Isocyanate Exposure Below Analytical Detection When a Paint Brush and Roller Are Used to Apply Moisture-Cure Polyurethane Paint.

Isocyanate exposure is known to be hazardous when polyurethane paints are applied with a spray gun, but less is known of exposure when paint is applied with a paint brush and roller. Concentrations of 1,6-hexamethylene diisocyanate (HDI) monomer and three HDI polymers were assessed when two moisture-cure polyurethane paints containing 31-35% isocyanates were applied with a paint roller and brush. Short-term 15-min samples were taken during paint application in an indoor test environment with no ventilation (n= 12); in an outdoor test environment (n= 11); and in an outdoor in-situ assessment (n= 22). The outdoor in-situ assessment involved the painting of a bus shelter and light poles at a public transit station over two night shifts. All isocyanate samples were below analytical detection. The analytical limits of detection for HDI monomer, HDI biuret, HDI isocyanurate, and HDI uretdione were 0.005, 0.84, 0.87, and 0.88 µg, respectively. The finding that isocyanate concentrations were below detection is attributed to the use of paint roller and brush which minimize paint aerosolization and the paint formulation itself which contained <1% of volatile HDI monomer.

Randomized trial of daclatasvir and asunaprevir with or without PegIFN/RBV for hepatitis C virus genotype 1 null responders.

BACKGROUND & AIMS: Patients with chronic hepatitis C virus (HCV) infection and prior null response (<2 log HCV RNA decline after ⩾ 12 weeks of PegIFN/RBV) have limited options. We evaluated daclatasvir plus once- or twice-daily asunaprevir in non-cirrhotic genotype 1 null responders. METHODS: In this randomized, phase 2a, open-label, 24-week treatment study, 101 patients received daclatasvir (60 mg) once-daily. In addition, 38 genotype 1b patients received asunaprevir (200mg) twice- (DUAL A1) or once-daily (DUAL A2); 36 genotype 1a and 5 genotype 1b patients received asunaprevir twice- (QUAD B1) or once-daily (QUAD B2) plus PegIFN/RBV; and 18 genotype 1a and 4 genotype 1b patients received asunaprevir twice-daily plus ribavirin (TRIPLE B3). The primary endpoint was undetectable HCV RNA 12 weeks post-treatment (sustained virologic response, SVR12). RESULTS: Across all groups, mean HCV RNA was ⩾ 6 log IU/ml, and 99% of patients had a non-CC IL28B genotype. SVR12 rates were 78% (A1), 65% (A2), 95% (B1), and 95% (B2). In B3, most genotype 1a patients experienced virologic breakthrough. The most common adverse events were headache, diarrhea, and asthenia. Grade 3-4 aminotransferase elevations were infrequent and not treatment-limiting. CONCLUSIONS: In genotype 1 null responders, daclatasvir plus twice-daily asunaprevir DUAL therapy is effective for most genotype 1b patients, and daclatasvir, asunaprevir, and PegIFN/RBV QUAD therapy is effective for nearly all genotype 1a and 1b patients; but neither DUAL nor TRIPLE therapy is effective for genotype 1a patients. Interferon-free regimens including daclatasvir and twice-daily asunaprevir for genotype 1 null responders should be tailored to subtype.

Estimation of mouth level exposure to smoke constituents of cigarettes with different tar levels using filter analysis.

A nicotine part-filter method can be applied to estimate smokers' mouth level exposure (MLE) to smoke constituents. The objectives of this study were (1) to generate calibration curves for 47 smoke constituents, (2) to estimate MLE to selected smoke constituents using Japanese smokers of commercially available cigarettes covering a wide range of International Organization for Standardization tar yields (1-21mg/cigarette), and (3) to investigate relationships between MLE estimates and various machine-smoking yields. Five cigarette brands were machine-smoked under 7 different smoking regimes and smoke constituents and nicotine content in part-filters were measured. Calibration curves were then generated. Spent cigarette filters were collected from a target of 50 smokers for each of the 15 brands and a total of 780 filters were obtained. Nicotine content in part-filters was then measured and MLE to each smoke constituent was estimated. Strong correlations were identified between nicotine content in part-filters and 41 out of the 47 smoke constituent yields. Estimates of MLE to acetaldehyde, acrolein, 1,3-butadiene, benzene, benzo[a]pyrene, carbon monoxide, and tar showed significant negative correlations with corresponding constituent yields per mg nicotine under the Health Canada Intense smoking regime, whereas significant positive correlations were observed for N-nitrosonornicotine and (4-methylnitrosoamino)-1-(3-pyridyl)-1-butanone.

