Multi-omic assessment shows dysregulation of pulmonary and systemic immunity to e-cigarette exposure.

Electronic cigarette (Ecig) use has become more common, gaining increasing acceptance as a safer alternative to tobacco smoking. However, the 2019 outbreak of Ecig and Vaping-Associated Lung Injury (EVALI) alerted the community to the potential for incorporation of deleterious ingredients such as vitamin E acetate into products without adequate safety testing. Understanding Ecig induced molecular changes in the lung and systemically can provide a path to safety assessment and protect consumers from unsafe formulations. While vitamin E acetate has been largely removed from commercial and illicit products, many Ecig products contain additives that remain largely uncharacterized. In this study, we determined the lung-specific effects as well as systemic immune effects in response to exposure to a common Ecig base, propylene glycol and vegetable glycerin (PGVG), with and without a 1% addition of phytol, a diterpene alcohol that has been found in commercial products. We exposed animals to PGVG with and without phytol and assessed metabolite, lipid, and transcriptional markers in the lung. We found both lung-specific as well as systemic effects in immune parameters, metabolites, and lipids. Phytol drove modest changes in lung function and increased splenic CD4 T cell populations. We also conducted multi-omic data integration to better understand early complex pulmonary responses, highlighting a central enhancement of acetylcholine responses and downregulation of palmitic acid connected with conventional flow cytometric assessments of lung, systemic inflammation, and pulmonary function. Our results demonstrate that Ecig exposure not only leads to changes in pulmonary function but also affects systemic immune and metabolic parameters.

Assessment of inhalation toxicity of cigarette smoke and aerosols from flavor mixtures: 5-week study in A/J mice.

Most flavors used in e-liquids are generally recognized as safe for oral consumption, but their potential effects when inhaled are not well characterized. In vivo inhalation studies of flavor ingredients in e-liquids are scarce. A structure-based grouping approach was used to select 38 flavor group representatives (FGR) on the basis of known and in silico-predicted toxicological data. These FGRs were combined to create prototype e-liquid formulations and tested against cigarette smoke (CS) in a 5-week inhalation study. Female A/J mice were whole-body exposed for 6 h/day, 5 days/week, for 5 weeks to air, mainstream CS, or aerosols from (1) test formulations containing propylene glycol (PG), vegetable glycerol (VG), nicotine (N; 2% w/w), and flavor (F) mixtures at low (4.6% w/w), medium (9.3% w/w), or high (18.6% w/w) concentration or (2) base formulation (PG/VG/N). Male A/J mice were exposed to air, PG/VG/N, or PG/VG/N/F-high under the same exposure regimen. There were no significant mortality or in-life clinical findings in the treatment groups, with only transient weight loss during the early exposure adaptation period. While exposure to flavor aerosols did not cause notable lung inflammation, it caused only minimal adaptive changes in the larynx and nasal epithelia. In contrast, exposure to CS resulted in lung inflammation and moderate-to-severe changes in the epithelia of the nose, larynx, and trachea. In summary, the study evaluates an approach for assessing the inhalation toxicity potential of flavor mixtures, thereby informing the selection of flavor exposure concentrations (up to 18.6%) for a future chronic inhalation study.

Developmental toxicity and neurotoxicity assessment of R-, S-, and RS-propylene glycol enantiomers in zebrafish (Danio rerio) larvae.

Propylene glycol (PG) is widely used in the foods, pharmaceuticals, oil industry, animal feed, cosmetics and other industries. Because of the existence of a chiral carbon center, PG forms R (Rectus)- and S (Sinister)-enantiomers. Currently, the toxicity study of its R-, S-enantiomers is still very scarce. In this study, we have assessed the developmental toxicity and neurotoxicity of the R-, S-, and RS-PG enantiomers in zebrafish larvae. We found that exposure to R-, S-, and RS-PG enantiomers did not significantly affect the basic developmental endpoints of embryos or larvae (i.e., embryonic movement, hatching, mortality, malformation, heartbeat, body length), indicating that R-, S-, and RS-PG exposures did not exhibit the basic developmental toxicity in zebrafish larvae. The toxicity of three enantiomers was lower than that of ethanol, and there was no significant difference between them. However, R-, S-, and RS-PG exposures with high doses could significantly change the eye diameter and locomotor activity of larval zebrafish, indicating that R-, S-, and RS-PG enantiomers of high doses could potentially exhibit the neurotoxicity and ocular developmental toxicity in zebrafish larvae. Therefore, the potential neurotoxicity and ocular developmental toxicity of R-, S-, and RS-PG enantiomers for infants and toddlers should be considered.

