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Kombinationseffekter av föroreningar (pdf 385 kB) - Naturvårdsverket

Kombinationseffekter av föroreningar (pdf 385 kB) - Naturvårdsverket

Kombinationseffekter av föroreningar (pdf 385 kB) - Naturvårdsverket

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English summary<br />

SWECO VIAK<br />

<strong>Kombinationseffekter</strong> <strong>av</strong> <strong>föroreningar</strong><br />

This report addresses the challenges associated with the calculation of the toxicity of<br />

mixtures of chemicals and the estimation of environmental and health risks of those mixtures.<br />

It is obvious that practical limitations precludes toxicity testing of all possible combinations of<br />

chemicals and concentrations – for instance, testing the toxicity of all combinations of only 10<br />

individual chemicals would require at least 1000 separate assays. As an alternative, the<br />

evaluation of mixture toxicity and risk is based on mathematical and statistical modelling.<br />

The reader is introduced to the most common models to classify and calculate mixture<br />

toxicity. Included are models assuming that 1) the chemicals act independently of each other<br />

in the organisms; 2) the chemicals h<strong>av</strong>e the same mechanism of toxicity, affect the same<br />

endpoint, or h<strong>av</strong>e the same chemical structure; 3) the chemicals interact with each other in<br />

synergistic or antagonistic ways. Physiologically based pharmacokinetic (PBPK) models<br />

describing metabolism and toxicity of mixtures are briefly presented, and new approaches to<br />

use quantitative structure-activity relationships (QSAR) to estimate toxicity of mixtures from<br />

predicted chemical characteristics of the mixtures are reviewed. Reviews of the scientific<br />

literature shows that the toxicity of 75-80 % of known mixtures of two to four chemicals can<br />

be safely calculated by concentration addition, which means that the contribution of each<br />

component to the mixture toxicity is proportional to its concentration in the mixture.<br />

Schematic decision trees are constructed in the report to help the assessor to evaluate the<br />

toxicity and risk of complex mixtures of more or less unknown composition. Whole mixture<br />

toxicity test at different concentrations is the simplest approach, although sometimes<br />

cumbersome if one or several components are very toxic. Mixtures can be fractionated<br />

based on successive bioassays, fractionated and recombined, fractionated in combination<br />

with identification and toxicity testing of the 10 most risky components, and chemically<br />

identified in combination with a multivariate effects analysis. Since the number of complex<br />

mixtures in the environment is just formidable, the report reviews efforts to develop criteria to<br />

prioritise among them and presents list of prioritised mixtures containing similar components,<br />

mixtures of known and predictable composition, and mixtures of occasional composition or<br />

appearance.<br />

The environmental and health risk of mixtures is often expressed by an index by which the<br />

exposure to an individual component is compared to a guideline or regulatory value of the<br />

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