Fish consumption guidelines consider the contaminant in the highest concentration and ignore interactions among the multiple contaminants present.  Mixture toxicity has been documented, but not among most environmental contaminants.  Methylmercury (MeHg) and polychlorinated biphenyl (PCB) compounds are the most prevalent and abundant fish contaminants in the U.S.  Literature suggests these two contaminants have additive effects, and that in zebrafish the two have similar modes of action and physiological endpoints.  To better understand mixture toxicity, the embryonic zebrafish model provides the opportunity to interrogate the potential toxicity of individual compounds in varying combinations.  Zebrafish, a small, complex organism, shares a highly-conserved anatomy and physiology with all vertebrates, and critical processes of zebrafish neurodevelopment are homologous to those in humans.  In this study, we used zebrafish to study the additive effects of MeHg and single PCB congeners (95, 118, 126).  Embryonic zebrafish were dechorionated and exposed to a broad concentration range of each PCB congener (0-100 μM) and MeHg (0.01-0.15 μM) to investigate their bioactivity.  MeHg was the most potent, with a benchmark dose (BMD<sub>10</sub>) of 0.17 μM and PCB 126 was similar with 0.22 μM.  PCB 95 and 118 were about 500x less potent than PCB 126 and MeHg in causing teratogenic effects.  When embryos were co-exposed to a concentration range of MeHg and a single concentration of PCB, the mixtures with congeners 126 and 95 shifted the dose-response curve, indicating an additive teratogenic effect.  Abnormal behavior was detected using the larval photomotor response for each chemical, with MeHg being most potent.  Co-exposures of MeHg and individual PCBs resulted in a significant shift of the BMD<sub>50</sub> for PCBs.  These preliminary results suggest that further testing of additive toxicity is warranted to evaluate if current fish consumption guidelines based on the single contaminant in highest concentration adequately protect human health.

Experimental evaluation of additive interactions in the toxicity of methylmercury and PCBs to zebrafish

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ACS Fall 2022

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