Abstract  The thermal diffusivities of 2-ethoxy-2-methylpropane (ETBE) and 2-methoxy-2-methylbutane (TAME) (mass purity > 0.990, GC) were measured by.the dynamic light scattering method. The investigated p T regions are T = (293 to 523) K and p = (4 to 10) MPa, including saturated liquid, saturated vapor, and liquid. The expanded relative uncertainty in thermal diffusivity was estimated to be less than 2.4% over the whole investigated range. The influences of temperature and pressure on thermal diffusivity were presented. The empirical correlation of thermal diffusivities for both saturated liquid/vapor and liquid were also proposed with absolute average relative deviations (AARDs) of 0.22 and 0.26% for saturated-liquid ETBE and TAME, 0.13 and 0.20% for saturated-vapor ETBE and TAME, and 0.23 and 0.69% for liquid ETBE and TAME, respectively.

Abstract  Both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of nephropathy. Glomerular injury is associated with tubulointerstitial inflammation, and many studies show that tubulointerstitial changes correlate well with progressive renal functional decline. Strong evidence supports the concept that once established, proteinuric glomerular injury can cause tubular injury. This review briefly summarizes the pathophysiological consequences of glomerular damage that are responsible for tubulointerstitial injury. It further focuses on tubule-derived renal injury biomarkers that may be used to monitor the progression of kidney disease. This monitoring is predicted to become increasingly useful as novel therapeutic interventions preventing progressive renal damage are introduced. In particular, biomarkers of kidney dysfunction, such as urinary podocytes, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, hematopoietic growth factor-inducible neurokinin 1, or periostin, might be useful in the diagnosis or detection of early nephropathy and risk assessment of kidney disease. However, these biomarkers require further study before they are used in routine screening or in guiding patient therapy.

Abstract  The increasing availability of large collections of chemical structures and associated experimental data provides an opportunity to build robust QSAR models for applications in different fields. One common concern is the quality of both the chemical structure information and associated experimental data. Here we describe the development of an automated KNIME workflow to curate and correct errors in the structure and identity of chemicals using the publicly available PHYSPROP physicochemical properties and environmental fate datasets. The workflow first assembles structure-identity pairs using up to four provided chemical identifiers, including chemical name, CASRNs, SMILES, and MolBlock. Problems detected included errors and mismatches in chemical structure formats, identifiers and various structure validation issues, including hypervalency and stereochemistry descriptions. Subsequently, a machine learning procedure was applied to evaluate the impact of this curation process. The performance of QSAR models built on only the highest-quality subset of the original dataset was compared with the larger curated and corrected dataset. The latter showed statistically improved predictive performance. The final workflow was used to curate the full list of PHYSPROP datasets, and is being made publicly available for further usage and integration by the scientific community.

Abstract  Increases in glomerular size and thickening of the glomerular basement membrane are constant features that accompany growth and maturation in animals. Yet, some animals have chronic progressive nephropathy characterized by glomerulosclerosis and tubulointerstitial fibrosis. In these animals, clinically significant reductions in glomerular filtration rate may compromise health, particularly when other renal diseases occur concomitantly. Progressive thickening of the glomerular basement membrane is accompanied by changes in its composition, which may be responsible for changes in podocyte morphology and proteinuria. Within the tubulointerstitium, generalized accumulation of fibronectin and thrombospondin are accompanied by blood vessel proliferation. Fragility of these blood vessels with intermittent bleeding may initiate an inflammatory process that leads to focal areas of tubular atrophy and scarring. The pathogenesis of these lesions is unknown. Genetic background, sex, and environmental factors influence the tempo of progressive sclerosis, although these factors are not primary determinants of this lesion. This review highlights the structural changes that occur in the kidney with aging. Because the lesions are structurally similar, information gleaned from studies of aging animals should be relevant to understanding the loss of renal function that occurs in aging humans.

Abstract  The addition of renewable fuels to gasoline, such as bio-alcohols or bio-ethers is required in order to be in compliance with current environmental directives. Nevertheless, they change fuel properties which could affect standards compliance, engine performance and air emissions. This paper studies the impact of ethanol (EtOH), isobutanol (iBtOH) or ethyl tert-butyl ether (ETBE) on the Reid Vapour Pressure (RVP), distillation curves, density and other related gasoline properties, which belong to the group of relevant specifications that affect engine operation. The main conclusion is that the addition of ETBE or iBtOH has important advantages over EtOH in terms of energy density, air/fuel ratio, vapour pressure, renewable content and other effects; it was also found that the addition of ETBE affects equally and linearly the properties of two kinds of base gasolines as compared with other studies. (C) 2015 Elsevier Ltd. All rights reserved.

