0000000000054733
AUTHOR
Axel Muttray
mRNA Induction and Cytokine Release of Inflammatory Mediators During In Vitro Exposure of Human Nasal Respiratory Epithelia to Acetaldehyde
Acetaldehyde has been shown to be cytotoxic and carcinogenic to the upper respiratory tract epithelium of rodents following long-term exposure. Most animal studies have concentrated on carcinogenicity and DNA-protein cross-link formation, while less is known about potential dose- and time-dependent induction of aldehyde-induced rhinitis in humans. In this in vitro study, 22 primary cell cultures established from inferior turbinate tissue of healthy individuals were exposed to acetaldehyde concentrations of 50 (German MAK value) or 500 ppm for 4 or 24 h. mRNA expression and protein levels of cytokines and other inflammatory mediators were quantified at the end of the 4- and 24-h exposures. C…
Internal exposure of firefighting instructors to polycyclic aromatic hydrocarbons (PAH) during live fire training
Firefighting instructors in live fire training are inevitably exposed to emissions containing, carcinogenic PAH. The study investigated PAH uptake in a group of firefighting instructors during short-term exposure in live fire training by urinary biomonitoring. Six firefighting instructors (non-smokers) completed five 2 h-training sessions each in a carbonaceous-fired simulation unit using self-containing breathing apparatuses (SCBA). Complying with a minimum time interval of six days between the individual training sessions, the participants provided urine samples before and immediately after, as well as 1, 3, 6, 9, 11, and 18 h after each training session. Samples were analyzed for 10 mono…
An acute exposure to ozone impairs human olfactory functioning
Ozone is a ubiquitous and irritant gas. We questioned whether an acute exposure to 0.2 ppm ozone impaired olfactory functioning.Healthy, normosmic subjects were exposed according to a parallel group design either to 0.2 ppm ozone (n = 15) or to sham (n = 13) in an exposure chamber for two hours. Possible irritating effects were assessed by questionnaire (range 0-5). The detection threshold of n-butanol was measured with the Sniffin' Sticks test before and after exposure. Olfactory thresholds were logarithmized and a two-way analysis of variance (ANOVA) with repeated measurements was carried out to test the effects of exposure (ozone vs. sham) and time (before vs. after exposure). Additional…
Acute exposure to 50ppm toluene does not increase sleepiness
Abstract The Pupillographic Sleepiness Test (PST) is a new neurophysiological method to assess sleepiness. In an exposure study to a constant exposure level of 50 ppm toluene on 20 healthy men, our aim was to find out, if increased sleepiness could be seen with PST. PST was performed before and after 4.5 h of exposure. General complaints were assessed with the Swedish Performance Evaluation System (SPES) self-assessment questionnaire, once before and during exposure. Values obtained during exposure were related to pre-exposure values. Parametric cross-over analysis of logarithmic Pupillary Unrest Index (PUI) values did not show an effect of toluene exposure. In a nonparametric cross-over an…
Effects of high doses of toluene on color vision.
High exposure to toluene may cause optic neuropathy and retinopathy, both associated with dyschromatopsia. Another solvent, ethanol, is known to induce acute blue-yellow dyschromatopsia. This study investigated the acute effects of high doses of toluene on color vision. Eight male printshop workers were examined before and after cleaning printing containers with pure toluene. After cleaning, concentrations of toluene in blood were between 3.61 and 7.37 mg/l. Color vision was tested with the Farnsworth panel D-15 test, the Lanthony desaturated panel D-15 test, and the Standard Pseudoisochromatic Plates part 2. For control of possible acute effects, eight workers of a metal-working factory wi…
Acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects.
