Urinary Polycyclic Aromatic Hydrocarbon Metabolites Are Associated with Biomarkers of Chronic Endocrine Stress, Oxidative Stress, and Inflammation in Adolescents: FLEHS-4 (2016–2020)

Abstract

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants of public health concern. Multiple biological mechanisms have been hypothesized to contribute to PAHs-associated adverse health effects. Little is known about the impact of PAHs on endocrine stress and inflammation in adolescence. We examined 393 Flemish adolescents (14–15 years) cross-sectionally, measured urinary concentrations of hydroxylated naphthalene, fluorene, phenanthrene and pyrene metabolites, and calculated the sum of all measured metabolites. We determined hair cortisol concentration (HCC) as endocrine stress biomarker, leucocyte counts and neutrophil–lymphocyte ratio (NLR) in peripheral blood as inflammatory biomarkers, and urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) concentration as oxidative stress biomarker. Exposure–response associations were analyzed by multiple regression, adjusted for a priori selected covariates. A doubling of 1-hydroxypyrene concentration was associated with a factor of 1.13 (95% CI: 1.03, 1.24) increase in HCC and a factor of 1.07 (95% CI: 1.02, 1.13) increase in 8-oxodG. Doublings of 2- and 3-hydroxyphenanthrene concentrations were associated with a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.00, 1.12) increase in 8-oxodG, respectively. Doubling of 2-hydroxyphenanthrene and of the sum of 2- and 3-hydroxyfluorene was associated with, respectively, a factor of 1.08 (95% CI: 1.02, 1.14) and 1.06 (95% CI: 1.01, 1.13) increase in NLR. Our results indicate the glucocorticoid pathway as a potential target for PAH exposure in adolescents and suggest oxidative stress, endocrine stress, and inflammation in adolescence as underlying mechanisms and early markers for PAH-related adverse health effects.

Urinary polycyclic aromatic hydrocarbon metabolites and their association with oxidative stress among pregnant women in Los Angeles

“…They have also been related to neurodevelopment [8] and childhood asthma [9], yet the biological mechanisms through which PAHs exhibit such toxicity are still debated. PAHs have been reported to induce oxidative stress, in ammation and endocrine disruptions, which may each individually or jointly have adverse effects on the pregnancy [10][11][12]. Speci cally, PAHs can induce an excess of reactive oxygen species (ROS), which would target DNA, proteins and lipids, resulting in their oxidation [12].…”

Early-life oxidative stress due to air pollution. A scoping review focusing on identifying potential ‘-OMICS’ biomarkers from body fluids

“…18.5 ± 0.52 µmol mol −1 of creatinine for the age groups (12-20 years)), but, none of these studies could confirm a significant association [39,[46][47][48]. Three additional studies used a panel of PAH metabolites and reported a significant association [40,41,50]. Li et al [40], suggested, based on the observed urinary PAH profile, that exposure occurs mostly through inhalation and therefore depends on ambient AP, as the atmospheric PAH profile of low molecular weight OH-PAHs is very similar, whereas larger urinary PAH concentrations reflect additional sources such as diet.…”

“…A similar trend has been observed in children [38-42, 46, 50, 53], children/adolescents [46], and adolescents [49], that is, an increase in AP is generally associated with an increase in the level of 8-OHdG or 8-oxodG in urine. It is worth mentioning that boys [8,41,50] might be more prone than girls [50], that the…”

“…These DNA adducts appear when guanine derivatives in the nuclear and mtDNA are oxidized. Fourteen studies reported a positive association between AP and markers of oxidative DNA damage, including 8-OHdG [20-22, 26, 30, 31, 38-41, 46-48, 53] and 8-oxodG [32,33,42,49,50,53].…”

Comprehensive investigation of persistent and mobile chemicals and per- and polyfluoroalkyl substances in urine of flemish adolescents using a suspect screening approach

“…The Flemish adolescents' spot urine samples investigated in this study were selected from the biobanked samples (n = 428, 14-15 years old adolescents; kept at -20℃) collected between September 2017 and June 2018 in the frame of the FLEHS IV reference biomonitoring study (2016-2020; approved by the Ethical Committee of the University Hospital of Antwerp, Belgium; Belgian Registry Number: B300201732753). The subset of samples (n = 83) were selected on the exposure load (high and low) calculated based on earlier quantitative analysis of 45 environmental chemicals (Buekers et al, 2021;Schoeters et al, 2022), such as phthalates and alternative plasticizers (Bastiaensen et al, 2021a), organophosphorus flame retardants (OPFRs) and plasticizers (Bastiaensen et al, 2021b), bisphenol analogues (Gys et al, 2021), and polycyclic aromatic hydrocarbon metabolites (Verheyen et al, 2021).…”