Composition of e-cigarette aerosols: A review and risk assessment of selected compounds.

The potential harms and benefits of e-cigarettes, or electronic nicotine delivery systems (ENDS), have received significant attention from public health and regulatory communities. Such products may provide a reduced risk means of nicotine delivery for combustible cigarette smokers while being inappropriately appealing to nicotine naive youth. Numerous authors have examined the chemical complexity of aerosols from various open- and closed-system ENDS. This body of literature is reviewed here, with the risks of ENDS aerosol exposure among users evaluated with a margin of exposure (MoE) approach for two non-carcinogens (methylglyoxal, butyraldehyde) and a cancer risk analysis for the carcinogen N-nitrosonornicotine (NNN). We identified 96 relevant papers, including 17, 13, and 5 reporting data for methylglyoxal, butyraldehyde, and NNN, respectively. Using low-end (minimum aerosol concentration, low ENDS use) and high-end (maximum aerosol concentration, high ENDS use) assumptions, estimated doses for methylglyoxal (1.78 × 10-3-135 µg/kg-bw/day) and butyraldehyde (1.9 × 10-4-66.54 µg/kg-bw/day) corresponded to MoEs of 227-17,200,000 and 271-280,000,000, respectively, using identified points of departure (PoDs). Doses of 9.90 × 10-6-1.99 × 10-4 µg/kg-bw/day NNN corresponded to 1.4-28 surplus cancers per 100,000 ENDS users, relative to a NNN-attributable surplus of 7440 per 100,000 cigarette smokers. It was concluded that methylglyoxal and butyraldehyde in ENDS aerosols, while not innocuous, did not present a significant risk of irritant effects among ENDS users. The carcinogenic risks of NNN in ENDS aerosols were reduced, but not eliminated, relative to concentrations reported in combustible cigarette smoke.

Synthesis and spectroscopic characterization of 13 C4 -labeled 4-cyano-2-oxobutyraldehyde semicarbazone: A metabolite of nitrofurazone.

Nitrofurazone usage in food-producing animals is prohibited in most countries, including the United States. Regulatory agencies regularly monitor its use in domestic, export/import animals' food products by measuring the semicarbazide (SEM) metabolite as a biomarker of nitrofurazone exposure. However, the use of SEM is controversial because it is also produced in food naturally and thus gives false positive results. A cyano-metabolite, 4-cyano-2-oxobutyraldehyde semicarbazone (COBS), is proposed as an alternate specific marker of nitrofurazone to distinguish nitrofurazone from treated or untreated animals. A synthetic method was developed to produce COBS via metallic hydrogenation of nitrofurazone. The product was isolated and characterized by one- and two-dimensional nuclear magnetic spectroscopy (NMR) experiments, Fourier-transform infrared spectroscopy (FT-IR), and mass spectrometry. The developed synthetic procedure was further extended to synthesize isotopically labeled 4-[13 C]-cyano-2-oxo- [2, 3, 4-13 C3 ]-butyraldehyde semicarbazone. Labeled COBS is useful as an internal standard for its quantification in food-producing animals. Thus, the developed method provides a possibility for its commercial synthesis to procure COBS. This is the first synthesis of the alternate specific marker metabolite of nitrofurazone for possible usage in regulatory analysis to solve a real-world problem.

Engineering of a butyraldehyde dehydrogenase of Clostridium saccharoperbutylacetonicum to fit an engineered 1,4-butanediol pathway in Escherichia coli.

1,4-Butanediol (1,4-BDO) is currently produced from succinate via six enzymatic reactions in an engineered Escherichia coli strain. Butyraldehyde dehydrogenase (Bld) and butanol dehydrogenase of Clostridium saccharoperbutylacetonicum were selected based on their activities of catalyzing the final two reactions in the 1,4-BDO pathway. To fit Bld into the non-natural 1,4-BDO pathway, we engineered it through random mutagenesis. Five Bld mutants were then isolated using a colorimetric Schiff's reagent-based method. Subsequent site-directed mutagenesis of Bld generated the two best Bld mutants, L273I and L273T, which produced 1,4-BDO titers fourfold greater than those of wild-type Bld. The enhanced 1,4-BDO titers obtained using L273I and L273T clearly correlated with their enhanced activities, which were caused by amino acid mutations at position 273 of Bld. The highest titer of 1,4-BDO (660 ± 40 mg/L) was obtained in a knock-out E. coli strain [ΔldhA ΔpflB ΔadhE ΔlpdA::K. lpd(E354K) Δmdh ΔarcA gltA(R164L)] coexpressing Bld273T+Bdh.

