The Scientific Committee is a central organ of ECETOC, meeting 6 times a year to peer-review and guide the work programme. ECETOC members have access online to detailed minutes of each meeting. It is the intention of this column to share key committee developments with a wider audience.
The Scientific Committee is a central organ of ECETOC, meeting 6 times a year to peer-review and guide the work programme. ECETOC members have access online to detailed minutes of each meeting. It is the intention of this column to share key committee developments with a wider audience:
Committee adopts “cardiac sensitisation’ report
At its April meeting, the Scientific Committee reviewed a report prepared by the task force on “cardiac sensitisation’ test methods and the report was consequently approved for publication.
Cardiac sensitisation means that the normal heart rhythm becomes perturbed, for example when halogenated or unsubstituted hydrocarbon vapours are inhaled, for a short time, in combination with high internal adrenaline levels (stress). The resulting cardiac arrhythmias may be fatal. Therefore, the cardiac sensitisation potential (and other toxicological properties) of fluorocarbon products needs to be known before those products can be safely used, especially in air-conditioning and fire-fighting applications. Although not a standard regulatory endpoint, the cardiac sensitisation test is a key element in the toxicological assessment of alternative halogenated hydrocarbon products.
The report reviews how cardiac sensitisation studies have been conducted on halogenated hydrocarbons (using the adrenaline-treated dog) and the way in which those test results are used in the prediction of human risk from acute exposure to high concentrations. Critical aspects of the test protocol are the selection of the dose of adrenaline used to “challenge’ the heart, and the definition of a positive response (i.e. cardiac arrhythmia). For risk assessment, i.e. extrapolation of the animal data to humans, no additional safety factors need to be applied. For improved risk assessment, human blood levels of the inhaled compounds can be estimated using biokinetic modelling. While the report discusses various possible alternatives to replace or refine the current dog model, the task force concludes that there is no clear alternative test system at present.
Little is known about the underlying biological mechanism of the cardiac sensitisation effect; cardiac sensitisation following exposure to halogenated hydrocarbons seems to be a complex event that is not fully understood at present. The report includes a summary of a separate paper drafted by one task force member entitled “Mechanisms involved in cardiac sensitization by volatile anesthetics’. It is published in Crit Rev Toxicol.
Input to European Commission Committees’ preliminary report on “use of the threshold of toxicological concern (TTC) approach for the safety assessment of chemical substances’
ECETOC’s Scientific Committee has provided comments on the work of the scientific committees of DG SANCO (SCHER, SCCP SCENIHR), i.e. now on the aforementioned report. It was judged that this draft report provides a clear and well-structured review of the principles and use of the TTC. However, the reservation expressed for non-oral routes of exposure are probably overstated for cases when it is clear that relevant data or correction factors for route-route extrapolation can be used. In this respect, the conclusions were considered unsatisfactory from a scientific point of view. The end-use of a chemical should not be the determining factor whether or not the TTC concept is applicable. In all cases, exposure data are necessary for using the TTC approach in a chemical’s risk assessment.
The report finishes with a discussion on potential applications of the TTC concept but this is limited to cosmetics. One area that can significantly benefit from the use of TTCs is in the implementation of REACH. New and effective paradigms for risk assessment will have to be tried if the expectations for delivery and reduced animal use are to be realised. ECETOC was active in developing the guidance on information requirements (RIP 3.3.), in which the TTC concept has been specifically mentioned. Therefore, the feedback given to the DG SANCO scientific committees was that this draft report on TTC would benefit in both balance and utility if it could also provide an opinion on the use of TTC in REACH.
Dr. John Doe, Syngenta
Scientific Committee Chairman