Search Results (70)

Phthalates are a widely used class of plasticizers known to cause various health issues. Although numerous review articles have addressed the multi-organ toxicities of Phthalates and their metabolites, a specialized review focusing on their nephrotoxicity remains scarce. In this study, the nephrotoxicity of Phthalates and their metabolites is summarized from the views of epidemiological and toxicological evidence. Epidemiological studies have demonstrated a correlation between Phthalate exposure and abnormal urinary albumin-to-creatinine ratio (ACR) as well as glomerular filtration rate (eGFR) in children. In contrast, for adults, the epidemiological evidence for the association between Phthalates and ACR/eGFR remains controversial, necessitating further investigation. In this review, we explore the potential mechanisms by which Phthalates and their metabolites may induce nephrotoxicity. These mechanisms include the following: (1) induction of oxidative stress in renal cells; (2) reduction in aldosterone levels; (3) dysregulation of the renin-angiotensin system; (4) activation of endoplasmic reticulum (ER) stress; (5) renal fibrosis; (6) disruption of sodium and water homeostasis; and (7) activation of the heat shock response defense system. Finally, based on the current understanding, we propose future research directions and necessary efforts to advance knowledge in this field. Full article

Many common chemicals are known or suspected to harm brain development, and children are particularly vulnerable, yet research on their long-term effects on mental health is limited. This study investigated the associations of early childhood exposure to endocrine disrupting and neurotoxic chemicals with the development of internalizing, externalizing, and attention-deficit/hyperactivity disorder (ADHD) symptoms from early childhood through adolescence in 387 children from the Rhea cohort in Crete, Greece. At age 4, serum concentrations of 3 organochlorine pesticides and 14 polychlorinated biphenyls, and urinary concentrations of 7 phthalate metabolites and 6 dialkyl phosphate metabolites were measured. Children’s symptoms were assessed via maternal reports at ages 4, 6, 11 and 15 years. Using generalized estimating equation models, the study found that early exposure to hexachlorobenzene (HCB) and dichlorodiphenyldichloroethylene (DDE) was associated with increased externalizing symptoms across ages in girls [beta (95% CI): 0.20 (0.04, 0.37) and 0.11 (0.01, 0.21), respectively]. Among girls, low molecular weight (LMW) phthalates were also linked to elevated internalizing and externalizing symptoms, as well as ADHD-related difficulties [beta (95% CI): 0.15 (0.04, 0.26), 0.13 (0.01, 0.25), and 0.13 (0.02, 0.24), respectively]. Additionally, exposure to organophosphate pesticides was associated with increased externalizing and ADHD symptoms [beta (95% CI): 0.13 (0.04, 0.22) and 0.12 (0.04, 0.20), respectively]. The findings suggest that early childhood exposure to environmental chemicals may have long-term effects on emotional and behavioral development, with pronounced effects observed only in girls. Full article

Antenatal depression affects 10–20% of pregnant women, with notable adverse outcomes for the neonates. Limited studies have indicated a potential link between exposure to phthalate metabolites and depression. The association between phthalate metabolites and depression in pregnant women is unknown. We sought to evaluate the association of exposure to phthalate metabolites with depression severity score in US pregnant women. This cross-sectional study used data collected by the National Health and Nutrition Examination Survey during 2005–2018 on pregnant adults who completed urinary profiles that examined 12 common phthalate metabolites. Linear and quantile sum regressions were used to evaluate the association between depressive symptoms (measured by the Patient Health Questionnaire, PHQ-9) and concentrations of phthalate metabolites. A total of 208 women were included in the analysis. These women’s mean (SD) age was 27.42 (5.78) years. We found that all the phthalates were associated with PHQ-9 scores except for mono (carboxyoctyl) and mono-isononyl phthalate. Similar results were observed with the association of high levels of phthalates with mild, moderate, and severe depression (PHQ-9 >4 vs. ≤4). All the phthalate metabolites remained significantly associated with depression scores in the adjusted analysis. Among all considered phthalate metabolites, a combination of MCNP, MBP, MiBP, MnBP, and MEHP contributed to the strongest association with higher depression scores. The relative importance was similar for MCNP (weight = 0.32) and MBP (weight = 0.31), followed by MiBP (weight = 0.12), MnBP (weight = 0.08), MEHP (0.07), and MEP (weight = 0.04) for depression scores. Our findings suggest that pregnant women with high exposure to phthalates are more likely to have higher depressive symptom scores. Full article

