Toxicity of binary mixtures of cadmium‐copper and carbendazim‐copper to the nematodeCaenorhabditis elegans

Abstract

For ecological risk assessment, the additive model may be used to empirically predict toxic mixture effects. Detailed toxicity tests were performed to determine whether effects of mixtures of copper-cadmium and copper-carbendazim on Caenorhabditis elegans were similar to the effects of the individual compounds. Effects on the course of reproduction, the length of the juvenile period, the length of the reproductive period, and body length were analyzed. Dose-response data were compared to the additive model and tested for four deviation patterns from additivity: No deviation, synergistic/antagonistic deviation, dose ratio-dependent deviation, dose level-dependent deviation. During the exposure, the cadmium-copper effect on reproduction changed from a synergistic, to a dose ratio-dependent deviation from additivity. More cadmium in the mixture decreased the toxicity and more copper increased the toxicity. The effect of copper-carbendazim on reproduction was synergistic at low dose levels and antagonistic at high dose levels and independent of time. Mixture effects on the juvenile and reproductive period were similar to single component effects. It was concluded that the observed time-dependence of toxic interactions was small and that interactions on the timing of reproduction were not found. The additive model underestimated mixture effects on reproduction and body length.

Mixtures of metals and polynuclear aromatic hydrocarbons elicit complex, nonadditive toxicological interactions in meiobenthic copepods

“…Although complex mixtures with many contaminants (e.g., Ͼ10) spanning diverse chemical classes have rarely been examined in aquatic organisms, results provide little support for synergistic or antagonistic toxicity [3,7,34]. Studies of binary interactions among contaminants are also infrequent but commonly report strong nonadditive interactions [1,6,8,35,36]. The observation that increasing contaminant diversity generally reduces the strength of contaminant nonadditive interactions has been noted previously [37,38], although few studies have been conducted investigating mixture effects of contaminants encompassing multiple chemical classes.…”

Challenges in risk assessment of multiple mycotoxins in food

“…According to the CA model, the joint action of multiple chemicals is the summation of individual toxicities, assuming the same Mode of Action (MoA) and/or at the same target cell, tissue or organ. In the IA model, the combined effects are estimated assuming that chemicals act independently by dissimilar MoA or at different target cells, tissues or organs and considers that the probability of toxicity from exposure to one chemical is independent from the probability of toxicity from exposure to another chemical in the mixture (Bliss, 1939;Jonker et al, 2004;Meek et al, 2011). These two reference models have found successful application to toxicological assessments of mixtures of similarly acting and dissimilarly acting compounds, both in ecotoxicology studies using a range of species (Backhaus et al, 2004;Faust et al, 2003;Loureiro et al, 2010) and in human toxicity studies using cell lines or animal models (Mueller et al, 2013;Tavares et al, 2013).…”

“…synergism at low doses and antagonism at higher doses) or on the ratio of doses between the compounds in the mixture (e.g. the extent of the synergism or the antagonism depends on the relative contribution of each compound in the mixture) (Jonker et al, 2004(Jonker et al, , 2005. Because MoA of chemicals in mixtures is often unknown or incompletely understood, a frequent option has been the application of both models of CA and IA for actual effect prediction, rather than making a theoretically based choice.…”

“…The CI indicates not only the type of interaction (additivity, synergism or antagonism) but also the magnitude of the interaction found. In addition, the conceptual models of CA and IA incorporating also a set of deviation functions within a nested framework (Jonker et al, 2004(Jonker et al, , 2005 have been effectively applied to the analysis of cytotoxic effects of mycotoxins mixtures (Tavares et al, 2013; Table 1). …”

“…Both CA and IA models were applied to derive potential interactions at concentrations below the individual IC 50 . Whereas the well-known CA model assumes that both toxins have a similar MoA, the IA model assesses the probability of toxicity from exposure to one mycotoxin being independent from the toxicity of the other toxin in the mixture (Jonker et al, 2004(Jonker et al, , 2005. A fairly good agreement was obtained for both models, in that antagonism was found after the CA model fit, while a dose level deviation was observed after IA modelling, where antagonism was observed at low dose levels and synergism at high dose levels.…”