Description and analysis of mixture toxicity (MIXTOX)

Dr Claus Svendsen

MIXTOX was financed within the EU programme "Environment and Climate" and a co-operation between the Netherlands, Sweden and the UK. The main aim of MIXTOX was to develop new concepts for the evaluation of mixture toxicity in soil. Experiments were conducted to assess the effects of binary (two chemicals) toxicant mixtures (copper, and the fungicides Carbendazim and Iprodione, plus the combinations of copper, zinc, lead and cadmium), on soil organisms. The mixtures were tested on invertebrates with different uptake routes and results show that mixtures of two metals generally act additive or antagonistic on the test animals. However, when looking in detail there were several examples among the datasets where at low concentration levels synergism occurred (effect-level effect on mixture toxicity), and where the mixture effect was affected by the ratio of the two elements in a mixture.

As real-world chemical mixtures occur in a variety of doses, these results indicated the need to go beyond the established concepts of synergy and antagonism. The more complex response patterns of dose level - or dose ratio - specific synergism and antagonism needed taking into account to enable a correct assessment of mixture effects.

It was primarily through the efforts of Dr Martijs Jonker (then a PhD student at Wageningen University with Jan Kammenga) that we were eventually able to describe and analyse these detailed patterns in our mixture toxicity data. Since the end of MIXTOX in 2000, we have worked together with Dr Jonker on developing his tools to address mixture data in the most biologically relevant way. The tools developed are described in the recent paper, “Jonker and Svendsen et al. Environmental Toxicology and Chemistry, Vol. 24, No. 10, pp. 2701–2713, 2005”. Both the tools and documentation for their use is available by clicking on Mixture Toxicity analysis tools.