In vitro and in vivo comparisons of fish-specific CYP1A induction relative potency factors for selected polycyclic aromatic hydrocarbons

Abstract

Induction of cytochrome P450 (CYP1A), as measured by liver ethoxyresorufin-O-deethylase (EROD) activity in juvenile rainbow trout (Oncorhynchus mykiss), was used to derive relative potency factors (RPFs) for several polycyclic aromatic hydrocarbons (PAHs), chosen for their induction potency in a rainbow trout liver cell line (RTL-W1). Potency for causing induction was estimated as the median effective concentration (EC50) from exposure-response curves. With the exception of phenanthrene, all PAHs tested induced EROD activity in juvenile trout, ranked as: benzo[k]fluoranthene>benzo[b]fluoranthene>benzo[b]fluorene>beta-napthoflavone>retene (7-isopropyl-1-methylphenanthrene). When induction potency was expressed relative to benzo[k]fluoranthene, RPFs ranged from 0.02 to 1, and the rank order in vivo was identical to the rank order with RTL-W1-derived values. The additivity of PAHs in mixtures in RTL-W1 cells was compared to whole-fish results from a previous study. EROD induction showed additive interactions for PAHs with exposure-response curves of similar slopes. This study demonstrates that assays of CYP1A induction using rainbow trout liver cells in culture would be a convenient substitute for assays with whole fish as part of testing programs for risk assessment of PAHs.