The in vitro ToxTracker and Aneugen Clastogen Evaluation extension assay as a tool in the assessment of relative genotoxic potential of e-liquids and their aerosols.

In vitro (geno)toxicity assessment of electronic vapour products (EVPs), relative to conventional cigarette, currently uses assays, including the micronucleus and Ames tests. Whilst informative on induction of a finite endpoint and relative risk posed by test articles, such assays could benefit from mechanistic supplementation. The ToxTracker and Aneugen Clastogen Evaluation analysis can indicate the activation of reporters associated with (geno)toxicity, including DNA damage, oxidative stress, the p53-related stress response and protein damage. Here, we tested for the different effects of a selection of neat e-liquids, EVP aerosols and Kentucky reference 1R6F cigarette smoke samples in the ToxTracker assay. The assay was initially validated to assess whether a mixture of e-liquid base components, propylene glycol (PG) and vegetable glycerine (VG) had interfering effects within the system. This was achieved by spiking three positive controls into the system with neat PG/VG or phosphate-buffered saline bubbled (bPBS) PG/VG aerosol (nicotine and flavour free). PG/VG did not greatly affect responses induced by the compounds. Next, when compared to cigarette smoke samples, neat e-liquids and bPBS aerosols (tobacco flavour; 1.6% freebase nicotine, 1.6% nicotine salt or 0% nicotine) exhibited reduced and less complex responses. Tested up to a 10% concentration, EVP aerosol bPBS did not induce any ToxTracker reporters. Neat e-liquids, tested up to 1%, induced oxidative stress reporters, thought to be due to their effects on osmolarity in vitro. E-liquid nicotine content did not affect responses induced. Additionally, spiking nicotine alone only induced an oxidative stress response at a supraphysiological level. In conclusion, the ToxTracker assay is a quick, informative screen for genotoxic potential and mechanisms of a variety of (compositionally complex) samples, derived from cigarettes and EVPs. This assay has the potential for future application in the assessment battery for next-generation (smoking alternative) products, including EVPs.

Economic value of information from an alert system on physiological imbalance in fresh cows.

Physiological imbalance is an abnormal physiological condition that cannot be directly observed but is assumed to precede subclinical and clinical diseases in the beginning of lactation. Alert systems to detect the physiological imbalance in a cow using Fourier transform mid-infrared spectroscopy in milk have been developed. The objective of this study was to estimate the value of information provided from such system with different indicator accuracies, herd prevalence and prices. A decision tree was created to model the probabilities of detection and associated costs of test outcome, intervention and occurrence of disease. We assumed that the negative effect of physiological imbalance was the development of subclinical ketosis and that this negative effect was prevented by drenching the cows with propylene glycol for 5 days. We simulated the economic impact of subclinical ketosis mediated through physiological imbalance to be $194 per case. The results showed that if the alert system was highly accurate (Se = 0.99/Sp = 0.99), and the prevalence of physiological imbalance was 30 %, the value of information provided from the system is $19 per cow-year. In case the prevalence is 5 % or 50 %, the value of information is $3 and $13, respectively. These estimates for the value do not cover the capital costs and operational costs of the alert system. This study furthermore clearly demonstrated that in order to estimate the value of information correctly, it is important to consider that drenching all cows and not drenching any of the cows are the two relevant alternative options in the absence of the alert system. In conclusion, the decision tree and sensitivity analysis developed in this study show that final economic results are highly variable to the prevalence of physiological imbalance and highest at an intermediate prevalence. Other relevant factors are the costs associated with drenching and the cost associated with treating false positives and not treating false negatives. In addition, this study highlights the benefits of simulation to pinpoint where additional information is needed to further quantify the economic value and required accuracy of an indication-based intervention system.

Marker-Independent In Situ Quantitative Assessment of Residual Cryoprotectants in Cardiac Tissues.

