Search

Safe and noninvasive methods for breast cancer screening with improved accuracy are urgently needed. Volatile organic compounds (VOCs) in biological samples such as breath and blood have been investigated as noninvasive novel markers of cancer. We investigated volatile organic compounds in urine to assess their potential for the detection of breast cancer. One hundred and ten women with biopsy-proven breast cancer and 177 healthy volunteers were enrolled. The subjects were divided into two groups: a training set and an external validation set. Urine samples were collected and analyzed by gas chromatography and mass spectrometry. A predictive model was constructed by multivariate analysis, and the sensitivity and specificity of the model were confirmed using both a training set and an external set with reproducibility tests. The training set included 60 breast cancer patients (age 34-88 years, mean 60.3) and 60 healthy controls (age 34-81 years, mean 58.7). The external validation set included 50 breast cancer patients (age 35-85 years, mean 58.8) and 117 healthy controls (age 18-84 years, mean 51.2). One hundred and ninety-one compounds detected in at least 80% of the samples from the training set were used for further analysis. The predictive model that best-detected breast cancer at various clinical stages was constructed using a combination of two of the compounds, 2-propanol and 2-butanone. The sensitivity and specificity in the training set were 93.3% and 83.3%, respectively. Triplicated reproducibility tests were performed by randomly choosing ten samples from each group, and the results showed a matching rate of 100% for the breast cancer patient group and 90% for the healthy control group. Our prediction model using two VOCs is a useful complement to the current diagnostic tools. Further studies inclusive of benign tumors and non-breast malignancies are warranted., (© 2021. The Author(s).)

Objectives: To test the reliability of the procedures (described in a previous article) for estimation of biological occupational exposure limits (BOELs)., Methods: Data on four organic solvents (styrene, ethyl benzene, isopropyl alcohol and tetrachloroethylene) were obtained from recent publications and added to previously cited data for 10 organic solvents. Regression analysis was used for statistical evaluation., Results and Discussion: The previously reported results obtained using 10 solvents were reproduced by the analysis with 14 solvents. Repeated randomized division of the 14 sets into two subgroups of equal size followed by statistical comparisons did not show a significant difference between two regression lines. This reproducibility suggests that the procedures used to estimate BOELs may be applicable across many solvents, and this may be of particular benefit for protecting the health of workers who work with skin-penetrating solvents.

