Phthalate Concentrations Research Articles

Quality and stability studies of red blood cell concentrates from umbilical cord blood compared to their adult counterparts.

Prematurity is a significant health issue due to its incidence and associated complications. Anemia is common in extremely preterm infants (EPI) and often requires transfusions. Red blood cells (RBC) from adult blood (AB) donors have been linked to oxygen-related complications in EPI, leading to the exploration of cord blood (CB) as an alternative source. However, standardization of CB-RBC manufacturing and comparison with AB-RBC characteristics are necessary before clinical studies can be conducted. This study investigated the quality and characteristics of leukoreduced, gamma-irradiated CB-RBC obtained using a commercial closed system from CB donations not meeting hematopoietic transplantation criteria. CB-RBC units were compared with AB-RBC units, both stored in saline-adenine-glucose-mannitol (SAGM). Various parameters, including hematological and biochemical characteristics, pH, 2,3-DPG levels, blood gases and potential toxicants, were evaluated during storage. CB-RBC units had acceptable initial quality parameters and a hematocrit (55±2%) comparable to AB-RBC. The main finding during storage was a faster rise in hemolysis compared to AB-RBC. Potassium (K+) significantly increased during storage in both sources. As expected, glucose levels decreased, and conversely, lactate levels increased, indicating similar patterns of anaerobic glycolysis during storage. pH decreased, affecting the oxygen dissociation curve due to reduced 2,3-DPG levels. After irradiation at 14 days of storage, CB-RBC were less stable as hemolysis and K+ significantly increased compared to AB-RBC at 24 hours. Phthalate concentrations, indicative of plasticizers, increased during storage, but significantly less in CB compared to AB-RBC. Most metals measured were within acceptable ranges. The quality of CB-RBC during storage is primarily influenced by levels of hemolysis and extracellular K+ content. Based on the analyzed parameters, we suggest that the expiration date for CB-RBC stored with SAGM should be set at 14 days, with transfusion occurring within <24 hours after irradiation.

Urinary concentrations of phthalate/DINCH metabolites and body mass index among European children and adolescents in the HBM4EU Aligned Studies: A cross-sectional multi-country study

BackgroundPhthalates are ubiquitous in the environment. Despite short half-lives, chronic exposure can lead to endocrine disruption. The safety of phthalate substitute DINCH is unclear. ObjectiveTo evaluate associations between urinary concentrations of phthalate/DINCH metabolites and body mass index (BMI) z-score among children and adolescents. MethodWe used Human Biomonitoring for Europe Aligned Studies data from 2876 children (12 studies, 6–12 years, 2014–2021) and 2499 adolescents (10 studies, 12–18 years, 2014–2021) with up to 14 phthalate/DINCH urinary metabolites. We used multilevel linear regression to assess associations between phthalate/DINCH concentrations and BMI z-scores, testing effect modification by sex. In a subset, Bayesian kernel machine regression (BKMR) and quantile-based g-computation assessed important predictors and mixture effects. ResultsIn children, we found few associations in single pollutant models and no interactions by sex (p-interaction > 0.1). BKMR detected no relevant exposures (posterior inclusion probabilities, PIPs < 0.25), nor joint mixture effect. In adolescent single pollutant analysis, mono-ethyl phthalate (MEP) concentrations were associated with higher BMI z-score in males (β = 0.08, 95 % CI: 0.001,0.15, per interquartile range increase in ln-transformed concentrations, p-interaction = 0.06). Conversely, mono-isobutyl phthalate (MiBP) was associated with a lower BMI z-score in both sexes (β = -0.13, 95 % CI: −0.19, −0.07, p-interaction = 0.74), as was sum of di(2-ethylhexyl) phthalate (∑DEHP) metabolites in females only (β = -0.08, 95 % CI: −0.14, −0.02, p-interaction = 0.01). In BKMR, higher BMI z-scores were predicted by MEP (PIP=0.90) and MBzP (PIP=0.84) in males. Lower BMI z-scores were predicted by MiBP (PIP=0.999), OH-MIDP (PIP=0.88) and OH-MINCH (PIP=0.72) in both sexes, less robustly by DEHP (PIP=0.61) in females. In quantile g-computation, the overall mixture effect was null for males, and trended negative for females (β = -0.11, 95 % CI: −0.25, 0.03, per joint exposure quantile). ConclusionIn this large Europe-wide study, we found age/sex-specific differences between phthalate metabolites and BMI z-score, stronger in adolescents. Longitudinal studies with repeated phthalate measurements are needed.