Experimental animal evidence and a growing body of observational studies suggest that prenatal exposure to phthalates may be a risk factor for childhood obesity. Using data from the Mount Sinai Children’s Environmental Health Study (MSCEHS), which measured urinary phthalate metabolites (including MEP, MnBP, MiBP, MCPP, MBzP, MEHP, MEHHP, MEOHP, and MECPP) during the third trimester of pregnancy (between 25 and 40 weeks) of 382 mothers, we examined adiposity outcomes—body mass index (BMI), fat mass percentage, waist-to-hip ratio, and waist circumference—of 180 children between ages 4 and 9. Our aim was to assess the effects of prenatal exposure to phthalates on these adiposity outcomes, with potential time-varying and sex-specific effects. We applied a novel Bayesian multivariate factor regression (BMFR) that (1) represents phthalate mixtures as latent factors—a DEHP and a non-DEHP factor, (2) borrows information across highly correlated adiposity outcomes to improve estimation precision, (3) models potentially non-linear time-varying effects of the latent factors on adiposity outcomes, and (4) fully quantifies uncertainty using state-of-the-art prior specifications. The results show that in boys, at younger ages (4–6), all phthalate components are associated with lower adiposity outcomes; however, after age 7, they are associated with higher outcomes. In girls, there is no evidence of associations between phthalate factors and adiposity outcomes. Full article

Background: The global rise in atopic diseases, like atopic dermatitis and allergic rhinitis, may be linked to prenatal exposure to endocrine-disrupting chemicals like phthalates, with potential sex-specific effects. Methods: We analyzed 558 mother–child pairs from the PROGRESS birth cohort in Mexico City. Maternal urinary phthalate metabolites were measured during the 2nd and 3rd trimesters. Atopic dermatitis and allergic rhinitis symptoms were assessed at ages 4–6 and 6–8 years using the International Study of Asthma and Allergies in Childhood survey. Weighted Quantile Sum Regression (WQS) was used to assess sex-specific mixture associations. Individual sex-specific phthalate associations were examined using modified Poisson models with inclusion of product terms and stratification. Models were adjusted for maternal age, education, parity, pre-pregnancy body mass index, and prenatal tobacco exposure. Results: We found that child sex modified associations between the 2nd trimester phthalate mixture and current atopic dermatitis symptoms at both 4–6 years (WQS*sex OR: 1.23, 95% CI: 1.00–1.60) and 6–8 years (WQS*sex OR: 1.46, 95% CI: 1.01–2.10). Among males, higher phthalate concentrations were positively associated with symptoms at both ages (OR: 1.10, 95% CI: 0.92, 1.32; OR: 1.16, 95% CI: 0.92, 1.46), while associations were negative in females (OR: 0.87, 95% CI: 0.73, 1.04; OR: 0.79, 95% CI: 0.62, 1.02). No sex-specific associations were found for 3rd trimester exposures. Individual metabolite analyses also showed effect modification by sex for 2nd trimester exposures. Conclusions: Prenatal exposure to phthalates is associated with atopic dermatitis symptoms in childhood in a sex-specific manner. Full article

