Indoor environment, physiological factors, and diet as predictors of halogenated flame retardant levels in stool and plasma of children from a Canadian cohort.

Exposure to halogenated flame retardants (HFRs) has been associated with various adverse effects on human health. Human exposure to HFRs mainly occurs through diet, ingesting contaminated dust, and inhaling contaminated air. Understanding and characterizing the variables linked to these exposure pathways is essential for developing effective risk assessment and mitigation strategies. We investigated indoor environment quality, physiological factors, and diet as potential predictors of HFRs concentration in children's plasma and stool. A selected number of HFRs, including polybrominated diphenyl ethers (PBDEs), Dechlorane-like compounds, and emerging halogenated flame retardants, were measured in children from eastern Quebec (Canada). Information on indoor environment quality, physiological factors, and diet was obtained through self-report questionnaires. Our results show that lower brominated compounds, which are more volatile, were primarily correlated to indoor environment quality. Notably, the use of air purifiers was associated with lower BDE47 and BDE100 levels in blood and newer residential buildings were associated with higher concentrations of BDE47. A significant seasonal variation was found in stool samples, with higher levels of lower brominated PBDEs (BDE47 and BDE100) in samples collected during summer. No association between household income or maternal education degree and HFRs was found. Among emerging compounds, Dec602 and Dec603 were associated with the most variables, including the use of air dehumidifiers, air conditioning, and air purifiers, and the child's age and body fat percentage.

Inhibition of canine parvovirus 2 (CPV-2) replication by TAT-scFv through targeting of the viral structural protein VP2 of CPV-2.

Canine parvovirus (CPV) causes severe infectious disease with a high mortality rate in dogs. CPV is still a major health issue of dogs in the clinic. Therefore, there is an urgent need to develop effective drugs to treat the disease. In this study, we fused the transactivating transcriptional activator peptide (TAT) with scFv. TAT-scFv was identified by Western blot. CCK8 kit was used to detect the toxicity of TAT-scFv to cells. The binding activity of TAT-scFv to CPV-2-VP2 was detected by DAS ELISA. The cell uptake rate of TAT-scFv was assessed by IFA. After infection with CPV-2, F81 cells were incubated by TAT-scFv. The replication of virus was measured to determine the neutralization effect of TAT-scFv on intracellular and extracellular viruses. Protein docking was used to predict the amino acid (AA) sites of VP2 binding to TAT-scFv. TAT-scFv was expressed in Escherichia coli and purified. The DAS ELISA showed that TAT-scFv could bind with CPV-2-VP2. We demonstrated that TAT-scFv entered cells in a dose-dependent and time-dependent manner and effectively inhibited the replication of CPV-2. Using protein docking, we determined the interaction pattern and found that the N-terminal region (AA 41-49) and the C-terminal region (AA 558) of VP2 interacted with the TAT-scFv. Taken together, these results suggest that, TAT-scFv may be a potential antiviral drug for inhibiting CPV-2 replication and controlling disease caused by CPV-2.

Thermal reaction products and formation pathways of two monoterpenes under in situ thermal desorption conditions that mimic vaping coil temperatures.

Vaping has become more popular and different brands and types of vaping devices have rapidly emerged. However, little is known about the potential health risks of human inhalation exposures to the volatile chemicals in the vapour, which includes both directly vaporised components of vaping liquid and their reaction products formed during vaping processes. This study investigated reaction products of two monoterpenes (α-pinene and terpinolene) that are used as flavouring agents in vaping liquids with a focus on the identification of reaction products and their formation pathways. The thermal desorption was conducted under an in situ condition that is in the range of heating coil temperature in vaping by thermally desorbing the chemicals at a temperature range of 100-300 °C. Additional clean air was introduced during the thermal desorption. 36 and 29 reaction products were identified from α-pinene and terpinolene, respectively, at a relative concentration of 0.01% and greater in the desorbed mixture. 3-Carene was the dominant reaction product of α-pinene, while reaction products of terpinolene was dominated by p-isopropenyltoluene. Several reaction pathways including ring opening, allylic oxidation, cyclo-etherification, Wagner-Meerwein rearrangement, epoxidation, cleavage and removal of partial structure, and dehydration were involved in the formation of various reaction products. These pathways and resulting relative concentrations of residual parent compound and reaction products were influenced by both temperature and amount of air present during thermal desorption. The study results demonstrate possible existence of reaction products from thermally labile chemicals like monoterpenes in vaping aerosols and can help inform policies regulating vaping devices and products to protect public health.