Association between phthalates exposure and myocardial damage in the general population: A cross-sectional study

BackgroundCardiovascular consequences of phthalates exposure have been given increasing attention, but the association of phthalates with subclinical cardiovascular disease (CVD) was unknown. Accordingly, this study aimed to investigate the association between phthalates exposure and high-sensitivity cardiac troponin I (hs-cTnI), a marker of myocardial injury, which was detectable in the subclinical stage of CVD. MethodsParticipants aged 6 years or older with available urinary phthalates metabolites and serum hs-cTnI concentrations were included in the National Health and Nutrition Examination Survey 2003–2004 cycle. Multivariable linear regression and weighted quantiles sum (WQS) regression were used to assess the association of hs-cTnI with individual phthalates and their co-exposure. Di-2-ethylhexylphthalate (ΣDEHP), high-molecular-weight phthalate (ΣHMWP), and low-molecular-weight phthalate (ΣLMWP) were defined as the molecular sum of phthalates metabolites in urine. Results2241 participants were finally included. The percent change of serum hs-cTnI concentrations related to per 1-standard deviation increase of logarithmic urinary phthalates concentrations was 3.4% (0.1–6.7, P = 0.04) for ΣDEHP, 3.6% (0.3–6.9, P = 0.03) for ΣHMWP, and 3.5% (0.2–6.8, P = 0.04) for ΣLMWP. Co-exposure to phthalates metabolites expressed as the WQS index also demonstrated a positive association with hs-cTnI. A similar association pattern was found in the population with no prior CVD. ConclusionsThis study indicated the potential of phthalates to myocardial injury which may occur even before clinically apparent CVD was identified, emphasizing the significance of reducing phthalates in the prevention of CVD.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age

In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations. Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences-0.07 (95% CI -0.13,-0.02),-0.09 (-0.15,-0.02),-0.08 (95% CI -0.14,-0.02), and-0.08 (-0.13,-0.03) μg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

Phthalate esters in water and sediment of Asunle stream of Obafemi Awolowo University, Ile-Ife, Nigeria: Distribution and human health risks

This study determined the concentrations and seasonal variations of phthalate esters (PAEs) in water and sediment samples of the receiving stream within the vicinity of the Obafemi Awolowo University, Ile-Ife dumpsite. The objective of this study was to evaluate the pollution status of the study area by determining the levels of PAEs in water and sediment samples. This assessment aimed to understand the presence and extent of phthalate ester pollution in the study area. Water and sediment samples were collected from six selected stations along the receiving stream for analysis that included one upstream and five downstream points for four months during both wet season and dry season. The liquid-liquid extraction (LLE) method was employed to extract PAEs from the water samples collected, while microwave extraction method was optimized for their extraction in sediment samples. Quantification of the PAEs was conducted using Gas Chromatography coupled with a quadrupole Mass Spectrometer (GC-MS) in this study. The mean concentration of phthalates varied in the water and sediment samples. In the water samples, the phthalate concentrations ranged from 1.88 ± 0.16 μg/L for diethyl phthalate to 15.74 ± 0.33 μg/L for di(2-ethylhexyl phthalate) (DEHP). Also, butylbenzyl phthalate and DEHP will pose potential carcinogenic risks when used for bathing and drinking purposes, due to their relatively higher carcinogenic risk values. In the sediment samples, the concentrations ranged from 0.09 ± 0.02 mg/kg for dimethyl phthalate to 14.27 ± 1.76 mg/kg for di(2-ethylhexyl phthalate). The seasonal variation analysis of PAE congeners revealed that higher levels were observed during the dry season in the collected samples. The study concluded that the stream was heavily contaminated with di(-2-ethylhexyl)phthalate at levels that gave cause for human health and environmental concerns.

