Rising evidence of both experimental and epidemiological studies suggests that phthalate exposure may contribute to increased risks of metabolic disorders. But there is limited research on the childhood dyslipidemia. Our cohort study was conducted in Xiamen city, Fujian Province, China. A total of 829 children (mean age 8.5 years) were included with collection of urine, blood samples and demographic data in May 2018 and followed up once a year from 2018 to 2020. We performed adjusted log-binomial regressions to examine associations between sex-specific tertiles of seven phthalate metabolites and dyslipidemia in visit 1, as well as persistent dyslipidemia and occasional dyslipidemia. We also used generalized estimating equation models (GEE) to explore the relationships between log-transformed phthalate metabolites and lipid profiles. In adjusted models, the prevalence and RRs of dyslipidemia increased with tertile group of mono-n-butyl phthalate (MnBP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), and summed di-(2-ethylhexyl) phthalate (∑DEHP) metabolites with a dose-response relationship in visit 1, as well as persistent dyslipidemia. Higher MnBP, ∑LMWP, MEHHP, MEOHP, and ∑DEHP concentrations were also associated with higher levels of log-transformed triglycerides (TG). Boys were more vulnerable to phthalates exposure than girls. In conclusion, children in China were widely exposed to phthalates, and phthalates exposure during childhood might significantly increase the risk of dyslipidemia and a higher level of lipid profiles, particularly in boys.

Currently, studies on the association between per-/polyfluoroalkyl substances (PFAS) concentrations and the renal function of residents, especially teenagers, living near fluorochemical industrial plants, are relatively rare, and not all these studies suggested associations. In this cross-sectional study, 775 local teenagers (11–15 years old) were included, and serum concentrations of 18 PFAS were measured. Perfluorooctanoic acid (PFOA) was found to be the dominant PFAS with a concentration of 22.3–3310 ng/mL (mean = 191 ng/mL), accounting for 71.5–99.1% of ΣPFAS. Statistical analyses demonstrated that internal exposure of perfluoroalkyl carboxylic acids (PFCA, C8–C10) was related to the plant. In addition, the prevalence rate of chronic kidney disease (CKD) (35.0%) in the participants was relatively high. A significantly positive association was observed between the increase in PFOA concentration and increasing risk of CKD (OR = 1.741; 95% CI: 1.004, 3.088; p = 0.048) by adjusting for gender, age, body mass index (BMI), and household income. Similar positive correlation was also observed in PFHpA with CKD (OR = 1.628, 95% CI: 1.031, 2.572; p = 0.037). However, no significant correlation was observed for concentrations of other PFAS and CKD (p > 0.05). Furthermore, linear regression analyses demonstrated that none of the PFAS concentrations were significantly correlated with estimated glomerular filtration rate (eGFR) or urine albumin/urine creatinine ratio (ACR) (p > 0.05). However, a significantly negative correlation was observed between PFOA concentration and abnormal ACR (β = −0.141, 95% CI: −0.283, 0.001; p = 0.048) after stratifying by CKD. Sensitivity analyses further confirmed these results. This cross-sectional study is the first, to our knowledge, to investigate the association between PFAS concentrations and renal function in teenagers living near a Chinese industrial plant. Further prospective and metabonomic studies are needed to interpret the results and clarify the biological mechanisms underlying this association.

