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.

Associations between maternal mono-(2-ethylhexyl) phthalate levels, nuclear receptor gene polymorphisms, and fatty acid levels in pregnant Japanese women in the Hokkaido study.

We assessed how the interaction between mono-(2-ethylhexyl) phthalate (MEHP) in maternal sera and the maternal genotypes associated with nuclear receptors affect fatty acid levels in a prospective birth cohort study of pregnant Japanese individuals (n = 437) recruited in Sapporo between 2002 and 2005. We analyzed MEHP and fatty acids using gas chromatography-mass spectrometry. Thirteen single nucleotide polymorphisms of peroxisome proliferator-activated receptor (PPAR) alpha, PPAR gamma (PPARG), PPARG coactivator 1A (PPARGC1A), PPAR delta, constitutive androstane receptor, liver X receptor (LXR) alpha, and LXR beta (LXRB) were analyzed using real-time PCR. Multiple linear regression models were used to confirm the influence of log10-transformed MEHP levels and maternal genotypes on log10-transformed fatty acid levels. When the effects of the interaction between MEHP levels and the maternal PPARGC1A (rs8192678) genotype on oleic acid levels were evaluated, the estimated changes (95 % confidence intervals) in oleic acid levels against MEHP levels, maternal PPARGC1A (rs8192678)-GA/AA genotype, and the interaction between them showed a mean reduction of 0.200 (0.079, 0.322), mean reduction of 0.141 (0.000, 0.283), and mean increase of 0.145 (0.010, 0.281), respectively, after adjusting for the perfluorooctanesulfonate level. The effects of the interaction between MEHP levels and maternal LXRB (rs2303044) genotype on linoleic acid levels was also significant (pint = 0.010). In conclusion, the interaction between MEHP and the maternal genotypes PPARGC1A (rs8192678) and LXRB (rs2303044) decreased fatty acid levels. Further, the interaction between MEHP and PPARGC1A (rs8192678) may have a greater effect on fatty acid levels than the interaction between PFOS and PPARGC1A.

Evaluation of reproductive hormones in Egyptian workers occupationally exposed to di-2-ethylhexyl phthalate (DEHP): a cross-sectional study.

OBJECTIVES: Di-2-ethylhexyl phthalate (DEHP) is ubiquitous, known as an endocrine disruptor. DEHP is a widespread prevalence in general and occupational populations which raised great public concerns due to its potentially harmful health effects on the male reproductive system. We aimed to assess occupational levels of DEHP on gonadotropin and gonadal hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) and evaluate its potential effects on Asp327Asn polymorphisms SHBG gene. METHODS: We measured the levels of DEHP of 90 male workers in one of polyvinyl chloride (PVC) industry plant using enzyme-linked immunosorbent assay. Sex hormones were examined and Asp327Asn polymorphisms SHBG gene were detected by PCR-RFLP in all participants. RESULTS: The workers were divided into low- and high- DEHP exposed groups based on the geometric mean (GM) levels (183.86 U/L) in serum. TT and TT: LH ratio were negatively correlated to DEHP levels (r=-0.213, p=0.038), (r=-0.225, p=0.027), respectively. The linear regression analysis revealed that a 10-fold increase of serum DEHP was found to be associated with 2.07 fold decreased in TT and a 2.26 fold decreased in TT/LH ratio. CONCLUSIONS: Serum testosterone is negatively associated with DEHP exposure in occupational workers.