Gestational exposure to environmental chemicals and epigenetic alterations in the placenta and cord blood mononuclear cells

BackgroundExposure to environmental chemicals such as phthalates, phenols, and polycyclic aromatic hydrocarbons (PAHs) during pregnancy can increase the risk of adverse newborn outcomes. We explored the associations between maternal exposure to select environmental chemicals and DNA methylation in cord blood mononuclear cells (CBMC) and placental tissue (maternal and fetal sides) to identify potential mechanisms underlying these associations.MethodThis study included 75 pregnant individuals who planned to give birth at the University of Cincinnati Hospital between 2014 and 2017. Maternal urine samples during the delivery visit were collected and analyzed for 37 biomarkers of phenols (12), phthalates (13), phthalate replacements (4), and PAHs (8). Cord blood and placenta tissue (maternal and fetal sides) were also collected to measure the DNA methylation intensities using the Infinium HumanMethylation450K BeadChip. We used linear regression, adjusting for potential confounders, to assess CpG-specific methylation changes in CBMC (n = 54) and placenta [fetal (n = 67) and maternal (n = 68) sides] associated with gestational chemical exposures (29 of 37 biomarkers measured in this study). To account for multiple testing, we used a false discovery rate q-values < 0.05 and presented results by limiting results with a genomic inflation factor of 1±0.5. Additionally, gene set enrichment analysis was conducted using the Kyoto Encyclopedia of Genes and Genomics pathways.ResultsAmong the 29 chemical biomarkers assessed for differential methylation, maternal concentrations of PAH metabolites (1-hydroxynaphthalene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 1-hydroxypyrene), monocarboxyisononyl phthalate, mono-3-carboxypropyl phthalate, and bisphenol A were associated with altered methylation in placenta (maternal or fetal side). Among exposure biomarkers associated with epigenetic changes, 1-hydroxynaphthalene, and mono-3-carboxypropyl phthalate were consistently associated with differential CpG methylation in the placenta. Gene enrichment analysis indicated that maternal 1-hydroxynaphthalene was associated with lipid metabolism and cellular processes of the placenta. Additionally, mono-3-carboxypropyl phthalate was associated with organismal systems and genetic information processing of the placenta.ConclusionAmong the 29 chemical biomarkers assessed during delivery, 1-hydroxynaphthalene and mono-3-carboxypropyl phthalate were associated with DNA methylation in the placenta.

Urinary metabolite concentrations of phthalate and plasticizers in infancy and childhood in the UNC baby connectome project

IntroductionExisting evidence suggests that exposure to phthalates is higher among younger age groups. However, limited knowledge exists on how phthalate exposure, as well as exposure to replacement plasticizers, di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHTP), change from infancy through early childhood. MethodsUrine samples were collected across the first 5 years of life from typically developing infants and young children enrolled between 2017 and 2020 in the longitudinal UNC Baby Connectome Project. From 438 urine samples among 187 participants, we quantified concentrations of monobutyl phthalate (MnBP), mono-3-carboxypropyl phthalate (MCPP), monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), and metabolites of di(2-ethylhexyl) phthalate (DEHP), diisonoyl phthalate (DiNP), DINCH and DEHTP. Specific gravity (SG) adjusted metabolite and molar sum concentrations were compared across age groups. Intraclass correlation coefficients (ICCs) were calculated among 122 participants with multiple urine specimens (373 samples). ResultsMost phthalate metabolites showed high detection frequencies (>80% of samples). Replacement plasticizers DINCH (58–60%) and DEHTP (>97%) were also commonly found. DiNP metabolites were less frequently detected (<10%). For some metabolites, SG-adjusted concentrations were inversely associated with age, with the highest concentrations found in the first year of life. ICCs revealed low to moderate reliability in metabolite measurements (ρ = 0.10–0.48) suggesting a high degree of within-individual variation in exposure among this age group. The first 6 months (compared to remaining age groups) showed an increased ratio of carboxylated metabolites of DEHP and DEHTP, compared to other common metabolites, but no clear age trends for DINCH metabolite ratios were observed. ConclusionMetabolites of phthalates and replacements plasticizers were widely detected in infancy and early childhood, with the highest concentrations observed in the first year of life for several metabolites. Higher proportions of carboxylated metabolites of DEHP and DEHTP in younger age groups indicate potential differences in metabolism during infancy.

