Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity

Ethanol is widely used in all kinds of products with direct exposure to the human skin (e.g. medicinal products like hand disinfectants in occupational settings, cosmetics like hairsprays or mouthwashes, pharmaceutical preparations, and many household products). Contradictory evidence about the safety of such topical applications of the alcohol can be found in the scientific literature, yet an up-to-date risk assessment of ethanol application on the skin and inside the oral cavity is currently lacking

ALDH2-deficiency as genetic epidemiologic and biochemical model for the carcinogenicity of acetaldehyde

Humans are cumulatively exposed to acetaldehyde from various sources including alcoholic beverages, tobacco smoke, foods and beverages. The genetic-epidemiologic and biochemical evidence in ALDH2-deficient humans provides strong evidence for the causal relationship between acetaldehyde-exposure due to alcohol consumption and cancer of the upper digestive tract. The risk assessment has so far relied on thresholds based on animal toxicology with lower one-sided confidence limit of the benchmark dose values (BMDL) typically ranging between 11 and 63 mg/kg bodyweight (bw)/day dependent on species and endpoint. The animal data is problematic for regulatory toxicology for various reasons (lack in study quality, problems in animal models and appropriateness of endpoints - especially cancer - for transfer to humans). In this study, data from genetic epidemiologic and biochemical studies are reviewed. The increase in the daily exposure dose to acetaldehyde in alcohol-consuming ALDH2-deficients vs. ALDH2-actives was about twofold. The acetaldehyde increase due to ALDH2 inactivity was calculated to be 6.7 mu g/kg bw/day for heavy drinkers, which is associated with odds ratios of up to 7 for head and neck as well as oesophageal cancer. Previous animal toxicology based risk assessments may have underestimated the risk of acetaldehyde. Risk assessments of acetaldehyde need to be revised using this updated evidence. (C) 2017 The Authors. Published by Elsevier Inc.Peer reviewe

Neue Methodenkombination aus dynamischer Festphasenextraktion, Gaschromatographie und Massenspektrometrie für den Einsatz in der forensisch-toxikologischen Haaranalytik

In der vorliegenden Arbeit wird eine neue Methodenkombination aus dynamischer Festphasenextraktion (Headspace solid-phase dynamic extraction, HS-SPDE), Gaschromatographie (GC) und Massenspektrometrie (MS) oder Tandem-Massenspektrometrie (MS/MS) vorgestellt und ihre Leistungsfähigkeit für die forensisch-toxikologische Untersuchung von Betäubungsmitteln in Haarproben getestet. Mittels HS-SPDE erfolgt die Extraktion der Analyten sowie eine Aufkonzentrierung, Derivatisierung und die nachfolgende Injektion in ein GC/MS- oder GC/MS/MS-System für den selektiven und sensitiven Nachweis. Alle Einzelschritte, außer Waschen und Zerkleinern der Haarproben, d.h. auch der Probenaufschluß werden ohne manuelle Intervention auf einem Autosampler-Roboter ausgeführt. HS-SPDE ist eine von der Festphasenmikroextration (Headspace solid-phase microextraction, HS-SPME) abgeleitete lösungsmittelfreie Extraktionstechnik. Der Headspace über der Probelösung wird mittels einer Spritze aktiv durch eine von innen mit Sorbens beschichtete Kapillare gespült (dynamische Extraktion). Die Desorption erfolgt durch Einführung der Kapillare in den heißen Injektor des GC-Systems. Die HS-SPDE/GC/MS-Methode wurde an der Analyse von Methadon mit Hauptmetabolit, sowie den Trimethylsilylderivaten von Cannabinoiden und den Trifluoracetylderivaten von Amphetaminen und Designerdrogen erprobt. Mit diesen Substanzklassen wird der Bereich der halbflüchtigen (Amphetamine) bis schwerflüchtigen (Cannabinoide) Substanzen abgedeckt, für den eine Headspace-Mikroextraktion besonders interessant ist, weil diese Substanzen mit konventionellen Headspace-Methoden nicht erfaßt werden können. Mit GC/MS wurden Nachweisgrenzen zwischen 0,03 und 0,19 ng/mg Haarmatrix und Präzisionen zwischen 1,4 und 14,6 % erzielt. Linearität wurde von 0,1-20 ng/mg mit Korrelationskoeffizienten zwischen 0,995 und 0,999 nachgewiesen. Darüberhinaus konnte mit Tandem-Massenspektrometrie die Empfindlichkeit gegenüber herkömmlicher Massenspektrometrie um Faktoren von 8 bis 35 je nach Substanz erhöht werden. Signifikant niedrigere Nachweisgrenzen zwischen 0,006 und 0,052 ng/mg und verbesserte Präzisionen zwischen 0,4 und 7,8 % wurden erzielt. Die Anwendbarkeit der Methode wurde durch die Analyse authentischer Haarproben von Drogenkonsumenten unter Beweis gestellt und mit Probenmaterial aus externen Ringversuchen abgesichert. Durch die vorliegende Arbeit wurde gezeigt, daß die HS-SPDE-Technik eine empfindliche und robuste Alternative für die Analyse komplexer Matrices darstellt. Erstmals wurden mit dieser Technik Routineverfahren entwickelt und validiert. Ein besonderer Vorzug des vollständig automatisierten SPDE-Verfahrens ist die Zeitersparnis im Vergleich zu traditionellen Verfahren der Probenvorbereitung wie Flüssig-Flüssig-Extraktion oder Festphasenextraktion

