Prevalence and clinical implications of heightened plastic chemical exposure in pediatric patients undergoing cardiopulmonary bypass.

BACKGROUND: Phthalate chemicals are used to manufacture plastic medical products, including many components of cardiopulmonary bypass (CPB) circuits. We aimed to quantify iatrogenic phthalate exposure in pediatric patients undergoing cardiac surgery and examine the link between phthalate exposure and postoperative outcomes. STUDY DESIGN AND METHODS: The study included pediatric patients undergoing (n=122) unique cardiac surgeries at Children's National Hospital. For each patient, a single plasma sample was collected preoperatively and two additional samples were collected postoperatively upon return from the operating room and the morning after surgery. Concentrations of di(2-ethylhexyl) phthalate (DEHP) and its metabolites were quantified using ultra high-pressure liquid chromatography coupled to mass spectrometry. RESULTS: Patients were subdivided into three groups, according to surgical procedure: (1) cardiac surgery not requiring CPB support, (2) cardiac surgery requiring CPB with a crystalloid prime, and (3) cardiac surgery requiring CPB with red blood cells (RBCs) to prime the circuit. Phthalate metabolites were detected in all patients, and postoperative phthalate levels were highest in patients undergoing CPB with an RBC-based prime. Age-matched (<1 year) CPB patients with elevated phthalate exposure were more likely to experience postoperative complications. RBC washing was an effective strategy to reduce phthalate levels in CPB prime. DISCUSSION: Pediatric cardiac surgery patients are exposed to phthalate chemicals from plastic medical products, and the degree of exposure increases in the context of CPB with an RBC-based prime. Additional studies are warranted to measure the direct effect of phthalates on patient health outcomes and investigate mitigation strategies to reduce exposure.

Association of endocrine disrupting chemicals levels in serum, environmental risk factors, and hepatic function among 5- to 14-year-old children.

Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are critical for growth and development during childhood, however, the association among the exposure level of EDCs such as Nonylphenol (NP), Bisphenol A (BPA), Dimethyl phthalate (DMP) in children and environmental risk factors, as well as hepatic function has not been elaborated. This study aimed to discuss this interesting relationship among NP, BPA, DMP concentrations in serum, environmental risk factors, hepatic function of 5- to 14-year-old children in industrial zone, residential zone and suburb in northern district of Guizhou Province, China. In Zunyi city, 1006 children participated in cross-sectional health assessments from July to August 2018, and their parents completed identical questionnaires on the environmental risk factors of EDCs exposure to mothers and children. Serum NP, BPA and DMP concentrations were measured by high performance liquid chromatography (HPLC). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were detected with automatic biochemical analyzer. The median concentrations of serum NP, BPA, and DMP in the participants were 45.85 ng/mL, 26.31 ng/mL and 31.62 ng/mL, respectively, which were higher than the environmental concentration limits of the U.S. National Environmental Protection Agency (EPA). Hair gels used during pregnancy, types of domestic drinking water, nail polish and cosmetics used by children were significantly positive correlated with serum NP concentration (P < 0.05). Gender, feeding pattern, plastic water cup used during pregnancy, hair spray and perfume use for children, duration of children birth, materials for baby bottle or cup and ways to plastic products were significantly positively correlated with serum BPA concentration (P < 0.05). Gender, perms used during pregnancy, hair spray and perfume use for children, using plastic lunch box during pregnancy, duration of children birth, exposure to pesticides, parents' occupations were significantly positively correlated with serum DMP concentrations (P < 0.05). Serum NP (ß = 0.296, P = 0.036) and DMP (ß = 0.316, P = 0.026) concentrations and TBIL level were significantly positively correlated. Serum NP concentration and the levels of IBIL (ß = 0.382, P = 0.006) are significantly positively correlated. Cosmetics used during pregnancy significantly increased AST level (ß = 2.641, P = 0.021). There was a positive correlation between the frequency of hair spray and perfume use for children and the AST (ß = 4.241, P = 0.022). NP, BPA and DMP, which were commonly detected in the serum of children aged 5-14 years old in Zunyi City, Northern Guizhou Province, China, were closely related to the environmental risk factors of exposure environment during pregnancy, infancy and school age. Exposure to NP, BPA and DMP would have negative effects on hepatic function, and these effects showed differences in gender and geographical location. Notably,The relationships were more evident in girls than in boys.