Endocrine Disruptors and Polycystic Ovary Syndrome: Phthalates

Objective: We aimed to investigate a possible role of the endocrine disruptors phthalates, di-2-ethylhexyl phthalate (DEHP) and mono (2-ethylhexyl) phthalate (MEHP), in polycystic ovary syndrome (PCOS) aetiopathogenesis. We also wished to evaluate the relationship between phthalates and metabolic disturbances in adolescents with PCOS. Methods: A total of 124 adolescents were included. Serum MEHP and DEHP levels were determined by high-performance liquid chromatography. Insulin resistance was evaluated using homeostasis model assessment-insulin resistance, quantitative Insulin Sensitivity Check Index, fasting glucose/insulin ratio, Matsuda index, and total insulin levels during oral glucose tolerance test. Participants were further subdivided into lean and obese subgroups according to body mass index (BMI). Results: Sixty-three PCOS and 61 controls, (mean age 15.2±1.5; range: 13-19 years) were enrolled. Serum DEHP and MEHP concentrations were not significantly different between PCOS and control groups. The mean (95% confidence interval) values of DEHP and MEHP were 2.62 (2.50-2.75) µg/mL vs 2.71 (2.52-2.90) µg/mL and 0.23 (0.19-0.29) µg/mL vs 0.36 (0.18-0.54) µg/mL in PCOS and the control groups respectively, p>0.05. Correlation analysis, adjusted for BMI, showed that both phthalates significantly correlated with insulin resistance indices and serum triglycerides in adolescents with PCOS. Conclusion: Serum DEHP and MEHP concentrations were not different between adolescents with or without PCOS. However, these phthalates are associated with metabolic disturbances such as dyslipidemia and insulin resistance, independently of obesity, in girls with PCOS.

Exposure of patients to di(2-ethylhexy)phthalate (DEHP) and its metabolite MEHP during extracorporeal membrane oxygenation (ECMO) therapy.

The plasticizer di(2-ethylhexyl)phthalate (DEHP) is often used for PVC medical devices, that are also largely used for intensive care medical treatments, like extracorporeal membrane oxygenation (ECMO) therapy. Due to the toxicological potential of DEHP, the inner exposure of patients with this plasticizer is a strong matter of concern as many studies have shown a high leaching potential of DEHP into blood. In this study, the inner DEHP exposure of patients undergoing ECMO treatment was investigated. The determined DEHP blood levels of ECMO patients and the patients of the control group ranged from 31.5 to 1009 µg/L (median 156.0 µg/L) and from 19.4 to 75.3 µg/L (median 36.4 µg/L), respectively. MEHP blood levels were determined to range from < LOD to 475 µg/L (median 15.9 µg/L) in ECMO patients and from < LOD to 9.9 µg/L (median 3.7 µg/L) in the control group patients, respectively. Increased DEHP exposure was associated with the number of cannulas and membranes of the ECMO setting, whereas residual diuresis decreased the exposure. Due to the suspected toxicological potential of DEHP, its use in medical devices should be further investigated, in particular for ICU patients with long-term exposure to PVC, like in ECMO therapy.

Reduction of exposure to plasticizers in stored red blood cell units.

INTRODUCTION: Plastic can be toxic and hazardous to an organism's health, but it is being widely used in our daily lives. Di-2-ethylhexyl-phthalate is the most common plasticizer in medical devices made of polyvinylchloride and is commonly found in soft bags storing red blood cell units. Di-2-ethylhexyl-phthalate and its degradation product mono-2-ethylhexyl-phthalate can migrate into human body fluids, for example, blood and tissues. The aim of the study was to assess the concentration of plasticizers in red blood cell units according to storage time and after mechanical rinsing using a cell salvage device. METHODS: Levels of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate were analysed in 50 unwashed red blood cell units using liquid chromatography coupled with tandem mass spectrometry. In addition, phthalate concentrations were measured before and after mechanical rinsing in six more washed red blood cell units with storage times ranging between 36 and 56 days. A linear regression model was determined by the daily increase of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate in the stored red blood cell units subject to their storage time (range = 4-38 days), and the effect of mechanical rinsing on their phthalate concentration was calculated. RESULTS: A linear correlation was found between storage time of unwashed red blood cell units and the concentration of di-2-ethylhexyl-phthalate (p < 0.001) or mono-2-ethylhexyl-phthalate (p < 0.001). Stored red blood cell units older than 14 days had significantly higher concentrations of both contaminants than red blood cell units of shorter storage time (p < 0.001). Mechanical rinsing in washed red blood cell units attained a reduction in the di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate concentration by a median of 53% (range = 18-68%; p = 0.031) and 87% (range = 68-96%; p = 0.031), respectively. CONCLUSION: Leaching of di-2-ethylhexyl-phthalate and mono-2-ethylhexyl-phthalate into red blood cell units depends on the duration of storage time. Plasticizers can be significantly reduced by mechanical rinsing using cell salvage devices, and thus, red blood cell units can be regenerated with respect to chemical contamination.

