TR 100 – Contribution to the Methodology for the Development of Acute Exposure Threshold Levels in Case of Accidental Chemical Release
TR 100 : Contribution to the Methodology for the Development of Acute Exposure Threshold Levels in Case of Accidental Chemical Release | July 2006
The ACUTEX project was a three-year research activity funded within the EU 5th Framework Programme for Research and Technology Development. Its objective was to develop the methodology, the software tools and a Technical Guidance Document (TGD) for establishing European Acute Exposure Threshold Levels (AETLs) in case of accidental chemical release. The methodology to derive AETLs is intended to speed-up the harmonised implementation of the Council Directive 96/82/EC known as the SEVESO II Directive on the control of major-accident hazards involving dangerous substances. In developing the methodology, the different national practices in industrial accident risk assessment, for both emergency and land-use planning, have been taken into account. The intention is that the new methodology would become a recommended and harmonised tool used by experts on the safety of production installations and be endorsed by risk decision-makers in the whole EU.
The project created a complementary system to other methodologies, whose values are widely used in Europe, including the US EPA AEGLs (Acute Exposure Guideline Levels). Potential users of the methodology will be able to derive AETLs based on varying doses (taking into account exposure concentration and duration) of toxic substances released from industrial facilities as a result of emergencies. AETLs are expected to support a number of safety related studies carried out for an industrial operation in one or more of the following areas:
safety management and risk assessment procedures of building and production installation operators;
emergency scenario development with estimates on realistic consequences based on the magnitude and duration of the release;
emergency response planning;
land-use planning where the responsible authorities use a risk based approach.
This report describes the particular contributions of ECETOC to the overall project, i.e.:
a comparison of currently available methodologies in Europe and in the US;
the definition of human health end-points for the target organs relevant for accidental chemical exposure;
the definition of the different AETL levels;
the proposal of methodological aspects for the use of assessment factors and time extrapolation to derive AETLs. The task force also undertook a comparison with the respective US EPA AEGL concepts.
The ECETOC task force arrived at the following definitions for the various toxicity levels.
Threshold level 3 should be split into two levels, one dealing with death for land-use planning purposes in case of accidental chemical release and the other one with life threatening conditions for emergency response purposes:
AETL-3a: the airborne concentration at which it is predicted that, after a specified exposure time, a certain percentage (e.g. 1, 5 or 50%) of the general population will die.
AETL-3b: the maximum airborne concentration at which it is predicted the general population could be exposed up to a specified exposure time without experiencing life threatening health effects or death.
Threshold level 2 should be represented by one exposure level that deals with the prevention of irreversible health effects and the impairment to escape. For each value it should be indicated whether it has been based on irreversible health effects or impaired ability to escape:
AETL-2: the maximum airborne concentration at which it is predicted the general population could be exposed up to a specified exposure time without experiencing or developing irreversible or other serious adverse health effects including symptoms that could lead to impairment to escape.
Threshold level 1 should be represented by one exposure level that deals with the prevention of reversible health effects (e.g. notable discomfort, irritation, or certain asymptomatic non-sensory effects):
AETL-1: the maximum airborne concentration at which it is predicted the general population could be exposed up to a specified exposure time without experiencing more than mild and reversible adverse health effects.
Sensory awareness will be represented by one exposure level that deals with the prevention of odour or other sensory stimuli (e.g. taste) that may be detected and lead to public complaining, concerns or even panic:
Level of Distinct Sensory Awareness (LDSA): the airborne concentration at which it is predicted that a proportion of the general population could experience sensory stimuli (e.g. odour) that may lead to public complaints, concerns or even panic.
AETL values are recommended to be developed for exposure periods of 10, 30, 60, 120, 240 and 480 minutes. Provision of concentration-time curves in the supporting documentation to allow for standardised interpolation should also be considered.
A review of the available scientific literature suggests that a general differentiation between susceptible and hypersusceptible subpopulations is not useful. Where indicated the additional intraspecies factor for a subpopulation should be derived on a case-by-case basis.
Target organs considered to be relevant for the development of AETLs are described with their toxicological endpoint as well as study protocols identified. This allows the investigation of specific endpoints in more detail. A grading system is proposed to describe the severity of the observed effect, thus allowing its allocation to one of the AETLs.
The definitions for AETLs imply conceptually that they are based on thresholds for the various health endpoints of concern. The point of departure to determine such threshold should therefore be the lowest effect concentration to which an appropriate assessment factor is applied.
Due to the many variables involved in inhalation dosimetry, for hazard assessment purposes those species that show the most human-like dosing pattern within the lung and the ensuing response should be given preference. It appears unwise to think in terms of a single ?best? animal model. Although, dogs and primates are the preferred species for assessing the toxicity associated with acute inhalation exposure, the use of studies performed with rodents, especially rats, is the standard procedure due to the lack of data on dogs and primates. However, if the data available for a particular chemical indicate that a species other than the rat is more relevant to the effect or mode of action in man, serious consideration should be given to the use of data from that species.
The mode of exposure in acute studies was also considered. It was concluded that, in deriving AETLs, results from nose-only acute inhalation studies are superior to those obtained from whole-body studies.
A practical methodology was developed to derive AETLs which is based on available data. It proposes appropriate assessment factors to deal with uncertainties in extrapolation of exposure time across species and takes into account the susceptibility of certain subpopulations.