Complementarity of plasma and stool for the characterization of children's exposure to halogenated flame retardants: Update on analytical methods and application to a Canadian cohort.

Sixteen halogenated flame retardants including Polybrominated diphenyl ethers (PBDEs), Dechlorane-like compounds, and emerging halogenated flame retardants were measured in stool and plasma samples from children aged 8.9-13.8 years old. Samples were obtained from a Canadian cohort investigating the effect of contaminants on children's neurodevelopment in the Estrie region, Québec, Canada. The method for stool analysis developed for this study showed good recovery for all targeted compounds (73%-93%) with associated relative standard deviation (RSD) in the range of 16.0%-30.7% for most compounds except for the thermosensitive BDE209, OBTMBI, and BTBPE, which showed slightly higher RSD, i.e., 49.3%, 37.2%, and 34.9% respectively. Complementarity investigation of stool and blood samples allowed us to better characterize human exposure to these halogenated flame retardants. Exposure patterns differed significantly between stool and blood, notably in the relative abundance of BDE47, BDE100, BDE99, and BDE153 and the detection frequencies of BDE209, syn-DP, anti-DP, and DBDPE. There was no correlation between the two matrices' PBDEs concentration levels except for BDE153 (rho = 0.44, p < 0.01). Our results indicate that future epidemiological studies may benefit from the use of stool as a complementary matrix to blood, especially investigations into chemical impacts on the gut microbiome. Results also revealed that children from the GESTE cohort, an Eastern Canadian semi-rural cohort, are exposed to both historical and emergent flame retardants.

Cellular vimentin promotes the nuclear transport of the HBoV1 structural protein VP1u.

Human bocavirus 1 (HBoV1) is an important pathogen causing lower respiratory tract infection. The VP1 unique region (VP1u), consisting of 129 amino acids at the N-terminus of the HBoV1 structural protein VP1, is an important component of virus infection. Bioinformatics analysis predicted that HBoV1 VP1u exhibits two bipartite nuclear localization signals (NLS) and contains four basic regions (BRs). The two potential bipartite NLSs consist of BR2 and 3 and BR3 and 4, respectively. In this study, we inserted the truncated vp1u sequences into a double EGFP fusion expression vector and confirmed the vimentin (VIM)-HBoV1 VP1u interaction by mass spectrometry and immunoprecipitation. The results of our IFA analysis showed that all four VP1u BRs displayed strong nuclear transport functions. We further demonstrated that VP1u interacted with VIM and that they colocalized in the cytoplasm. VP1u expression in the cells enhanced the VIM expression, and the VP1u expression also increased upon VIM overexpression, although it was not affected by VIM knockdown. Upon VIM overexpression, VP1u nucleation was significantly enhanced, but was inhibited by VIM downregulation. These results indicate that the VP1u-VIM interaction could be involved in the nuclear transport of VP1u. VP1u nucleation might further affect HBoV1 replication and infection. This study could potentially help clarify the function of VP1u by further revealing the HBoV1 nuclear transport mechanism and provide a new approach for elucidating the molecular mechanism of HBoV1 replication.

In-situ TD-GCMS measurements of oxidative products of monoterpenes at typical vaping temperatures: implications for inhalation exposure to vaping products.

Vaping is gaining in popularity. However, there is still much that remains unknown about the potential risk and harms of vaping. Formation of oxidative products is one of such areas that are not well understood. In this study, we used an in-situ thermal desorption GC/MS method to investigate the formation of oxidative products of several monoterpenes at or below typical vaping temperatures. Among the five tested monoterpenes, the unchanged portion of the parent compound in the vapour varied from 97 to 98% for myrcene to 11-28% for terpinolene. The majority of formed oxidative products in the vapour have a molecular weight of 134 (loss of two hydrogens), 150 (insertion of one oxygen and loss of two hydrogen atoms) or 152 (insertion of one oxygen atom). Three products, likely to be p-(1-propenyl)-toluene, ß-pinone and fenchol were also observed. This is the first in-situ thermal desorption GC/MS study to investigate the possible formation of oxidative products of monoterpenes, one of the major components in vaping liquids, at temperatures that are relevant to the vaping process. Although the toxicity of inhaling these oxidative products is not clear yet, allergic and irritation reactions associated with oxidized monoterpene oils are well documented. Therefore, potential adverse effects of inhaling these oxidative products during vaping could be investigated to help support human risk assessment.