Large-Scale Implementation and Flaw Investigation of Human Serum Suspect Screening Analysis for Industrial Chemicals.

Non-targeted analysis (NTA), including both suspect screening analysis (SSA) and unknown compound analysis, has gained increasing popularity in various fields for its capability in identifying new compounds of interests. Current major challenges for NTA SSA are that (1) tremendous effort and resources are needed for large-scale identification and confirmation of suspect chemicals and (2) suspect chemicals generally show low matching rates during identification and confirmation processes. To narrow the gap between these challenges and smooth implementation of NTA SSA methodology in the biomonitoring field, we present a thorough SSA workflow for the large-scale screen, identification, and confirmation of industrial chemicals that may pose adverse health effects in pregnant women and newborns. The workflow was established in a study of 30 paired maternal and umbilical cord serum samples collected at delivery in the San Francisco Bay area. By analyzing LC-HRMS and MS/MS data, together with the assistance of a combination of resources including online MS/MS spectra libraries, online in silico fragmentation tools, and the EPA CompTox Chemicals Dashboard, we confirmed the identities of 17 chemicals, among which monoethylhexyl phthalate, 4-nitrophenol, tridecanedioic acid, and octadecanedioic acid are especially interesting due to possible toxicities and their high-volume use in industrial manufacturing. Similar to other previous studies in the SSA field, the suspect compounds show relatively low MS/MS identification (16%) and standard confirmation (8%) rates. Therefore, we also investigated origins of false positive features and unidentifiable suspected features, as well as technical obstacles encountered during the confirmation process, which would promote a better understanding of the flaw of low confirmation rate and encourage gaining more effective tools for tackling this issue in NTA SSA.

Moderate Folic Acid Supplementation in Pregnant Mice Results in Altered Methyl Metabolism and in Sex-Specific Placental Transcription Changes.

SCOPE: Many pregnant women have higher folic acid (FA) intake due to food fortification and increased vitamin use. It is reported that diets containing five-fold higher FA than recommended for mice (5xFASD) during pregnancy resulted in methylenetetrahydrofolate reductase (MTHFR) deficiency and altered choline/methyl metabolism, with neurobehavioral abnormalities in newborns. The goal is to determine whether these changes have their origins in the placenta during embryonic development. METHODS AND RESULTS: Female mice are fed control diet or 5xFASD for a month before mating and maintained on these diets until embryonic day 17.5. 5xFASD led to pseudo-MTHFR deficiency in maternal liver and altered choline/methyl metabolites in maternal plasma (increased methyltetrahydrofolate and decreased betaine). Methylation potential (S-adenosylmethionine:S-adenosylhomocysteine ratio) and glycerophosphocholine are decreased in placenta and embryonic liver. Folic acid supplemented diet results in sex-specific transcriptome profiles in placenta, with validation of dietary expression changes of 29 genes involved in angiogenesis, receptor biology or neurodevelopment, and altered methylation of the serotonin receptor 2A gene. CONCLUSION: Moderate increases in folate intake during pregnancy result in placental metabolic and gene expression changes, particularly in angiogenesis, which may contribute to abnormal behavior in pups. These results are relevant for determining a safe upper limit for folate intake during pregnancy.

Integrating Intersectionality Into the Exposome Paradigm: A Novel Approach to Racial Inequities in Uterine Fibroids.

Intersectionality is a critical theoretical framework that emphasizes the influence of intersecting systems of oppression on the lived experiences of people marginalized by inequity. Although applications of intersectionality are increasing in public health, this framework is absent in environmental health, which has instead focused on the exposome, a paradigm that considers the totality of an individual's environmental exposures across the life course.Despite advancements in the biological complexity of exposome models, they continue to fall short in addressing health inequities. Therefore, we highlight the need for integrating intersectionality into the exposome. We introduce key concepts and tools for environmental health scientists interested in operationalizing intersectionality in exposome studies and discuss examples of this innovative approach from our work on racial inequities in uterine fibroids.Our case studies illustrate how interlocking systems of racism and sexism may affect Black women's exposure to environmental chemicals, their epigenetic regulation of uterine fibroids, and their clinical care. Because health relies on biological and social-structural determinants and varies across different intersectional positions, our proposed framework may be a promising approach for understanding environmental health inequities and furthering social justice.

Phthalate and Bisphenol Exposure during Pregnancy and Offspring Nonverbal IQ.

