Context: epsilon-Caprolactam is an important industrial chemical with a relatively low human toxicity; of importance is the irritations that occur after exposure to epsilon-caprolactam as aerosols or vapors.Objective: The aim of this study was to examine symptoms and objective effects, which occur on the mucous membranes of the eyes and the upper respiratory tract.Methods: A total of 52 healthy volunteers (26 women and 26 men, aged between 19 and 50 years) were exposed by random to different epsilon-caprolactam concentrations (0.05, 0.5 and 5.0mg/m(3)) and the control condition (0.0mg/m(3)) for 6h on four consecutive days. Eye blinking frequency, tear film break-up time, eye redness, nasal flows and resistance, olfactory function as well as total protein and interleukin-8 in nasal lavage fluid were determined daily before, during and after exposure. Questionnaires were used to record both subjective symptoms and personality factors.Results: There were no significant specific effects on the subjective and objective endpoints examined. Statistical analysis yielded no evidence of concentration-response relationships. Evaluation of olfactory symptoms showed that the duration of the stay in the chamber and not the epsilon-caprolactam concentration was decisive for the perception of impure air. Personality factors had no significant influence on the reported symptoms.Conclusions: Exposure to epsilon-caprolactam concentrations of 5.0mg/m(3) at maximum for 6h did not cause chemosensory effects on the upper respiratory tract or eyes of healthy volunteers. Therefore, the concentration of 5.0mg/m(3) corresponds to the No Observed Adverse Effect Level (NOAEL).

Ein mittlerweile klassisches Werk der Arbeitsmedizin ist jetzt in der 4. Auflage erschienen. Das Kapitel über die gesetzlichen Grundlagen beinhaltet die arbeitsmedizinischen Bezüge zum System der sozialen Sicherung, den staatlichen Arbeitsschutz und – ausführlich – Arbeitsunfall und Berufskrankheit. Es folgen die Rechtsgrundlagen der betriebsärztlichen Tätigkeit. Die Gliederung des Kapitels „Berufskrankheiten“ orientiert sich an der Berufskrankheitenliste. Die Ausführungen zu den einzelnen Berufskrankheiten liefern dem Sozialmediziner wichtige Informationen, wenn Fragen zur Prävention und Wiedereingliederung zu beantworten sind. Sie bieten auch eine Hilfestellung bei der Frage, ob der begründete Verdacht auf eine Berufskrankheit vorliegt und somit eine Berufskrankheitenanzeige zu erstatten ist. In den Literaturverzeichnissen fehlen allerdings wichtige Links oder sind veraltet.

There is a need of guidance on how local irritancy data should be incorporated into risk assessment procedures, particularly with respect to the derivation of occupational exposure limits (OELs). Therefore, a board of experts from German committees in charge of the derivation of OELs discussed the major challenges of this particular end point for regulatory toxicology. As a result, this overview deals with the question of integrating results of local toxicity at the eyes and the upper respiratory tract (URT). Part 1 describes the morphology and physiology of the relevant target sites, i.e., the outer eye, nasal cavity, and larynx/pharynx in humans. Special emphasis is placed on sensory innervation, species differences between humans and rodents, and possible effects of obnoxious odor in humans. Based on this physiological basis, Part 2 describes a conceptual model for the causation of adverse health effects at these targets that is composed of two pathways. The first, "sensory irritation" pathway is initiated by the interaction of local irritants with receptors of the nervous system (e.g., trigeminal nerve endings) and a downstream cascade of reflexes and defense mechanisms (e.g., eyeblinks, coughing). While the first stages of this pathway are thought to be completely reversible, high or prolonged exposure can lead to neurogenic inflammation and subsequently tissue damage. The second, "tissue irritation" pathway starts with the interaction of the local irritant with the epithelial cell layers of the eyes and the URT. Adaptive changes are the first response on that pathway followed by inflammation and irreversible damages. Regardless of these initial steps, at high concentrations and prolonged exposures, the two pathways converge to the adverse effect of morphologically and biochemically ascertainable changes. Experimental exposure studies with human volunteers provide the empirical basis for effects along the sensory irritation pathway and thus, "sensory NOAEChuman" can be derived. In contrast, inhalation studies with rodents investigate the second pathway that yields an "irritative NOAECanimal." Usually the data for both pathways is not available and extrapolation across species is necessary. Part 3 comprises an empirical approach for the derivation of a default factor for interspecies differences. Therefore, from those substances under discussion in German scientific and regulatory bodies, 19 substances were identified known to be human irritants with available human and animal data. The evaluation started with three substances: ethyl acrylate, formaldehyde, and methyl methacrylate. For these substances, appropriate chronic animal and a controlled human exposure studies were available. The comparison of the sensory NOAEChuman with the irritative NOAECanimal (chronic) resulted in an interspecies extrapolation factor (iEF) of 3 for extrapolating animal data concerning local sensory irritating effects. The adequacy of this iEF was confirmed by its application to additional substances with lower data density (acetaldehyde, ammonia, n-butyl acetate, hydrogen sulfide, and 2-ethylhexanol). Thus, extrapolating from animal studies, an iEF of 3 should be applied for local sensory irritants without reliable human data, unless individual data argue for a substance-specific approach.

