Decreased Serum Vaccine Antibody Concentrations as Critical Outcome of Exposure to Perfluorinated Compounds

Abstract

Background: Experimental toxicology studies suggest that immunotoxicity may occur at low-level exposures to perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), two persistent contaminants of food, drinking water, and a variety of consumer products. Aims: To determine the association of PFC exposure with antibody response to childhood vaccinations. Methods: In a prospective study of a birth cohort from the National Hospital in Faroe Islands, 656 consecutive singletons were recruited at birth, and 459 were examined at age 7 years. Serum was analyzed for PFOS and PFOA and for specific antibody concentrations against tetanus and diphtheria toxoids. A total of 412 children also had a serum analysis at age 5 years. Multiple regression analysis and structural equation models were used to determine the association between exposures and antibody concentrations. Benchmark dose calculations were carried out to compare the findings with current exposure limits. Results: PFOS and PFOA measured at ages 5 and 7 years showed strong negative associations with antibody concentrations at age 7 years. When both were included in a structural equation model, a doubled exposure was associated with differences of -59% (95% CI: -23%, -78%) and -65% (-30%, -82%) in diphtheria and tetanus antibody concentrations, respectively. Further analyses suggested that cumulated exposures measured both at age 5 and 7 contributed to the associations and that they could not be reliably attributed to any single compound. Using different dose-effect assumptions, benchmark dose levels were found to be about 1.3 ng/mL for PFOS and 0.3 ng/mL for PFOA at a benchmark dose response of 5%. Conclusions: These findings suggest that immunotoxicity may be a critical effect of human exposure to perfluorinated compounds, and that antibody response to childhood immunizations is a useful and relevant outcome. The strong associations observed are remarkable, and the calculated benchmark dose levels suggest that current exposure limits for PFOS and PFOA may be as much as 1000-fold too high.