BACKGROUND: Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester. OBJECTIVE: We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age. METHOD: The study sample consisted of 1,282 mother-child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002-2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at <18, 18-25, and >25 wks of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test-Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy. RESULTS: Higher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular weight phthalates=-1.7 (95% CI: -3.1, -0.3)]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di-n-octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex. CONCLUSIONS: We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.

Use of stored serum in the study of time trends and geographical differences in exposure of pregnant women to phthalates.

BACKGROUND: Exposure to some phthalate diesters has been associated with adverse reproductive health outcomes in both rodents and humans indicative of anti-androgenic effects. Exposure during sensitive periods of development, such as prenatally, is of particular concern. OBJECTIVES: We wished to investigate whether phthalate metabolites measured in maternal serum samples from historical birth cohorts can be used to assess prenatal exposure. Further, we aimed to study temporal and geographical trends in phthalate exposure across three different birth cohorts. METHODS: We compared phthalate metabolite levels in maternal serum samples from an Australian (1989-91) and a Danish (1997-2001) birth cohort with levels in serum and urine samples from a recent Danish birth cohort (2012-14). Samples were analysed for 32 phthalate metabolites from 15 phthalate diesters by isotope-diluted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Correlations between metabolites were tested by Spearman rank correlation test, and differences between the cohorts were tested by Mann-Whitney U test. RESULTS: Overall, we observed large variations in serum phthalate metabolite levels between individuals. Secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) in serum were weakly to moderately and positively correlated to the levels measured in urine, and secondary metabolites of DEHP were also moderately to strongly and significantly correlated in serum. Correlations with mono-(2-ethyl-hexyl) phthalate (MEHP) and mono-iso-nonyl phthalate (MiNP), the two primary metabolites of DEHP and DiNP, were inconsistent, and we found indications of sample contamination. We observed some significant differences in phthalate metabolite levels between the three cohorts with generally higher levels in the older birth cohorts. CONCLUSION: Based on comparison across two older birth cohorts and a recent cohort, our results support the concept that historical biobanked serum samples may be used for assessment of prenatal exposure to phthalates when using serum levels of the monoesters of the low-molecular weight (LMW) phthalates and the secondary metabolites of the high-molecular weight (HMW) phthalates. Serum phthalate measurements are, however, not suitable for human biomonitoring and should only be used to exploit historical samples from cohorts, where urine samples were not collected. Our findings suggest that phthalate exposure may have decreased over time from the early 1990s to the 2010s.

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus.

Endocrine disrupting chemicals (EDCs) are exogenous substances that interfere with the stability and regulation of the endocrine system of the body or its offspring. These substances are generally stable in chemical properties, not easy to be biodegraded, and can be enriched in organisms. In the past half century, EDCs have gradually entered the food chain, and these substances have been frequently found in maternal blood. Perinatal maternal hormone levels are unstable and vulnerable to EDCs. Some EDCs can affect embryonic development through the blood-fetal barrier and cause damage to the neuroendocrine system, liver function, and genital development. Some also effect cross-generational inheritance through epigenetic mechanisms. This article mainly elaborates the mechanism and detection methods of estrogenic endocrine disruptors, such as bisphenol A (BPA), organochlorine pesticides (OCPs), diethylstilbestrol (DES) and phthalates (PAEs), and their effects on placenta and fetal health in order to raise concerns about the proper use of products containing EDCs during pregnancy and provide a reference for human health.

Inverse associations of bisphenol A and phthalate metabolites with serum bilirubin levels in Korean population.

