Structural equation modeling of immunotoxicity associated with exposure to perfluorinated alkylates

Exposure to perfluorinated alkylate substances (PFASs) is associated with immune suppression in animal models, and serum concentrations of specific antibodies against certain childhood vaccines tend to decrease at higher exposures. As such, we investigated the immunotoxic impacts of the three major PFASs in a Faroese birth cohort. A total of 464 children contributed blood samples collected at age 7 years. PFAS concentrations and concentrations of antibodies against diphtheria and tetanus were assessed in serum at age 7 years, and results were available from samples collected at age 5. In addition to standard regressions, structural equation models were generated to determine the association between three major PFASs measured at the two points in time and the two antibody concentrations. Concentrations of all three 7-year PFAS concentrations were individually associated with a decrease in concentrations of antibodies, however, it was not possible to attribute causality to any single PFAS concentration. Hence, the three 7-year concentrations were combined and showed that a 2-fold increase in PFAS was associated with a decrease by 54.4% (95% CI: 22.0%, 73.3%) in the antibody concentration. If considering both the age-5 and age-7 concentrations of the three major PFASs, the exposure showed a slightly greater loss. These analyses strengthen the evidence of human PFAS immunotoxicity at current exposure levels and reflect the usefulness of structural equation models to adjust for imprecision in the exposure variables.