Development and validation of fish-specific toxic equivalency factors for polychlorinated dibenzo-P-dioxins, dibenzofurans, and biphenyls

Feral fish in the Great Lakes are contaminated with mixtures of polychlorinated dibenzo-p-dioxin (PCDD), dibenzofuran (PCDF) and biphenyl (PCB) congeners, and fish early life stages are extremely sensitive to mortality caused by these compounds. Because of the complex mixtures of these congeners in fish tissue, toxic equivalency factors (TEFs), which describe the potency of individual congeners relative to the prototype congener, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been proposed for use in ecological risk assessment. This research sought to validate the TEF method for fish early life stage risk assessment by (1) completing the list of TEFs for the endpoint of rainbow trout early life stage mortality, (2) determining whether congeners act additively, (3) determining whether TEFs in different species are similar, and (4) determining TEFs in a fish cell culture system. Results indicated that TEFs for PCBs were lower in rainbow trout early life stages than mammals, and that this could not be attributed to increased elimination. Most congeners acted additively to produce early life stage mortality when administered as pairs. However, two congener pairs showed differences from additivity, and a complex mixture of PCDD, PCDF and PCB congeners, simulating the ratio found in Lake Michigan lake trout, showed antagonism. These differences from additivity were smaller than risk assessment safety factors. The TEF for one important PCB congener (PCB #126) for producing early life stage mortality was similar in lake trout and rainbow trout, suggesting that TEFs are similar between these two species. TEFs for PCDDs and PCDFs determined in the rainbow trout gonadal cell line (RTG-2) for cytochrome P4501A mRNA induction were similar to TEFs for rainbow trout early life stage mortality. TEFs for PCBs, however, were consistently higher in cell culture, and mono-ortho-substituted PCBs induced P4501A mRNA in cell culture while they had no effect in rainbow trout early life stages. A mixture simulating the ratios of congeners in feral Lake Michigan lake trout acted additively in cell culture, suggesting that this bioassay accurately predicts TCDD-like activity of mixtures of PCDD, PCDF and PCB congeners.