Objective Main objective of this study was to examine the chemosensory effects of formaldehyde on hyposensitive and hypersensitive males at concentrations relevant to the workplace. Attention focused on objective effects on and subjective symptoms of the mucous membranes of the eyes, the nose, the upper respiratory tract and olfactory function. Methods Forty-one male volunteers were exposed for 5 days (4 h per day) in a randomised schedule to the control condition (0 ppm) and to formaldehyde concentrations of 0.5 and 0.7 ppm and to 0.3 ppm with peak exposures of 0.6 ppm, and to 0.4 ppm with peak exposures of 0.8 ppm, respectively. Peak exposures were carried out four times a day over a 15-min period of time. Subjective pain perception induced by nasal application of carbon dioxide served as indicator for sensitivity to sensory nasal irritation. The following parameters were examined before and after exposure: subjective rating of symptoms and complaints (Swedish Performance Evaluation System), conjunctival redness, eye-blinking frequency, self-reported tear film break-up time and nasal flow rates. In addition, the influence of personality factors on the volunteer’s subjective scoring was examined (Positive And Negative Affect Schedule). Results Formaldehyde exposures to 0.7 ppm for 4 h and to 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min caused no significant sensory irritation of the measured conjunctival and nasal parameters. No differences between hypo- and hypersensitive subjects were seen. Nevertheless, statistically significant differences were noted for olfactory symptoms, especially for the ‘perception of impure air’. These subjective complaints were more pronounced in hypersensitive subjects. Conclusions Formaldehyde concentrations of 0.7 ppm for 4 h and of 0.4 ppm for 4 h with peaks of 0.8 ppm for 15 min did not cause adverse effects related to irritation, and no differences between hypo- and hypersensitive subjects were observed.

Forty-one volunteers (male non-smokers, aged 32 +/- 9.6 yrs) were tested for susceptibility towards unspecific nasal irritation (sensitivity towards CO2) in order to define subgroups of hypersensitive and hyposensitive subjects. Blood samples were taken and the expression (mRNA level) of the GSH-dependent formaldehyde dehydrogenase gene (FDH, identical to alcohol dehydrogenase 5, ADH5; EC 1.2.1.46) was measured in leukocytes by quantitative real-time RT-PCR with TaqMan probes. FDH is the most important enzyme for the metabolic inactivation of FA. Blood samples were exposed to 150 mu M formaldehyde (FA) for 2 h and the induction of DNA-protein crosslinks (DPX) in leukocytes was measured by means of a modification of the alkaline comet assay (i.e., by assessing the reduction of DNA migration induced by gamma-radiation). Removal of DPX was determined by the abolition of FA-induced reduction in DNA migration within 4 h after the end of the exposure. Furthermore, the induction of sister chromatid exchange (SCE) in cultured lymphocytes was studied after treatment of whole blood cultures with FA (150 mu M). A correlation analysis was performed for all parameters tested for the whole study group and for hypersensitive and hyposensitive subgroups. The results indicate that despite large differences in CO2-sensitivity, the susceptibility towards nasal irritation was not related to the induction of genotoxic effects (DPX, SCE) in peripheral blood or to the protection of blood cells against FA-induced effects (expression of FDH, repair capacity for FA-induced DPX). There was no correlation between CO2-sensitivity and the expression of FDH. There was also no close correlation between the various indicators of cellular sensitivity towards FA-induced genotoxic effects and no subgroups were identified with particular mutagen sensitivity towards FA. (C) 2011 Elsevier B.V. Published by All rights reserved.