Background: Environmental tobacco smoke (ETS) exposes adolescents to various environmental toxins, potentially affecting their developmental health. However, limited research exists on the associations between ETS exposure and the bodily burdens of environmental chemicals on adolescents. This study aimed to investigate the relationship between ETS exposure and the concentration of various environmental chemicals in adolescents, utilizing urinary cotinine as an objective biomarker. Methods: Data from 828 adolescents aged 12–17 years participating in the Korean National Environmental Health Survey (KoNEHS) were analyzed. ETS exposure was assessed via self-reported questionnaires and confirmed by urinary cotinine measurements. Levels of 33 environmental chemicals, including heavy metals, polycyclic aromatic hydrocarbons (PAHs), phthalates, phenols, volatile organic compounds (VOCs), and per- and polyfluoroalkyl substances (PFASs), were measured. Statistical analyses were conducted after adjusting for covariates. Results: Adolescents exposed to ETS showed significantly higher urinary cotinine and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) concentrations than non-exposed adolescents. Additionally, significant positive correlations were observed between urinary cotinine levels and metabolites of PAHs (NAP, OHFlu), phenols (BPA, BPS), phthalates (MMP), and VOCs (t,t-MA) after adjustments. However, ETS exposure was not significantly associated with heavy metal concentrations. Conclusions: This study described the association between ETS exposure and environmental chemicals. A trend has been identified between ETS exposure in adolescents and increased bodily concentrations of various environmental chemicals, including PAHs, phenols, phthalates, and VOCs. As adolescence is a critical developmental period of vulnerability to environmental toxins, reducing ETS exposure to protect adolescents’ health and prevent potential lifelong health effects should be emphasized. This study was based on a cross-sectional design, and some confounding factors and measurement limitations may exist. Therefore, caution is needed in interpreting causality, and further research is recommended to determine more precise causality and long-term health effects. Full article

Background/Objectives: Phthalates are endocrine-disrupting chemicals that are commonly used in plastic consumer products and food packaging, with growing evidence suggesting that they have a potential role in obesity. This study aimed to investigate the association between urinary concentrations of phthalate metabolites and both general and abdominal obesity among adult males in Spain. Methods: We analysed data from 1124 male participants of the Aragon Workers’ Health Study (AWHS) collected between 2011 and 2014 in Zaragoza, Spain. Eleven urinary phthalate metabolites were measured and adjusted for creatinine levels. Multivariate logistic regression models were used to evaluate associations between phthalate exposure and general and abdominal obesity, controlling for dietary and lifestyle factors. Dose–response relationships were explored using restricted cubic spline models. Results: Higher urinary concentrations of di(2-ethylhexyl) phthalate (∑DEHP) and two of its metabolites—mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)—were significantly associated with general obesity. The adjusted odds ratios were: ∑DEHP [OR = 1.26; 95% CI: 1.01, 1.58], MEOHP [OR = 1.24; 95% CI: 1.00, 1.53], and MEHHP [OR = 1.26; 95% CI: 1.03, 1.55]. In contrast, mono-isobutyl phthalate (MiBP) was inversely associated with abdominal obesity [OR = 0.73; 95% CI: 0.57, 0.93]. Conclusions: These findings suggest a positive association between exposure to DEHP and its metabolites and general obesity. This highlights the potential importance of environmental exposures as modifiable factors in obesity prevention and supports the need for further investigation in nutritional and public health contexts. Full article

Phthalates are widely used plasticizers that can leach from consumer products and pose potential health risks, particularly to infants whose developing systems are vulnerable to environmental toxicants. While various exposure pathways have been identified, the contribution of dermal absorption from disposable diapers remains inadequately characterized. This study recruited 66 infants from Guangzhou, a representative city in southern China. Paired disposable diaper and urine samples were collected from each participant. Six phthalates in the diapers and nine metabolites in the urine were quantitatively analyzed. The predominant phthalate detected in the diapers was bis-2-ethylhexyl phthalate (DEHP, with a median concentration of 1670 ng/g, range: 678–5200 ng/g), followed by di-n-butyl phthalate (DnBP, 948 ng/g, range: 189–5980 ng/g), di-iso-butyl phthalate (DiBP, 333 ng/g, range: 16.1–4910 ng/g), and diethyl phthalate (DEP, 252 ng/g, range: 116–3350 ng/g). In urine, metabolites of DEHP (mEHP, mEHHP, and mEOHP) were the most abundant (87.1 ng/mL), followed by mnBP (metabolites of DnBP, 44.6 ng/mL), mEP (metabolites of DEP, 33.7 ng/mL), and miBP (metabolites of DiBP, 13.9 ng/mL). A positive correlation was observed between DnBP levels in diapers and mnBP levels in urine (r = 0.259, p = 0.035). Additionally, several urinary metabolites (miBP, mnBP, and mEP) were positively associated with a biomarker of DNA oxidative damage, 8-hydroxydeoxyguanosine (r = 0.265–0.316, p < 0.01). The estimated daily uptake of DEP, DiBP, DnBP, and DEHP through dermal absorption from diapers accounted for 44.9%, 19.5%, 15.1%, and 7.76% of total exposure to these phthalates, respectively. These findings suggest that dermal absorption from diapers is a significant exposure pathway for infants. Given that both the amount of exposure and the contribution of dermal uptake are higher in younger infants, further attention is warranted to understand the potential effects of transdermal phthalate exposure on infant growth and development. Full article