Association between prenatal phthalate exposure and ano-genital indices among offsprings in an Israeli cohort

BackgroundIn-utero phthalate exposure was shown to be associated with shortened anogenital distance (AGD) in male newborns, but findings among female are inconsistent. While phthalate exposure among pregnant women in Israel is widespread, no study has examined the association with offspring AGD. The objective of the current study was to investigate the association between maternal phthalates urinary concentration and offspring AGD at time of delivery among a birth cohort in Israel. MethodsWe measured spot urinary concentration of monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexylphthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP) among women presenting to the delivery room at Shamir Medical Center in Israel. Birthweight, length and AGD were measured in all newborns using a standardized protocol. Each AGD measurement was adjusted to weight (ano-genital index). Confounders included socio-demographic characteristics, comorbidities and obstetrical history. Univariate and multivariate analyses assessed the associations between phthalates, confounders and AGD. ResultsOverall, 193 mother and infant were analyzed. All newborns were born at term and had normal Apgar scores. Mean maternal age was 32 ± 4.7 years old. Mean birth weight and pregnancy week were 3183 ± 498 g and 39 ± 1.3, respectively. Median (IQR) urinary phthalate concentration adjusted to creatinine (ug/g) were 3.96 (2.2–6.6), 1.22 (0.7–2), 10.84 (7–20.4), 6.36 (3.3–11.2) and 0.64 (0.4–1.1) for MBP, MBzP, MECPP, MEHHP and MEOHP, respectively. Univariate comparison showed a significant association between higher than median MBzP concentration, higher Ano-Fourchetal index (AFI: 4.4 vs. 4.1, p = 0.037) and Ano-clitoral index (ACI: 11.5 vs. 10.4, p = 0.032) in infants. Total urinary phthalates concentration ≥26.25 μg/g was significantly associated with smaller penile width index (3.5 vs. 3.7, p = 0.022), higher ACI (11.6 vs. 10.3, p = 0.013) and a trend towards significance for higher AFI (4.3 vs. 4.1, p = 0.055). Following multivariate linear regression only PWI remained significantly associated with total phthalate urinary concentration. ConclusionsMaternal urinary phthalates concentration at delivery were not associated with female AGD, but total urinary phthalate concentration were inversely associated with penile width.

Silicone wristbands reveal ubiquitous human exposure to ortho-phthalates and non-ortho-phthalate plasticizers in Southern California

In the United States and abroad, ortho-phthalates and non-ortho-phthalate plasticizers continue to be used within a diverse array of consumer products. Prior California-specific biomonitoring programs for ortho-phthalates have focused on rural, agricultural communities and, to our knowledge, these programs have not measured the potential for exposure to non-ortho-phthalate plasticizers. Therefore, the potential for human exposure to ortho-phthalates and non-ortho-phthalate plasticizers have not been adequately addressed in regions of California that have higher population density. Since there are numerous sources of ortho-phthalates and non-ortho-phthalate plasticizers in population-dense, urban regions, the objective of this study was to leverage silicone wristbands to quantify aggregate ortho-phthalate and non-ortho-phthalate plasticizer exposure over a 5-day period across two different cohorts (2019 and 2020) of undergraduate students at the University of California, Riverside (UCR) that commute from all over Southern California. Based on 5 d of aggregate exposure across two different cohorts, total ortho-phthalate plus non-ortho-phthalate plasticizer concentrations ranged, on average, from ∼100,000–1,000,000 ng/g. Based on the distribution of individual ortho-phthalate and non-ortho-phthalate plasticizer concentrations, the concentrations of di-isononyl phthalate (DiNP, a high molecular weight ortho-phthalate), di (2-ethylhexyl) phthalate (DEHP, a high molecular weight ortho-phthalate), and di-2-ethylhexyl terephthalate (DEHT, a non-ortho-phthalate plasticizer) detected within wristbands were higher than the remaining seven ortho-phthalates and non-ortho-phthalate plasticizers measured, accounting for approximately 94–97% of the total mass depending on the cohort. Overall, our findings raise concerns about chronic DiNP, DEHP, and DEHT exposure in urban, population-dense regions throughout California.

