Many chemicals, including pollutants from large-scale use that have been banned or phased out, have been identified in human tissues in recent studies [2–4]. However, it is unclear whether or not the levels observed present a significant risk to human health. Understanding better how humans and other animal species are exposed to chemical substances and assessing the health significance of such exposure are requirements of the REACH initiative. Deploying a high proportion of analytical resources to monitor those compounds with physico-chemical properties that indicate persistence, bioaccumulation and toxicity is therefore a positive strategy. However, POPs may not be the only chemicals of concern as we learn more about the behaviour of other substances. Human exposure to chemical substances can be via multiple pathways. The major routes of possible human exposure to chemical substances include occupational (i.e. the working environment), inhalation of air (outdoor and indoor), ingestion of dust, ingestion of water, ingestion of food and absorption via the skin (for example, application of cosmetics). Depending upon the physicochemical properties of the substance, one exposure pathway may predominate over others but this is not the case for all chemicals. For example, it is considered that human exposure to polybrominated diphenyl ether flame retardants is mediated by both dust ingestion and by the diet [5]. Primary concerns about human or environmental exposure are often directed towards a single, discrete substance. However, in some cases degradation or transformation products may also be regarded as hazardous and thus a number of related chemicals (starting compound, metabolites and/or degradation products) may require consideration during risk assessment. Additionally, many organic chemicals consist of homologous series or may comprise a number of isomers, requiring the measurement of a suite of similar compounds. The resulting analytical data may need to reflect the combined measurement of large numbers of similar compounds of varying toxicity.