Oxidative stress markers, trace elements, and endocrine disrupting chemicals in children with Hashimoto's thyroiditis.

In this study, we aimed to investigate whether bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) exposure have any association with Hashimoto's thyroiditis (HT) and its biomarkers and to determine whether oxidative stress biomarkers and trace element levels showed any alterations in children with HT. We found that superoxide dismutase and glutathione peroxidase activities are lower in HT group from control (24% and 46%, respectively, p < 0.05). Zinc levels were significantly lower in HT group vs. control. In addition, the levels of mono-(2-ethylhexyl) phthalate (MEHP) which is the primary metabolite for DEHP, were markedly higher in HT group compared to control (p < 0.05). A negative correlation was observed between urinary BPA levels and fT4. In children with HT, oxidant/antioxidant balance is changed and these differences may be related by EDC exposure, the importance of which should be elucidated with further studies.

Bisphenol A and phthalate levels in adolescents with polycystic ovary syndrome.

Endocrine disruptors have been proposed in the etiology of polycystic ovary syndrome (PCOS) as they have the potency to interfere with hormone-sensitivity systems. The aim of this study was to evaluate the levels of bisphenol A (BPA) and phtalates in adolescents with PCOS. Sixty-two girls with PCOS and 33 controls, age 12-18 years were enrolled in the study. The diagnosis of PCOS was made using modified Rotterdam criteria. Urinary BPA levels were measured using high-performance liquid chromatography. Di-(2-ethylhexyl)-phthalate (DEHP), the most commonly used phthalate and mono-(2-ethylhexyl)-phthalate (MEHP), its main metabolite were measured by using high-performance liquid chromatography. Adolescents with PCOS had markedly increased BPA levels (15.89 µg/g creatine ± 1.16) when compared with the control group (7.30 µg/g creatine ± 1.38) (p = .016). In adolescents with PCOS, BPA was significantly correlated with polycystic morphology on ultrasound but not with obesity androgen levels, or other metabolic parameters. Patients with PCOS (DEHP: 0.40 ppm ± 0.24, MEHP: 0.13 ppm ± 0.23) and controls (DEHP: 0.49 ppm ± 0.27, MEHP: 0.14 ppm ± 0.3) had similar serum phtalate concentrations (p = .7 and p = .3, respectively). Exposure to specific endocrine disruptors such as BPA could modify neuroendocrine, reproductive, and metabolic regulation favoring PCOS development in adolescents.

Estimation of plasma levels of bisphenol-A & phthalates in fertile & infertile women by gas chromatography-mass spectrometry.

BACKGROUND & OBJECTIVES: Bisphenol-A (BPA) and phthalates are utilized widely in consumer products. Due to their ubiquitous presence in the environment, a concern is expressed worldwide about their possible effect on human reproductive health. This study was conducted to compare the internal exposure of BPA and phthalates (using their metabolites as biomarkers) in plasma samples of infertile and fertile women. METHODS: A sensitive gas chromatographic-mass spectrometric (GC-MS) method was developed to simultaneously quantify BPA and four phthalate monoester metabolites [namely mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] in human plasma. The method was validated using charcoal-stripped human plasma. Activated charcoal was also utilized to reduce contamination from reagents. The method was designed to account for and/or eliminate background contamination from all sources. RESULTS: The limit of quantification for the method was 5 ng/ml for MMP and MBzP, while 1 ng/ml for BPA, MEHP and MEHHP, respectively. The precision and accuracy were well within the acceptable range. BPA was detectable in 77 per cent of plasma samples of infertile women and 29 per cent of fertile women. All the four phthalate metabolites were detected in plasma samples of both fertile and infertile women. INTERPRETATION & CONCLUSIONS: A GC-MS was developed and validated to estimate the BPA and four phthalate monoester metabolites in human plasma. It was utilised to analyse the plasma samples from fertile and infertile women. The infertile women showed significantly higher plasma concentrations of MBzP, BPA and MEHHP as compared to fertile women. The levels of MMP and MEHP were not significantly different between the two groups. Further studies need to be done to confirm these preliminary findings.