Bisphenol A (BPA) and phthalates are endocrine disruptors that can induce oxidative stress. Serum bilirubin has antioxidant properties and may serve as a biomarker of oxidative stress. The objective of this study was to explore the relationship of BPA and phthalates with serum bilirubin levels in a Korean population. Urinary concentrations of BPA and six phthalate [mono-n-butyl phthalate (MnBP), mono-iso-butyl phthalate (MiBP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl-5- hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono-benzyl phthalate (MBzP)] were measured in 709 participants. Serum concentrations of BPA and three phthalate metabolites [MnBP, MiBP, and mono-(2-ethylhexyl) phthalate (MEHP)] were measured in 752 participants. After excluding missing variables, associations between above chemicals and serum bilirubin levels were analyzed using multivariate linear regression with age, sex, BMI, GGT, GOT, GPT, and alcohol intake adjustment. Participants were further stratified by sex. Among the urinary chemicals, BPA and four phthalate metabolites (MnBP, MEOHP, MEHHP and MECPP) were inversely associated with serum bilirubin levels (BPA: ß = - 0.071, P < 0.0001; MnBP: ß = - 0.055, P = 0.025; MEOHP: ß = - 0.101, P < 0.0001; MEHHP: ß = - 0.106, P < 0.0001; MECPP: ß = - 0.052, P = 0.003). In a case of serum chemicals, only MiBP showed significantly positive association (ß = 0.036, P = 0.016). After stratification by sex, the associations of urinary BPA remained both in male and female, of which urinary phthalates disappeared in female. The association of serum MiBP was disappeared after stratification. Urinary BPA and phthalate metabolites were inversely associated with serum bilirubin levels, whereas serum MiBP showed positive association with bilirubin. These results could provide clues for understanding the mechanisms of endocrine disruptor from oxidative stress to excretion from our body.

Exposure to phthalates and bisphenol A is associated with higher risk of cardiometabolic impairment in normal weight children.

Some obese individuals have normal metabolic profile, and some normal-weight persons have impaired metabolic status. Our hypothesis was that one of the potential underlying factors for such differences in cardiometabolic profiles might be the exposure to some environmental chemicals. This study aimed to investigate the association of serum bisphenol A (BPA) and phthalate metabolites with cardiometabolic risk factors in children and adolescents independent of their weight status. This case-control study was conducted on a subsample of 320 participants of a national school-based surveillance program in Iran. We measured serum BPA and phthalate metabolites by gas chromatography mass spectrophotometry. We compared them in children and adolescents with and without excess weight and those with and without cardiometabolic risk factors (80 in each group). We categorized the concentrations of chemicals to tertiles and then we applied logistic regression models after adjustment for potential confounding factors. The concentrations of BPA and some metabolites of phthalates were significantly different in the four groups studied. MEHP concentration was associated with higher odds ratio of cardiometabolic risk factors in participants with normal weight (OR, 95% CI 2.82, 1.001-7.91) and those with excess weight (OR, 95% CI 3.15, 1.27-7.83). MBP concentration increased the odds ratio of cardiometabolic risk factors only in normal weight children and adolescents (OR, 95% CI 6.59, 2.33-18.59, P < 0.001). In participants without cardiometabolic risk factor, MMP and MEHHP were significantly associated with increased risk of excess weight (OR, 95% CI 5.90, 1.21-28.75 and 7.82, 1.5-41.8, respectively). This study showed that the association of BPA and phthalate with cardiometabolic risk factors is independent of the weight status. Our findings suggest that the metabolic impairment in some normal weight children and normal metabolic profile of some obese children can be, in part, related to exposure to these environmental chemicals. Graphical abstract.

Development and validation of a bioanalytical assay based on liquid chromatography-tandem mass spectrometry for measuring biomarkers of exposure of alternative plasticizers in human urine and serum.

Alternative plasticizers (APs) have been increasingly used in the last decade to replace conventional phthalate esters, in particular di(2-ethylhexyl) phthalate (DEHP), due to the toxicity of the latter. However, there is currently very little data about the toxicity of and exposure to APs. No method exists so far for the analysis of multiple exposure biomarkers. The objective of this work consisted in developing a simple bioanalytical procedure for the analysis of multiple exposure biomarkers of APs in human urine and serum. Focus was set on metabolites of di(2-propylheptyl) phthalate (DPrHpP), di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP) and di-2-ethylhexyl adipate (DEHA). A sample preparation protocol was developed and optimized using Oasis HLB solid-phase extraction (SPE) cartridges. Subsequently, an instrumental method based on liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS) was optimized. Following established guidelines, the sample preparation and instrumental methods were validated in terms of recovery, matrix effects, carry-over, linearity, limits of quantification, within- and between-run precision and trueness. Obtained results were satisfactory for all compounds except for one of the metabolites of DEHA (i.e., mono(2-ethylhexyl) adipate (MEHA)). A pilot biomonitoring study was carried out to assess the method's ability to detect and quantify target analytes in human urine and serum. In urine, most analytes could be detected with frequencies ranging from 8% for mono(2-ethyl-5-hydroxyhexyl) adipate (OH-MEHA) and cyclohexane-1,2-dicarboxylic mono hydroxyisononyl ester (OH-MINCH) to 92% for mono(2-ethyl-5-oxohexyl) adipate (oxo-MEHA), whilst most compounds could not be detected in serum, except for mono(2-ethylhexyl) terephthalate (MEHTP) and mono-(2-propyl-6-hydroxyheptyl) phthalate (OH-MPrHpP) which were detected in all samples. The obtained results show that the developed method can be used to simultaneously analyse multiple exposure biomarkers to APs in human urine and serum.