The plastic manufacturing industry has a crucial role in the global economy with a significant impact in a wide range of fields. The chemical risk to which workers are potentially exposed is difficult to characterize and strictly related to both the products and processes adopted. Among the chemicals used, we can cite styrene, phenol, butadiene and phthalates, but nano- and microplastic particles can also be released in the work environment. In this pilot study, we present for the first time an NMR-based metabolomic approach for assessing urinary profiles of workers employed in a plastic manufacturing company. Urine samples from twelve workers and thirteen healthy volunteers were collected and analyzed by NMR spectroscopy. Forty-six urinary metabolites belonging to different chemical classes were univocally identified and quantified. The dataset so obtained was then subjected to multivariate statistical analysis to characterize each profile and highlight any differences. An alteration in some metabolites involved in several pathways, such as amino acid metabolism and NAD metabolism, was found, and a strong impact on gut microflora was also speculated. Ultimately, our work has the objective of adding a tile to the knowledge of biological effects possibly related to occupational exposure even if it is below the threshold limit values. Full article

Background: Humans are consistently and increasingly exposed to phthalate products, but the effect of the combined exposure to phthalates on myocardial injury remains largely unexplored. The present study aimed to explore the effect of the combined exposure to phthalates on myocardial injury. Methods: A total of 1237 male adults (aged ≥20) without coronary artery disease (CAD) from the National Health and Nutrition Examination Survey (NHANES) in 1999–2004 were included in the current study. Multiple linear regression, Bayesian kernel machine regression (BKMR), and a weighted quantile sum (WQS) model were employed to examine the associations of urinary phthalate metabolites with two cardiac injury biomarkers, including troponin T (TNT) and troponin I, using four highly sensitive assays (Abbott, Chicago, IL, USA; Siemens, Erlangen, Germany; and Ortho, Raritan, NJ, USA) (TNIA, TNIS, TNIO). Results: According to the linear regression analysis, mono-(3-carboxypropyl) phthalate (MCPP, a metabolite of di-n-octyl phthalate) was found to be positively associated with serum TNT; a positive association was found between mono-isobutyl phthalate (MiBP, a metabolite of di-isobutyl phthalate) and TNIA, as well as MiBP and TNIS. Mono-benzyl phthalate (MBzP, a metabolite of butyl benzyl phthalate) and MCPP were positively associated with serum TNIO. The BKMR analyses showed a positive overall relationship of serum TNT, TNIA, TNIS, and TNIO with increased concentrations of phthalate metabolites. The WQS model showed MCPP and MBzP were the top two contributors to being an increased risk for elevated TNT levels. MCPP and mono-ethyl phthalate (MEP, a metabolite of diethyl phthalate) were identified as the leading contributors to increased TNIA and TNIS. MCPP and MBzP were the dominant contributors to elevated TNIO. Conclusions: As a combined mixture, phthalate metabolites were positively associated with serum TNT and TNI among adults without CAD, indicating the potential toxic effect of phthalate exposure on cardiac injury. Full article

