The risks from exposure to mixture of chemicals : adequately evaluated ?

Excerpts selected by GreenFacts of a summary of a recent state-of-the-art report and of a Preliminary Opinion approved for Public Consultation on  Toxicity and Assessment of Chemical Mixtures expressed by the non-food Scientific Committees of the EU Commission.

1. – THE REPORT details the scientific state of the art findings of a project on mixture toxicology and ecotoxicology commissioned by the  European Commission, DG Environment.

According to it, there is strong evidence that chemicals with common specific modes of action work together to produce  combination effects that are larger than the effects of each mixture component applied singly. In the case of such combinations of chemicals that interact with the same sub-system of an organism, the concept of dose addition is applicable for the prediction of their effects when the toxicities of individual mixture components are known.

The currently available scientific evidence as well as pragmatic considerations, says the report, support the idea of adopting dose addition as the preliminary default concept for the assessment and prediction of mixture effects. Indeed, deviations from predicted additivity, indicative of synergisms or antagonisms, are comparatively rare, relatively small and largely confined to mixtures with only a few compounds.

This approach, says the report is borne out by current practice in many regulatory bodies in the EU, USA and by recommendations of international bodies.

There is however, according to the report, decisive evidence derived from studies relevant to human toxicology and to ecotoxicology  that have been conducted with mixtures composed of chemicals with diverse modes of action, indicating that the effects of such mixtures are higher than those of the individual components when each component is present at doses equal to, or below a no-effect level.

Whether or not risks arise from combined exposures in such cases can only be decided on the basis of better information on  human populations and wild life which is currently missing,  according to the report., Also, uncertainty factors used in chemical-by-chemical risk assessment could offer insufficient room to allow for mixture effects for all possible realistic mixtures.

The scientific state of the art of mixture toxicology shows that mixture risk assessment in the EU is necessary, in order to avoid underestimations of risks that might occur under the current paradigm of considering substances on a chemical-by-chemical basis. In the meantime,  it shows also that it is also feasible as demonstrated by a multitude of risk assessment methods already in use by international bodies & EU member states.

As a matter of facts,  the report states that there is strong evidence that it is possible to predict the toxicity of chemical mixtures with reasonable accuracy and precision. There is no need for the experimental testing of each and every conceivable mixture, which would indeed make risk assessment unmanageable.

2.- THE OPINION is the Preliminary Opinion approved for Public Consultation on  Toxicity and Assessment of Chemical Mixtures expressed by the three  independent non-food Scientific Committees of the EU Commission SCCS, SCHER and SCENHIR.

Based on the analysis of the available scientific literature, their conclusions are that :

(1) Under certain conditions, chemicals may act jointly in a way that the overall level of toxicity is being affected;

(2) Chemicals with common modes of action may act jointly to produce combination effects that are larger than the effects of each mixture component applied singly. These effects can be described by dose/ concentration addition;

(3) For chemicals acting independently, no robust evidence is available that exposure to a mixture of such substances is of health concern if the individual chemicals are present at or below their zero-effect levels;

(4) Interactions (including antagonism, potentiation, synergies) usually occur at medium or high dose levels (relative to the lowest effect levels). At low exposure levels, they are either not occurring or toxicologically insignificant;

(5) In view of the almost infinite number of possible combinations of chemicals to which humans and environmental species are exposed, some form of initial filter to allow a focus on mixtures of potential concern is necessary. Several criteria for such screening are offered;

(6) With regard to the assessment of chemical mixtures, a major knowledge gap at the present time is the rather limited number of chemicals for which there is sufficient information on their mode of action. Currently, there is neither an agreed inventory of mode of actions, nor a defined set of criteria how to characterise a mode of action for data-poor chemicals;

(7) If no mode of action information is available, the dose/concentration addition method should be preferred over the independent action approach. Prediction of possible interaction requires expert judgement and hence needs to be considered on a case-by case basis.

Based upon these conclusions, a decision tree for evaluating the risk of chemical mixtures is proposed by the Committees.


1. State of the Art Report on Mixture Toxicity – Final Report, Executive Summary December 2009 .

A project on mixture toxicology and ecotoxicology commissioned by the European Commission, DG Environment. State of the Art Report on Mixture Toxicity – Final Report, Executive Summary December 2009 . Study Contract of the EU Commission Nr 070307/2007/485103/ETU/D.1 Contractor: The School of Pharmacy University of London (ULSOP) . Note that the Commission services do not accept any liability with regard to the contents of this document.

2. Toxicity and Assessment of Chemical Mixtures -(Preliminary Opinion approved for Public Consultation Scientific Committee on Consumer Safety (SCCS), Scientific Committee on Health and Environmental Risks (SCHER), Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR),) June 2011.



Note:  the short excerpts proposed by GreenFacts of international reports on health and environment are not verified by its Scientific Board.

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