Background
Extensive efforts are devoted to human risk evaluations of chemicals and much regulatory guidance exists to help deliver consistency across these risk assessments. This guidance normally assumes that given a similar risk quotient, all substances will potentially present equivalent risks. Clearly, this assumption is mitigated by the properties of substances and where (and how) they are used. In order that resources can effectively be targeted within the risk assessment process, there is a need to develop tools that might be able to consistently and reliably identify what are the substances (and uses of these substances) that constitute the most significant routes of exposures for humans.
The intake fraction1 (iF) provides a possible basis for such a tool, which would potentially enable those substances that may present significant risks (by virtue of their exposure) to be identified together with the relative importance of exposure routes that may be of concern. The concepts inherent within the intake fraction also enable it to be used to help establish risk-related priorities for action.
Objectives
The concept of the intake fraction is well-documented. But its application is currently limited. It is envisaged that the intake fraction is potentially a useful tool both for prioritising human health risk assessment efforts and serving as unbiased benchmark when evaluating the outputs of risk assessments themselves. The objectives of the project are therefore to review recent European risk assessments, carried out under the Existing Substances Regulation, with a view to :
- Establishing the extent to which the intake fraction might be usefully applied to target/focus resources, including the development of the iF concepts to account for both human and ecological toxicokinetics. This work is likely to involve the creation of appropriate models.
- Based upon this, to consider the application of the iF to the processes relevant for the assessment of human risks within the European regulatory environment e.g. for prioritisation and use in the development of the targeted testing of chemicals.
- Identify whether further guidance would be helpful in order to either improve their outputs or the integrity of their supporting data.
Scope
The risk assessments (RARs) for priority substances should serve as one prime input for this project. It is anticipated that these will be reviewed, together with other information available from the literature and databases of internal exposure, to assess the consistency in the interpretation and use of measured exposure data (including biomarkers) versus model predictions in human exposure calculations for occupational, consumer and environmental scenarios. Differences in approaches and assumptions identified across the various RARs that significantly impact exposure calculations should be discussed.
Based on the above review and analysis, comments and/or recommendations should be provided on :
- Improving general guidance for performing technically-sound, consistent human exposure assessments
- Identifying future monitoring programmes for specific substances where default assumptions could be logically refined based on reliable exposure measurements
- The relative merits of existing models available for the prediction of indirect human exposures (dose) to chemicals within the environment.
One further output that is envisaged for the project is a database that enables the derived human exposure estimates for each substance to be entered along with other attributes of the substance such as physical chemical properties, use category, production/consumption tonnages and environmental emission estimates to air, water and soil. This database will then be used for exploratory data analysis. Specific questions to be addressed would include:
- What are the statistics of the various exposure metrics? (e.g. occupational, consumer, and environmental exposure estimates, environmental emission factors [emissions normalised to production/consumption], source to dose ratios [exposure estimate normalised to emission].
- Are outliers apparent and if so what is the likely cause?
- Can the various exposure metrics be correlated to one another? (e.g. what is the magnitude of occupational versus environmental exposures across substances)
- Can the various exposure metrics be correlated to substance properties that are consistent with first principles?
- Are systematic differences in the magnitude of exposure estimates evident when comparing model predictions with real world measurements?
- Can the substances logically be categorised into low, intermediate and high exposure classes?