Forty-one volunteers (male non-smokers) were exposed to formaldehyde (FA) vapours for 4 h/day over a period of five working days under strictly controlled conditions. For each exposure day, different exposure concentrations were used in a random order ranging from 0 up to 0.7 p.p.m. At concentrations of 0.3 and 0.4 p.p.m., four peaks of 0.6 or 0.8 p.p.m. for 15 min each were applied. During exposure, subjects had to perform bicycle exercises (∼80 W) four times for 15 min. Blood samples, exfoliated nasal mucosa cells and nasal biopsies were taken before the first and after the last exposure. Nasal epithelial cells were additionally sampled 1, 2 and 3 weeks after the end of the exposure period. The alkaline comet assay, the sister chromatid exchange test and the cytokinesis-block micronucleus test were performed with blood samples. The micronucleus test was also performed with exfoliated nasal mucosa cells. The expression (mRNA level) of the glutathione (GSH)-dependent formaldehyde dehydrogenase (FDH, identical to alcohol dehydrogenase 5; ADH5; EC 1.2.1.46) was measured in blood samples by quantitative real-time reverse transcription-polymerase chain reaction with TaqMan probes. DNA microarray analyses using a full-genome human microarray were performed on blood samples and nasal biopsies of selected subgroups with the highest FA exposure at different days. Under the experimental conditions of this study, inhalation of FA did not lead to genotoxic effects in peripheral blood cells and nasal mucosa and had no effect on the expression of the FDH gene. Inhalation of FA did also not cause alterations in the expression of genes in a microarray analysis with nasal biopsies and peripheral blood cells.

Associations between occupational styrene exposure and cognitive as well as psychomotor functions were investigated with a view to answering three questions: (1) are the published results for neurobehavioural impairment reproducible, (2) if such effects exist, are they related to current or to chronic exposure and (3) if effects exist, are there reductions in the effects during an exposure-free period.

PURPOSE OF THE STUDY The purpose of this study is to examine the effectiveness of several types of personal respiratory protection equipment at styrene exposed laminators under real work place conditions. SUBJECTS AND METHOD 99 male styrene exposed workers were examined. During their lamination activities the average styrene concentrations in air ranged between 30 to 60 ppm (maximum: 205 ppm). The laminators were followed during an usual workweek from Monday to Thursday. The external styrene exposure was measured by means of passive active carbon badges. The excretion of mandelic acid (MA) and phenyl glyoxylic acid (PGA) in end-of-shift urine samples was used to quantify the internal styrene load. During the work shift some laminators did not use respiratory protection masks. The majority used either a half face mask with active carbon filter or an air purifying respirator. RESULTS The respiratory masks were worn during an average between 31% and 72% of the work time. The styrene concentrations of the ambient air were -depending on the activity- in the range of 30 to 60 ppm. The end-of-shift concentrations of MA and PGA in urine samples varied considerably, their means range from 153 to 606 mg/g creatinine. The comparison shows that workers with air purifying respirators experience the lowest internal styrene body burden in spite of high external exposures. Their effectiveness during usual working condition was around 83% whereas the use of half face masks with active carbon filters reduce styrene exposure only of 26% as an average. CONCLUSIONS The use of styrene-containing resins in boatbuilding can be associated with increased external styrene exposure of the laminators. During the use of different types of respiratory protection masks it is shown that only the application of air purifying respirators leads to a significant reduction of the internal styrene body burden of 83% when worn during 72% of the total work time. In this way it is possible to comply with or to stay clearly below the biological limit value of 600 mg MA + PGA/g creatinine (BAT-value).

