Does the potency of polycyclic aromatic hydro-carbons (PAHs) for inducing CYP1A1 in juvenile trout (Oncorhynchus mykiss) predict dioxin-like toxicity in early life stages?

We have shown that chronic exposure of rainbow trout larvae to retene, an alkyl-substituted phenanthrene, causes dioxin-like toxicity. Clinical signs included exposure-related increases in mortality, cytochrome P4501A1 (CYP1A1) induction, edema, hemorrhaging, craniofacial abnormalities and gill pathology before swim up. Results suggest that rapidly metabolized PAH share the same mechanism of toxicity as the more persistent and toxic chlorinated PAH (CPAH), i.e. oxidative stress due to prolonged CYP1A1 induction. If correct, this model predicts that the chronic toxicity of PAH to larvae should increase with their potency for mixed function oxygenase (MFO) induction. The rank order of potency for chlorinated PAH (CPAH) in causing blue sac disease is the same as the relative potency of these congeners for inducing CYP1A1. Using the median effective concentration (EC50) from exposure–response curves, fish-specific toxic equivalency factors (TEFs) were derived for several PAHs in vitro. This rank order predicted TEFs derived in vivo using juvenile trout. With the exception of phenanthrene, all PAHs tested induced MFO activity in juvenile trout and were ranked as follows: benzo[k]fluoranthene>benzo[b]fluoranthene>benzo[b]fluorene>retene. We are currently developing quantitative structure activity relationships to relate chemical structure and potency of PAH for CYP1A1 induction and using these TEFs to determine if short-term CYP1A1 induction in juvenile trout can predict chronic toxicity to larvae of PAH and PAH mixtures. This may provide the tools for rapidly assessing the risk of ubiquitous PAH from any source to early life stages of fish.