Household indoor air quality in northeast China: On-site inspection and measurement in 399 Tianjin area residences

There has been an increased concern on indoor air quality (IAQ) in residences since the majority of individuals’ time is mainly spent indoors. We inspected and measured indoor environmental parameters in 399 homes in northeast China in order to study IAQ. We systematically measured multilevel environmental parameters (physical, chemical, and biological) in children’s bedrooms during all seasons. The results indicated that the median values for indoor temperature, relative humidity, total volatile organic compounds (TVOC), and formaldehyde concentrations throughout the year were within the Chinese national standards. However, the median carbon dioxide concentrations exceeded 1000 ppm during spring, autumn, and winter. In the same seasons, the air change rate (ACR) was below the minimum required level of 0.5 h−1. Di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP) were predominantly detected in settled dust, displaying median concentrations of 126.9, 41.5, and 16.3 μg/g, respectively. Notably, phthalate concentrations were significantly higher in urban houses as compared to rural houses. Furthermore, median concentrations of Dermatophagoides farinae (Der f) and endotoxin were 689.4 ng/g and 3689.1 EU/g, respectively, trending higher in winter than summer. There was a negative correlation between ACR and chemical pollutants (TVOC, formaldehyde, and DiBP). In conclusion, northeast Chinese homes had poor indoor air quality with ubiquitous exposure to modern chemical compounds and insufficient ventilation.

Associations of prenatal exposure to phthalates and their mixture with lung function in Mexican children

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children’s lung function was evaluated at ages 8–13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (β = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (β = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, β = −0.017, 95 %CI: −0.066, 0.026; FVC, β = −0.014, 95 %CI: −0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.

Hair product use and urinary biomarker concentrations of non-persistent endocrine disrupting chemicals among reproductive-aged Black women

BackgroundStudies have shown an association between hair product use and adverse health outcomes. Scientists have hypothesized that exposure to endocrine-disrupting chemicals (EDCs) drives these associations, but few studies have directly evaluated associations between hair product use and biomarkers of EDCs. Even more limited are studies of Black women, who frequently use EDC-containing products (e.g., hair relaxers). ObjectiveWe estimated associations between hair product use and EDC biomarker concentrations. MethodsWe leveraged cross-sectional data from the Study of Environment, Lifestyle, and Fibroids, a cohort of females aged 23–34 years who self-identified as Black/African American from the Detroit-metropolitan area (USA; n = 425). On structured questionnaires, participants reported their past 24-h and past 12-month use of hair products, including relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food. We quantified urinary concentrations of 19 phthalate/phthalate alternative metabolites, 7 phenols, and 4 parabens using high performance liquid chromatography isotope dilution tandem mass spectrometry. EDC biomarker concentrations were creatinine-adjusted and natural log-transformed. We used multivariable linear regression to estimate mean percent differences in EDC biomarker concentrations and 95% confidence intervals (CIs) associated with hair product use, adjusting for sociodemographic confounders. ResultsHair product use was associated with greater concentrations of multiple EDC biomarkers. Notably, use of hair products in the previous 24 h (compared with non-use) was associated with 16.2% (95% CI = 0.7%, 35.9%), 35.0% (95% CI = 2.6%, 77.6%), and 32.3% (95% CI = 8.8%, 92.0%) higher concentrations of mono-isobutyl phthalate, methyl paraben, and ethyl paraben, respectively. Use of hair relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food in the past 12 months was also associated with higher concentrations of multiple phthalate, phenol, and paraben biomarkers. ConclusionHair product use was associated with higher biomarker concentrations of multiple phthalates, phenols, and parabens. These findings suggest that hair products are potentially important exposure sources for hormonally-active chemicals among Black women.

Freshwater water quality criteria for phthalate esters and recommendations for the revision of the water quality standards

With increasing urbanization and rapid industrialization, more and more environmental problems have arisen. Phthalates (PAEs) are the foremost and most widespread plasticizers and are readily emitted from these manufactured products into the environment. PAEs act as endocrine-disrupting chemicals (EDCs) and can have serious impacts on aquatic organisms as well as human health. In this study, the water quality criteria (WQC) of five PAEs (dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP) and di(2-ethylhexyl) phthalate (DEHP)) for freshwater aquatic organisms were developed using a species sensitivity distribution (SSD) and a toxicity percentage ranking (TPR) approach. The results showed that long-term water quality criteria (LWQC) of PAEs using the SSD method could be 13.7, 11.1, 2.8, 7.8, and 0.53 μg/L, respectively. Criteria continuous concentrations (CCC) of PAEs were derived using the TPR method and determined to be 28.4, 13.1, 1.3, 2.5, and 1.6 μg/L, respectively. The five PAEs are commonly measured in China surface waters at concentrations between ng/L and μg/L. DBP, DEHP, and di-n-octyl phthalate (DnOP) were the most frequently detected PAEs, with occurrence rates ranging from 67% to 100%. The ecological risk assessment results of PAEs showed a decreasing order of risk at the national level, DEHP, DBP, DMP, DEP, DnOP. The results of this study will be of great benefit to China and other countries in revising water quality standards for the conservation of aquatic species.