Abstract The German MAK value of 1-methoxypropanol-2 has been fixed at 100 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects. Twenty subjects were exposed in a crossover design to 100 ppm 1-methoxypropanol-2 and to air in an exposure chamber for 4 h. Subjective symptoms were assessed by questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1β and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1β, 6 and 8, tumor necrosis factor α, granulocyte-m…
Comparison of subjective olfaction ratings in patients with and without olfactory disorders
AbstractObjective:Olfactory dysfunction is common. The reliability of self-assessment tools for smell testing is still controversial. This study aimed to provide new data about the accuracy of olfactory self-assessment compared with a standardised smell test.Design:Prospective, controlled, cohort study of patients with olfactory disorders and healthy controls.Subjects:Ninety-six patients with a smell deficit and 71 controls were asked to rate their sense of smell on a visual analogue scale. Their olfactory abilities were also evaluated with the Sniffin' Sticks tests.Results:The whole cohort showed a significant correlation between visual analogue scale smell scores and Sniffin' Sticks total…
mRNA-induction and cytokine release during in vitro exposure of human nasal respiratory epithelia to methyl methacrylate
Abstract Background Methyl methacrylate (MMA) has been reported to cause histopathological changes in rodent nasal epithelium after inhalation challenges. Data in humans are lacking. Methods In this in vitro design 22 primary cell cultures taken from inferior turbinate tissue of healthy individuals were exposed to MMA concentrations of 50 ppm (German MAK-value) and 200 ppm. mRNA expression and cytokine release of inflammatory mediators were quantified after 4 h and after 24 h. Controls were exposed to synthetic air. Q-PCR analysis was performed for TNF-α, IL-1β, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2. ELISA assays were performed from culture supernatants for TNF-α, IL-1β, IL-6, IL-8, MCP…
Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners
One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of t…
Acute effects of low doses of methyl parathion on human EEG.
Abstract Biological monitoring of workers exposed to organophosphates consists mainly of measuring serum or erythrocyte cholinesterase activity. However, animal experiments and a field study suggest that quantitative analysis of EEG may be more sensitive. In a parallel group design, 25 farmers were investigated, spraying methyl parathion or water for 50 min. EEG was recorded before and after spraying. Serum and erythrocyte cholinesterase activity was compared with intraindividual pre-exposure values. Plasma methyl parathion concentrations ranged up to 12.1 μg/l, methyl paraoxon was not detectable. Based on plasma concentrations, two exposed subgroups were defined. In EEG recorded with close…
Methods of Ascertainment of Personal Damage in Germany
The chapter illustrates the historical, judicial and juridical framework of personal injury assessment and compensation in Germany, describing the expert’s qualification and competences and detailing the ascertainment methodology and criteria of evaluation utilised for identifying, describing and estimating any personal injury, its temporary and permanent consequences and the causal value/link between the event and the injury and between the injury and the impairment/disability.
Pressure pain thresholds: Subject factors and the meaning of peak pressures.
Background The assessment of pressure pain has become an integral part in pain research. The distribution of pressure under a plunger can be uneven. However, measurements based on conventional devices show the applied force or mean pressure, failing to take local pressure peaks into account. Our main question was whether peak pressures under the probe are responsible for pain onset. Methods A force-controlled algometer was fitted with a newly developed pressure-indicating film. Pressure pain thresholds (PPTs) of 100 healthy subjects (57 men, age 18-66 years) were assessed at 29 sites across the body. Each site was measured three times, nonconsecutively and presented in randomized order. For…
Effects of Visually Induced Motion Sickness on Emergency Braking Reaction Times in a Driving Simulator
Objective: The study explores associations of visually induced motion sickness (VIMS) with emergency braking reaction times (RTs) in driving simulator studies. It examines the effects over the progression of multiple simulated drives. Background: Driving simulator usage has many advantages for RT studies; however, if it induces VIMS, the observed driving behavior might deviate from real-world driving, potentially masking or skewing results. Possible effects of VIMS on RT have long been entertained, but the progression of VIMS across simulated drives has so far not been sufficiently considered. Method: Twenty-eight adults completed six drives on 2 days in a fixed-base driving simulator. At f…
Acute effects of 1,1,1-trichloroethane on human olfactory functioning.
Background Animal experiments indicate that 1,1,1-trichloroethane can cause degeneration of the olfactory epithelium. The effects of 1,1,1-trichloroethane on human odor perception still have not been investigated. The goal of this study was to learn more about acute effects of 1,1,1-trichloroethane. Methods Twelve healthy, nonsmoking students were exposed to 200 and 20 ppm (control) 1,1,1-trichloroethane in an exposure chamber for 4 hours according to a crossover design. Olfactory functioning was investigated with the Sniffin’ Sticks. The test includes the determination of the detection threshold for n-butanol and an odor identification test. Results After 1 hour of exposure to 200 ppm 1,1,…
Effect of nighttime aircraft noise exposure on endothelial function and stress hormone release in healthy adults.