Background: Ethyl glucuronide (EtG) in urine is considered a specific marker of recent ethanol consumption. There is an ongoing debate about whether inhalation or transdermal resorption of sanitizer ethanol is the underlying cause for positive EtG findings after hand disinfection., Methods: Desderman(®) pure (Schülke & Mayr GmbH, Norderstedt) with 78.2g 96% (v/v) ethanol/100g and approx. 10% 2-propanol was used for multiple hand disinfection without and under an exhauster. Simulating a common working day in a clinic, 5 co-workers of our lab used the sanitizer 32 fold within 8h and 2 persons were merely exposed to the sanitizer vapor but without any dermal sanitizer contact. Any additional ethanol intake or exposition was reliably excluded. Spot urine was collected at baseline, after 1, 2, 4, 6 … 14, and finally 24h after the first sanitizer use. A validated LC-MS/MS was used for MRM and MS(3) of EtG and qualitative analyses of ethyl sulfate and 2-propyl glucuronide., Results: Multiple hand disinfection caused positive EtG findings of up to 2.1mg/L or 1.7mg/g creatinine in 4 out of 5 test persons and even of 0.6mg/L or 0.8mg/g for 2 controls which were merely exposed to the sanitizer vapor but without any sanitizer contact. EtG results between the clinical (0.5mg/g) and the forensic (0.1mg/g) cut-off were obtained even 6h after the last sanitizer exposition. An exhauster prevented the sanitizer vapor inhalation and reduced the EtG excretion to mostly below the detection limit of 0.02mg/g. The maximum value was 0.09mg/g. Ethyl sulfate and 2-propyl glucuronide (2-PpG) were detectable only in the EtG positive samples. 2-PpG is a metabolite of 2-propanol, which is quite frequently used in disinfectants. Thus, the detection of this substance can be used in cases of odd EtG results as an indicator of (unintended) sanitizer exposition., Conclusion: Ethanol from hand sanitizers is predominantly incorporated by the respiratory tract but not via the skin. It can cause a distinct ethyl glucuronide excretion and thus analytically true-positive but forensically false-positive EtG findings in the urine of ethanol abstaining persons. Since accidental ethanol inhalation can occur quite frequently in the working place or even private household, such a situation should always be considered when EtG is used as a marker of recent ethanol consumption., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Alcohol ketoacidosis is a frequently missed diagnosis, but is well described in the literature. We present a case of ketoacidosis, likely alcohol ketoacidosis, in a 40 y-old chronic alcoholic patient. The detection of trace serum isopropanol prompted a discussion of alcohol ketoacidosis versus toxic isopropanol ingestion or a combination of both, including comparisons with citations in current literature., Methods: The automated instruments used to analyze the patient's urine, blood, and serum samples are described., Results: The initial impression was severe metabolic acidosis with an increased anion gap and normal serum glucose and whole blood lactate. Testing for potential toxic ingestions detected only increased serum acetone and trace serum isopropanol. A urinalysis positive for ketones and an increased serum β-hydroxybutyrate concentration clenched the diagnosis of ketoacidosis., Conclusion: Ketoacidosis with an increased anion gap in the absence of hyperglycemia or glycosuria in a chronic alcoholic patient should prompt the evaluation for alcohol ketoacidosis. Trace serum isopropanol may be worrisome for a toxic ingestion, but this finding in severe ketoacidosis may be explained by the reversible action of the enzyme alcohol dehydrogenase. Markedly increased serum isopropanol with a low serum acetone:isopropanol ratio would be more indicative of a toxic isopropanol ingestion., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: Sevoflurane is an inhalation halogenated anaesthetic widely used in day and paediatric surgery. We were interested in evaluating biological markers of exposure to sevoflurane, which should improve the health surveillance of occupationally exposed personnel., Methods: A group of 36 subjects (13 male, 23 female) occupationally exposed to volatile anaesthetics in paediatric operating rooms was studied in a 2-week survey. Post-shift urine samples and specimens from passive samplers (for personal monitoring) were collected after 1.75-6 h morning exposure and analysed by headspace gas chromatography-mass spectrometry (GC-MS). Multiple determinations were assumed as independent values (in total, n = 78: 24 from men, 54 from women; 25 from smokers, 53 from non-smokers)., Results: Median sevoflurane external values were 0.13 parts per million (ppm) (range 0.03-18.82) (n = 78), urinary sevoflurane 0.6 microg/l urine (ND-18.5)(n = 76) and total urinary hexafluoro-isopropanol (HFIP) 0.49 mg/l urine (ND-6833.4) (n = 75). A lower limit of detection (LOD) was achieved for urinary sevoflurane (0.03 microg/l urine), allowing quantitation of all but one of the samples; >25% of urine samples were unquantifiable by HFIP and were assigned a value equal to half the LOD of 0.10 mg/l(urine). Urinary sevoflurane correlated well with breathing-zone data (r2 = 0.697 at log-log linear regression), whereas total urinary HFIP (r2 = 0.562 at log-log linear regression) seemed to be better described by a three-parameter logistic function and appeared to be influenced by smoking habits. Biological indices corresponding to National Institute for Occupational Safety and Health (NIOSH) exposure limits, calculated as means of linear regression slope and y intercept, were 3.9 mug/l(urine) and 1.4 microg/l urine for sevoflurane (corresponding to 2 ppm and 0.5 ppm, respectively), and 2.66 mg/l urine and 0.82 mg/l urine for HFIP., Conclusions: On the basis of our data, urinary unmodified, sevoflurane seems to be a more sensitive and reliable biomarker of short-term exposure to sevoflurane with respect to total urinary metabolite HFIP, which appears to be influenced by physiological and/or genetic individual traits, and seems to provide an estimate of integrated exposure.

