Mixtures measuring toxicity

Many chemicals have a mixture of toxic, corrosive, flammability, and reactivity risks. The Material Safety Data Sheet or MSDS for a chemical contains detailed safety information that is not presented on the label. This includes acute and chronic health effects, first aid and firefighting measures, what to do in case of a spill, and ecological and disposal considerations. 

The problem of the application of any TD model in ecotoxicology to mixtures is that there is an extreme lack of data on toxic effects of mixtures measured as a function of time. Almost all studies focus on the effects of the mixture after a fixed exposure period only, which is of limited use for the application of dynamic approaches. 

Complete information on pollution available. If all contaminants present in the sample have been analysed using conventional physical or chemical methods, the application of bioassays provides further information e.g. on toxicity interactions and bioavailability. It has to be emphasised that for multiple contamination, bioassays reveal an overall combined toxicity response to the bioavailable part of each contaminant present in the mixture. The identification of the bioavailable fraction of a particular substance by relating the measured effect to the measured concentration of the chemical is only possible for a single substance contamination (only one toxic chemical present). Although it may be tempting for risk assessors, the response of multiple pollution cannot be used to calculate the bioavailable fraction (percentage of the total concentration of a compound) of a particular chemical from the mixture, unless toxicant... 

Ah-receptor-mediated toxicity is particularly associated with the highly toxic compound 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), commonly referred to as dioxin. TCDD, and the concept of toxicity equivalency factors (TEFs) based on TCDDs, will be dealt with in Chapter 7. The main point to make at this juncture is that the toxicity of each individual coplanar congener in a mixture can be expressed in terms of a toxic equivalent calculated relative to the toxicity of dioxin. Summation of the toxic equivalents of the individual coplanar PCBs gives a measure of the toxicity of the whole mixture, as expressed through the Ah receptor mechanism. 

SHARED MECHANISM OF ACTION—AN INTEGRATED BIOMARKER APPROACH TO MEASURING THE TOXICITY OF MIXTURES... 

Four examples will now be given of such mechanistic biomarker assays that can give integrative measures of toxic action by pollutants, all of which have been described earlier in the text. Where the members of a group of pollutants share a common mode of action and their effects are additive, TEQs can, in principle, be estimated from their concentrations and then summated to estimate the toxicity of the mixture. In these examples, toxicity is thought to be simply related to the proportion of the total number sites of action occupied by the pollutants and the toxic effect additive where two or more compounds of the same type are attached to the binding site. 

Particular attention is given to the development of new mechanistic biomarker assays and bioassays that can be used as indices of the toxicity of mixtures. These biomarker assays are typically based on toxic mechanisms such as brain acetylcholinesterase inhibition, vitamin K antagonism, thyroxin antagonism, Ah-receptor-mediated toxicity, and interaction with the estrogenic receptor. They can give integrative measures of the toxicity of mixtures of compounds where the components of the mixture share the same mode of action. They can also give evidence of potentiation as well as additive toxicity. 

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