Aims Aircraft noise disturbs sleep, and long-term exposure has been shown to be associated with increases in the prevalence of hypertension and an overall increased risk for myocardial infarction. The exact mechanisms responsible for these cardiovascular effects remain unclear. Methods and results We performed a blinded field study in 75 healthy volunteers (mean age 26 years), who were exposed at home, in random order, to one control pattern (no noise) and two different noise scenarios [30 or 60 aircraft noise events per night with an average maximum sound pressure level (SPL) of 60 dB(A)] for one night each. We performed polygraphy during each study night. Noise caused a worsening in sleep…
Acute effects on the human EEG after an external exposure to 200 ppm methanol
Objectives: Even low concentrations of organic solvents may cause acute effects on the human central nervous system. The German MAK (threshold limit value) of methanol is 200 ppm. The aim of this study was to investigate whether acute exposure to 200 ppm methanol causes adverse effects, measured by EEG, and moreover, whether it is possible to differentiate between sedative and excitatory effects with this method. Methods: Twelve healthy subjects were exposed for 4 h to 200 ppm and to 20 ppm (control) in an exposure chamber in a cross-over design. The EEG was recorded before (reference) and at the end of each exposure with, the subject's eyes closed and opened and during a choice reaction te…
The role of expert evaluation for microsleep detection
Abstract Recently, it has been shown by overnight driving simulation studies that microsleep density is the only known sleepiness indicator which rapidly increases within a few seconds immediately before sleepiness related crashes. This indicator is based solely on EEG and EOG and subsequent adaptive pattern recognition. Accurate microsleep recognition is very important for the performance of this sleepiness indicator. The question is whether expensive evaluations of microsleep events by a) experts are necessary or b) non-experts provide sufficient evaluations. Based on 11,114 microsleep events in case a) and 12,787 in case b) recognition accuracies were investigated utilizing (i) artificia…
Further development of a commercial driving simulation for research in occupational medicine
Objectives: The purpose of this study was to refine a commercial car driving simulation for occupational research. As the effects of ethanol on driving behavior are well established, we choose alcohol as a test compound to investigate the performance of subjects during simulation. Materials and Methods: We programmed a night driving scenario consisting of monotonous highway and a rural road on a Foerst F10-P driving simulator. Twenty healthy men, 19-30 years, participated in a pilot study. Subjects were screened for simulator sickness, followed by training on the simulator one hour in total. Experiments were performed in the morning on a separate day. Participants were randomized into eithe…
The Candy Smell Test in Clinical Routine
Background The “Candy Smell Test” (CST) has been introduced as a new testing method for the evaluation of the human sense of smell. In contrast to other established orthonasal smell tests, the CST addresses the retronasal application of odors, typical for food aroma effects during mastication and swallowing. The aim of this study was to evaluate the CST in a clinical setting in patients with olfactory dysfunction and normal controls against the Sniffin’ Sticks test. Furthermore, cutoff points for normal and pathological results in the CST should be determined. Methods The olfactory performance of 96 patients presenting with olfactory disorders and 71 healthy controls was evaluated with the …
The best way to assess visually induced motion sickness in a fixed-base driving simulator
Abstract Objective Driving simulator usage is becoming more widespread, yet many users still experience substantial motion sickness-like symptoms induced by optical flow, called visually induced motion sickness (VIMS). The Fast Motion sickness Scale (FMS) allows for continuous on-line assessment of VIMS. Using mixed models for ordinal data, this study investigated how to optimally analyze FMS data, and then used the resulting models to examine the development of symptoms over time in detail. Additionally, the study explored the impact of specific VIMS-inducing road elements. Methods Twenty-eight healthy young adults without prior simulator experience completed six courses on two days in a f…
Blue-yellow deficiency in workers exposed to low concentrations of organic solvents
Objectives: To evaluate the effects of low concentrations of organic solvents on color vision. Methods: Color vision was examined in 24 workers exposed to mixtures of solvents and in 24 control subjects. Exposure to mixtures was below the threshold-limit values. Color vision ability was assessed using the Ishihara plates (to screen for congenital dyschromatopsia), the Farnsworth panel D-15 test, the Lanthony desaturated panel D-15 test, and the Standard Pseudoisochromatic Plates part 2 (SPP2 test). Results: The comparatively less sensitive Farnsworth panel D-15 test failed to show any difference between the groups, but the Lanthony panel D-15 desaturated test as well as the SPP2 test showed…
Early stress response of human nasal respiratory epithelia after exposure to 1-methoxypropanol-2
To evaluate the impact of 1-methoxypropanol-2 (MEP) for the stimulation of an inflammatory response in human respiratory mucosa, we exposed 22 primary cell cultures of nasal respiratory epithelia of healthy individuals to MEP concentrations at the level of the German MAK-value (100 ppm) and to the 10-fold concentration (1000 ppm). After 4 and 24h we analyzed the transcription of TNF-alpha, IL-1beta, IL-6, IL-8, MCP-1, GMCSF, Cox-1 and Cox-2 by quantitative PCR as well as the release of the respective cytokines by ELISA. At both MEP concentrations we observed a significant increase of TNF-alpha-, IL-1beta-, IL-6- and Cox-2-transcripts after 4h. After 24h cytokine transcription of TNF-alpha, …
Intoxication with a tropenol ester.