The Quality of Alcohol Products in Vietnam and Its Implications for Public Health

Four homemade (artisanally manufactured and unrecorded) and seven commercial (industrially manufactured and taxed) alcohol products from Vietnam were collected and chemically analyzed for toxicologically relevant substances. The majority of both types had alcohol contents between 30 and 40% vol. Two homemade samples contained significantly higher concentrations of 45 and 50% vol. In one of these homemade samples the labeled alcoholic strength was exceeded by nearly 20% vol. All other analyzed constituents of the samples (e.g., methanol, acetaldehyde, higher alcohols, esters, metals, anions) were found in concentrations that did not pose a threat to public health. A peculiarity was a homemade sample of alcohol with pickled snakes and scorpions that contained 77% vol of alcohol, allegedly used as traditional Chinese medicine. Based on this small sample, there is insufficient evidence to conclude that alcohol quality, beyond the effects of ethanol, has an influence on health in Vietnam. However, future research with larger samples is needed

Determination of Osmolality in Beer to Validate Claims of Isotonicity

Alcohol-free beer is increasingly marketed with the claim “isotonic”. According to the European Food Safety Authority (EFSA), isotonic beverages should have an osmolality in a range of 270–330 mOsmol/kg. A method to determine osmolality in beer using an automatic cryoscope was applied and validated in this study. Isotonic and hypotonic beers can be measured directly, while hypertonic beers have to be diluted into the linear range of the instrument. As proven in several different beer matrices, the assay was linear with an average correlation coefficient of 0.998. The limits of detection and quantitation were 2 and 10 mOsmol/kg, so that the sensitivity of the method was judged sufficient to control the isotonic range. The measurement uncertainty expressed as coefficient of variation was less than 1% interday. The applicability of the method was proven by measurement of 86 beer samples. Our study has shown that the cryoscopic method is fit for the purpose to validate claims of isotonicity in food control

Formaldehyde in Alcoholic Beverages: Large Chemical Survey Using Purpald Screening Followed by Chromotropic Acid Spectrophotometry with Multivariate Curve Resolution

A strategy for analyzing formaldehyde in beer, wine, spirits, and unrecorded alcohol was developed, and 508 samples from worldwide origin were analyzed. In the first step, samples are qualitatively screened using a simple colorimetric test with the purpald reagent, which is extremely sensitive for formaldehyde (detection limit 0.1 mg/L). 210 samples (41%) gave a positive purpald reaction. In the second step, formaldehyde in positive samples is confirmed by quantitative spectrophotometry of the chromotropic acid-formaldehyde derivative combined with Multivariate Curve Resolution-Alternating Least Squares (MCR-ALS). Calculation of UV-VIS and 13C NMR spectra confirmed the monocationic dibenzoxanthylium structure as the product of the reaction and disproved the widely cited para,para-quinoidal structure. Method validation for the spectrophotometric procedure showed a detection limit of 0.09 mg/L and a precision of 4.2–8.2% CV. In total, 132 samples (26%) contained formaldehyde with an average of 0.27 mg/L (range 0–14.4 mg/L). The highest incidence occurred in tequila (83%), Asian spirits (59%), grape marc (54%), and brandy (50%). Our survey showed that only 9 samples (1.8%) had formaldehyde levels above the WHO IPCS tolerable concentration of 2.6 mg/L

Ethyl Carbamate in Alcoholic Beverages from Mexico (Tequila, Mezcal, Bacanora, Sotol) and Guatemala (Cuxa): Market Survey and Risk Assessment