Levels of phthalate acid esters and sex hormones and their possible sources in traffic-patrol policemen in Chongqing.

To investigate the correlation between the air phthalate acid ester (PAE) exposure and serum PAE concentration and the effects of PAE exposure on reproductive health among Chongqing traffic-patrol policemen. In 2013, 32 traffic-patrol policemen working in an area with poor air quality in Chongqing and 28 traffic-patrol policemen working in an area with good air quality were selected. Their blood levels of 14 PAEs and six reproductive hormones were determined. Air samples were collected from four traffic-patrol platforms. The concentrations of 14 PAEs in the air samples were evaluated. All 14 PAEs were detected in the blood samples. The concentrations of seven PAEs in the total suspended particulate, namely, dimethyl phthalate, diethyl phthalate, dibutyl phthalate, bis (2-ethox-yethyl) phthalate, dihexyl phthalate, benzyl butyl phthalate, and bis (2-n-butoxyethyl) phthalate, were positively and significantly associated with the blood levels of these PAEs in the participants. All the sex hormone levels measured here were significantly different between the participants from the two areas. The PAE concentrations in the blood samples were correlated with the reproductive hormone levels in the participants. Air PAE pollution may be a major source of PAE exposure in the traffic-patrol policemen of Chongqing.

Serum levels of phthalates and bisphenol-A in patients with primary ovarian insufficiency.

OBJECTIVES: Phthalates and bisphenol-A (BPA) may pose a risk for human reproduction. Adverse effects of endocrine disturbing chemicals on animal ovaries have been proposed previously. This study was designed to measure the concentrations of phthalate diesters or their metabolites in serum to evaluate their relevance with primary ovarian insufficiency (POI). METHODS: This study was designed as a cross sectional and case-control study. The study group consisted of 30 women diagnosed with POI whereas 30 healthy fertile women without any systemic diseases were recruited as a control group. The two groups were matched with respect to age and body mass index and tobacco smoking. Serum phthalate diesters and BPA levels were measured in both groups. RESULTS: The mean serum level of mono-buthyl phthalate (MBP) was statistically significantly higher in POI group than in control group (8.45 ± 4.2 vs. 5.0 ± 3.47 ng/mL, p < .001). Other serum phthalate metabolites and BPA concentrations were similar among the groups. CONCLUSIONS: Serum levels of BPA and phthalate metabolites are increased in women diagnosed with POI. However, MBP is the most significant one among them. MBP may be a contributing risk factor in the development of POI.

Human exposure to bisphenol AF and diethylhexylphthalate increases susceptibility to develop differentiated thyroid cancer in patients with thyroid nodules.

Pollutants represent potential threats to the human health, being ubiquitous in the environment and exerting toxicity even at low doses. This study aims at investigating the role of fifteen multiclass organic pollutants, assumed as markers of environmental pollution, most of which exerting endocrine-disrupting activity, in thyroid cancer development. The increasing incidence of differentiated thyroid cancer (DTC) may be related to the rising production and environmental dissemination of pollutants. Fifty-five patients, twenty-seven with diagnosis of benign thyroid nodules and twenty-eight suffering from differentiated thyroid cancer, were enrolled and the concentration levels of seven bisphenols, two phthalates (i.e. di(2-ethylhexyl) phthalate (DEHP) and its main metabolite, mono-(2-ethyl-hexyl) phthalate) (MEHP)), two chlorobenzenes, (1,4-dichlorobenzene and 1,2,4,5-tetrachlorobenzene), and 3 phenol derivatives (2-chlorophenol, 4- nonylphenol, and triclosan) were determined in their serum by using a validated analytical method based on high performance liquid chromatography with ultraviolet tandem fluorescence detection. A significant relationship was found between malignancy and the detection in the serum of both bisphenol AF and DEHP. Indeed, their presence confers a more than fourteen times higher risk of developing differentiated thyroid cancer. Relationship between these two pollutants and the risk of malignancy was dose-independent and not mediated by higher thyroid stimulating hormone levels. Even if a conclusive evidence cannot still be drawn and larger prospective studies are needed, the exposure to low doses of environmental endocrine-disrupting contaminants can be considered consistent with the development of thyroid cancer.