Phthalate exposure and reproductive hormones and sex-hormone binding globulin before puberty - Phthalate contaminated-foodstuff episode in Taiwan.

BACKGROUND: In May 2011, a major incident involving phthalates-contaminated foodstuffs occurred in Taiwan. Di-(2-ethylhexyl) phthalate (DEHP) was added to foodstuffs, mainly juice, jelly, tea, sports drink, and dietary supplements. Concerns arose that normal pubertal development, especially reproductive hormone regulation in children, could be disrupted by DEHP exposure. OBJECTIVE: To investigate the association between phthalate exposure and reproductive hormone levels among children following potential exposure to phthalate-tainted foodstuffs. METHODS: A total of 239 children aged <12 years old were recruited from 3 hospitals in north, central, and south Taiwan after the episode. Structured questionnaires were used to collect the frequency and quantity of exposures to 5 categories of phthalate-contaminated foodstuffs to assess phthalate exposure in children. Urine samples were collected for the measurement of phthalate metabolites. The estimated daily intake of DEHP exposure at the time of the contamination incident occurred was calculated using both questionnaire data and urinary DEHP metabolite concentrations. Multiple regression analyses were applied to assess associations between phthalate exposure and reproductive hormone levels in children. RESULTS: After excluding children with missing data regarding exposure levels and hormone concentrations and girls with menstruation, 222 children were included in the statistical analyses. After adjustment for age and birth weight, girls with above median levels of urinary mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and sum of mono-(2-ethylhexyl) phthalate concentrations had higher odds of above median follicle-stimulating hormone concentrations. Girls with above median estimated average daily DEHP exposures following the contamination episode also had higher odds of sex hormone-binding globulin above median levels. CONCLUSIONS: Phthalate exposure was associated with alterations of reproductive hormone levels in girls.

Direct and transgenerational effects of low doses of perinatal di-(2-ethylhexyl) phthalate (DEHP) on social behaviors in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is an endocrine disrupting chemical commonly used as a plasticizer in medical equipment, food packaging, flooring, and children's toys. DEHP exposure during early development has been associated with adverse neurobehavioral outcomes in children. In animal models, early exposure to DEHP results in abnormal development of the reproductive system as well as altered behavior and neurodevelopment. Based on these data, we hypothesized that developmental exposure to DEHP would decrease social interactions and increase anxiety-like behaviors in mice in a dose-dependent manner, and that the effects would persist over generations. C57BL/6J mice consumed one of three DEHP doses (0, 5, 40, and 400 µg/kg body weight) throughout pregnancy and during the first ten days of lactation. The two higher doses yielded detectable levels of DEHP metabolites in serum. Pairs of mice from control, low, and high DEHP doses were bred to create three dose lineages in the third generation (F3). Average anogenital index (AGI: anogenital distance/body weight) was decreased in F1 males exposed to the low dose of DEHP and in F1 females exposed to the highest dose. In F1 mice, juvenile pairs from the two highest DEHP dose groups displayed fewer socially investigative behaviors and more exploratory behaviors as compared with control mice. The effect of DEHP on these behaviors was reversed in F3 mice as compared with F1 mice. F1 mice exposed to low and medium DEHP doses spent more time in the closed arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. The generation-dependent effects on behavior and AGI suggest complex mechanisms by which DEHP directly impacts reproductive and neurobehavioral development and influences germline-inherited traits.