We developed a new assay method for fluoride anion (F(-)) a specific metabolite of sarin. Trimethyifluorosilane (TMFS) was derivatized from F(-) with trimethylsilanol, and TMFS was detected with a GC-flame ionization detector (FID) and capillary column system. The linear range, detection limit and recovery rate were 0.02-10 ppm, 0. 01 ppm and 97.3-103.0%, respectively. The patients were reported to be exposed only once to the toxic substance (a bolus exposure). F(-) excretion in urine of the hospitalized patients demonstrated three or four peaks. Other common metabolites of sarin and by-products such as methylphosphonic acid (MPA) and isopropyl alcohol (IPA) also showed two or three peaks. These results suggested that the patients were exposed to not only sarin but also fluoride and isopropyl alcohol containing by-products. The sum of MPA excreted was 0.3-90 mM, far exceeding the human lethal dose of sarin. The residual acetyicholine esterase activity of erythrocytes on admission (4.7-57.2% of the individual reference value) of the patients showed statistically significant relationships only with the initial values of F(-) and the isopropyl methylphosphonate. This evidence also suggested the exposure to fluoride and isopropyl alcohol-containing by-products.

Objectives: The aim of this study was to determine the dose-effect relationship between solvent exposure and acute neurobehavioural effects at the worksite., Methods: In a balanced design, ten workers in a Swiss foundry were monitored for 15 days at ten different times during work. Urine samples were taken in the morning and at the time of examination, and personal exposure to isopropanol and methylformate was measured with active samplers. Neurobehavioural tests such as postural balance (bipedal, bipedal blind, monopedal), simple reaction time and digit span of the Neurobehavioural Evaluation System (NES2) and a combined memory and reaction-time test, the combi-test, were performed. A rating of well-being, and the last consumption of alcohol, caffeine, nicotine and medication were reported., Results: Average environmental concentrations of isopropanol were at 44 ppm ( +/- 16 ppm), and at 36 ppm (+/-21 ppm) for methylformate. Maximum values of personal exposure to isopropanol reached barely the maximal allowable concentration (MAC) value (400 ppm); the methylformate personal exposure of three workers exceeded the MAC value (100 ppm). Urine concentrations of methanol were high (3.1 +/- 2.3 mg/l in the morning, 7.8 +/- 4.9 mg/l after exposure) compared with the results of other studies; concentrations of isopropanol were rather low (0.88 +/- 0.73 mg/l after exposure)., Conclusions: Nevertheless, between personal exposure and biomonitoring, linear correlation was found. Methylformate exposure correlated with methanol and formic acid concentration in the urine, and isopropanol exposure with its concentration in the urine. With the neurobehavioural tests used, no solvent effect in relation to the dose could be determined.

Two instances of finding abnormally high concentrations of acetone in urine (0.10 g/dL and 0.052 g/dL) without any measurable amounts of ethanol (<0.005 g/dL) or isopropanol (<0.005 g/dL) prompted a survey of the elimination kinetics of isopropanol and its metabolite acetone in humans. In a hospital patient who had ingested denatured alcohol, the elimination half-life (t(1/2)) of acetone during detoxification was 27 h and not 3-5 h as reported by other workers. Several other literature reports of individuals who had ingested isopropanol as well as controlled studies after administration of moderate amounts of acetone and/or isopropanol support the notion of a long elimination half-life of 17-27 h for acetone compared with a t(1/2) of 1-3 h for isopropanol.

A 48-year-old man with an extensive history of alcoholism was found dead at home. He was lying face down on a carpet. There was evidence of gastric aspiration at autopsy and histologic examination. The distribution of ethanol was very unusual (concentrations in mg/100 mL or mg/100 g): femoral blood, 257 and 273 (two samples); heart blood, 643; vitreous humor, 763; urine, 84; bile, 616; liver, 250; and gastric, 4660 (2470 mg/53 g). In addition, this man ingested isopropanol, and, according to the history, may also have ingested acetone in the form of nail polish remover. The distribution of both isopropanol and acetone was as expected, which was approximately in proportion to the aqueous content of the respective tissues. It is proposed that agonal or postmortem aspiration of the ethanol-rich vomitus and postmortem fermentation could account for the apparently elevated concentrations of ethanol in heart blood and bile. The elevated vitreous ethanol could be explained if ethanol diffused across the eye in the agonal phase or postmortem from gastric aspirate in the carpet. The relatively low urinary ethanol concentration would be consistent with a recent binge-drinking episode, which allowed only a limited time period for excretion into an already partially full, but relatively ethanol-free, bladder.