English Abstract Acceptable risk levels of compounds are primarily based
on the toxicological characteristics of a single compound. In the real life
situation, man is exposed to a wide variety of compounds. The joint action
of these compounds can result in either addition, antagonism or
potentiation. In case of potentiation, the resulting toxicity may be a
potential hazard. In the risk assessment of non-genotoxic compounds, safety
or uncertainty factors are used to correct for inter- and intraspecies
variation and measurement errors. For genotoxic compounds the maximum
tolerable dose and negligible dose have been set. It has become more and
more practice to use the same safety factor for accouting for the
interactions between compounds in a mixture. It is therefore necessary to
gain insight in the joint action of compounds and in the chance that
addition, antagonism or potentiation may occur. In the context of setting
standards, interactions occurring at low doses (at the
no-observed-adverse-effect level) are of special interest. Interactions
between different compounds may influence the toxicokinetics or
toxicodynamics of the compounds. It can be anticipated that at low doses,
interaction is likely to occur at a fundamental biological level, i.e. at
receptor level and/or enzyme level. This report provides an overview of the
joint action of chemicals and forms a starting point for the subproject
'Combination-toxicology' which has been started on the laboratory of
Toxicology, RIVM.