Human exposure to organic contaminants is widespread. Many of these contaminants show adverse health effects on human population. Human biomonitoring (HBM) follows the levels and the distribution of biomarkers of exposure (BoE), but it is usually done in a targeted manner. Suspect and non-targeted screening (SS/NTS) tend to find BoE in an agnostic way, without preselection of compounds, and include finding evidence of exposure to predicted, unpredicted known and unknown chemicals. This study describes the application of high-resolution mass spectrometry (HRMS)-based SS/NTS workflow for revealing organic contaminants in urine of a cohort of 200 children from Slovenia, aged 6–9 years. The children originated from two regions, urban and rural, and the latter were sampled in two time periods, summer and winter. We tentatively identified 74 BoE at the confidence levels of 2 and 3. These BoE belong to several classes of pharmaceuticals, personal care products, plasticizers and plastic related products, volatile organic compounds, nicotine, caffeine and pesticides. The risk of three pesticides, atrazine, amitraz and diazinon is of particular concern since their use was limited in the EU. Among BoE we tentatively identified compounds that have not yet been monitored in HBM schemes and demonstrate limited exposure data, such as bisphenol G, polyethylene glycols and their ethers. Furthermore, 7 compounds with unknown use and sources of exposure were tentatively identified, either indicating the entry of new chemicals into the market, or their metabolites and transformation products. Interestingly, several BoE showed location and time dependency. Globally, this study presents high-throughput approach to SS/NTS for HBM. The results shed a light on the exposure of Slovenian children and raise questions on potential adverse health effects of such mixtures on this vulnerable population.

Persistent and mobile chemicals (PMs) and per- and polyfluoroalkyl substances (PFAS) are groups of chemicals that have received recent global attention due to their potential health effects on the environment and humans. In this study, exposure to a broad range of PMs and PFAS was investigated in Flemish adolescents’ urine samples (n = 83) using a suspect screening approach. For this purpose, three sample preparation methods were evaluated, and a basic liquid-liquid extraction was optimized for urine analysis based on the extraction efficiency of PMs (53–80%) and PFAS (>70%). In total, 9 PMs were identified in urine samples at confidence levels (CL) 1–3 and, among them, acetaminophen, 4-aminophenol, 2,2,6,6-tetramethyl-4-piperidone, trifluoroacetic acid (TFAA), sulisobenzone, ethyl sulfate, and 1,2-benzisothiazol-3(2H)-one 1,1-dioxide were confirmed at CL 1 and 2. In addition, the detection and identification of 2,2,6,6-tetramethyl-4-piperidone, 4-aminophenol, TFAA, and m-(2,3-epoxypropoxy)-N,N-bis(2,3-epoxypropyl) aniline (CL 3), has been reported for the first time in human urine in this study. For PFAS, only 2 compounds were identified at CL 4, implying that urine is not a suitable matrix for suspect screening of such compounds. A significant difference between sexes was observed in the detection rate of identified PMs, in particular for acetaminophen, 4-aminophenol, and sulisobenzone. The findings of this study can be used in future human biomonitoring programs, such as by including the newly identified compounds in quantitative methods or monitoring in other human matrices (e.g., serum).

Metals may affect adversely cardiovascular system, but epidemiological evidence on the associations of priority-controlled metals including antimony (Sb), arsenic (As), cadmium, lead, and thallium with children's blood pressure (BP) was scarce and inconsistent. We conducted two panel studies with 3 surveys across 3 seasons among 144 and 142 children aged 4–12 years in Guangzhou and Weinan, respectively. During each seasonal survey, urine samples were collected for 4 consecutive days and BP was measured on the 4th day. We obtained 786 BP values and urinary metals measurements at least once within 4 days, while 773, 596, 612, and 754 urinary metals measurements were effective on the health examination day (Lag 0), and the 1ˢᵗ, 2ⁿᵈ, and 3ʳᵈ day preceding BP measurement (Lag 1, lag 2 and lag 3), respectively. We used linear mixed-effect models, generalized estimating equations and multiple informant models to assess the associations of individual metal at each lag day and accumulated lag day (4 days averaged, lag 0–3) with BP and hypertension, and Bayesian Kernel Machine Regression to evaluate the relations of metals mixture at lag 0–3 and BP outcomes. We found Sb was positively and consistently related to systolic BP (SBP), mean arterial pressure (MAP), and odds of having hypertension within 4 days, which were the strongest at lag 0 and declined over time. And such relationships at lag 0–3 showed in a dose-response manner. Meanwhile, Sb was the only contributor to the relations of mixture with SBP, MAP, and odds of having hypertension. Also, synergistic interaction between Sb and As was significant. In addition, modification effect of passive smoking status on the association of Sb and SBP was more evident in passive smokers. Accordingly, urinary Sb was consistently and dose-responsively associated with increased BP and hypertension, of which Sb was the major contributor among children.