Carcinogenicity of butyraldehyde in rats by a two-year inhalation study.

We conducted a two-year inhalation study of butyraldehyde using F344/DuCrlCrlj rats. The rats were exposed to 0, 300, 1,000 and 3,000 ppm (v/v) for 6 hr/day, 5 days/ week for 104 weeks using whole-body inhalation chambers. The incidence of squamous cell carcinoma of the nasal cavity was increased in the 3,000 ppm groups of both male and female rats, with Fisher's exact test and the Peto test indicating that the incidence was significant. In addition to squamous cell carcinoma in the nasal cavity, in the 3,000 ppm groups one male had an adenosquamous carcinoma, one male had a carcinosarcoma, one male had a sarcoma NOS (Not Otherwise Specified), and one female had a squamous cell papilloma in the nasal cavity. The combined incidence of squamous cell carcinoma, adenosquamous carcinoma and carcinosarcoma was significantly increased in male rats and the combined incidence of squamous cell papilloma and carcinoma was significantly increased in female. Based on these results, we conclude that there is clear evidence of butyraldehyde carcinogenicity in male and female rats.

Theoretical-Experimental Study of the Action of Trace Amounts of Formaldehyde, Propionaldehyde, and Butyraldehyde as Inhibitors of the Ziegler-Natta Catalyst and the Synthesis of an Ethylene-Propylene Copolymer.

The copolymer synthesis process can be affected by failures in the production process or by contaminating compounds such as ketones, thiols, and gases, among others. These impurities act as an inhibiting agent of the Ziegler-Natta (ZN) catalyst affecting its productivity and disturbing the polymerization reaction. In this work, the effect of formaldehyde, propionaldehyde, and butyraldehyde on the ZN catalyst and the way in which it affects the final properties of the ethylene-propylene copolymer is presented by analyzing 30 samples with different concentrations of the mentioned aldehydes along with three control samples. It was determined that the presence of formaldehyde 26 ppm, propionaldehyde 65.2 ppm, and butyraldehyde 181.2 ppm considerably affect the productivity levels of the ZN catalyst; this effect increases as the concentration of aldehydes is higher in the process; likewise, these impurities affect the properties of the final product, such as the fluidity index (MFI), thermogravimetric analysis (TGA), bending, tension, and impact, which leads to a polymer with low-quality standards and less resistance to breakage. The computational analysis showed that the complexes formed by formaldehyde, propionaldehyde, and butyraldehyde with the active center of the catalyst are more stable than those obtained by the ethylene-Ti and propylene-Ti complexes, presenting values of -40.5, -47.22, -47.5, -5.2 and -1.3 kcal mol-1 respectively.

The association of aldehydes exposure with diabetes mellitus in US population: NHANES 2013-2014.