Inkjet-printed flexible non-enzymatic lactate sensor with high sensitivity and low interference using a stacked NiOx/NiOx-Nafion nanocomposite electrode with clinical blood test verification.

In this paper, we present a flexible, inkjet-printed, non-enzymatic lactate sensor with high sensitivity and specificity, using a stacked nickel oxide-Nafion nanocomposite/nickel oxide working electrode. Instead of deploying a pure Nafion film on the top of the nickel oxide particles, the nickel oxide-Nafion nanocomposite layer in the new electrode scheme functions not only as an anti-interfering layer but also a reactive layer and the bottom pure nickel oxide layer free from interfering substances mainly participates in the redox reaction to enhance the sensing current. Experimental results show that the sensor with a working electrode printed using a 30 µL NiOx ink and a mixture of 30 µL NiO and 4 µL Nafion ink can exhibit an anti-interference ability of >95%, a sensitivity of 20.56 nA/mM/mm2, and limit of detection (LoD) of 0.27 mM satisfying the criteria for human lactate detection. In clinical trial, blood plasma test results show that lactate levels detected using this sensor have a strong linear correlation coefficient square of 0.959 with those measured using the colorimetry method used in hospitals, indicating its potential for application in the management of patients with abnormal lactate values requiring intensive care.

The immune complex transfer enzyme immunoassay: Mechanism of improved sensitivity compared with conventional sandwich enzyme immunoassay.

Immune complex transfer enzyme immunoassay (ICT-EIA) is one of the technologies which enables ultrasensitive measurements of protein biomarkers. The ICT-EIA uses two types of beads and sandwich-shaped immune complexes are transferred from the 1st bead to the 2nd bead in the assay. The purpose of the study is to reveal the reason why the ICT-EIA achieves ultrasensitive measurements by making a detailed comparison between conventional sandwich enzyme immunoassay (Sand-EIA) and ICT-EIA. ICT-EIAs for cytokines were developed and the sensitivities were compared with the sandwich EIAs. ICT-EIAs had about 100 times higher sensitivities because of markedly decreased non-specific signals derived from non-specific binding of detection antibody conjugates onto the polystyrene bead. The results have enabled us to show the importance of reducing non-specific signals in EIAs to obtain higher sensitivities. This methodology should be more valuable if combined with a different label detection system such as digital counting or immuno-PCR, which may enable the detection of single target protein molecules in the near future.

Prenatal bisphenol A and birth outcomes: MOCEH (Mothers and Children's Environmental Health) study.

Bisphenol A (BPA) is used primarily in the production of polycarbonate plastics and epoxy resins. Widespread exposure to BPA has created a great deal of concern regarding its potential adverse effects on human health. This study examined the relationship between prenatal BPA exposure and birth outcomes, including birth weight, birth length, and ponderal index considering gender difference. A multi-center birth cohort study, Mothers and Children's Environmental Health (MOCEH) has been established in Korea since 2006. Study subjects are 757 pregnant women from the original cohort, who had their urinary BPA level measured during the third trimester, as well as information on birth outcome, prior medical history, psychosocial status, health behavior, environmental exposure as well as socio-demographic characteristics. Regression analysis was performed to assess the effect of BPA on birth outcome. The geometric mean concentration of BPA in pregnant women was 1.29 µg/L (1.87 µg/g creatinine) during late pregnancy. Urinary BPA concentrations were shown to be higher in women with a higher income level. Univariate regression analysis revealed a significant association between BPA levels and birth weight. In adjusted analysis, the second tertile of maternal BPA exposure exhibited an increase in birth weight, relative to the first tertile (p=0.04). These relationships were more pronounced in male neonates. Also, prenatal exposure to BPA was associated with an increase of ponderal index in total, and especially female neonates. This study shows that the association of prenatal exposure to BPA with anthropometric measures, such as birth weight and birth length, differed by gender. Further study is required to more fully elaborate this relationship between prenatal BPA exposure and birth outcome.

