Immunotoxicity of Perfluoroalkylated Compounds

Abstract

The following chapter reports on the health impacts of perfluoroalkylated compounds in the context of in vitro and in vivo immunotoxicology studies as well as epidemiology studies. In general, elevated serum PFAA levels reported in adults and children correlate with observed changes in health to include decreases in serum vaccine titers and IgE levels, or increases in antinuclear antibodies, asthma, the common cold, and gastroenteritis. Laboratory studies demonstrate direct, in vitro effects of perfluorinated compounds modulating TNF-α, IL-6 and IFN-γ. These studies may be linked mechanistically to alterations reporting decreases in vaccine antibody titers in human reports and dose-responsive, decreases in IgM antibody production in animal models. To some extent, perfluoroalkylated compounds are thought to modulate gene regulation via peroxisome proliferator activated receptor alpha (PPARα) and to a lesser extent via peroxisome proliferator activated receptor gamma (PPARγ), yet species differences affecting the expression of this receptor complicates this interpretation as an underlying mechanism in humans. Mechanisms of action beyond PPAR-mediated effects represents new directions and are also discussed. As we learn more about the relationship between perfluoroalkylated compounds and emerging health issues, this may challenge current benchmark thresholds in drinking water to ensure adequate protection for human health.