Polycyclic aromatic hydrocarbons (PAHs) are known to adversely affect fish through activation of aryl hydrocarbon receptor 2 (AhR). Most studies have focused on 16 priority PAHs, but chlorinated and brominated PAHs are more potent than the parent PAHs in studies using mammalian AhRs. Despite being detected in fish species in situ, no studies have examined their toxicity. The present study investigated the effect of positioning and degree of chlorination and bromination on potency relative to an unsubstituted PAH for in vitro activation of zebrafish (Danio rerio) AhR2 and potency for zebrafish early life-stage mortality. Anthracene did not activate the AhR2, but chlorination and bromination strongly affected potency in a position-dependent manner. Seven of 11 halogenated PAHs activated the AhR2 with potency generally increasing with number of substitutions. Bromination had a larger effect on potency than chlorination. Potency for early life-stage toxicity followed the same rank order as that for AhR2 activation. The domain of applicability of an existing cross-species predictive framework was expanded to include halogenated PAHs, representing a significant advancement in risk assessment with immediate utility. Due to their potency and occurrence in the environment, there is a need to objectively assess the risks posed by this class of chemicals.
Keywords: aryl hydrocarbon receptor; bromination; chlorination; polycyclic aromatic hydrocarbon; quantitative adverse outcome pathway; toxicity.