Associations of phthalate concentrations in floor dust and multi-surface dust with the interior materials in Japanese dwellings.

Phthalates are widely used as plasticizers in numerous products. However, there has been some concern about the various effects they may have on human health. Thus, household phthalate levels are an important public health issue. While many studies have assessed phthalate levels in house dust, the association of these levels with building characteristics has scarcely been examined. The present study investigated phthalate levels in house dust samples collected from the living areas of homes, and examined associations between these phthalate levels and the interior materials. Dust was collected from two portions of the living area: floor dust from the entire floor surface, and multi-surface dust from objects more than 35 cm above the floor. The levels of seven phthalates were measured using gas chromatography/mass spectrometry in selective ion monitoring mode. Phthalate levels were higher in multi-surface dust than in floor dust. Among floor dust samples, those from dwellings with compressed wooden flooring had significantly higher levels of di-iso-butyl phthalate compared to those with other floor materials, while polyvinyl chloride (PVC) flooring was associated with higher di-2-ethylhexyl phthalate (DEHP) levels. Among multi-surface dust samples, higher levels of DEHP and di-iso-nonyl phthalate (DINP) were found in samples from homes with PVC wallpaper than without. The number of PVC interior materials was significantly positively correlated with the levels of DEHP and DINP in multi-surface dust. The phthalate levels in multi-surface dust were associated with the interior surface materials, and those in floor dust were directly related to the flooring materials. Our findings show that when using house dust as an exposure assessment, it is very important to note where the samples were collected from. The present report provides useful information about the association between phthalates and dust inside dwellings, which will assist with establishing public health provisions.

Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate (DEHP) for PVC production workers, using personal air sampling and urinary metabolite monitoring.

Because of troubling reports of high urinary metabolite levels and adverse reproductive health effects in workers exposed to di(2-ethylhexyl)phthalate (DEHP) in occupational settings, concern about exposure to DEHP in occupational settings is increasing. However, the contributions of different routes of exposure to DEHP are unclear. We used personal air sampling and biomonitoring to determine the contribution of inhalation exposure to the body burden of DEHP in the workplace. Eighty-nine workers (high-exposure group: 66 raw-materials workers; low-exposure group: 23 administrative workers) were recruited from three polyvinyl chloride (PVC) factories. Urinary levels of mono(2-ethylhexyl) phthalate (MEHP), (mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were measured in pre-shift and post-shift samples. The geometric means of airborne concentrations of DEHP were 5.3 µg/m3 (low-exposure group) and 32.7 µg/m3 (high-exposure group) (P<0.01). Correlation analysis showed a consistently significant association between airborne DEHP concentration and urinary DEHP metabolite levels in the high-exposure group. Calculating daily DEHP intake based on total urinary metabolite levels showed that the geometric means of total daily urinary metabolite levels of DEHP were 9.2 µg/kg/day (low-exposure group) and 15.5 µg/kg/day (high-exposure group) (P<0.01). A quartile analysis of all workers showed a significant trend toward an association between the individual contribution of inhalation exposure to DEHP and urinary DEHP metabolite levels, for which the mean inhalation contribution was 46.7% in the highest quartile. We conclude that inhalation-absorbed airborne DEHP significantly increased the total body burden of DEHP in these occupationally exposed workers.

The use of coenzyme Q0 as a template in the development of a molecularly imprinted polymer for the selective recognition of coenzyme Q10.

In this work, a novel molecularly imprinted polymer (MIP) for use as a solid phase extraction sorbent was developed for the determination of coenzyme Q10 (CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial oxidative phosphorylation and a powerful antioxidant agent found in low concentrations in biological samples. This fact and its high hydrophobicity make the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised using coenzyme Q0 as the template, methacrylic acid as the functional monomer, acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker and benzoyl peroxide as the initiator. Various parameters affecting the polymer preparation and extraction efficiency were evaluated. Morphological characterisation of the MIP and its proper comparison with C18 as a sorbent in solid phase extraction were performed. The optimal conditions for the molecularly imprinted solid phase extraction (MISPE) consisted of 400 µL of sample mixed with 30 mg of MIP and 600 µL of water to reach the optimum solution loading. The loading was followed by a washing step consisting of 1 mL of a 1-propanol solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After clean-up, the CoQ10 in the samples was analysed by high performance liquid chromatography. The extraction recoveries were higher than 73.7% with good precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5 µg g(-1), respectively, and a linear range between 7.5 and 150 µg g(-1) of tissue was achieved. The new MISPE procedure provided a successful clean-up for the determination of CoQ10 in a complex matrix.