Abstract  Alcohol drinking increases the risk for a number of cancers. Currently, the highest risk (Group 1) concerns oral cavity, pharynx, larynx, esophagus, liver, colorectum, and female breast, as assessed by the International Agency for Research on Cancer (IARC). Alcohol and other beverage constituents, their metabolic effects, and alcohol-related unhealthy lifestyles have been suggested as etiological factors. The aim of the present survey is to evaluate the carcinogenic role of acetaldehyde in alcohol-related cancers, with special emphasis on the genetic-epidemiological evidence. Acetaldehyde, as a constituent of alcoholic beverages, and microbial and endogenous alcohol oxidation well explain why alcohol-related cancers primarily occur in the digestive tracts and other tissues with active alcohol and acetaldehyde metabolism. Genetic-epidemiological research has brought compelling evidence for the causality of acetaldehyde in alcohol-related cancers. Thus, IARC recently categorized alcohol-drinking-related acetaldehyde to Group 1 for head and neck and esophageal cancers. This is probably just the tip of the iceberg, since more recent epidemiological studies have also shown significant positive associations between the aldehyde dehydrogenase ALDH2 (rs671)*2 allele (encoding inactive enzyme causing high acetaldehyde elevations) and gastric, colorectal, lung, and hepatocellular cancers. However, a number of the current studies lack the appropriate matching or stratification of alcohol drinking in the case-control comparisons, which has led to erroneous interpretations of the data. Future studies should consider these aspects more thoroughly. The polymorphism phenotypes (flushing and nausea) may provide valuable tools for future successful health education in the prevention of alcohol-drinking-related cancers.

Abstract  Tertiary butyl alcohol (TBA) was administered to groups of 15 female B6C3F1 mice in drinking water at concentrations of 0, 2.0 or 20 mg TBA ml(-1), for 14 days, for assessment of gross and histological changes in the liver and thyroid, thyroid hormones (T3, T4, and TSH), total hepatic cytochrome P450 (Cyp) content, specific Cyp activities and quantitative PCR analysis of specific Cyp enzymes (Cyp1a1, Cyp2b9, Cyp2b10, Cyp3a11), sulfuryltransferases (ST1a1, ST2a2, and STn) and glucuronyltransferases (UGT1a1, UGT2b1, and UGT2b5). Phenobarbital (PB) was administered to a positive control group by oral gavage at a daily dose of 80 mg kg(-1). TBA caused, on day 14, a reduction in circulating T3 (12-15% decrease) and a dose-dependent reduction in T4 (13-22% decrease), with no evidence of thyroid pathology. Two of five livers examined in the 20 mg TBA ml(-1) dose group showed mild, diffuse centrilobular hypertrophy. On day 14, Cyp 7-benzoxyresorufin-O-debenzylase activity was significantly induced 12-fold by TBA at 20 mg ml(-1), and 1.8-fold at the 2.0 mg TBA ml(-1) concentration. Cyp 7-pentoxyresorufin-O-dealkylase activity was slightly induced (2.1-fold) by 20 mg TBA ml(-1) on day 14. Quantitative PCR analysis of gene transcripts showed a significant induction of Cyp2b10 and ST1a1 with both TBA concentrations, and a slight induction of Cyp2b9 at 20 mg TBA ml(-1) only. PB induced all phase I and phase II gene transcripts except for Cyp1a1 and Cyp2b9. These findings suggest that TBA, at and below doses used in chronic studies, is an inducer of phase I and phase II liver enzymes, with resulting decreases in circulating thyroid hormones in B6C3F1 mice.