BACKGROUND: The association of mixed aldehydes exposure with diabetes remains unclear. OBJECTIVE: We aimed to explore associations between serum aldehydes concentration and diabetes. METHODS: We analyzed associations between aldehydes and diabetes using data from 1795 participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2014 by multiple logistic regression models. Bayesian kernel machine regression (BKMR) was used to evaluate the combined association of serum aldehydes on prediabetes and diabetes. RESULTS: Isopentanaldehyde increased the risk of diabetes 2.09 fold (95%CI:1.05-4.16) in the highest tertile, compared to the lowest-tertile concentration after adjusting for covariates, with a p-value for trend (P-t) equal to 0.041, in females. The adjusted OR of prediabetes with a 95% CI for the highest tertile was 0.52(0.28, 0.97) for benzaldehyde in females (P-t = 0.034). We also found associations in the male group between butyraldehyde and diabetes for the second (OR:2.80, 95%CI:1.35-5.79) and third (OR:2.59, 95%CI:1.30-5.17) tertile levels (P-t = 0.010). The risk of diabetes increased 2.55 fold (95%CI: 1.26-5.16, P-t = 0.008), in subjects in the highest tertile of hexanaldehyde concentration. Other aldehydes did not show a statistically significant association with diabetes or prediabetes. The BKMR model showed a positive association of mixed aldehydes with diabetes in males, and butyraldehyde showed a significant positive trend with the highest posterior inclusion probability (PIP = 0.85). Mixed aldehydes increased female's risk from prediabetes to diabetes in which isopentanaldehyde had the highest posterior inclusion probability (PIP = 0.67). CONCLUSIONS: The mixed aldehydes might increase the risk of suffering from diabetes in males and accelerate the progression of diabetes in females, in which butyraldehyde and isopentanaldehyde play the most important roles.

Identification of volatile sulfur-containing compounds and the precursor of dimethyl sulfide in cold-pressed rapeseed oil by GC-SCD and UPLC-MS/MS.

Volatile sulfur-containing compounds (VSCs) provide an important contribution to foods due to their special odors. In this study, VSCs in 21 cold-pressed rapeseed oils (CROs) from 9 regions in China were extracted and separated by headspace solid-phase microextraction combined with gas chromatography coupled with sulfur chemiluminescence detection. 19 VSCs were identified by authentic standards, and the total concentration of VSCs in all CROs ranged from 49.0 to 18129 µg/kg. Dimethyl sulfide (DMS), with its high odor activity value (7-14574), was the most significant aroma contributor to the CROs. Furthermore, S-methylmethionine (SMM) in rapeseed was first affirmed by ultra-performance liquid chromatography-tandem mass spectrometry and isotope quantitation. The positive correlation coefficient between DMS and SMM was 0.793 (p < 0.05), which confirmed SMM as a crucial precursor of DMS in CROs. This study provided a theoretical basis for selecting rapeseed materials by the distribution of essential VSCs and the source of DMS.

n-Butanol and ethanol production from cellulose by Clostridium cellulovorans overexpressing heterologous aldehyde/alcohol dehydrogenases.

With high cellulolytic and acetic/butyric acids production abilities, Clostridium cellulovorans is promising for use to produce cellulosic n-butanol. Here, we introduced three different aldehyde/alcohol dehydrogenases encoded by bdhB, adhE1, and adhE2 from Clostridium acetobutylicum into C. cellulovorans and studied their effects on ethanol and n-butanol production. Compared to AdhE2, AdhE1 was more specific for n-butanol biosynthesis over ethanol. Co-expressing adhE1 with bdhB produced a comparable amount of butanol but significantly less ethanol, leading to a high butanol/ethanol ratio of 7.0 and 5.6 (g/g) in glucose and cellulose fermentation, respectively. Co-expressing adhE1 or adhE2 with bdhB did not increase butanol production because the activity of BdhB was limited by the NADPH availability in C. cellulovorans. Overall, the strain overexpressing adhE2 alone produced the most n-butanol (4.0 g/L, yield: 0.22 ±â€¯0.01 g/g). Based on the insights from this study, further metabolic engineering of C. cellulovorans for cellulosic n-butanol production is suggested.

Synthesis of short-chain hydroxyaldehydes and their 2,4-dinitrophenylhydrazone derivatives, and separation of their isomers by high-performance liquid chromatography.

An easy to handle high-performance liquid chromatography (HPLC) method for the separation of structural isomers of short-chain aldehydes as their hydrazones is presented. Some aldehydes were not available as reference compounds, therefore, synthesis routes for these hydroxy-aldehydes and their dinitrophenylhydrazone derivatives are reported. The reported method has a detection limit of 2.4-16.1µg/L for the hydrazones and shows good linearity and reproducibility for various tested aldehydes.

In vitro determination of volatile compound development during starter culture-controlled fermentation of Cucurbitaceae cotyledons.

