thus be used to carry out tiered risk assessments of increasing complexity (initial, or screening, intermediate, or refined stages of assessment). The availability of such options for uncertainty and sensitivity analysis should facilitate the consideration of such issues in future decision making.