Variations in repeated serum concentrations of UV filters, phthalates, phenols and parabens during pregnancy.

BACKGROUND: Biobank serum samples from longitudinal mother-child cohorts have been used to estimate prenatal exposures to endocrine disrupting chemicals (EDCs). However, the knowledge about variations in serum concentrations of non-persistent chemicals during pregnancy is limited. OBJECTIVE: To describe the within- and between-person variations in serum concentrations of non-persistent chemicals and changes over trimesters, including phthalate metabolites, parabens, phenols, and UV filters. DESIGN: Longitudinal study with repeated blood samples from 128 healthy pregnant women during pregnancy. SETTING: Population based study at a University Hospital in Copenhagen 1999-2001. METHODS: 503 repetitive prenatal serum samples from 128 pregnant women taken at approximately gestational week 12, 20, 30 and 40 were analyzed for 7 UV filters, 32 metabolites of 15 phthalate diesters, 8 phenols and 7 parabens by LC-MS/MS. RESULTS: Ten of 32 phthalate metabolites from six out of 15 phthalate diesters, two of seven parabens, two of eight phenols and three of seven UV filters were measurable in more than half of the serum samples. Of these chemicals, mono­ethyl phthalate (MEP), mono­iso­nonyl phthalate (MiNP), mono­iso­decyl phthalate (MiDP), 4­methylbenzophenone (4­MBP), 4­hydroxybenzoephenone (4­HBP) and n­propyl paraben (nPrP) had intra-class correlation coefficients (ICC) above 0.4 in both adjusted and unadjusted analyses (0.427-0.795), indicating low within-person variation. The serum concentration of UV filters 4­MBP and 4­HBP significantly increased throughout pregnancy, also after adjusting for seasonal variation (4­HBP: effect estimates 0.142-0.437, p < 0.001. 4­MBP: effect estimates 0.156-0.458, p < 0.002.). CONCLUSION: MEP, MiNP, MiDP, 4­MBP, 4­HBP and nPrP were measurable in >50% of serum samples and showed low within-person variation. Thus, it is possible with acceptable accuracy to evaluate maternal exposure during pregnancy for these non-persistent chemicals using one or more biobank serum samples. The here presented adjusted ICC values can in addition be applied as adjustment of residual variation in future studies that evaluate outcomes related to prenatal exposures.

[The decade hemogram of workers of phthalate industry].

The article presents decade dynamics of hemogram of workers started their labor activity in factories of terephthalic acid, purifed terephthalic acid and polyethylene terephthalate. The study established a hemodynamics depended on career pattern, characterizing hematologic shifts i.e. decreasing of content of red blood elements, adaptative compensatory reactions of white blood, increasing of sensitization and allergizing.

Phthalate metabolites in maternal and cord plasma and their relations to other selected endocrine disruptors and steroids.

Endocrine disruptors (EDs) are known to have harmful effects on the human endocrine system; special effort is actually given to the exposure during pregnancy. Humans are usually exposed to a mixture of EDs, which may potentiate or antagonize each other, and the combined effect may be difficult to estimate. The main phthalate monoesters monoethyl-, mono-n-butyl-, monoisobutyl-, monobenzyl-, mono-(2-ethylhexyl)-, mono-(2-ethyl-5-hydroxyhexyl)- and mono-(2-ethyl-5-oxohexyl) phthalate were determined in 18 maternal (37th week of pregnancy) and cord plasma samples using liquid chromatography-tandem mass spectrometry. Previously determined levels of selected bisphenols, parabens and steroids were also considered in this study. In cord blood, there were significantly higher mono-n-butyl phthalate levels than in maternal blood (p=0.043). The results of multiple regression models showed that maternal plasma phthalates were negatively associated with cord plasma androstenedione, testosterone and dehydroepiandrosterone and positively associated with estradiol and estriol. For estriol, a cumulative association was also observed for sumabisphenols. To the best of our knowledge, this is the first pilot study evaluating the effect of prenatal exposure by multiple EDs on newborn steroidogenesis. Our results confirmed phthalate accumulation in the fetal area and disruption of fetal steroidogenesis. This preliminary study highlights the negative impacts of in utero EDs exposure on fetal steroidogenesis.

