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Background:Chemicals legislation worldwide is based predominantly on risk assessments carried out on individual substances.In recent years, there has been political and scientific debate on whether increasing exposure to low concentrations of a large number of chemical substances as they appear in different compartments might cause adverse effects to human health and the environment. Directly related to this, the question arises whether the approach to safety in the current chemicals regulations is adequate or whether additional measures are needed to adequately record and assess potential combined effects.
The EU Environment Council and the EU Commission have been addressing this concern since 2009, which has lead to the issue of the "State of the Art Report on Mixture Toxicity" (Consultant: Kortenkamp) by the Directorate-General for Environment (DG Env). The scientific committees of the European Commission, SCCS, SCHER, and SCENIHR, also commented on the issue in an opinion entitled "Toxicity and Assessment of Chemical Mixtures" (2011). In 2012, the European Commission gave the European Council an official answer on how combined effects in mixtures of chemicals can be regulated. A corresponding progress report is expected to be published before 2015.
In parallel, a WHO/IPCS framework was created with the goal of providing assistance with prioritization, where co-exposures of a variety of chemicals are expected (Meek et al, 2011).
Substances that are mixtures themselves (multi-constituent substances, MCS; substances of unknown or variable composition, complex mixtures or biological materials, UVCB) and products that contain more than one chemical (for example, cosmetics, pesticides) are correspondingly regulated in the EU. There are also mixtures of chemicals jointly emitted from production sites, during transportation or consumption. The composition may be known and assessed accordingly (for example, waste water). The most varied group comprises mixtures of substances as a result of emission from various sources and multiple pathways.
As not all mixtures that appear in the compartments can be subjected to a cumulative risk assessment, it is important to set up suitable filter systems to allow prioritization of mixtures (for example, exposure, grouping of the substances by mode of action).
Where the mode of action is unknown, an additive effect of the individual components could be assumed by default, as proposed by the scientific committees and as the first of four phases in the WHO/ICPS framework.
However, an additive effect is only expected for substances with the same mode of action and is therefore a very conservative assumption. In reality, the substances often have an independent effect; in other words, either through different modes of action or else in different target organs. In these cases, no robust evidence is available that exposure to a mixture of such substances is of health or environmental concern if the individual chemicals are present at or below their zero-effect levels. Interactions (including synergies and antagonism synergies) usually occur only at medium or high dose levels.
According to the scientific committees, empirical evidence shows that the effect of mixtures on the environment or health is determined by a small number of hazardous chemicals. It therefore seems excessive to call for a cumulative risk assessment for all mixtures. Furthermore, examinations of relevant environmental samples show that the assessment of (dangerous) individual components generally exposes any environmental concerns and that a cumulative risk assessment is only necessary in exceptional cases (Price et al. 2009).
In view of this situation, the fact that assessments of mixtures have rarely been performed in the industry up to now therefore does not appear to be a shortcoming per se. Scenarios with the same mode of action and high exposures are rarely considered in daily practice or can be adequately assessed using existing methods (for example, analysis of individual substances).
For practical considerations, the evaluation of mixtures should be aimed at realistic scenarios and not just be a combination of worst-case scenarios. To be able to ensure this, it is necessary to develop tools that could help identify relevant mixtures of concern.
Evonik therefore supports the decision tree model developed by CEFIC. This is a pragmatic screening tool that helps to identify and assess potential combined effects of mixtures of chemical substances in the environment. The model builds on the assessment framework of the WHO/ICPS combined with the decision tree of the EU’s scientific bodies and the assessment of the maximum cumulative ratio (Price and Han, 2011).
If the tool is used consistently, we consider the obligatory performance of a combination check for mixtures to be excessive. Most of the existing chemical regulations therefore cover the risks inherent in mixtures. In specific, well-founded cases, potential combined effects can be considered in a cumulative risk assessment.References: Han X. and Price P. 2011. Int. J. Environ. Res. Public Health 2011, 8, 4729-4745 Kortenkamp A, Backhaus T, Faust M (2009). State of the Art Report on Mixture Toxicity. Meek ME, Boobis AR, Crofton KM, Heinemeyer G, Raaij MV, Vickers C (2011), Risk assessment of combined exposure to multiple chemicals: A WHO/IPCS framework.
Regul Toxicol Pharmacol 60; p. 1- p. 14. doi: 10.1016/j.yrtph.2011.03.010 Price P. and Han X. 2011. Int. J. Environ. Res. Public Health 8, 2212-2225