Background: Daily-use products, including personal care products, household products, and dietary supplements, often contain ingredients that raise concerns regarding harmful chemical exposure. Endocrine-disrupting chemicals (EDCs) found in daily-use products are associated with numerous adverse health effects. Methods: This pilot study explores the relationship between concentrations of EDCs in urine samples and products used 24 h prior to sample collection, and ingredients of concern in those products, in 140 adults of reproductive age in Northern Nevada. Results: Having higher numbers of products and ingredients of concern, especially in the personal care category, was associated with higher levels of mono-(-ethyl-5-carboxypentyl) phthalate (MECPP). Similarly, taking more supplements was associated with higher levels of methylparaben (MePB). In contrast, using household products with more ingredients of concern was associated with lower levels of monobutyl phthalate (MBP). Generally, women used more products, were exposed to more ingredients of concern and had higher urinary metabolites than men. Participants who rated themselves as being in poor/fair health were exposed to more personal care and supplement ingredients of concern than those in better health. Interestingly, those in excellent health also took supplements with more ingredients of concern. Conclusions: Greater product use and more ingredients of concern are associated with urinary metabolites of known EDCs and self-ratings of poor health. Women and people who take supplements are at greater risk, and even people who consider themselves to be healthy can be highly exposed. More education among the general public is needed to make people aware of the presence of these chemicals in their everyday products so they can make efforts to avoid them. Full article

Phthalates are widely used chemicals with ubiquitous human exposure. Evidence indicated that phthalate exposure was associated with an increased risk of aging-related diseases. Klotho is a transmembrane protein with anti-aging functions, and its association with phthalates remains unknown. To find the association between phthalate exposure and serum α-Klotho, a cross-sectional study was performed in 4482 adults (40–79 years old) who completed the National Health and Nutrition Examination Survey (NHANES) (2007–2016). As shown in the results of multivariable linear regression analyses, mono(carboxynonyl) phthalate (MCNP) and mono-n-butyl phthalate (MBP) were inversely associated with α-Klotho, and the regression coefficients of MCNP and MBP were −1.14 (95% confidence interval (CI): −2.00, −0.27) and −0.08 (95% CI: −0.14, −0.02). Subgroup analyses based on the quartiles of each phthalate metabolite showed that both MCNP and MBP were only inversely associated with α-Klotho in the subgroups of the highest levels. For mono-isobutyl phthalate (MIBP), the inverse association with α-Klotho was only statistically significant in the subgroup of the lowest level, and the regression coefficient was −26.87 (95% CI: −52.53, −1.21). Our findings suggest that α-Klotho might be involved in the association of phthalate exposure with aging-related diseases. Future research investigating the causality between phthalates and α-Klotho and its underlying mechanisms is encouraged. Full article

Development is a continuous process, but few studies have assessed the simultaneous impact of prenatal and postnatal phthalate exposure on children’s behavioral and emotional development. A total of 491 mother–child pairs from the general population in southern Taiwan were studied from 2021 to 2022. Urinary concentrations of bisphenol A (BPA) and phthalate metabolites—mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), mono-benzyl phthalate (MBzP), and mono-2-ethylhexyl phthalate (MEHP)—were measured in pregnant mothers during the second trimester and in their corresponding children aged 1.5 to 3 years. Behavioral symptoms in children were evaluated using the Child Behavior Checklist (CBCL). Odds ratios (ORs) represent a 1-unit increase in log10-transformed creatinine-corrected maternal urine concentrations. Prenatal maternal urinary MnBP levels were associated with total problems (OR = 19.32, 95% CI: 1.80–43.13, p = 0.04), anxiety (OR = 33.58, 95% CI: 2.16–521.18, p = 0.01), and sleep problems (OR = 41.34, 95% CI: 1.04–1632.84, p = 0.04) in children. Additionally, urinary MnBP levels in children correlated with total problems (OR = 7.06, 95% CI: 1.01–49.05, p = 0.04) and internalizing problems (OR = 11.04, 95% CI: 1.27–95.72, p = 0.01). These findings suggest that prenatal and postnatal exposure to dibutyl phthalate (DBP), metabolized as MnBP, distinctly affects children’s behavioral development. Full article

Based on toxicological evidence, children’s exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6–12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children’s total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS—IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: −8.8%; 95% CI: −16.7, −0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children’s exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a “urine concentration bias” that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations. Full article

We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005–2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (−0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (−0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (−0.26, 0.75) and 0.35 (−0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (−0.06, 0.07) and 0.00 (−0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings. Full article