Cryomedium toxicity is a major safety concern when transplanting cryopreserved organs. Therefore, thorough removal of potentially toxic cryoprotective agents (CPAs) is required before transplantation. CPAs such as dimethyl-sulfoxide (DMSO), propylene glycol (PG), and formamide (FMD), routinely employed in ice-free cryopreservation (IFC), have advantages in long-term preservation of tissue structures compared with conventional cryopreservation employing lower CPA concentrations. This study evaluated the impact of potential residual CPAs on human cardiac valves. Raman microspectroscopy and Raman imaging were established as nondestructive marker-independent techniques for in situ quantitative assessment of CPA residues in IFC valve tissues. In detail, IFC valve leaflets and supernatants of the washing solutions were analyzed to determine the washing efficiency. A calibration model was developed according to the CPA's characteristic Raman signals to quantify DMSO, PG and FMD concentrations in the supernatants. Single point Raman measurements were performed on the intact tissues to analyze penetration properties. In addition, Raman imaging was utilized to visualize potential CPA residues. Our data showed that washing decreased the CPA concentration in the final washing solution by 99%, and no residues could be detected in the washed tissues, validating the multistep CPA removal protocol routinely used for IFC valves. Raman analysis of unwashed tissues showed different permeation characteristics depending on each CPA and their concentration. Our results demonstrate a great potential of Raman microspectroscopy and Raman imaging as marker-independent in situ tissue quality control tools with the ability to assess the presence and concentration of different chemical agents or drugs in preimplantation tissues.

Physical and chemical assessment of 1,3 Propanediol as a potential substitute of propylene glycol in refill liquid for electronic cigarettes.

Electronic cigarette has the potential to serve as a tobacco cessation aid if the prerequisites which are safety and efficacy in term of nicotine delivery are achieved. The nicotine-based liquids are mainly composed by propylene glycol and glycerol playing the important role of airborne carriers. 1,3 propanediol is proposed as a propylene glycol substitute to potentially improve the thermal stability, nicotine delivery and to decrease inhaled flavors concentrations. We have implemented various thermal, physicochemical and computational methods to evaluate the use of 1,3 propanediol as a substitute (or additional ingredient) to propylene glycol in e-liquids compositions. Our results indicate that 1,3 propanediol is stable upon heating when electronic cigarette are used in recommended conditions. We demonstrate that 1,3 propanediol gave better thermic profile compared to propylene glycol and glycerol, showing less thermal decomposition by-products. In addition, 1,3 propanediol gives to nicotine a more basic environment ensuring a high level of free base nicotine form. We have also established a quantum mechanical based computational method to validate e-liquids as flavor enhancer. Our findings showed that globally 1,3 propanediol seems to have better flavoring properties than glycerol and propylene glycol. Finally, 1,3 propanediol seems to induce quite similar aerodynamic properties compared to propylene glycol and glycerol.

Exploitation of acid-tolerant microbial species for the utilization of low-cost whey in the production of acetic acid and propylene glycol.

Whey from cheese and yoghurt production operations contains useful constituents such as whey protein and lactose. However, the separation and extraction processes are difficult and costly, and hence, whey has limited end user demand and is typically disposed of as waste. Treatment and disposal of these high BOD wastes are both energy intensive and expensive. However, improper disposal of these wastes can pollute surface and ground water resources. The use of these low or negative cost substrates for the production of value-added products such as acetic acid and propylene glycol (PG) is of great significance in changing overhead costs to revenue streams. The present study focuses on bioproduction of acetic acid and PG from whey lactose and whey powder containing lactose and protein as an alternative to high cost nutritive medium. It was found that Lactobacillus buchneri, an acid-tolerant bacterium, is able to ferment lactose at pH ~ 4.2 to low molecular weight compounds such as acetic acid and PG each at 25-30 g L-1 concentration when using lactose as a major carbon substrate. The typical molar ratio of acetic acid to PG was close to 1:1 at the end of fermentation. The productivity of acetic acid and PG was improved using a high cell density fermentation with cotton cheesecloth as an immobilization matrix. The use of whey powder with immobilized fermentation system showed a similar performance to that of cultures fed with pure lactose at pH 4.2, resulting in a 57% conversion of lactose in whey to acetate and PG in total, against a stoichiometric maximum of 72%.