#1053 The exposure of phthalates and alternative plasticizers among chronic kidney disease patients during COVID-19 pandemic

Abstract Background and Aims Phthalates are widely used in many consumer products as plasticizer and well known to be detrimental to human health. Phthalates mainly disrupt the endocrine system. Recently, phthalate exposures are revealed to be associated with decreased kidney function and increased albuminuria. Risk perception levels and behavioral patterns of CKD patients have been changing with COVID-19 pandemic. However, the effect of these changes on the environmental chemical exposures has not been investigated. We aimed to investigate the environmental chemical phthalates and alternative plasticizer exposure levels during COVID-19 pandemic among CKD patients. Method We analyzed the data from a study with a prospective cohort of CKD patient, namely the Study on Kidney disease and EnviromenTal CHemicals (SKETCH, Clinical Trial No. NCT04679168). This cohort included patients with CKD who visited the participating hospitals for the first time between June and October 2020 and followed up to December 2022. Demographic data, behavioral characteristics including hygienic behavior and social distancing, and laboratory data were collected prospectively. Thirty-seven metabolites from 9 light phthalates, 12 heavy phthalates, and 16 alternative plasticizers were measured in urine samples. Results The level of light phthalates and alternative plasticizers during the COVID-19 pandemic significantly increased, and heavy phthalates concentrations decreased compared to the pre-pandemic levels. During the 1-year follow-up period, the level of risk perception for infectious disease including COVID-19 significantly decreased. During the 1-yr pandemic period, light phthalate levels decreased for the first 6-month period, and significantly increased for the second 6-month. Heavy phthalates levels were decreased steadily. However, alternative plasticizer levels were maintained during the 1-yr follow-up period. Heavy phthalates levels were significantly higher in the higher risk perception group. However, heavy phthalates levels were not different according to the behavioral patterns. In contrast, the levels of light phthalates and alternative plasticizers were not different according to either behavioral strengthening or risk perception. Conclusion COVID-19 pandemic was associated with decreased exposure of heavy phthalates and increased exposure of light phthalates and alternative plasticizers. During the COVID-19 pandemic, levels of light phthalate exposures initially decreased at first 6-month period and gradually increased. This trend of environmental chemicals exposure might be associated with the change of risk perception levels.

High concentrations of phthalates affect the early development of the sea urchin Paracentrotus lividus

The toxicity of three phthalates (PAEs) - butylbenzyl phthalate (BBP), diethyl phthalate (DEP), and di-(2-ethylhexyl) phthalate (DEHP) - was tested on the Mediterranean sea urchin Paracentrotus lividus. Fertilized eggs were exposed to environmental and high PAE concentrations for 72 h. The potential toxic effects on larval development and any morphological anomalies were then assessed to estimate PAEs impact. Environmental concentrations never affected development, while high concentrations induced toxic effects in larvae exposed to BBP (EC50: 2.9 ×103 µg/L) and DEHP (EC50: 3.72 ×103 µg/L). High concentrations caused skeletal anomalies, with a slight to moderate impact for DEP/DEHP and BBP, respectively. PAE toxicity was: BBP>DEHP>DEP. In conclusion, the three PAEs at environmental concentrations do not pose a risk to sea urchins. However, PAE concentrations should be further monitored in order not to constitute a concern to marine species, especially at their early developmental stages.

