Mixtures/multiple exposures

Scope
Mixtures/multiple exposures describes the ways to deal with exposures to mixtures (multiple exposures).

How to deal with the exposure to multiple exposures and how it affects certain health outcomes is an important gap in knowdledge. Some WPs (Wp 1.5 cross cutting issues, and WP 1.3 exposure-health effect) are trying to develop some methods about this issue.

Description

Some information is given about multiple exposures to chemicals only.

Different interactions between chemicals are addition, antagonism and synergism.

Addition of chemicals is a non-interactive process. This means that in a chemical mixture the different chemicals do not affect the toxicity of each other. All chemicals individually contribute to the toxicity of the mixture and act in a similar way. The contribution of a chemical in a mixture depends on the dose of the chemical in the mixture.

Antagonism is the negative effect of chemicals on each others toxic action. The different chemicals have an inhibitor effect on each other.

Synergism is the positive effect of chemicals on each others toxic mechanism. The different chemicals have a strengthened effect on each other

Methods can be based on determine the hazard of each individual component in a mixture (component based methods) or determine the hazard of the whole mixture. For component based methods it’s necessary to determine the combination of the chemical mixture, the different target organs and mode of action (MOA) of the individual chemicals.

Component based methods include:

• Hazard index (HI), toxicity equivalent factors (TEF), relative potency factors (RPF) - all applicable for chemicals which do have the same toxic effect and toxic mode of action.
• Response addition - applicable for chemicals with different toxic effect and different mode of action
• cumulative RPF - applicable for a mixture which contains chemicals with the same toxic effect, but different mode of action)
• Binary weight of evidence (BINWOE) - applicable for interaction between chemicals. For using this method the interaction between chemicals in a mixture should be known.

Whole mixtures methods include:

• Cancer slope factors - the dose-response of different chemicals in a mixture is measured (the risk of developing a tumour (response) after exposure to a chemical mixture (dose) is determined)
• reference dose and reference concentration - estimate of the daily exposure of a human population to a chemical mixture at which no health effect will occur
• effect-directed analysis - determine which chemical or complex of chemicals have a biological effect
• pattern recognition techniques and multivariate regression models - determine whole mixtures and there possible health effect
• toxicogenomic - effect of a wide variety of chemicals in a mixture on molecular level can be detected

Information about non-chemicals not yet available

Some more epidemiological considerations how to deal¨with mixtures

In the real world, people are often exposed to multiple exposures simultaneously and to mixtures of exposures rather than one single component. It is not easy to describe effects of mixtures, as the data are often lacking for adequate description.

Methods to allow for these types of exposures have been used a lot in the epidemiology. One method is to select an indicator, which characterise a certain mixture. Examples are the use of ozone as an indicator for photochemical smog; the use of PM10 for the general air pollution mixture. The indicator is then used to represent the mixture.

This approach can be refined by taking into account two or more indicators of the mixture. An example would be to use PM10, N02 and O3 as indicators of general air pollution. The problem of ‘double-counting’ can play a role here.

Another method is to account for important known interaction effects within a certain mixture (known important interaction effects asbestos and smoking, diesel and some allergens) and to allow for that in the Exposure response relationship.

Another more toxicological method is the relative potency factors of which toxicity equivalence factors (TEF) are a special case. This approach can be used for a well-defined class of agents that operate through a common mode of action for the same health outcome. Examples of this approach are the relative potency factors for some carcinogenic polycyclic aromatic hydrocarbons and the TEF for dioxin-like compounds.

References

To be included (if wanted?) - ask Anne

Definition

Information limited to chemicals, which is not useful for this study. I (Anne) will try to find out if there is any info on combined exposure to noise and air pollution.

Result

For multiple exposures to noise and air pollution (as in case study) no information/ methods have been found yet.