Prevalence of Contact Allergens in Personal Care Products for Babies and Children.

BACKGROUND: Personal care products marketed for babies and children are often regarded as "safe" or "gentle." However, little is known about the prevalence of contact allergens in these types of products. OBJECTIVE: This study assessed the prevalence of important sensitizers in personal care products marketed for babies and children. A secondary objective of this study was to determine whether a product's cost correlates with content of sensitizing ingredients. METHODS: The ingredient lists of 533 unique personal care products were analyzed for presence of fragrance, betaines, propylene glycol, methylchloroisothiazolinone, methylisothiazolinone, formaldehyde, lanolin, and neomycin. Price per ounce was determined for each product as well. CONCLUSIONS: Most personal care products for babies and children contain 1 or more sensitizers. Products containing more sensitizers tend to cost less than those without any sensitizing ingredients.

A toxicity cost function approach to optimal CPA equilibration in tissues.

There is growing need for cryopreserved tissue samples that can be used in transplantation and regenerative medicine. While a number of specific tissue types have been successfully cryopreserved, this success is not general, and there is not a uniform approach to cryopreservation of arbitrary tissues. Additionally, while there are a number of long-established approaches towards optimizing cryoprotocols in single cell suspensions, and even plated cell monolayers, computational approaches in tissue cryopreservation have classically been limited to explanatory models. Here we develop a numerical approach to adapt cell-based CPA equilibration damage models for use in a classical tissue mass transport model. To implement this with real-world parameters, we measured CPA diffusivity in three human-sourced tissue types, skin, fibroid and myometrium, yielding propylene glycol diffusivities of 0.6 × 10-6 cm2/s, 1.2 × 10-6 cm2/s and 1.3 × 10-6 cm2/s, respectively. Based on these results, we numerically predict and compare optimal multistep equilibration protocols that minimize the cell-based cumulative toxicity cost function and the damage due to excessive osmotic gradients at the tissue boundary. Our numerical results show that there are fundamental differences between protocols designed to minimize total CPA exposure time in tissues and protocols designed to minimize accumulated CPA toxicity, and that "one size fits all" stepwise approaches are predicted to be more toxic and take considerably longer than needed.

Assessment of toxicity and tolerability of a combination vehicle; 5% Pharmasolve, 45% Propylene glycol and 50% Polyethylene glycol 400 in rats following repeated intravenous administration.

The selection of a suitable vehicle for administration of NCEs in non-clinical studies is always a challenge for poorly soluble compounds. Challenge is increased if the dose formulation is intended for intravenous (i.v.) administration where isotonic, biologically compatible pH and solution form is an absolute requirement. Vehicle toxicity and tolerability data are not readily available for a number of combination vehicles therefore, an i.v. tolerability studies was planned in rats with 5% v/v Pharmasolve (NMP), 45% v/v Propylene glycol (PG) and 50% v/v Polyethylene glycol (PEG) 400 combination, at dose volume of 0.5, 1, 2 and 5 mL/kg body weight for 28 days. The vehicle combination was administered via lateral tail vein and effects on clinical signs, body weights, feed consumption, clinical pathology and histopathology were evaluated. Clinical signs of toxicity like tremors, convulsions and death were noticed at 5 mL/kg during the course of the study. At 2 mL/kg, injection site injury without systemic toxicity was noticed. In conclusion, 1 mL/kg of a combination vehicle of 5% NMP, 45% PG and 55% PEG 400 can be administered intravenously once-a-day up to 28 days without any discomfort or injury to rats.

Functional genomic assessment of 2, 2-bis (bromomethyl)-1, 3-propanediol induced cytotoxicity in a single-gene knockout library of E. coli.