Mechanistic screening of reproductive toxicity in a novel 3D testicular co-culture model shows significant impairments following exposure to low-dibutyl phthalate concentrations

To improve the mechanistic screening of reproductive toxicants in chemical-risk assessment and drug development, we have developed a three-dimensional (3D) heterogenous testicular co-culture model from neonatal mice. Di-n-butyl phthalate (DBP), an environmental contaminant that can affect reproductive health negatively, was used as a model compound to illustrate the utility of the in vitro model. The cells were treated with DBP (1 nM to 100 µM) for 7 days. Automated high-content imaging confirmed the presence of cell-specific markers of Leydig cells (CYP11A1 +), Sertoli cells (SOX9 +), and germ cells (DAZL +). Steroidogenic activity of Leydig cells was demonstrated by analyzing testosterone levels in the culture medium. DBP induced a concentration-dependent reduction in testosterone levels and decreased the number of Leydig cells compared to vehicle control. The levels of steroidogenic regulator StAR and the steroidogenic enzyme CYP11A1 were decreased already at the lowest DBP concentration (1 nM), demonstrating upstream effects in the testosterone biosynthesis pathway. Furthermore, exposure to 10 nM DBP decreased the levels of the germ cell-specific RNA binding protein DAZL, central for the spermatogenesis. The 3D model also captured the development of the Sertoli cell junction proteins, N-cadherin and Zonula occludens protein 1 (ZO-1), critical for the blood–testis barrier. However, DBP exposure did not significantly alter the cadherin and ZO-1 levels. Altogether, this 3D in vitro system models testicular cellular signaling and function, making it a powerful tool for mechanistic screening of developmental testicular toxicity. This can open a new avenue for high throughput screening of chemically-induced reproductive toxicity during sensitive developmental phases.

Assessment of Phthalate Esters and Physiological Biomarkers in Bottlenose Dolphins (Tursiops truncatus) and Killer Whales (Orcinus orca).

There is growing concern about the potential adverse health effects of phthalates (PAEs) on human health and the environment due to their extensive use as plasticizers and additives in commercial and consumer products. In this study, we assessed PAE concentrations in serum samples from aquarium-based delphinids (Tursiops truncatus, n = 36; Orcinus orca, n = 42) from California, Florida, and Texas, USA. To better understand the physiological effects of phthalates on delphinids, we also explored potential correlations between phthalates and the biomarkers aldosterone, cortisol, corticosterone, hydrogen peroxide, and malondialdehyde while accounting for sex, age, and reproductive stage. All PAEs were detected in at least one of the individuals. ΣPAE ranges were 5.995-2743 ng·mL-1 in bottlenose dolphins and 5.372-88,675 ng·mL-1 in killer whales. Both species displayed higher mean concentrations of DEP and DEHP. PAEs were detected in newborn delphinids, indicating transference via placenta and/or lactation. Linear mixed model results indicated significant correlations between aldosterone, month, location, status, and ΣPAEs in killer whales, suggesting that aldosterone concentrations are likely affected by the cumulative effects of these variables. This study expands on the knowledge of delphinid physiological responses to PAEs and may influence management and conservation decisions on contamination discharge regulations near these species.

The associations between pre-conception urinary phthalate concentrations, the serum metabolome, and live birth among women undergoing assisted reproduction

BackgroundPhthalates are ubiquitous endocrine disruptors. Past studies have shown an association between higher preconception urinary concentrations of phthalate metabolites and lower fertility in women; however, the biological mechanisms remain unclear. Our exploratory study aimed to understand the metabolites and pathways associated with maternal preconception phthalate exposure and examine if any may underline the association between phthalate exposure and live birth using untargeted metabolomics. MethodsParticipants (n = 183) were part of the Environment and Reproductive Health (EARTH) study, a prospective cohort that followed women undergoing in vitro fertilization (IVF) at the Massachusetts General Hospital Fertility Center (2005–2016). On the same day, women provided a serum sample during controlled ovarian stimulation, which was analyzed for metabolomics using liquid chromatography coupled with high-resolution mass spectrometry and two chromatography columns, and a urine sample, which was analyzed for 11 phthalate metabolites using targeted approaches. We used multivariable generalized linear models to identified metabolic features associated with urinary phthalate metabolite concentrations and live birth, followed by enriched pathway analysis. We then used a meet-in-the-middle approach to identify overlapping pathways and features. ResultsMetabolic pathway enrichment analysis revealed 43 pathways in the C18 negative and 32 pathways in the HILIC positive columns that were significantly associated (p < 0.05) with at least one of the 11 urinary phthalate metabolites or molar sum of di-2-ethylhexyl phthalate metabolites. Lipid, amino acid, and carbohydrate metabolism were the most common pathways associated with phthalate exposure. Five pathways, tryptophan metabolism, tyrosine metabolism, biopterin metabolism, carnitine shuttle, and vitamin B6 metabolism, were also identified as being associated with at least one phthalate metabolite and live birth following IVF. ConclusionOur study provides further insight into the metabolites and metabolomics pathways, including amino acid, lipid, and vitamin metabolism that may underlie the observed associations between phthalate exposures and lower fertility in women.