Risk assessment of endocrine disrupting phthalates and hormonal alterations in children and adolescents.

Risk assessment and hormone evaluation were carried out for di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP), endocrine disrupting chemicals (EDCs), in 302 Korean children (n = 223) and adolescents (n = 79) (< age 19). Urinary and serum concentrations of DEHP, MEHP (mono(2-ethylhexyl) phthalate), DBP, MBP (monobutyl phthalate), and PA (phthalic acid, a common final metabolite of phthalates) were detected in children and adolescents. Daily exposure levels were estimated to be 16.45 ± 36.50 µg/kg b.w./day for DEHP, which is one-third of the tolerable daily intake (TDI) value (50 µg/kg b.w./day), but 14 out of 302 participants had a hazard index (HI = intake/TDI) value >1. The mean daily exposure level of DBP was 1.23 ± 1.45 µg/kg b.w./day, which is one-eighth of the TDI value (10 µg/kg b.w./day), but 1 out of 302 participants had a HI value > 1. Positive correlations were observed between serum DBP or MEHP, and serum estradiol (E2) and/or luteinizing hormone (LH) in prepubescent children. In addition, serum MBP levels were found to be negatively correlated with serum triiodothyronine (T3) or thyroxine (T4) in male participants, and serum DEHP levels with serum thyroid stimulating hormone (TSH) in female adolescents. Low-density lipoprotein (LDL) levels were positively correlated with serum PA levels in children and adolescents. DEHP, DBP or its metabolites may be associated with altered hormone levels in children and adolescents. Data suggest that exposure levels of DEHP and DBP in Korean children need to be reduced to levels below TDI to protect them from EDC-mediated toxicities. Abbreviations: DBP: dibutyl phthalate; DEHP: di(2-ethylhexyl) phthalate; E2: estradiol; EDC: endocrine disrupting chemical; EFSA: European Food Safety Authority; FSH: follicle stimulating hormone; HDL: high density lipoprotein; HI: hazard index; LDL: low density lipoprotein; LH: luteinizing hormone; MEHP: mono(2-ethylhexyl) phthalate; MBP: monobutyl phthalate; PA: phthalic acid; PPAR: peroxisome proliferator-activated receptor gamma; PVC: polyvinyl chloride; T3: triiodothyronine; T4: thyroxine; TDI: tolerable daily intake; TG: triglyceride; TSH: thyroid stimulating hormone; UPLC/MS/MS: Ultra Performance Liquid Chromatography/Tandem Mass Spectrometry; WWF: World Wildlife Fund.

The role of oxidative stress in cardiometabolic risk related to phthalate exposure in elderly diabetic patients from Shanghai.

The effect of human exposure to phthalates and consequent contribution to the development of cardiometabolic health problems is unknown. However, oxidative stress has been established as playing an important role in the pathogenesis of cardiometabolic outcomes. In this study, we aimed to explore whether exposure to phthalate metabolites could induce cardiometabolic risk by increasing oxidative stress in a diabetic population from Shanghai. We collected paired blood and urine samples from a total of 300 volunteers, and measured 10 phthalate metabolites in urine and biomarkers of oxidative stress from serum including glucose and lipid levels, and liver and kidney damage. The insulin resistance (IR) risk was assessed by the surrogate indices including homeostasis model assessment-insulin resistance (HOMA-IR) and triglyceride glucose (TyG). We used multivariable linear regression to assess the association between phthalates and these physiological parameters. Mediation and modification analyses were performed to identify the role that oxidative stress played in the underlying mechanisms. The results showed that most of the determined phthalate metabolites were positively associated with HOMA-IR, 8­hydroxy­2'­deoxyguanosine (8-OHDG), and malondialdehyde (MDA). In the mediation analysis, only γ­glutamiltransferase (GGT) was found to be a significant mediator of the association between phthalates and TyG. In the modification analysis, exposure to phthalates strengthened the association between oxidative stress (MDA and 8-OHDG) and HOMA-IR. Our findings demonstrate that exposure to phthalates might be positively associated with elevated IR and oxidative stress. The direct participation (mediation effect) of GGT might play an important mechanism in promoting IR.