Mixtures and interactions

Drinking water can be considered as a complex mixture that consists of tens , hundreds or thousands of chemicals of which the composition is qualitativ ely and quantitatively not fully known. From a public health point of view it is most relevant to answer the question of whether chemicals in drinking water interact in a way that results in an increased overall response as c ompared to the sum of the responses to the individual chemicals in the mixt ure, or indeed in an effect that is simply a summation of the expected effe cts of the individual chemicals. Present methods for risk assessment of mix tures rely heavily on some form of additivity model, unless data are adequa te for a direct risk assessment of the mixture of concern in its entirety. The "dose-addition" concept ("simple similar action") is the most common ap proach to risk assessment of mixtures and it is applicable over the whole r ange of exposure levels from low non-toxic to toxic levels when all chemica ls in the mixture act in a similar way. However, in toxicity studies at env ironmentally relevant exposure scenarios the mixtures that meet such condit ions are the exception rather than the rule. In that case the "effect addit ion" model has to be followed assuming "independent joint action". For thes e compounds now experimental data have indicated that the results at low ex posure levels are probably difficult to predict based on response additivit y found at higher dose levels. Thus, although the additivity models are mat hematically simple, they require assumptions about the mechanisms of action and the high-to-low dose extrapolation. Therefore, theoretical considerati ons in risk assessment of chemical mixtures should be verified by simple ca se studies. Up till now, the number of environmentally relevant mixtures to which a direct risk assessment has been devoted is limited. Even if toxici ty data on individual compounds are available, we are still facing the imme nse problem of extrapolation of findings obtained at relatively high exposu re concentration in laboratory animals to man being exposed to (much) lower concentrations. Therefore the prioritization of compounds for further rese arch and the extrapolation to low doses should be considered as key issues in the assessment of possible health risks from exposure to chemical mixtur es such as drinking water. (C) 2000 Elsevier Science Ltd. All rights reserv ed.