Dermal absorption and hydrolysis of methylparaben in different vehicles through intact and damaged skin: using a pig-ear model in vitro.

Currently, there is a trend to reduce of parabens use due to concern about the safety of their unmetabolised forms. This paper focused on dermal absorption rate and effectiveness of first-pass biotransformation of methylparaben (MP) under in-use conditions of skincare products. 24-h exposure of previously frozen intact and tapestripped (20 strips) pig-ear skin to nine vehicles containing 0.1% MP (AD, applied dose of 10 µg/cm²), resulted in 2.0-5.8%AD and 2.9-7.6%AD of unmetabolised MP, and 37.0-73.0%AD and 56.0-95.0%AD of p-hydroxybenzoic acid, respectively, in the receptor fluid. The absorption rate of MP was higher from emulsions than from hydrogels, from enhancer-containing vehicles than from enhancer-free vehicles, and when skin was damaged. Experiments confirmed that the freezing of pig-ear skin slightly reduces hydrolysis of MP. After 4-h exposure of intact freshly excised and intact frozen stored skin, amount of

Supersaturated polymeric micelles for oral cyclosporine A delivery.

Polymeric micelles provide a promising platform for improving oral absorption of poorly soluble drugs. However, improved understanding of how drug retention within the hydrophobic micelle core can reduce drug absorption is required. We designed supersaturated polymeric micelles (Super-PMs) to increase molecularly dissolved drug concentration and gain an insight into the effect of the degree of supersaturation on oral absorption of cyclosporine A (CsA) in rats. The drug release from Super-PMs increased with an increase in initial supersaturation degrees in micelles. The cellular uptake of coumarin-6 was reduced by the retention of drug in polymer micelles. The transport flux of CsA across Caco-2 monolayer was increased with initial supersaturation degrees of 0.81-3.53 (p < 0.05). However, increase in supersaturation to 5.64 actually resulted in decreased CsA transport. The same trend was observed in a rat in vivo absorption study, in which the highest bioavailability of 134.6 ± 24.7% (relative to a commercial product, Sandimmun Neoral®, p<0.01) was achieved when the supersaturation degree was 3.53. These results demonstrated that Super-PMs were a promising drug delivery system for compounds with low aqueous solubility. This study also provided an experimental proof for the hypothesis that moderately supersaturated formulations are valuable alternative to high supersaturation formulations, resulting in optimal in vivo performance, and the degree of supersaturation should be carefully controlled to optimize drug absorption.

Membrane assisted micro-solid phase extraction of pharmaceuticals with amino and urea-grafted silica gel.

Individual polar sorbents with surface-displayed amino groups (APS) and non-nucleophilic urea-groups (UPS), were prepared by chemical modification of granular silica gel with bifunctional silane coupling reagents. In this preliminary study, they were separately employed for micro-solid phase extraction (µ-SPE) of the quarternary salt of Amitriptyline (Ami), Carbamazepine (Cbz), Ketoprofen (Ket) and Diclofenac (Dfn) from aqueous samples in conjunction with high performance liquid chromatography. The resulting enrichment factors for both APS and UPS are comparable and exceeded those of µ-SPE involving commercial C18-silica gel sorbents. The presence of highly polar, but non-basic and non-nucleophilic surfaces on UPS prompted the development of a UPS-based µ-SPE method. Good linear correlation was found over a concentration range of 0-50 µg L(-1) with limits of detection ranging from 0.66 to 2.36 µg L(-1)). Limits of quantification between 1.61 and 7.88 µg L(-1) were obtained. HPLC analyses indicated that relative recoveries of 123% for Ami, 65.6% for Cbz, 71.2% for Ket and 66.5% for Dfn were obtained during µ-SPE of spiked (10 µg L(-1)) environmental water samples with percentage relative standard deviations (%RSD) of between 2.1% and 12.6%.