The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders.

Recent research suggests the maternal environment may be especially important for the risk of developing autism spectrum disorders (ASD). In particular maternal infections, micronutrient deficiencies, obesity, and toxicant exposures are likely to interact with genetic risk factors to disrupt fetal brain development. OBJECTIVES: The goal of this paper is to investigate the plausibility of maternal toxicant exposure and nutritional status as causal factors in the development of ASD. METHODS: This paper reviews current research investigating the hypothesis that maternal toxicant exposure and prenatal micronutrient intake are important modifiable risk factors for ASD. RESULTS: Zinc, copper, iron, and vitamin B9 are identified as specific micronutrients with relevance to the etiology of ASD. Specific toxicants induce a maternal inflammatory response leading to fetal micronutrient deficiencies that disrupt early brain development. Importantly, maternal micronutrient supplementation is associated with reduced risk of ASD. Furthermore, animal studies show that micronutrient supplementation can prevent the teratogenicity and developmental neurotoxicity of specific toxicants. DISCUSSION: These findings lead to the hypothesis that maternal infection, obesity, and toxicant exposures (e.g. valproic acid, endocrine disrupting plasticizers, ethanol, and heavy metals) are all environmental risk factors for ASD that lead to fetal micronutrient deficiencies resulting from a maternal inflammatory response. It could be possible to use markers of inflammation and micronutrient status to identify women that would benefit from micronutrient supplementation or dietary interventions to reduce the risk of ASD. However, more research is needed to demonstrate a causal role of fetal micronutrient deficiencies and clarify the underlying mechanisms that contribute to ASD.

Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: The Hokkaido study on environment and children's health.

Di-2-ethylhexyl phthalate (DEHP) is one of the most widely used phthalates. Metabolites of DEHP are detectable in majority of the population. Findings on adverse health outcomes, particularly birth weight in association with prenatal exposure to DEHP remain equivocal. Besides, there is insufficient evidence to address influence on metabolic function from epidemiological studies. Thus, our objective was to investigate cord blood adipokine levels and birth size in association with prenatal DEHP exposure in prospective birth cohort study. Mono-2-methylhexyl phthalate (MEHP), primary metabolite of DEHP was determined as exposure by using maternal blood sample of 3rd trimester. Leptin and adiponectin levels in cord blood were measured as markers of metabolic function. Birth weight and length were obtained from birth record. Association between maternal MEHP levels and cord blood adiponectin and leptin levels, birth weight and ponderal index (PI) were examined for 167 mother-child pairs who had both MEHP and cord blood adipokine measurements. The median MEHP level was 8.81ng/ml and the detection rate was 100%. There was no sex difference in MEHP levels. Both leptin and adiponectin levels were higher in girls than in boys. MEHP level was positively associated with adiponectin level among boys and was negatively associated with leptin level among girls. MEHP level were negatively associated with PI only in girls and this could be due to decreased leptin level. This study suggested that prenatal DEHP exposure may be associated with cord blood adipokine and birth size. The influence potentially be sex-specific and could be more significant in girls.

The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty.

Exposure to environmental chemicals can affect genetic and epigenetic molecular pathways and may cause altered growth and development. Among those exposures, endocrine-disrupting chemicals (EDCs) are of particular concern as humans are abundantly exposed to these chemicals by various means in every period of life. Several well-known environmental chemicals, including phthalates and bisphenol A (BPA), are classified as EDCs. These EDCs are suggested to play roles in early onset of puberty in girls. The aim of this study is to determine plasma phthalate (di(2-ethylhexyl)phthalate [DEHP] and its main metabolite mono(2-ethylhexyl)phthalate [MEHP]) and urinary BPA levels in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). This study was performed on newly diagnosed idiopathic central precocious puberty (CPP) patients (n = 42) and peripheral precocious puberty (PPP) (n = 42) patients, who were admitted to Keçiören Training and Research Hospital, Clinic of Pediatric Endocrinology between August 2012 and -July 2013. Nonobese healthy girls (n = 50) were used as the control group. Urinary BPA levels were not statistically different in control, PPP and CPP groups (medians 10.91, 10.63 and 10.15 µg/g creatinine, respectively; p > 0.05). Plasma DEHP levels were significantly higher in PPP group when compared to control. Plasma MEHP levels were not significantly different in control and PPP groups (p > 0.05). However, in CPP group, both plasma DEHP and MEHP levels were significantly higher than control and PPP groups. This study showed that phthalates might play a role in the occurence of CPP in girls.

Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3†months of age.

BACKGROUND: Several studies have suggested potential links of phthalates to obesity in children and adults. Limited evidence, however, has been available for the relations between diethylhexyl phthalate (DEHP) and obesity-related markers or body mass change in early life. METHODS: 128 healthy pregnant women were recruited and, after delivery, their newborns' first urine and umbilical cord blood samples were collected. We measured urinary levels of two DEHP metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). We also measured the levels of leptin, total cholesterol and triglyceride (TG) in cord serum, and used them along with weight, length, head circumference and ponderal index (PI, 100 g/cm(3)) at birth, as obesity-related markers, and estimated the relations between DEHP metabolites and obesity-related markers using generalised linear models. For the evaluation of body mass increase by early life DEHP exposure, body mass index (BMI) z-score change during 3 months after birth by DEHP metabolites in the first urine samples of the newborns were evaluated using logistic regression. RESULTS: DEHP exposure was associated with decrease of PI and increase of TG (PI, ß=-0.11, p=0.070 and TG, ß=0.14, p=0.027), especially for boys (PI, ß=-0.13, p=0.021; and TG, ß=0.19, p=0.025). Moreover, DEHP exposure was positively associated with body mass increase during 3 months after birth (change of BMI z-scores, OR=4.35, p=0.025). CONCLUSIONS: Our findings suggest that DEHP exposure may affect body mass change in early life through changes of obesity-related markers.

Increased Serum Phthalates (MEHP, DEHP) and Bisphenol A Concentrations in Children With Autism Spectrum Disorder: The Role of Endocrine Disruptors in Autism Etiopathogenesis.

The aim of this study was to investigate the relationship between autism spectrum disorders development and exposure to mono-(2-ethylhexyl)-phthalate (MEHP), di-(2-ethylhexyl)-phthalate (DEHP), and bisphenol A (BPA), 1 of the endocrine disruptors, among phthalates. The study included 48 children with autism spectrum disorder (27 boys, 21 girls) and 41 healthy subjects (24 boys, 17 girls) as controls. Serum MEHP, DEHP, and BPA levels were measured by using high-performance liquid chromatography. Children with autism spectrum disorder had significantly increased serum MEHP, DEHP, and BPA concentrations (0.47 ± 0.14 µg/ml, 2.70 ± 0.90 µg/ml, 1.25 ± 0.30 ng/ml) compared to healthy control subjects (0.29 ± 0.05 µg/ml, 1.62 ± 0.56 µg/ml, 0.88 ± 0.18 ng/ml) respectively (P = .000). The fact that higher serum MEHP, DEHP, and BPA were found levels in the autism spectrum disorder group compared to healthy controls suggests that endocrine disruptors may have a role in the pathogenesis of autism spectrum disorders.

Comparative study on the migration of di-2-ethylhexyl phthalate (DEHP) and tri-2-ethylhexyl trimellitate (TOTM) into blood from PVC tubing material of a heart-lung machine.

