The report "Combined toxic effects of multiple chemical exposures" was produced by The Norwegian Scientific Committee for Food Safety (VKM) in 2008 at a request of the Norwegian Food Safety Authority (Mattilsynet).

Since the VKM report was published in 2008 there has been an increasing focus on effects of multiple chemical exposures on both human and animal health and on the environment.

The publicity in various types of media on effects referred to as cocktail effects, combination effects, multiple stressors etc. reflects a growing public concern and a corresponding demand for identification and regulation of mixtures of chemicals that may pose a risk to public health or to the environment.

When compared to scientific literature on combined toxic effects of multiple chemical exposures published after 2008, the theoretical principles for the descriptions of methods and the guidelines given in the VKM report are still applicable.

Furthermore, recent publications do not reveal scientific evidence or concepts in conflict with the conclusions given in the VKM report.

The dose addition approach is based on assumption of a similar mode of action within groups of chemicals. However, no generally agreed criteria for grouping of substances exist.

 If substances act by different modes of action, adverse effects are considered unlikely if individual substances are present at doses below their respective zero effect level.

It has been discussed that experimentally derived NOAELs do not necessarily represent the true zero effect levels, and it cannot be excluded that exposure at the NOAELs might contribute to effects. If no information on mode of action is available, the use of dose addition is considered sufficiently protective.

Interactions seem to be less likely to occur at doses below the effect levels for the individual components than at higher doses, but more experimental studies are required to determine interaction at realistic exposures. 

The proposed procedure for risk assessments of chemicals in mixtures presented in the report from 2008 is still applicable and may be used where this is relevant and there are available data.

The Scientific Panel on Plant Protection Products performs risk assessment of pesticides as a basis for approval of plant protection products (PPPs) on the Norwegian market. In these assessments combined effects of all ingredients present in the PPPs are addressed.

In environmental risk assessments, where end points for higher hierarchical levels such as populations and communities of organisms are used, test procedures and considerations other than those described in the VKM report may be needed.