The effects of Lactobacillus plantarum UFLA CH3, Pediococcus acidilactici UFLA BFFCX 27.1, and Torulaspora delbrueckii UFLA FFT2.4 inoculation on the volatile compound profile of fermentation of Cucumeropsis mannii cotyledons were investigated. Different microbial associations were used as starters. All associations displayed the ability to ferment the cotyledons as judged by lowering the pH from 6.4 to 4.4-5 within 24h and increasing organic acids such as lactate and acetate. The population of lactic acid bacteria (LAB) and yeasts increased during fermentation. In the fermentation performed without inoculation (control), the LAB and yeast populations were lower than those in inoculated assays at the beginning, but they reached similar populations after 48 h. The Enterobacteriaceae population decreased during the fermentation, and they were not detected at 48 h in the L. plantarum UFLA CH3 and P. acidilactici UFLA BFFCX 27.1 (LP+PA) and L. plantarum UFLA CH3, P. acidilactici UFLA BFFCX 27.1, and T. delbrueckii UFLA FFT2.4 (LP+PA+TD) samples. The assays inoculated with the yeast T. delbrueckii UFLA FFT2.4 exhibited the majority of volatile compounds (13 compounds) characterized by pleasant notes. The LP+PA+TD association seemed to be appropriate to ferment C. mannii cotyledons. It was able to control the Enterobacteriaceae population, and achieved high concentrations of esters and low concentrations of aldehydes and ketones.

Synthesis of core-shell structured zeolite-A@mesoporous silica composites for butyraldehyde adsorption.

A simple sol-gel process is followed to construct a thin layer of mesoporous silica shell core-shell structure on micrometer sized and nanometer sized zeolite A (micro-zeolite A@SiO2 and nano-zeolite A@SiO2 respectively). Further thickness of the silica shells has been tuned from 20 to 50 nm while the zeolite A particle size changes from nanometer to micrometer. Pores of the silica shells arranged orderly on the crystal-faces of zeolite-A cores. Typically, adsorption amount of the butyraldehyde towards these core-shell composite materials is investigated well and is verified to be almost double than that of the pristine zeolite A. Interestingly the nano-zeolite A core containing core-shell composite absorbs maximum butyraldehyde (314 mg/g) compared to the micro-zeolite A (266 mg/g), even if the mesoporous shell thickness of the nano-zeolite A@SiO2 composites is less (20 nm) than that of micro-zeolite A@SiO2 (50 nm). Both of these values are significantly larger than the pristine zeolite A (nano-zeolite A; 151 mg/g and micro-zeolite A; 146 mg/g).

Solid-phase polyethylene glycol conjugation using hydrophobic interaction chromatography.

PEGylation is a widely applied approach to improve the pharmacokinetic and pharmacodynamic properties of protein therapeutics. The current solution-phase PEGylation protocols often suffer from poor yield of homogeneously PEGylated bioactive products and hence fall short of being commercially attractive. To improve upon these techniques, here we developed a novel, solid-phase PEGylation methodology using a hydrophobic interaction chromatography (HIC) resin. Two variations of the HIC-based PEGylation are described that are tailored towards conjugation of proteins with hydrophobicity index above (lysozyme) and below (fibroblast growth factor 1, FGF-1) that of the mPEG-butyraldehyde (mPEG) chain used. In the case of lysozyme, the protein was first immobilized on the HIC, and the HIC-bound protein was then conjugated by passing over the column. In the case of FGF-1, the mPEG solution was first immobilized on the HIC, and the FGF-1 solution was then passed through the column. Circular dichroism (CD) spectroscopy demonstrated HIC-based PEGylation almost retained the secondary structures of proteins. Bioactivity assay showed that the recovery of activity of HIC-based PEGylated rhFGF-1 (i.e. 92%) was higher than that of liquid-phase PEGylated rhFGF-1 (i.e. 61%), while HIC-based PEGylated lysozyme showed the same activity recovery (i.e. 7%) as the liquid-phase PEGylated form. For specific proteins, the HIC-based solid-phase PEGylation maybe offer a more promising alternative than the current PEGylation methods and is expected to have a major impact in the area of protein-based therapeutics.