Concomitant Gastric Acid Suppressants on the Survival of Patients with Non-Small-Cell Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Meta-Analysis.

Background: The influence of concomitant use of gastric acid suppressants (AS) on survival of patients with non-small-cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is inconsistent according to previous studies. We performed a meta-analysis to evaluate the effect of additional AS in patients with NSCLC taking TKIs. Methods: Relevant observational studies were identified by a search of Medline, Embase, and Web of Science databases. Only studies with multivariate analyses were included. A random-effect model was used to combine the results. Results: Thirteen retrospective studies with 12259 patients were included. Pooled results showed that concomitant use of AS was associated with worse progression-free survival (PFS, adjusted hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.31 to 1.89, P < 0.001; I 2 = 65%) and overall survival (OS, adjusted HR: 1.38, 95% CI: 1.19 to 1.61, P < 0.001; I 2 = 70%) in NSCLC patients taking TKIs. Sensitivity analysis limited to studies including NSCLC with EGFR mutation showed consistent results (HR for PFS: 1.53, P=0.003; HR for OS: 1.43, P=0.001). Subgroup analyses indicated that the association between concomitant use of AS and poor survival was not significantly affected by the category of AS used (proton pump inhibitors or histamine type-2 receptor antagonists) or the country of the study (Asian or non-Asian, P for subgroup analysis all >0.05). Conclusions: Concomitant use of AS in patients with NSCLC taking TKIs may be associated with poor survival outcomes.

Distributionally robust optimization for fire station location under uncertainties.

Emergency fire service (EFS) systems provide rescue operations for emergencies and accidents. If properly designed, they can decrease property loss and mortality. This paper proposes a distributionally robust model (DRM) for optimizing the location of fire stations, the number of fire trucks, and demand assignment for long term planning in an EFS system. This is achieved by minimizing the worst-case expected total cost, including fire station construction cost, purchase cost for fire trucks, transportation cost, and penalty cost for not providing adequate service. The ambiguity in demands and travel durations distributions are captured through moment information and mean absolute deviation. A cutting plane method is used to solve the problem. Due to fact that it is computationally intensive for larger problems, two approximate methods are introduced; one that uses linear decision rules (LDRs), and another that adopts three-point approximations of the distributions. The results show that the heuristic method is especially useful for solving large instances of DRM. Extensive numerical experiments are conducted to analyze the model's performance with respect to different parameters. Finally, data obtained from Hefei (China) demonstrates the practical applicability and value of the model in designing an EFS system in a large metropolitan setting.

In Utero Exposure to Persistent Organic Pollutants and Childhood Lipid Levels.

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low- and high-density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6-7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p = 0.003), and non-significantly with HDL-C (p = 0.06) and TL (p = 0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p = 0.04), LDL-C (p = 0.04), and TL (p = 0.02). Our data indicate that in utero exposures to POPs may be associated with long lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data.

Intermediate volatile organic compounds emissions from vehicles under real world conditions.

Real-world vehicle emission factors (EFs) for the total intermediate volatile organic compounds (total-IVOCs) and volatile organic compounds (VOCs) from mixed fleets of vehicles were quantified in the Yangtze tunnel in Shanghai. Relationships of EFs of IVOCs with fleet compositions and vehicle speed as well as secondary organic formation potentials (SOAFPs) from IVOCs and VOCs were studied. Multiple linear regression (MLR) was used to estimate EFs of total-IVOCs for gasoline and diesel vehicles. IVOCs were classified into unresolved complex mixtures (unspeciated cyclic compounds and branched alkanes (b-alkanes)) and speciated targets (11 n-alkanes and ten polycyclic aromatic hydrocarbons (PAHs)). The results showed that the average EF of total-IVOCs was 24.9 ± 7.8 mg/(km·veh), which was comparable to that of VOCs. Unspeciated cyclic compounds and b-alkanes dominated the main composition (~77% and ~19%), followed by n-alkanes (~4%) and PAHs (~1%). EFs of IVOCs showed a significant, positive relationship with diesel vehicle fractions (p < 0.05). EFs of IVOCs dropped notably with the decrease of the diesel vehicle fractions. SOAFP produced by the total organic compounds (IVOCs + VOCs) was 8.9 ± 2.5 mg/(km·veh), in which up to 86% of SOAFP was from IVOCs. Estimated EFs of total-IVOCs for gasoline vehicles and diesel vehicles were 15.3 and 219.8 mg/(km·veh) respectively. Our results demonstrate that IVOCs emitted from diesel vehicles are the main emission sources under real world conditions and significant contributions of IVOCs emissions to SOA formation is evident, which indicates the necessity of making control policies to reduce IVOCs emissions from vehicles.

