Toxicological
studies have revealed the adverse impacts of organophosphate
flame retardants (OPFRs) on the respiratory system, while there is
a lack of epidemiological evidence, and information for risk assessment
remains insufficient. Herein, we investigated the associations of
urinary metabolites of OPFRs with the lung function in 987 adults
participating in the U.S. National Health and Nutrition Examination
Survey 2011–2012. The elevation of three primary metabolites
of chlorinated OPFRs [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP),
bis(2-chloroethyl) phosphate (BCEP), and bis(1-chloro-2-propyl) phosphate
(BCIPP)] was related to pulmonary dysfunction in a sample-weighted
regression model. Each one-unit increase in the log-transformed levels
of BDCIPP and BCEP was related to 91.52 and 79.34 mL reductions in
the forced vital capacity (FVC). Each one-unit elevation in BCIPP
was correlated with 130.86, 153.56, 302.26, and 148.24 mL reductions
in forced expiratory volume 1st second (FEV1), FVC, peak
expiratory flow rate (PEF), and forced expiratory flow at 25-75% of
FVC (FEF25–75%), respectively. Then, an adverse
outcome pathway (AOP) framework was constructed using the Comparative
Toxicogenomics Database, the Toxicity Forecaster, and the GeneCards
database. Based on the weight of the evidence, BDCIPP, BCEP, BCIPP,
and their parent compounds (TDCIPP, TCEP, and TCIPP) may affect the
IL-6/Janus kinase/signal transducer and activator of transcription
(JAK/STAT) pathway, induce airway remodeling, and impair the lung
function. Additionally, tobacco smoke exposure may modify the effects
of BDCIPP on the lung function (P
int <
0.05) and affect the IL-6-mediated AOP. These results suggested that
chlorinated OPFRs were associated with pulmonary dysfunction via the
IL-6/JAK/STAT pathway.