Background: Efforts to address the high depression rates among training physicians have been implemented at various levels of the U.S. medical education system. The cumulative effect of these efforts is unknown. Objective: To assess how the increase in depressive symptoms with residency has shifted over time and to identify parallel trends in factors that have previously been associated with resident physician depression. Design: Repeated annual cohort study. Setting: U.S. health care organizations. Participants: First-year resident physicians (interns) who started training between 2007 and 2019. Measurements: Depressive symptoms (9-item Patient Health Questionnaire [PHQ-9]) assessed at baseline and quarterly throughout internship. Results: Among 16965 interns, baseline depressive symptoms increased from 2007 to 2019 (PHQ-9 score, 2.3 to 2.9; difference, 0.6 [95% CI, 0.3 to 0.8]). The prevalence of baseline predictors of greater increase in depressive symptoms with internship also increased across cohorts. Despite the higher prevalence of baseline risk factors, the average change in depressive symptoms with internship decreased 24.4% from 2007 to 2019 (change in PHQ-9 score, 4.1 to 3.0; difference, similar to 1.0 [CI, similar to 1.5 to similar to 0.6]). This change across cohorts was greater among women (4.7 to 3.3; difference, similar to 1.4 [CI, similar to 1.9 to similar to 0.9]) than men (3.5 to 2.9; difference, similar to 0.6 [CI, similar to 1.2 to similar to 0.05]) and greater among nonsurgical interns (4.1 to 3.0; difference, similar to 1.1 [CI, similar to 1.6 to similar to 0.6]) than surgical interns (4.0 to 3.2; difference, similar to 0.8 [CI, similar to 1.2 to similar to 0.4]). In parallel to the decrease in depressive symptom change, there were increases in sleep hours, quality of faculty feedback, and use of mental health services and a decrease in work hours across cohorts. The decrease in work hours was greater for nonsurgical than surgical interns. Further, the increase in mental health treatment across cohorts was greater for women than men. Limitation: Data are observational and subject to biases due to nonrandom sampling, missing data, and unmeasured confounders, limiting causal conclusions. Conclusion: Although depression during physician training remains high, the average increase in depressive symptoms associated with internship decreased between 2007 and 2019.

Objective Associations between occupational styrene exposures and impairment of visual functions were investigated with a view to answering three questions: (1) are the published findings for colour vision deficiencies and impaired contrast sensitivity to reproduce in a new study approach, (2) if such effects exist, are they related to current or chronic exposures and (3) if effects exist, are there reductions in the effects during an exposure-free period? Methods Workers from a boat building plant were examined in groups of current low [ n = 97, mean mandelic acid (MA) + phenylglyoxylic acid (PGA) = 51 mg/g creatinine], medium ( n = 115, mean = 229 mg/g creatinine) and high ( n = 30, mean = 977 mg/g creatinine) level exposure to styrene. Job tenure was about 6 years. In addition, subgroups chronically exposed to low-short ( n = 34, lifetime weighted mean 200 mg/g creatinine for 6 years) and high-long ( n = 17, mean = 660 mg/g creatinine, 15 years) styrene levels were analysed. The examinations were carried out during normal working days and during the company holidays. Colour vision was investigated with the Lanthony desaturated panel D-15d using the colour confusion index (CCI) as a relevant variable. Contrast sensitivity was investigated with the Vistech charts VCTS 6500 using frequency-related results as well as total scores as variables. Co-variance analyses with repeated measurements and multiple linear regressions were used for statistical analysis. Results There was no evidence of significant associations between exposure parameters and CCI. This is true for the analyses with all participants as well as for those with the subgroups with high-long versus low-short exposure. Thus, no exposure related changes in the relevant variables were found during the exposure-free period. The analyses for contrast sensitivity show similar results. The largest portions of the variances in both tests were explained by age. German as mother tongue covered a considerable portion of the CCI variances. Education, long-term alcohol use and job tenure explain only partly significant portions of the test variances exhibited. Conclusion Both acute styrene exposure levels of 40 ppm (range of standard deviation up to 54 ppm) and long term exposures to 27 ppm (range of standard deviation up to 44 ppm with higher exposure levels in the past) for a period of about 15 years were not identified as causing elevated risks for the investigated parameters of colour vision and contrast sensitivity. This statement contradicts the published results for styrene-related colour vision deficiencies but it seems to be compatible with published results for contrast sensitivity due to styrene exposure.