Medical devices like blood tubing often consist of PVC material that requires the addition of plasticizers. These plasticizers may migrate into the blood leading to an exposure of the patients. In this study the migration behavior of three different blood tubing sets (PVC material with two different plasticizers and silicone as control material) applied on a heart-lung machine standardly used for cardiopulmonary bypass (CPB) in children was studied. We analyzed the total plasticizer migration by analysis of both, the parent compounds as well as their primary degradation products in blood. Additionally, the total mass loss of the tubing over perfusion time was examined. The PVC tubing plasticized with DEHP (di-2-ethylhexyl phthalate) was found to have the highest mass loss over time and showed a high plasticizer migration rate. In comparison, the migration of TOTM (tri-2-ethylhexyl trimellitate) and its primary degradation products was found to be distinctly lower (by a factor of approx. 350). Moreover, it was observed that the storage time of the tubing affects the plasticizer migration rates. In conclusion, the DEHP substitute TOTM promises to be an effective alternative plasticizer for PVC medical devices particularly regarding the decreased migration rate during medical procedures.

Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features.

Internal levels of selected endocrine disruptors (EDs) (i.e., perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di-2-ethylhexyl-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and bisphenol A (BPA)) were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs) of same subjects, gene expression levels of a panel of nuclear receptors (NRs), namely estrogen receptor α (ERα) estrogen receptor ß (ERß), androgen receptor (AR), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptor γ (PPARγ) and pregnane X receptor (PXR) were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERß, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health.

Simultaneous determination of polyvinylchloride plasticizers di(2-ethylhexyl) phthalate and tri(2-ethylhexyl) trimellitate and its degradation products in blood by liquid chromatography-tandem mass spectrometry.

Di(2-ethylhexyl) phthalate (DEHP) and tri(2-ethylhexyl) trimellitate (TEHTM or TOTM) are common plasticizers that are also largely used for PVC medical devices, e.g. bags and tubing for blood transfusions and infusions. The leachability of medical devices is a well-known situation of increasing toxicological concern. To assess the migration of plasticizers from PVC medical devices into human blood we developed and validated an analytical method for the determination of DEHP and TOTM in combination with the determination of their primary degradation products mono(2-ethylhexyl) phthalate (MEHP), 1,2-di(2-ethylhexyl) trimellitate (1,2-DEHTM) and 2-mono(2-ethylhexyl) trimellitate (2-MEHTM). The presented method involves liquid-liquid extraction of the analytes from the blood followed by the subsequent analytical separation and detection using LC-MS/MS analysis. The validation of the procedure showed a good precision in the range of 1.8 to 5.3%. Mean accuracy ranged from 86% for 1,2-DEHTM to 109% for MEHP. LOQ was found to be 2 to 5µg/L for each of the analytes. Additionally, the method is characterised by its wide linear range up to 2mg/L each for the degradation products of TOTM to 100mg/L for the parent plasticizer DEHP. The presented method promises to be of major advantage for further studies as it allows for the first time the simultaneous determination of DEHP and TOTM in human blood in combination with the analysis of their degradation products that render possible to investigate the leachability of a broad range of PVC medical devices in human blood using only one analytical method.

Phthalate exposure and reproductive parameters in young men from the general Swedish population.

BACKGROUND: In animals, exposure to certain phthalates negatively affects the male reproductive function. Human results are conflicting and mostly based on subfertile males, in whom the association between exposure and reproductive function may differ from the general population. OBJECTIVES: To study if levels of phthalate metabolites were associated with semen quality and reproductive hormones in general Swedish men. METHODS: We recruited 314 young men delivering semen, urine and blood samples at the same visit. We analyzed reproductive hormones and several semen parameters including progressive motility and high DNA stainability (HDS)-a marker for sperm immaturity. In urine, we analyzed metabolites of phthalates, including diethylhexyl phthalate (DEHP). We studied associations between urinary levels of the metabolites and seminal as well as serum reproductive parameters, accounting for potential confounders. RESULTS: DEHP metabolite levels, particularly urinary mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), were negatively associated with progressive sperm motility, which was 11 (95% CI: 5.0-17) percentage points lower in the highest quartile of MECPP than in the lowest. Further, men in the highest quartile of the DEHP metabolite monoethylhexyl phthalate had 27% (95% CI: 5.5%-53%) higher HDS than men in the lowest quartile. CONCLUSIONS: DEHP metabolite levels seemed negatively associated with sperm motility and maturation.