Nonadditive effects of PAHs on early vertebrate development: Mechanisms and implications for risk assessment

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. Traditionally, much of the research has focused on the carcinogenic potential of specific PAHs, such as benzo(a)pyrene, but recent studies using sensitive fish models have shown that exposure to PAHs alters normal fish development. Some PAHs can induce a teratogenic phenotype similar to that caused by planar halogenated aromatic hydrocarbons, such as dioxin. Consequently, mechanism of action is often equated between the two classes of compounds. Unlike dioxins, however, the developmental toxicity of PAH mixtures is not necessarily additive. This is likely related to their multiple mechanisms of toxicity and their rapid biotransformation by CYP1 enzymes to metabolites with a wide array of structures and potential toxicities. This has important implications for risk assessment and management as the current approach for complex mixtures of PAHs usually assumes concentration addition. In this review we discuss our current knowledge of teratogenicity caused by single PAH compounds and by mixtures and the importance of these latest findings for adequately assessing risk of PAHs to humans and wildlife. Throughout, we place particular emphasis on research on the early life stages of fish, which has proven to be a sensitive and rapid developmental model to elucidate effects of hydrocarbon mixtures.