30-Day Immunotoxicity Study of PFMOAA in C57BL/6 Mice

Abstract

Within the past five years, two classes of per- and polyfluoroalkyl substances (PFAS) were phased out of production in the U.S., which led to the development and production of PFAS to replace these two major classes. One family of these PFAS are perfluoro-ether carboxylic acids (PFECA), which have emerged in the public and scientific arenas due to their presence in drinking water systems across the U.S., including Wilmington, NC. Although manufacturers have touted them as having more favorable environmental and toxicological properties very little is known about the toxicity and environmental fate these emerging PFECA. One compound, perfluoro-2-methoxyacetic acid (PFMOAA), was identified as the dominant PFECA in the Cape Fear River, in concentrations as high as 35,000 ng/L. There is very little mention of PFMOAA in the publicly available scientific literature and to our knowledge, we are the first to investigate its potential for toxic effects. In this 30-day study, we orally administered 25,000, 2,500,000, or 250,000,000 ng/L of PFMOAA in water to male and female C57BL/6 mice and investigated immune and liver alterations following exposure. Mice given PFMOAA showed no signs of overt toxicity during the study and no evident changes were observed in liver mass or peroxisomal enzyme activity. While mild alterations in splenic and thymic lymphocyte sub-populations were observed in males, these results do not point to any definitive alterations in immune function. Ultimately, we concluded that the doses administered were too low to achieve an internal dose sufficient to induce changes to immune endpoints, likely due to rapid excretion of PFMOAA in mice. Further investigation into serum and organ concentrations of PFMOAA as well its effects on antibody production will be more conclusive of immunotoxic effects.