Kinetic and reaction mechanism of generated by-products in a photocatalytic oxidation reactor: Model development and validation.

Photocatalytic oxidation is a promising technology to control air pollution. However, the formation of hazardous by-products hinders the commercialization application of this technology. This paper reports the development of a novel by-products predictive model considering the mass transfer of the pollutant in the gas phase and kinetic reaction in the solid phase. Two challenge compounds from ketone group (acetone and methyl ethyl ketone) were examined for model validation in a continuous Photocatalytic Oxidation (PCO) reactor with TiO2 coated on silica fiber felts. A possible reaction pathway for degradation of each challenge compound was proposed based on identified by-products using analytical methods (GC-MS and HPLC). Formaldehyde, Acetaldehyde, Propionaldehyde, Ethanol, and acetic acid were detected as by-products of the Acetone and Methyl Ethyl Ketone in the PCO reactor. Different possible reaction rate scenarios were evaluated to find the best expression fitted to experimental data at the steady-state condition. The obtained reaction coefficients were then used to validate the model under various operating conditions, namely concentration, relative humidity, irradiation, and velocity variations. Higher concentration and irradiation, as well as lower relative humidity and velocity, resulted in more by-products generation. It was also observed that with enhancing residence time, mineralization efficiency (or CO2 formation) and by-products generation increases through PCO reaction. The model validation provided acceptable accuracy for both steady-state and transient conditions. Finally, the Health Risk Index was used to investigate the implications of generated by-products on human health under varying operating conditions.

A review on the analytical procedures of halogenated flame retardants by gas chromatography coupled with single quadrupole mass spectrometry and their levels in human samples.

Halogenated flame retardants (HFRs) market is continuously evolving and have moved from the extensive use of polybrominated diphenyl ether (PBDE) to more recent introduced mixtures such as Firemaster 550, Firemaster 680, DP-25, DP-35, and DP-515. These substitutes are mainly composed of non-PBDEs HFRs such as 2-ethyl-hexyl tetrabromobenzoate (TBB), bis(2-ethylhexyl) tetrabromophthalate (TBPH), 1,2-bis-(2,4,6-tribromophenoxy) ethane (BTBPE) and decabromodiphenyl ethane (DBDPE). Other HFRs commonly being monitored include Dechlorane Plus (DP), Dechlorane 602 (Dec602), Dechlorane 603 (Dec603), Dechlorane 604 (Dec604), 5,6-dibromo-1,10, 11, 12,13,13-hexachloro- 11-tricyclo[8.2.1.02,9]tridecane (HCDBCO) and 4,5,6,7-tetrabromo-1,1,3-trimethyl-3-(2,3,4,5-tetrabromophenyl)-2,3-dihydro-1H-indene (OBTMPI). This review aims at highlighting the advances in the past decade (2010-2020) on both the analytical procedures of HFRs in human bio-specimens using gas chromatography coupled with single quadrupole mass spectrometry and synthesizing the information on the levels of these HFRs in human samples. Human specimen included in this review are blood, milk, stool/meconium, hair and nail. The review summarizes the analytical methods, including extraction and clean-up techniques, used for measuring HFRs in biological samples, which are largely adopted from those for analysing PBDEs. In addition, new challenges in the analysis to include both PBDEs and a wide range of other HFRs are also discussed in this review. Review of the levels of HFRs in human samples shows that PBDEs are still the most predominant HFRs in many cases, followed by DP. However, emerging HFRs are also being detected in human despite of the fact that both their detection frequencies and levels are lower than PBDEs and DP. It is clearly demonstrated in this review that people working in the industry or living close to the industrial areas have higher HFR levels in their bodies.

4,5,6,7-Tetrabromo-2,3-dihydro-1,1,3-trimethyl-3-(2,3,4,5-tetrabromophenyl)-1H-indene (OBTMPI): Levels in humans and in silico toxicological profiles.