Ethyl carbamate (EC) is a recognized genotoxic carcinogen, with widespread occurrence in fermented foods and beverages. No data on its occurrence in alcoholic beverages from Mexico or Central America is available. Samples of agave spirits including tequila, mezcal, bacanora and sotol (n=110), and of the sugarcane spirit cuxa (n=16) were purchased in Mexico and Guatemala, respectively, and analyzed for EC. The incidence of EC contamination was higher in Mexico than in Guatemala, however, concentrations were below international guideline levels (<0.15 mg/L). Risk assessment found the Margin of Exposure (MOE) in line with that of European spirits. It is therefore unlikely that EC plays a role in high rates of liver cirrhosis reported in Mexico

Absinthism: a fictitious 19th century syndrome with present impact

Absinthe, a bitter spirit containing wormwood (Artemisia absinthium L.), was banned at the beginning of the 20th century as consequence of its supposed unique adverse effects. After nearly century-long prohibition, absinthe has seen a resurgence after recent de-restriction in many European countries. This review provides information on the history of absinthe and one of its constituent, thujone. Medical and toxicological aspects experienced and discovered before the prohibition of absinthe are discussed in detail, along with their impact on the current situation. The only consistent conclusion that can be drawn from those 19th century studies about absinthism is that wormwood oil but not absinthe is a potent agent to cause seizures. Neither can it be concluded that the beverage itself was epileptogenic nor that the so-called absinthism can exactly be distinguished as a distinct syndrome from chronic alcoholism. The theory of a previous gross overestimation of the thujone content of absinthe may have been verified by a number of independent studies. Based on the current available evidence, thujone concentrations of both pre-ban and modern absinthes may not have been able to cause detrimental health effects other than those encountered in common alcoholism. Today, a questionable tendency of absinthe manufacturers can be ascertained that use the ancient theories of absinthism as a targeted marketing strategy to bring absinthe into the spheres of a legal drug-of-abuse. Misleading advertisements of aphrodisiac or psychotropic effects of absinthe try to re-establish absinthe's former reputation. In distinction from commercially manufactured absinthes with limited thujone content, a health risk to consumers is the uncontrolled trade of potentially unsafe herbal products such as absinthe essences that are readily available over the internet

Determination of the biologically active flavour substances thujone and camphor in foods and medicines containing sage (Salvia officinalis L.)

BACKGROUND: The sage plant Salvia officinalis L. is used as ingredient in foods and beverages as well as in herbal medicinal products. A major use is in the form of aqueous infusions as sage tea, which is legal to be sold as either food or medicine. Sage may contain two health relevant substances, thujone and camphor. The aim of this study was to develop and validate an analytical methodology to determine these active principles of sage and give a first overview of their concentrations in a wide variety of sage foods and medicines. RESULTS: A GC/MS procedure was applied for the analysis of α- and β-thujone and camphor with cyclodecanone as internal standard. The precision was between 0.8 and 12.6%, linearity was obtained from 0.1 - 80 mg/L. The recoveries of spiked samples were between 93.7 and 104.0% (average 99.1%). The time of infusion had a considerable influence on the content of analytes found in the teas. During the brewing time, thujone and camphor show an increase up to about 5 min, after which saturation is reached. No effect was found for preparation with or without a lid on the pot used for brewing the infusion. Compared to extracts with ethanol (60% vol), which provide a maximum yield, an average of 30% thujone are recovered in the aqueous tea preparations. The average thujone and camphor contents were 4.4 mg/L and 16.7 mg/L in food tea infusions and 11.3 mg/L and 25.4 mg/L in medicinal tea infusions. CONCLUSIONS: The developed methodology allows the efficient determination of thujone and camphor in a wide variety of sage food and medicine matrices and can be applied to conduct surveys for exposure assessment. The current results suggest that on average between 3 and 6 cups of sage tea could be daily consumed without reaching toxicological thresholds

Determination of Diethyl Phthalate and Polyhexamethylene Guanidine in Surrogate Alcohol from Russia

Analytical methods based on spectroscopic techniques were developed and validated for the determination of diethyl phthalate (DEP) and polyhexamethylene guanidine (PHMG), which may occur in unrecorded alcohol. Analysis for PHMG was based on UV-VIS spectrophotometry after derivatization with Eosin Y and 1H NMR spectroscopy of the DMSO extract. Analysis of DEP was performed with direct UV-VIS and 1H NMR methods. Multivariate curve resolution and spectra computation methods were used to confirm the presence of PHMG and DEP in the investigated beverages. Of 22 analysed alcohol samples, two contained DEP or PHMG. 1H NMR analysis also revealed the presence of signals of hawthorn extract in three medicinal alcohols used as surrogate alcohol. The simple and cheap UV-VIS methods can be used for rapid screening of surrogate alcohol samples for impurities, while 1H NMR is recommended for specific confirmatory analysis if required