Characteristics of microplastics and their effects on phthalates and microbial activity in greenhouse soil after long-term planting

As an exogenous pollutant, the microplastics accumulated in soil could alter microbial activity. The use of plastic mulch in greenhouse vegetable planting not only enhances vegetable yield and quality, but also leads to the formation and accumulation of microplastics in the soil over time. It is essential to determine the characteristics of microplastics and microorganisms in soils with varying years of planting is crucial for ensuring vegetable quality and quantity. Therefore, this study investigated the abundance and particle size of microplastics, the concentration of phthalates (PAEs), and the dynamics of soil microbial activity in greenhouse soils with different planting years (5, 10, 15, 20, 25, and 30 years). Results showed that microplastics increased in abundance, particle size, and PAEs concentration as planting years progressed. Specifically, the abundance of microplastics rose from 70.0 ± 8.7 to 224.0 ± 10.4 items/kg, with the proportion of microplastics sized 0–2 mm increasing from 14.02 to 69.11 %, and the total PAEs concentration in the soil escalating from 0.31 to 1.89 mg/kg. Additionally, Bacteroidetes and Actinobacteria levels increased, correlating with organic matter degradation. Metabolic pathway linked to degradation were enriched according to KEGG analysis. Correlation analysis revealed that microplastics notably decreased soil pH, creating an acidic environment that boosted urease activity and the relative abundance of Nitrospirae. This study sheds light on the accumulation characteristics of microplastics and their impact on soil microbial activity following prolonged planting.

Dust dynamics: distribution patterns of semi-volatile organic chemicals across particle sizes in varied indoor microenvironments.

An extensive analysis of the distribution patterns of three distinct classes of semi-volatile organic chemicals (SVOCs)-phthalates (PAEs), organophosphate flame retardants (OPFRs), and polycyclic aromatic hydrocarbons (PAHs)-across four distinct size fractions of dust (25, 50, 100, and 200μm) was conducted. The dust samples were sourced from AC filter, covered car parking lots, households, hotels, mosques, and car floors. To generate the four fractions, ten dust samples from each microenvironment were pooled and sieved utilizing sieving apparatus with the appropriate mesh size. Selected SVOCs were quantified utilizing gas chromatography-mass spectrometry in electron impact (EI) mode. Results unveiled diverse contamination levels among dust fractions, showcasing car parking lot dust with the lowest chemical contamination, while car floor dust displayed the highest levels of PAHs and OPFRs, peaking at 28.3µg/g and 43.2µg/g, respectively. In contrast, mosque and household floor dust exhibited the highest concentrations of phthalates, with values of 985µg/g and 846µg/g, respectively. Across the analyzed microenvironments, we observed a trend where concentrations of SVOCs tended to rise as dust particles decreased in size, forming a visually striking pattern. This phenomenon was particularly pronounced in dust samples collected from car floors and parking lots. Among SVOCs, PAEs emerged as the predominant contributors with > 90% followed by OPFRs and PAHs. The high levels of OPFRs in car floor dust align logically with the fact that numerous interior components of cars are treated with OPFRs, within a compact indoor microenvironment, to comply to fire safety regulations. Furthermore, petroleum products are a major source of PAHs in the environment and all the sampled cars in the study had combustion engines. Consequently, car dust is more likely to be polluted with PAHs stemming from petroleum combustion. Although previous investigations have noted an increase in heavy metals and brominated flame retardants with decreasing dust particles, this is the first study analyzing these SVOCs in different fractions of dust from various microenvironments. However, aside from two specific microenvironments, the observed pattern of escalating SVOC concentrations with smaller dust particle sizes was not corroborated among the examined microenvironments. This divergence in concentration trends suggests the potential involvement of supplementary variables in influencing SVOC distributions within dust particles.