Nonadditive effects of PAHs on Early Vertebrate Development: mechanisms and implications for risk assessment

Health Canada, Health Products and Food Branch, Bureau of Chemical Safety, Ottawa, Ontario K1A0L2, Canada.
Toxicological Sciences (Impact Factor: 3.85). 06/2008; 105(1):5-23. DOI: 10.1093/toxsci/kfm303
Source: PubMed


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.

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Available from: Richard Di Giulio, Jan 06, 2016
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