Functional gene fingerprinting of chemicals could be used to understand the direct gene-chemical interaction in the process of toxification from a genome-wide scale. 2, 2-bis (bromomethyl)-1, 3-propanediol (BMP) is a brominated flame retardant with widespread production but with very limited toxicological data. Here the cytotoxicity of BMP was assessed by Escherichia coli (E. coli) functional genome-wide knockout mutants screening and the underlying molecular mechanism was investigated. The median inhibition concentration (IC50) of BMP was 1.608 ± 0.078 mg/ml after 24 h exposure. 119 initial, including 66 sensitive and 53 resistant single gene mutants, were identified by a full library screening of BMP at the concentration of IC50. The resistant genes were significantly enriched in nucleobase-containing compound biosynthetic process (GO: 0034654) by gene ontology (GO) biological process analyses, which suggested that the pathway of DNA repair is a critical cellular process in the survival of cells exposed to BMP. Meanwhile, function annotation of all BMP responsive genes suggested the mechanism of BMP was associated with DNA damage, oxidative stress and cellular transmembrane transport process. Many genes were exclusively responsive to BMP comparing with other chemicals that has been assessed by E. coli mutant screening approach, which indicated that BMP has a distinct mode of toxic action. Overall, the functional genomic screening approach presented here provides a great tool to assess the cellular toxicological mechanism of environmental chemicals.

Hospital Impact After a Chemical Spill That Compromised the Potable Water Supply: West Virginia, January 2014.

In January 2014, a chemical spill of 4-methylcyclohexanemethanol and propylene glycol phenyl ethers contaminated the potable water supply of approximately 300,000 West Virginia residents. To understand the spill's impact on hospital operations, we surveyed representatives from 10 hospitals in the affected area during January 2014. We found that the spill-related loss of potable water affected many aspects of hospital patient care (eg, surgery, endoscopy, hemodialysis, and infection control of Clostridium difficile). Hospital emergency preparedness planning could be enhanced by specifying alternative sources of potable water sufficient for hemodialysis, C. difficile infection control, and hospital processing and cleaning needs (in addition to drinking water). (Disaster Med Public Health Preparedness. 2017;11:621-624).

Assessment of skin sensitization under REACH: A case report on vehicle choice in the LLNA and its crucial role preventing false positive results.

In the EU, chemicals with a production or import volume in quantities of one metric ton per year or more have to be tested for skin sensitizing properties under the REACH regulation. The murine Local Lymph Node Assay (LLNA) and its modifications are widely used to fulfil the data requirement, as it is currently considered the first-choice method for in vivo testing to cover this endpoint. This manuscript describes a case study highlighting the importance of understanding the chemistry of the test material during testing for 'skin sensitization' of MCDA (mixture of 2,4- and 2,6-diamino-methylcyclohexane) with particular focus on the vehicle used. While the BrdU-ELISA modification of the LLNA using acetone/olive oil (AOO) as vehicle revealed expectable positive results. However, the concentration control analysis unexpectedly revealed an instability of MCDA in the vehicle AOO. Further studies on the reactivity showed MCDA to rapidly react with AOO under formation of various imine structures, which might have caused the positive LLNA result. The repetition of the LLNA using propylene glycol (PG) as vehicle did not confirm the positive results of the LLNA using AOO. Finally, a classification of MCDA as skin sensitizer according to the Globally Harmonized System (GHS) was not justified.

Assessment of cell viability and permeation enhancement in presence of lipid-based self-emulsifying drug delivery systems using Caco-2 cell model: Polysorbate 80 as the surfactant.