Abstract  Methyl tertiary butyl ether (MTBE) is widely used in gasoline as an oxygenator and octane enhancer. There is also an interest in using the ethyl tertiary butyl (ETBE) and methyl tertiary amyl (TAME) ethers. We measured the blood, water, and olive oil/air partition coefficients in vitro of MTBE, ETBE, TAME and tertiary butyl alcohol (TBA), a metabolite of MTBE and ETBE. The results indicate similar uptake and distribution behavior for the three ethers and a slight affinity for fatty tissues. The partition coefficients of TBA indicate that this metabolite is not excreted via the lungs to any great extent and that it is preferentially distributed in body water. Further, we exposed 10 healthy male volunteers to MTBE vapor at 5, 25 and 50 ppm for 2 h during light physical exercise. Uptake and disposition were studied by measuring MTBE and TBA in inhaled and exhaled air, blood and urine. Low uptake, high post-exposure exhalation, and low blood clearance indicate slow metabolism of MTBE relative to many other solvents. A low recovery of TBA in urine (below 1% of uptake) indicates further metabolism of TBA. The concentration of MTBE and TBA in blood was proportional to exposure level suggesting linear kinetics up to 50 ppm. The half life of 7-10 h in blood and urine indicates that TBA would be more suitable than the parent compound as a biomarker for MTBE exposure. Subjective ratings (discomfort, irritative symptoms, CNS effects) and eye (redness, tear film break-up time, conjunctival damage, blinking frequency) and nose (peak expiratory flow, acoustic rhinometry, inflammatory markers in nasal lavage) measurements indicated no or minimal effects of MTBE.

Abstract  Pregnant CD-1 mice (30 per group) and female New Zealand White rabbits (15 per group) were exposed by inhalation to 0, 1000, 4000 and 8000 ppm methyl tertiary-butyl ether (MTBE) vapor for 6 h a day during gestational days (GD) 6-15 and 6-18, respectively. Maternal body weights, clinical observations and food consumption were recorded throughout gestation for both species. At scheduled euthanization (GD 18 for mice and GD 29 for rabbits), fetuses were weighed, sexed and examined for external, visceral (including craniofacial) and skeletal alterations. For both species, the pregnancy rate was high and equivalent across all groups; no pregnant animals died or aborted. There were no does that delivered early, but there were three mouse dams in the control group and two dams in the 4000 ppm group that delivered early and were removed from the study. In mice, maternal body weights, body weight gain, corrected maternal gestational weight change and food consumption were significantly reduced in mice at 8000 ppm. Hypoactivity and ataxia were observed in dams exposed to 4000 and 8000 ppm. Gestational parameters affected at 8000 ppm included post-implantation loss (due to increased late resorptions and dead fetuses) and altered sex ratio (decreased males); fetal body weights per litter were reduced at 4000 and 8000 ppm. There was a significantly increased incidence of cleft palate at 8000 ppm; this resulted in increased incidences of pooled external and visceral malformations and of total malformations at this exposure concentration. There were also treatment-related increases in the incidence of individual skeletal variations at 4000 and 8000 ppm. In rabbits, maternal weight gain and food consumption were significantly reduced at 4000 and 8000 ppm. Relative liver weights were also reduced at 8000 ppm. All gestational parameters were equivalent across all groups, including pre- and post-implantation loss, fetal sex ratios, litter size and fetal weights/litter. There was no evidence of treatment-related teratogenicity observed at any dose tested in rabbits. The no-observed-effect levels (NOELs) for maternal and developmental toxicity were both 1000 ppm in mice and 1000 ppm and at least 8000 ppm, respectively, in rabbits.

Abstract  This report has been prepared by TRC Environmental Corporation (TRC) for ARCO Chemical Company. It presents the results and conclusions from an odor and taste thresholdevaluation project conducted at TRC's Odor Laboratory in February, 1993.The gasoline oxygenates Methyl Tertiary Butyl Ether (MTBE) and Ethyl Tertiary Butyl Ether (ETBE) were evaluated for their odor detectibility and recognition thresholds in air and water as well as their taste threshold in water. MTBE (99.9% purity) and ETBE (99.0-99.5% purity) were obtained from ARCO Chemical Company.