The antimicrobial agent triclosan (TCS) has attracted much attention worldwide because of its pervasive existence in the human body and environment. TCS exposure has been reported to be associated with decreased male reproductive function. However, few studies have investigated these associations in humans. To examine the relationship between TCS in urine and male semen quality. A total of 406 men from a reproductive clinic were enrolled in this study. Urinary TCS concentrations were determined by ultra-high performance liquid chromatography–electrospray ionization tandem mass spectrometry. Sixteen semen parameters were assessed according to the guidelines of World Health Organization (WHO), including parameters for volume, count, motility, and motion. We used multivariate linear regression models and restricted cubic splines to estimate the linear and non-linear associations between TCS exposure and semen parameters, respectively. Logistical regression models were further applied to explore the associations with abnormal semen quality. TCS was detected in 74.6% of urine specimens. The monotonous trend of TCS tertiles and continuous TCS levels with all semen quality parameters were not observed in multivariate linear regression models (p > 0.05). However, compared with those in the lowest tertile, subjects in the second tertile showed significantly higher linearity and wobble (p < 0.05), indicating potential effects on sperm motion. In the models using restricted cubic splines with 3–5 knots, there were no significant non-linear associations between TCS exposure and any semen quality parameter. In addition, TCS tertiles were not associated with the risk of abnormal semen quality (i.e., count and motility) in the logistical regression models. Our results revealed that low-level TCS exposure may have limited (none or modest) effects on male semen quality, potentially inducing some fluctuations. Further mechanistic studies on low levels of exposure are needed.

The potential effect of gestational exposure to phthalates on the lung function levels during childhood is unclear. Therefore, we examined this association at different ages (from 4 to 11 years) and over the whole childhood. Specifically, we measured 9 phthalate metabolites (MEP, MiBP, MnBP, MCMHP, MBzP, MEHHP, MEOHP, MECPP, MEHP) in the urine of 641 gestating women from the INMA study (Spain) and the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁) and FEV₁/FVC in their offspring at ages 4, 7, 9 and 11. We used linear regression and mixed linear regression with a random intercept for subject to assess the association between phthalates and lung function at each study visit and for the overall childhood, respectively. We also assessed the phthalate metabolites mixture effect on lung function using a Weighted Quantile Sum (WQS) regression. We observed that the phthalate metabolites gestational levels were consistently associated with lower FVC and FEV₁ at all ages, both when assessed individually and jointly as a mixture, although most associations were not statistically significant. Of note, a 10% increase in MiBP was related to lower FVC (−0.02 (−0.04, 0)) and FEV₁ z-scores (−0.02 (−0.04, −0.01) at age 4. Similar significant reductions in FVC were observed at ages 4 and 7 associated with an increase in MEP and MnBP, respectively, and for FEV₁ at age 4 associated with an increase in MBzP. WQS regression consistently identified MBzP as an important contributor to the phthalate mixture effect. We can conclude that the gestational exposure to phthalates was associated with children's lower FVC and FEV₁, especially in early childhood, and in a statistically significant manner for MEP, MiBP, MBzP and MnBP. Given the ubiquity of phthalate exposure and its established endocrine disrupting effects in children, our findings support current regulations that limit phthalate exposure.