BACKGROUND While the effects of medicinal products are investigated in depth before approval, often very little is known about the intermediates occurring during synthesis. The pharmacological properties of these intermediates can differ substantially from those of the end product. AIMS To describe a work accident involving intoxication with such an intermediate, tropenol ester. CASE REPORT A healthy 40-year-old chemical-technical operative erroneously used a scrubbing brush that had just been used to clear up tropenol ester, contaminating his work clothes. Presumably, contact was made with his skin when removing his work clothes later. Shortly thereafter, he developed signs of anticholiner…
The impact of solvent mixtures on neurobehavioral performance: conclusions from epidemiological data.
Abstract The review of epidemiological studies investigating the neurobehavioral effects of occupational exposure to solvent mixtures sought to contribute to the following issues: (1) Identification of affected cognitive and motor functions. (2) Identification of sensitive neuropsychological tests. (3) Analysis of exposure–effect relationships. The approach was based on the meta-analytical method of effect size estimates. Fifty-three groups from occupational studies were included in the meta-analysis. Forty-eight neuropsychological performance variables could be analyzed as they were included in at least three studies. Seventeen articles provided detailed information on the constituents of …
Urine tropenol ester levels in workers handling tiotropium bromide synthesis: implications for exposure prevention and biomonitoring
Tropenol ester is a highly toxic anticholinergic substance and an intermediate used in industrial production of the bronchodilator tiotropium bromide. The aim of this study was to systematically test workers involved in its production for tropenol ester in urine to identify any exposure pathways and define additional preventive measures. Twelve workers performing tasks involving potential exposure to tropenol ester were repeatedly monitored at the end of each production cycle. Medical exams revealed no symptoms of acute poisoning with tropenol ester, but biological monitoring of urine showed 36 positive findings in 79 samples, with tropenol ester concentrations ranging between the detection…
External and internal exposure of wine growers spraying methyl parathion.
Organophosphates, used in agriculture, are readily absorbed through the skin. We investigated the relationship between dermal and inhalative methyl parathion exposure and the plasma levels. Twenty-three healthy wine growers sprayed the insecticide for 50 min. Fluorescent brilliant sulfoflavin was added to the spraying fluids and filter papers were fixed on the subjects. The filter papers were used to evaluate the amount of brilliant sulfoflavine on the unprotected skin fluorometrically. Inhalative exposure was measured with personal air sampler. Plasma concentrations of methyl parathion and its metabolite methyl paraoxon were determined with gas chromatography. Cholinesterase activity in se…
The exposure of healthy volunteers to 200 ppm 1,1,1-trichloroethane increases the concentration of proinflammatory cytokines in nasal secretions
Objectives: Irritating effects of organic solvents have usually been measured by means of questionnaires. The aim of the present study was to evaluate the sensitivity of different methods of detecting subclinical irritating effects. Methods: Twelve healthy, non-smoking students were exposed to 200 ppm and to 20 ppm 1,1,1-trichloroethane in an exposure chamber, using a crossover design. The amounts of interleukins (IL)-1β, IL-6 and IL-8 and prostaglandin E2 (PGE2) in nasal secretions were measured. Mucociliary transport time was determined with the saccharine test. Ciliary beat frequency of nasal epithelial cells was measured with video-interference contrast microscopy. Subjective symptoms w…