Chlorinated Organophosphate Flame Retardants Impair the Lung Function via the IL-6/JAK/STAT Signaling Pathway

Abstract

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.

Exposure to OPFRs Is Associated with Obesity and Dysregulated Serum Lipid Profiles: Data from 2017–2018 NHANES

“…Marital status was classified into married/living with a partner, widowed/divorced/separated, and never married. Family PIR was divided into 4 groups: <1, 1-1.99, 2-3.99, and ≥4 [31].…”

Exposure to OPFRs is associated with obesity and dysregulated serum lipid profiles: data from 2017-2018 NHANES

“…Marital status was classi ed into married/living with partner, widowed/divorced/separated, and never married. Family PIR was divided into 4 groups: <1, 1-1.99, 2-3.99, ≥ 4 [27].…”

Discovering Novel Organophosphorus Compounds in Wastewater Treatment Plant Effluents through Suspect Screening and Nontarget Analysis

“…2 Numerous studies have documented the ubiquity of OPCs across a variety of environmental matrices, including air, 4−6 dust, 7,8 water, 2,3,9 and sediment, 10,11 as well as foodstuffs 12 and biological samples. 1,13 More importantly, their association with a range of toxicity and health effects, such as endocrine disruption, 14,15 thyroid cancer risk, 16 pulmonary dysfunction, 17 and reproductive toxicity, 3,18 has been established through toxicological and epidemiological studies.…”

“…Organophosphorus compounds (OPCs) have been extensively used as organophosphorus flame retardants (OPFRs), plasticizers, pesticides, and antioxidants for several decades. − Driven by the regulatory restrictions on polybrominated diphenyl ethers, , OPFRs have been mass-produced with global consumption exceeding 700,000 tons in 2017, accounting for over 30% of the total flame retardant usage . Numerous studies have documented the ubiquity of OPCs across a variety of environmental matrices, including air, − dust, , water, ,, and sediment, , as well as foodstuffs and biological samples. , More importantly, their association with a range of toxicity and health effects, such as endocrine disruption, , thyroid cancer risk, pulmonary dysfunction, and reproductive toxicity, , has been established through toxicological and epidemiological studies.…”