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introduction

Welcome to MERLIN-Expo.

About

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, * flexible, * 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.

History

The assessment of risks to human health from chemicals is of major concern for policy and industry and benefits all citizens. It is mainly based on the exposure and the dose-response assessment.

Exposure assessment is generally considered to be the weakest point in risk assessment because currently available tools show major flaws (e.g. lack of integrated approach for assessment of combined stressors, use of ‘worst-case’ scenarios leading to over-conservative results, lack of uncertainty/sensitivity tools for identifying the important exposure drivers, output provided in terms of intake rates because environmental multimedia and PBPK models are not integrated, standardisation processes not considered).

To overcome these drawbacks, the 2-FUN project (http://www.2-fun.org), funded under the EU 6th Framework Programme, produced a prototype software containing a library of models, coupling environmental multimedia and pharmacokinetic models.

This software, the 2-FUN tool, resulted to be an innovative and useful instrument for the assessment of human health risks from exposure to chemicals. However, the 2-FUN tool was a 'prototype' and not a 'standardised' software.

The 4FUN project took the results from the 2-FUN project to the market following thorough standardization processes and dissemination activities. The outcome is the tool you are reading about now: MERLIN-Expo.

introduction.txt · Last modified: 2017/05/19 14:22 by boris