abstract

Environmental contaminants such as PCBs have been the source of increasing concern for their potential environmental and human health effects. We performed in vitro dose-response experiments to quantify the direct immunotoxicity of different PCB congeners in humans, mice and marine mammals, to quantify inter-species differences and determine if the conformation of PCB congeners can predict their immunotoxic potential (assessed on neutrophil and monocyte phagocytosis, as well as B and T lymphocyte proliferation). Results to date demonstrate structure (non-ortho (NO), mono-ortho (MO) and di-ortho (DO)-substituted congeners) sometimes helps predict toxicity, with DO PCBs generally reducing phagocytosis in most species, while NO did not. Nevertheless, species susceptibility sometimes appears to be more important, with most PCBs increasing lymphocyte proliferation in humans and marine mammals, but approximately half the congeners decreasing it in mice. Overall, our results highlight the differences between species, question the use of the conventional mouse model to predict toxicity in other species, and offers initial support to the hypothesis that the structure of PCBs may help predict their immunotoxicity, which is not solely associated with dioxin-like mechanisms. In view of those findings, we have designed species-specific modeling to assess the likelihood of adverse health effects at the cell level, given real-life exposure of those cells, as measured by blood concentrations in "naturally" exposed individuals and populations, and the effects demonstrated upon in vitro exposure. Such model can help determine the percentage of the population likely to suffer a given magnitude of adverse effects on the immune system, and predict the impact of increased or decreased environmental exposure on the health of exposed populations. A better characterization of the immunotoxic effects of PCBs in different species will improve our ability to perform more focused, precise and relevant risk assessment for marine mammal and human health.

acknowledgements

This work was supported by a grant from the NOAA Oceans and Human Health Initiative.