PURPOSE: Lipid-based self-emulsifying drug delivery systems (SEDDS) are commonly used for solubilizing and enhancing oral bioavailability of poorly water-soluble drugs. However, their effects on viability of intestine epithelial cells and influence on membrane permeation are poorly understood. The present study was undertaken for safety assessment of lipid-based formulations containing medium-chain fatty acid esters as lipids and polysorbate 80 as the surfactant using the Caco-2 in vitro model. Any possible paracellular permeation enhancement through Caco-2 monolayers by the nontoxic formulations was also investigated. METHODS: Mixtures of monoglyceride (Capmul MCM EP or 708G) or propylene glycol monoester (Capmul PG-8 NF) of medium chain fatty acids with polysorbate 80, with and without the incorporation of a medium-chain triglyceride (Captex 355), were prepared. After suitable dilution with aqueous culture medium, the formulations were incubated with a series of Caco-2 cultures of different maturity. Cell viability and membrane integrity were assessed. Any effects of nontoxic formulations on the transport of the fluorescent dye, Lucifer yellow, through Caco-2 monolayers were also determined. RESULTS: Formulations containing 1:1 ratios of monoglyceride or propylene glycol monoester to triglyceride (30% polysorbate 80, 35% monoglyceride or monoester and 35% triglyceride) were best tolerated by Caco-2 cells. Increased maturity obtained through longer culture durations rendered Caco-2 cells greater tolerance towards lipid-based formulations, and maximum tolerance to lipid-based formulations was observed with Caco-2 monolayers after being cultured for 21-23days. Furthermore, extent of cell membrane rupture caused by lipid-surfactant mixtures correlated positively with levels of cytotoxicity, suggesting a potential underlying mechanism. Permeation studies using Caco-2 monolayer model revealed that certain formulations significantly enhanced paracellular transport activities. CONCLUSIONS: Lipid-based SEDDS containing mixtures of monoglyceride (or monoester) and triglyceride of medium chain fatty acids formed fine microemulsions and were significantly less toxic than other formulations. Fully differentiated Caco-2 monolayer was more resistant to lipid-surfactant mixtures than less mature cultures. Certain formulations were also capable of enhancing paracellular permeation.

In vitro human epidermal permeation of nicotine from electronic cigarette refill liquids and implications for dermal exposure assessment.

Nicotine plus flavorings in a propylene glycol (PG) vehicle are the components of electronic cigarette liquids (e-liquids), which are vaporized and inhaled by the user. Dermal exposure to nicotine and e-liquids may occur among workers in mixing and filling of e-cigarettes in the manufacturing process. Inadvertent skin contact among consumers is also a concern. In vitro nicotine permeation studies using heat-separated human epidermis were performed with surrogate and two commercial e-liquids, neat and aqueous nicotine donor formulations. Steady-state fluxes (Jss), and lag times (tlag) were measured for each formulation. In addition, transient (4 h) exposure and finite dose (1-10 µl/cm2) experiments were undertaken using one commercial e-liquid. Average Jss (µg/cm2/h) from formulations were: nicotine in PG (24 mg/ml): 3.97; commercial e-liquid containing menthol (25 mg/ml nicotine): 10.2; commercial e-liquid containing limonene (25 mg/ml nicotine): 23.7; neat nicotine: 175. E-liquid lag times ranged from 5 to 10 h. Absorbed fraction of nicotine from finite doses was ≈0.3 at 48 h. The data were applied to transient exposure and finite dose dermal exposure assessment models and to a simple pharmacokinetic model. Three illustrative exposure scenarios demonstrate use of the data to predict systemic uptake and plasma concentrations from dermal exposure. The data demonstrate the potential for significant nicotine absorption through skin contact with e-cigarette refill solutions and the neat nicotine used to mix them.

Economic value of ionophores and propylene glycol to prevent disease and treat ketosis in Canada.

A partial budget model was developed to evaluate the economic value of Rumensin Controlled Release Capsule (CRC) boluses when administered before calving to reduce disease and increase milk production. After accounting for disease incidences in a herd and the percentage by which Rumensin CRC can reduce them, and the increase in milk production attributable to administration of Rumensin CRC, the return on investment (ROI) per lactation was 4:1. Another partial budget model was developed to estimate the economic value of propylene glycol (PG) to treat ketosis when diagnosed by 3 different cow-side tests or when administered to all cows without using any cow-side testing. After accounting for the sensitivity and specificity of each test, ROI per lactation ranged from 2:1 to 4:1. The ROI was 2:1 when no cow-side testing was used. In conclusion, prevention of diseases that occur in the postpartum period and treatment of ketosis after calving yielded a positive ROI that varies based on disease incidence and method of diagnosis.

