Predictability of the Toxicity of a Multiple Mixture of Dissimilarly Acting Chemicals to Vibrio Fischeri

Abstract

Abstract-A promising tool for the risk assessment of chemical mixtures is the prediction of their toxicities from the effects of the individual components. For that purpose, concentration addition is uniformly regarded as valid for mixtures of similarly acting chemicals. Whether this concept or the competing notion of independent action is more appropriate for mixtures of dissimilarly acting chemicals is still in dispute. Therefore, the presented study analyzed and compared the predictive capabilities of both concepts for a multiple mixture designed of strictly dissimilarly acting compounds. Experimental investigations were conducted using a longterm bioluminescence inhibition assay with Vibrio fischeri. Results show an excellent predictive power of independent action, while concentration addition overestimates the mixture toxicity. Thus, the precise prediction of mixture toxicities depends on a valid assessment of the similarity/dissimilarity of the mixture components. However, concentration addition underestimates the EC50 of the mixture only by a factor of less than three. As the similarity of components is often unknown for mixtures found in the environment, it is concluded that concentration addition may give a realistic worst case estimation of mixture toxicities for risk assessment procedures.

Mixture toxicity of three toxicants with similar and dissimilar modes of action to Daphnia magna

“…In experiments with similarly acting toxicants the observed effects were found to be in good agreement with CA predictions. IA predictions, however, underestimated the mixture effects by as much as a factor of four (Backhaus et al, 2000a;. The ternary mixture results of the present study also showed that CA and IA predicted the mixture effect equally well (Table 2).…”

“…Several studies have applied both CA and IA in evaluating the predictability of mixture effects (Backhaus et al, 2000a(Backhaus et al, , b, 2003Faust et al, 2001Faust et al, , 2003Arrhenius et al, 2004). The results indicate that IA produces accurate predictions of the effects of multi-component mixtures of strictly dissimilarly acting toxicants tested on algae and bacteria.…”

Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action.

“…We were able to show that significant mixture effects occurred when the chemicals were mixed at levels equal to 50% of their individual NOEC. The effects of combinations of estrogenic chemicals were predicted on the basis of concentration-response relationships of individual mixture components ("fixed mixture ratio design") Backhaus et al 2000). We found that the additivity predictions calculated by using the concept of concentration addition (CA) (Loewe and Muischnek 1926) proved to agree excellently with experimental observations.…”

Effects on the Photosynthetic Activity of Algae after Exposure to Various Organic and Inorganic Pollutants: Review

“…This is not only due to the use of chemical mixtures in pesticide formulations and tank mixtures and the resulting co-occurrence in agricultural areas, but just as much because of the in-depth knowledge of their physiological mode of action [87]. These facts make them ideal candidates for testing mixture models based on the chemical mode of action and understanding the physiological mechanisms behind possible interactions [85,90]. Mixture toxicity studies focused on single species [85,86], natural communities in laboratory experiments [3,82,91], or outdoor microcosms and mesocosms [83,[92][93][94] data.…”