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Exposure to multiple environmental pollutants is ubiquitous and inevitable, but studies investigating their exposure effects on oxidative stress or inflammation have mainly been restricted to single-pollutant models. This study investigated the association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation. Using a cross-sectional study in adults, we measured urinary concentrations of metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) and phthalates (mPAEs), urinary oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine, and 9 inflammatory biomarkers in paired blood samples. The associations of urinary OH-PAHs and mPAEs with oxidative stress and inflammation biomarkers were evaluated by different statistical models. The Bayesian kernel machine regression and quantile g-computation was used to examine the joint effects, and increased levels of urinary concentrations of OH-PAHs and mPAEs were associated with elevated 8-hydroxy-2'-deoxyguanosine level and white blood cell counts. Exposure to polycyclic aromatic hydrocarbons contributed more significantly to inflammation, while exposure to phthalates contributed more to oxidative stress. Monoisobutyl phthalate was identified as the most significant metabolite contributing to elevated oxidative stress levels. 1-Hydroxypyrene was negatively associated with platelet, and monomethyl phthalate was significantly positively associated with interleukin 6 in multivariate linear regression. The restricted cubic spline analysis revealed non-linear patterns of 3-hydroxyfluorene with white blood cell, lymphocyte, neutrophil, and C-reactive protein. The results indicated significant associations between increased co-exposure to polycyclic aromatic hydrocarbons and phthalates with elevated oxidative stress and inflammation. Further investigation is needed to elucidate the underlying biological mechanisms and to determine the potential public health implications., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Children are highly vulnerable to environmental pollutants, especially endocrine-disrupting chemicals (EDCs). Previous research has linked both organic UV filters and phthalates exposure to adiposity and pubertal development in children. Nevertheless, the individual and collective effects of these chemicals on this population remain poorly understood. In this study, twelve organic UV filters and metabolites, six phthalate metabolites and two oxidative stress biomarkers were analyzed in a prospective follow-up study in Shanghai, China after a baseline study conducted 1.5 years earlier. Results revealed a positive association between exposure to individual organic UV filters or their mixture and levels of 8-OHdG (β ranging from 0.242 to 0.588, P < 0.05), a marker of oxidative DNA damage. BP-3 and OD-PABA made a greater contribution to oxidative DNA damage than other UV filters. Levels of 8-OHdG were also positively correlated with single phthalate metabolites and their mixture, with MnBP and MMP contributing the most. Stratified analysis found that these associations were mainly observed in girls. Our mixture analysis revealed cumulative risks of oxidative DNA damage when there was co-exposure to these two kinds of EDCs. These results underscore the importance of considering the risks associated with organic UV filters and the necessity of evaluating the effects of all these pollutants, both individually and in mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Epidemiological studies have suggested that phthalate exposures are associated with increased risks of thyroid cancer and benign nodule, while the underlying mechanisms are largely unknown. Here, we explored the mediation effects of oxidative stress (OS) biomarkers in the associations between phthalate exposures and the risks of thyroid cancer and benign nodule. Urine samples collected from 143 thyroid cancer, 136 nodule patients, and 141 healthy controls were analyzed for 8 phthalate metabolites and 3 OS biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F 2α (8-isoPGF 2α )]. Multivariable linear or logistic regression models were used to explore the associations of OS biomarkers with phthalate metabolite concentrations and the risks of thyroid cancer and nodule. The mediation role of OS biomarkers was also investigated. Urinary monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethylhexyl) phthalate (MEHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were positively associated with at least 2 OS biomarkers (all P-values<0.01), and part of these positive associations varied in different subgroups. All 3 OS biomarkers were positively associated with the risks of thyroid nodule and cancer (P-values<0.001). The mediation analysis showed that OS biomarkers significantly mediated the associations between urinary MEHOP concentration and nodule, as well as between urinary MMP, MEHP, and MEHHP concentrations and cancer and nodule, with the estimated proportions of mediation ranging from 15.8% to 85.6%. Our results suggest that OS is a potential mediating mechanism through which phthalate exposures induce thyroid carcinogenesis and nodular formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD., Methods and Findings: Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation [SD] 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and F2-isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F2-isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z-score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F2-isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (β = 0.13 [95% CI: 0.05, 0.21], p = 0.001), KIM-1 (β = 0.30 [95% CI: 0.21, 0.40], p < 0.001), 8-OHdG (β = 0.10 [95% CI: 0.06, 0.13], p < 0.001), and F2-isoprostane (β = 0.13 [95% CI: 0.01, 0.25], p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m2 (95% CI: -0.75, -0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure., Conclusions: Although BPA and phthalate metabolites were not associated with clinical renal endpoints such as eGFR or proteinuria, there was a consistent pattern of increased tubular injury and oxidative stress over time, which have been shown to affect renal function in the long term. This raises concerns about the potential for clinically significant changes in renal function in relation to exposure to common environmental toxicants at current levels., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HT reports NIDDK grants and consultancy agreements with Retrophin, Goldfinch Bio, Chemocentryx and Otsuka Pharmaceutical.