Abstract  A simple procedure for the determination of methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), ethyl butyl ether (EBE), tert-amyl methyl ether (TAME), benzene, toluene, ethylbenzene, and xylenes (BTEX) in water using headspace (HS) solid-phase microextraction (HS-SPME) was developed. The analysis was carried out by gas chromatography (GC) equipped with flame ionization detector (FID) and 100% dimethylpolysiloxane fused capillary column. A 2(7-4) Plackett-Burman design for screening and a central composite design (CCD) for optimizing the significant variables were applied. Fiber type, extraction temperature, sodium chloride concentration, and headspace volume were the significant variables. A 65 Ám poly(dimethylsiloxane)-divinylbenzene (PDMS-DVB) SPME fiber, 10 degrees C, 300 g/l, and 20 ml of headspace (in 40 ml vial) were respectively chosen for the best extraction response. An extraction time of 10 min was enough to extract the ethers and BTEX. The relative standard deviation (R.S.D.) for the procedure varied from 2.6 (benzene) to 8.5% (ethylbenzene). The method detection limits (MDLs) found were from 0.02 (toluene, ethylbenzene, and xylenes) to 1.1 Ág/l (MTBE). The optimized method was applied to the analysis of the rivers, marinas and fishing harbors surface waters from Gipuzkoa (North Spain). Three sampling were done in 1 year from June 2002 to June 2003. Toluene was the most detected analyte (in 90% of the samples analyzed), with an average concentration of 0.56 Ág/l. MTBE was the only dialkyl ether detected (in 15% of the samples) showing two high levels over 400 Ág/l that were related to accidental fuel spill.

Abstract  Male and female Sprague-Dawley rats of different ages at the start of the experiments (12 day embryos, and 7 and 25 weeks old) were administered fromaldehyde in drinking water at different doses (2,500 or 1,500, 1,000, 500, 100, 50, 10, 0 ppm). An increased incidence of leukemias and of gastro-intestinal tumors was observed in formaldehyde treated rats. Gastro-intestinal tumors are exceptionally rare in the rats of the colony used. These results, together with the ones obtained by other Authors on rats exposed by inhalation to formaldehyde, indicate that this compound is an experimental multipotential carcinogen. The experimental results presented in this report give scientific support to the epidemiological observation of a higher incidence of leukemias and of gastro-intestinal cancers among the people occupationally exposed.

Abstract  In Catalonia (northeast Spain), a monitoring program was carried out to determine methyl tert.-butyl ether (MTBE), its main degradation products, tert.-butyl alcohol (TBA), tert.-butyl formate (TBF), and other gasoline additives, the oxygenate dialkyl ethers ethyl tert.-butyl ether, tert.-amyl methyl ether and diisopropyl ether and the aromatic compounds benzene, toluene, ethylbenzene and xylene (BTEX) in 21 groundwater wells that were located near different gasoline point sources (a gasoline spill and underground storage tank leakage). Purge-and-trap coupled to gas chromatographyûmass spectrometry was optimised for the simultaneous determination of the above mentioned compounds and enabled to detect concentrations at ng/l or sub-Ág/l concentrations. Special attention was given to the determination of polar MTBE degradation products, TBA and TBF, since not much data on method performance and environmental levels are given on these compounds in groundwater. All samples analysed contained MTBE at levels between 0.3 and 70 Ág/l. Seven contaminated hot spots were identified with levels up to US Environmental Protection Agency drinking water advisory (20û40 Ág/l) and a maximum concentration of 670 Ág/l (doubling the Danish suggested toxicity level of 350 Ág/l). Samples with high levels of MTBE contained 0.1û60 Ág/l of TBA, indicating (but not proving) in situ degradation of parent compound. In all cases, BTEX was at low concentrations or not detected showing less solubility and persistence than MTBE. This fact confirms the suitability of MTBE as a tracer or indicator of long-term gasoline contamination than the historically used BTEX.

Abstract  T-Butyl alcohol (TBA) was administered in drinking water to F344/N rats and B6C3F1 mice for two years using 60 animals/dose/sex/species. Male rats received doses of 0. 1.25. 2.5. or 5 mg/ml and females received 0, 2.5, 5, or 10 mg/ml. resulting in average daily doses of approximately 85, 195, or 420 mg TBA/kg body weight for males and 175, 330, or 650 mg/kg for females. Ten rats per group were evaluated after 15 months. Male and female mice received doses of 0, 5, 10, or 20 mg/m, resulting in average daily doses of approximately 535, l,035, or 2.065 mg TBA/kg body weight for males and 510, 1,015, or 2,105 mg/kg for females. Survival was significantly reduced in male rats receiving 5mg/ml, female rats receiving 10 mg/ml, and male mice receiving 20 mg/ml. Long-term exposure to TBA produced increased incidences of renal tubule adenoma and carcinoma in male rats; transitional epithelial hyperplasia of the kidney in male and female rats; follicular cell adenoma of the thyroid in female mice: and follicular cell hvperplasia of the thyroid and inflammation and hyperplasia of the urinary bladder in male and female mice. In addition, a slight increase in follicular cell adenoma or carcinoma of the thyroid (combined) in male mice may have been related to the administration of TBA.