Exposure to mixtures of chemical substances: is there a need for regulations?

The setting of standards for individual substances is an important tool in the protection of human health. However, it has been a topic of discussion for many years whether only this type of standard-setting will meet common goals for health protection, since humans are exposed to a large variety of chemical substances from many different sources in variable concentrations and by different routes of exposure. The complexity of this problem makes it difficult to answer this question and almost impossible to quantify the answer. It is common knowledge that combined exposure to chemical substances may cause synergism. However, these examples are referring to relatively high levels of exposure. In present environmental and occupational practice, exposure to individual chemicals has usually been reduced to acceptable levels. The key question is whether exposure to mixtures at levels of the single components near or below no-observed-adverse-effect levels can still cause adverse effects. Few countries have incorporated procedures concerning combination toxicity in their policy regarding chemical substances. If so, the uncertainty in these procedures is considerable because of lack of relevant data. This usually leads to a conservative approach. Roughly two approaches can be distinguished for systemic toxicants: introduction of an (extra) uncertainty factor or application of the additivity principle. In the Netherlands, for systemic toxicants a safety factor was introduced in 1989 to account for combination effects. Problems related to this approach have led to adaptations in procedures and a reconsideration of the chosen safety factor.