Mixed exposure to brominated flame retardants adversely affects vaccine-induced antibody titers: Risk prioritization and benchmark dose modeling.

Abstract

The association between brominated flame retardant (BFRs) exposure and measles, mumps, and rubella vaccine (MMR) antibody responses was investigated using the National Health and Nutrition Examination Survey (2003-2004). Using multivariate linear regression and restricted cubic spline (RCS) model, we found significant inverse association between single BFR exposure (BB-153 and BDE-100) and mumps antibody levels (P < 0.05). Mixed BFR exposure synergistically reduced antibody levels across mumps and rubella vaccines, with BB-153 identified as the dominant contributor for mumps (PIP = 0.460). Benchmark dose modeling revealed immunotoxicity thresholds for a 10% antibody reduction: BB-153 (BMDL₁₀ = 46.73pg/g serum) for mumps, BDE-153 (BMDL₁₀ = 258.27pg/g serum) for rubella. While the exposure levels of most people in this study were below these thresholds, dose-response trends were still observed at sub-threshold concentrations. Enrichment analyses via Comparative Exploratory functional enrichment analysis suggested that BFR exposure may be associated with immune-related pathways. However, these findings are hypothesis-generating and do not represent definitive mechanistic evidence. Further experimental studies are needed to validate these potential biological mechanisms. Sensitivity analyses confirmed robust associations, and independent toxic effects were observed in females. This is the first study to examine the relationship between BFR exposure and MMR vaccine effects, highlighting the need for enhanced monitoring and a revised framework for assessing immunotoxicity.