Limited human exposure and toxicity data are currently available for 4,5,6,7-Tetrabromo-2,3-dihydro-1,1,3-trimethyl-3-(2,3,4,5-tetrabromophenyl)-1H-indene (OBTMPI), a flame retardant often used for high temperature application of various polymer materials. Levels of OBTMPI in a cohort population that includes children and their co-residing parents (n = 217) in Canada were determined. Detection frequency of OBTMPI in the samples was 22.6%. OBTMPI levels were in general at sub-to low ng/g lipid weight level with a 95th percentile at 15.6 ng/g lipid weight. Compared to an earlier study conducted in 2008-2009 in the same region, results from this study show an increase in both detection frequency and concentration of OBTMPI. In silico toxicity predictions using Multicase CaseUltra and Leadscope Model Applier suggested that OBTMPI, and its possible metabolites in humans, while unlikely to be carcinogenic or mutagenic, exhibit some estrogen antagonist, androgen antagonist and estrogen binding capability reflective of possible endocrine disrupting properties.

Danggui Sini decoction protects against oxaliplatin-induced peripheral neuropathy in rats.

The effects of Danggui Sini decoction on peripheral neuropathy in oxaliplatin-induced peripheral is established. The results indicated that Danggui Sini decoction treatment significantly reduced the current amplitude of dorsal root ganglia cells undergoing agonists stimuli compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly inhibited the inflammatory response of dorsal root ganglia cells compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly enhanced the amounts of Nissl bodies in dorsal root ganglia cells compared to the Model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment improved ultra-microstructures of dorsal root ganglia cells. In conclusion, Danggui Sini decoction protected against neurotoxicity of oxaliplatin-induced peripheral neuropathy in rats by suppressing inflammatory lesions, improving ultra-microstructures, and enhancing amounts of Nissl bodies.

Lipopolysaccharide-Induced Acute Lung Injury Is Associated with Increased Ran-Binding Protein in Microtubule-Organizing Center (RanBPM) Molecule Expression and Mitochondria-Mediated Apoptosis Signaling Pathway in a Mouse Model.

BACKGROUND Acute lung injury (ALI) is a severe and life-threatening disorder treated in intensive care units. This study aimed to determine molecules or associated signaling pathways that are involved in lipopolysaccharide (LPS)-induced inflammation in an ALI model. MATERIAL AND METHODS An ALI mouse model was established by administering LPS (25 mg/kg via intratracheal instillation). Thirty-two ALI mice were divided into Model-4 h, Model-8 h, Model-12 h, and Model-24 h groups, while another 8 mice without LPS treatment were assigned as the Control group. Hematoxylin-eosin (HE) staining was used to evaluate inflammation of lung tissues. Wet weight/dry weight (W/D) ratio and myeloperoxidase (MPO) activity of lung tissue in ALI mice were evaluated. Expressions of Bcl-2, Bcl-XL, Bak, Bax, cleaved caspase-3 (C-caspase-3), and Ran-binding protein in microtubule-organizing center (RanBPM) were determined using Western blot analysis. RESULTS LPS administration caused obvious inflammatory cell infiltration of lung tissues in ALI mice. The W/D ratio of ALI mouse lung tissues was significantly higher in Model groups than in the Control group (p<0.05). MPO activity of ALI mice was remarkably higher in Model groups compared to the Control group (p<0.05). LPS-induced ALI model mice exhibited significantly higher levels of C-caspase 3 lung tissues compared to the Control group (p<0.05). LPS-induced ALI model mice had significantly lower Bcl-XL/Bcl-2 and remarkably higher Bak/Bax expression compared with the Control group (p<0.05). LPS-induced ALI model mice displayed obviously higher RanBPM expression than in the Control group (p<0.05). CONCLUSIONS Lipopolysaccharide-induced acute lung injury is associated with increased RanBPM molecule expression and with mitochondria-mediated apoptosis signaling pathway in a mouse model.

Synthesis and Electrochemical Behavior of LiFePO4-xFx (x = 0.05, 0.1, 0.15, 0.2) by Solvothermal Method.

The F-doped LiFePO4 material was prepared through a simple solvothermal method by applying hydrofluoric acid as the source of fluorine. The obtained LiFePO3.85F0.15 at 0.1 C and 10 C delivered a higher capacity of 153.185 and 81.972 mAh · g-1 compared with LiFePO4 at 0.1 C and 10 C (143.351 and 48.707 mAh·g-1).