The association of co-exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) with blood cell-based inflammatory biomarkers is largely unknown. We conducted a panel study of 144 children aged 4–12 years, with up to 3 repeated visits across 3 seasons. For each visit, we collected the first-morning urine for 4 consecutive days and fasting blood on the day of physical examination. We developed a gas chromatography/tandem mass spectrometry method to detect the metabolites of 10 PAHs (OH-PAHs) and 10 PAEs (mPAEs) in urine samples. We employed linear mixed-effects models to evaluate the individual associations of each OH-PAH and mPAE with blood cell-based inflammatory biomarkers over different lag times. Bayesian kernel machine regression (BKMR) and quantile g-computation were used to evaluate the overall associations of OH-PAHs and mPAEs mixtures with blood cell-based inflammatory biomarkers. After multiple adjustments, we found positive associations of summed hydroxylphenanthrene (∑OHPHE), summed OH-PAHs, and mono-n-butyl phthalate with inflammatory biomarkers such as neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the systemic immune-inflammation index (SII) at lag 0 (the day of physical examination). Each 1% increase in ∑OHPHE was related to a 0.18% (95% confidence interval: 0.10%, 0.25%) increase in SII, which was the strongest among the above associations. The results of BKMR and quantile g-computation suggested that co-exposure to PAHs and PAEs mixture was associated with an elevated white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and SII, to which ∑OHPHE and 1-hydroxypyrene (1-OHPYR) might be the major contributors. In addition, gender and age modified the associations of ∑OHPHE and 1-OHPYR with inflammatory biomarkers, where girls and younger children were more susceptible. In conclusion, co-exposure to PAHs and PAEs was associated with elevated inflammation in children, in which ∑OHPHE and 1-OHPYR might play important roles.

Accelerating evidence of endocrine-related morbidity has raised alarm about the ubiquitous use of phthalates in the human environment, but studies have not directly evaluated mortality in relation to these exposures. To evaluate associations of phthalate exposure with mortality, and quantify attributable mortality and lost economic productivity in 2013–4 among 55–64 year olds. This nationally representative cohort study included 5303 adults aged 20 years or older who participated in the US National Health and Nutrition Examination Survey 2001–2010 and provided urine samples for phthalate metabolite measurements. Participants were linked to mortality data from survey date through December 31, 2015. Data analyses were conducted in July 2020. Mortality from all causes, cardiovascular disease, and cancer. Multivariable models identified increased mortality in relation to high-molecular weight (HMW) phthalate metabolites, especially those of di-2-ethylhexylphthalate (DEHP). Hazard ratios (HR) for continuous HMW and DEHP metabolites were 1.14 (95% CI 1.06–1.23) and 1.10 (95% CI 1.03–1.19), respectively, with consistently higher mortality in the third tertile (1.48, 95% CI 1.19–1.86; and 1.42, 95% CI 1.13–1.78). Cardiovascular mortality was significantly increased in relation to a prominent DEHP metabolite, mono-(2-ethyl-5-oxohexyl)phthalate. Extrapolating to the population of 55–64 year old Americans, we identified 90,761–107,283 attributable deaths and $39.9–47.1 billion in lost economic productivity. In a nationally representative sample, phthalate exposures were associated with all-cause and cardiovascular mortality, with societal costs approximating $39 billion/year or more. While further studies are needed to corroborate observations and identify mechanisms, regulatory action is urgently needed.

Organophosphate esters (OPEs) are widely added to various industrial and consumer products, and are mainly used as flame retardants and plasticizers. Existing epidemiological studies suggest that OPE exposure may be linked to increased blood pressure (BP) and hypertension risk in adults. However, it remains unclear whether OPE exposure is associated with increased BP in children and adolescents. Here, we investigated the associations between OPE exposure and BP levels in 6–18-year-old children and adolescents from a cross-sectional study in Liuzhou, China. OPE metabolites were determined in spot urine samples (n = 1194) collected between April and May 2018. Three measurements of systolic and diastolic BP for each participant were averaged as study outcomes. Associations of OPE exposure with age-, sex- and height-standardized BP were assessed using linear regression models. We found that each natural log unit increment of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with a 0.06 standard deviation unit (95% confidant interval (CI): 0.01, 0.11) increase in systolic BP z-score. When conducting stratified analysis based on sex, age, and BMI category, BDCIPP was shown to be positively associated with systolic/diastolic BP z-score in females, but not in males. The associations between bis(2-butoxyethyl) phosphate (BBOEP) and systolic/diastolic BP z-score were pronounced in adolescents, but not in children. Moreover, a significant positive association between 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and diastolic BP z-score was observed in obese subjects. The present study provides the first evidence that OPE exposure was related to increased BP in children and adolescents. Given the scarcity of high-quality evidence supporting these results, the health effects of OPEs are warrant investigation in well-designed prospective studies.