New developments in mixture toxicity research

Dr David Spurgeon

We are currently initiating a series of studies to develop, test and validate the methods and models applicable to mixture toxicity assessment to improve their general applicability for specific assessment. The basic models we focus on are the Independent Action (IA) model and the Concentration Addition (CA) model. These are used as the bases for combined assessments of chemicals from different categories and sub-groups.

Chemical mixtures used in trials of these models include combinations from the following chemical groups:

  1. Baseline chemicals, e.g. non-specifics acting on membranes (e.g. polycyclic aromatic hydrocarbons, PAHs),
  2. Reactive chemicals, e.g. aromatic amines,
  3. Specific acting chemicals, e.g. pesticides, biocides, pharmaceuticals,
  4. Metals (e.g. cadmium).

 

 

The priority list of chemicals for our mixture effect assessment studies contains combinations of prioritised toxic substances from category 1, 3 and 4. The focus is mainly on category 3. The diversity of the species tested means that in some cases category 3 chemicals may act as category 1 or 2, e.g. the insecticides may act on some plant species as a baseline or reactive toxic agent, or fungicides and insecticides may act on some animals as category 1 chemicals.

The focus is on three main hypotheses:

  1. Most combinations of chemicals from all categories will follow either the IA or the CA models as appropriate to their respective mode of action;
  2. Combinations of chemicals affecting different molecular targets involved in complex physiological processes, such as nerve functioning, will act through the CA model, since joint effects on different targets will be mediated through a common effect pathway;
  3. Combinations of chemicals working through different specific pathways will act through independent action. This group of mixtures will show the greatest propensity for significant interactive toxicity (i.e. the presence of synergistic or antagonistic effects).