Two-Dimensional Black Phosphorus: An Emerging Anode Material for Lithium-Ion Batteries.

Two-dimensional black phosphorus (2D BP), an emerging material, has aroused tremendous interest once discovered. This is due to the fact that it integrates unprecedented properties of other 2D materials, such as tunable bandgap structures, outstanding electrochemical properties, anisotropic mechanical, thermodynamic, and photoelectric properties, making it of great research value in many fields. The emergence of 2D BP has greatly promoted the development of electrochemical energy storage devices, especially lithium-ion batteries. However, in the application of 2D BP, there are still some problems to be solved urgently, such as the difficulty in the synthesis of large-scale high-quality phosphorene, poor environmental stability, and the volume expansion as electrode materials. Herein, according to the latest research progress of 2D BP in the field of energy storage, we systematically summarize and compare the preparation methods of phosphorene and discuss the basic structure and properties of BP, especially the environmental instability and passivation techniques. In particular, the practical application and challenges of 2D BP as anode material for lithium-ion batteries are analyzed in detail. Finally, some personal perspectives on the future development and challenges of BP are presented.

Correlations of phthalate metabolites in urine samples from fertile and infertile men: Free-form concentration vs. conjugated-form concentration.

In previous studies, the total content of urinary phthalate metabolites was commonly used to evaluate human exposure to phthalates. However, phthalate metabolites are mainly present in urine in two forms, conjugated and free. These metabolite forms in urine are more relevant to the biotransformation pathways of the phthalates in humans. Therefore, the concentration of these forms is more relevant to exposure related health outcomes than total content. In this study, instead of measuring total content, the free- and conjugated-form concentrations of phthalate metabolites in the urine of fertile and infertile men were measured. The main metabolites in urine of both groups are monoethyl phthalate (MEP) and the di-(2-ethylhexyl) phthalate (DEHP) metabolites. The geometric means of their both conjugated- and free-forms in the infertile group were higher than in the fertile group, specifically, 24.3 and 43.4 µg/g creatinine vs 8.5 and 28.9 µg/g creatinine, respectively, for MEP, and 50.0 and 9.1 µg/g creatinine vs 39.1 and 8.4 µg/g creatinine, respectively for total DEHP metabolites. We investigated the correlations of free- and conjugated-form phthalate metabolite concentrations between the infertile and fertile group as well as among different phthalate metabolites. The results showed that there was a statistically significant difference between the infertile and fertile group for monobenzyl phthalate (MBzP) in both free-form and conjugated-form. However, there was only a statistically significant difference between the two groups for conjugated-form MEP and MEHP, and no statistically significant difference between the two groups for free-form MEP and MEHP. The results of the Pearson correlation test revealed that the correlations between DEHP metabolites and the correlations between mid-sized phthalate metabolites (mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP) and mono-benzyl phthalate (MBzP)) were stronger than between these two clusters of metabolites. This study is the first attempt to examine possible effects of conjugated-form concentrations of phthalate metabolites on human fertility. The results of this study suggest that conjugated-form and free-form concentrations of urinary phthalate metabolites may be appropriate biomarkers for assessing human exposure to phthalates and association with health outcomes.

Artificial turf infill associated with systematic toxicity in an amniote vertebrate.

Artificial athletic turf containing crumb rubber (CR) from shredded tires is a growing environmental and public health concern. However, the associated health risk is unknown due to the lack of toxicity data for higher vertebrates. We evaluated the toxic effects of CR in a developing amniote vertebrate embryo. CR water leachate was administered to fertilized chicken eggs via different exposure routes, i.e., coating by dropping CR leachate on the eggshell; dipping the eggs into CR leachate; microinjecting CR leachate into the air cell or yolk. After 3 or 7 d of incubation, embryonic morphology, organ development, physiology, and molecular pathways were measured. The results showed that CR leachate injected into the yolk caused mild to severe developmental malformations, reduced growth, and specifically impaired the development of the brain and cardiovascular system, which were associated with gene dysregulation in aryl hydrocarbon receptor, stress-response, and thyroid hormone pathways. The observed systematic effects were probably due to a complex mixture of toxic chemicals leaching from CR, such as metals (e.g., Zn, Cr, Pb) and amines (e.g., benzothiazole). This study points to a need to closely examine the potential regulation of the use of CR on playgrounds and artificial fields.