Valeur économique des ionophores et du propylèneglycol pour prévenir la maladie et traiter l'acétonémie au Canada. Un modèle de budget partiel a été développé pour évaluer la valeur économique des bolus de capsules à libération contrôlée (CLC) de Rumensin lors de l'administration avant le vêlage afin de réduire les maladies et d'accroître la production de lait. Après avoir tenu compte de l'incidence des maladies dans un troupeau et du pourcentage par lequel la CLC de Rumensin peut les réduire et de l'augmentation de la production de lait attribuable à l'administration de la CLC de Rumensin, le rendement du capital investi (RCI) par lactation était de 4:1. Un autre modèle de budget partiel a été développé pour estimer la valeur économique du propylèneglycol (PG) afin de traiter l'acétonémie lors du diagnostic par 3 tests différents pour les vaches ou lors de l'administration à toutes les vaches sans le recours à des tests auprès des vaches. Après avoir tenu compte de la sensibilité et de la spécificité de chaque test, le RCI par lactation s'échelonnait de 2:1 à 4:1. Le RCI était de 2:1 lorsqu'aucun test auprès des vaches n'était utilisé. En conclusion, la prévention des maladies qui se produit dans la période postpartum et le traitement de l'acétonémie après le vêlage a donné un RCI positif qui varie selon l'incidence de maladies et la méthode de diagnostic.(Traduit par Isabelle Vallières).

Assessment of the dietary intake of propylene glycol in the Korean population.

An improved method for the analysis of propylene glycol (PG) in foods using a gas chromatography-flame ionisation detector (GC-FID), with confirmation by GC-MS, was validated by measuring several analytical parameters. The PG concentrations in 1073 products available in Korean markets were determined. PG was detected in 74.1% of the samples, in a concentration range from the limit of detection (n.d., 0.39 µg ml(-1)) to 12,819.9 mg kg(-1). The Korea National Health and Nutrition Examination Survey (KNHANES) 2011-2013 reported the mean intake levels of PG from all sources by the general population and consumers were 26.3 mg day(-1) (0.52 mg kg(-1) day(-1)) and 34.3 mg day(-1) (0.67 mg kg(-1) day(-1)), respectively. The 95th percentile intake levels of the general population and consumers were 123.6 mg day(-1) (2.39 mg kg(-1) day(-1)) and 146.3 mg day(-1) (2.86 mg kg(-1) day(-1)), respectively. In all groups of the general population, breads were the main contributors to the total PG intake. These reports provide a current perspective on the daily intake of PG in the Korean population.

Cytotoxicity assessment of lipid-based self-emulsifying drug delivery system with Caco-2 cell model: Cremophor EL as the surfactant.

PURPOSE: Caco-2 cells are used extensively for in vitro prediction of intestinal drug absorption. However, toxicity of excipients and formulations used can artificially increase drug permeation by damaging cell monolayers, thus providing misleading results. The present study aimed to investigate cytotoxicity of common lipid-based excipients and formulations on Caco-2 cells. METHODS: Medium-chain monoglycerides alone or in mixture with the surfactant Cremophor EL, with and without a medium-chain triglyceride, were prepared and incubated with Caco-2 cells from a series of culture stages with varying maturity. Cell viability was evaluated and cell membrane integrity assessed. RESULTS: Cytotoxicity of lipid-based formulations was influenced by the maturity of Caco-2 cells and formulation composition. One-day culture was most sensitive to lipids. When cultured for 5days, viability of Caco-2 cells was significantly improved. The 21-day Caco-2 monolayers maintained the highest survival rate. Microemulsion formulations exhibited significantly less cytotoxicity than neat lipids or surfactant at all stages of cell maturity, and microemulsions containing 1:1 mixtures of monoglyceride and triglyceride appeared to be best tolerated among all the formulations tested. Mechanistically, the observed cytotoxicity was partially due to lipid-induced rupture of cell membrane. CONCLUSIONS: Microemulsions of lipid-surfactant mixtures have less cytotoxicity than lipid alone. Maturity of Caco-2 cells renders significant resistance to cytotoxicity, and monolayers with 21-day maturity are more relevant to in vivo conditions and appear to be a more accurate in vitro model for cytotoxicity assessment.

Toxicological and analytical assessment of e-cigarette refill components on airway epithelia.

There are over 2.6 million users of e-cigarettes in the United Kingdom alone as they have been promoted as a safer alternative to traditional cigarettes. The addition of flavours and aromas has also proven to be popular with younger generations. In this review, we survey the range of studies in the short timeframe since e-cigarettes reached the market to draw attention to the health associated risks and benefits of their introduction. We complement this review with a case study reporting on the composition of selected e-cigarette refills with particular emphasis on the toxicological activity of its components on lung cells.