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Projets (par axe de recherche)

PROJETS (PAR AXE DE RECHERCHE)

Réhabilitation & workability

Interdisciplinary workplaces intervention strategies in MSD

Work-related musculoskeletal disorders are a persistent and expensive health challenge in all industrial countries including Switzerland. The cost of work-related MSD in Switzerland has been estimated to about 2-4 billion CHF per year. A relatively small group of patients causes relatively high health services costs and long absenteeism from work and furthermore show a high risk to loose workability.

This research aims to address the work-related MSD management issue through a cross-disciplinary intervention involving both clinical and occupational health competencies (rheumatology, occupational medicine, rheumatology, work psychology, ergonomics).

A cohort study of workers enduring MSD are selected from volunteering companies and randomised into two groups. Workers from the control group will benefit from an usual MSD management strategy involving a classic clinical therapy and the providing of basic information (i.e. info about ergonomics). Workers from the intervention group will benefit from a case-management including work-hardening treatment and workplace intervention.

The comparison of health and work-related variables prior and after intervention in the two groups will be used to assess the intervention efficiency and its economic benefits.

Work ability index (WAI) and ageing workers

The principal aim of our study is to develop a clinical method of follow-up of the ageing workers, in different services of the Administration (Canton de Vaud, Western Switzerland). Based on a standardized interview (risk assessment, subjective point of view of the volunteers about protective factors and solutions for prevention), questionnaires (WAI, Karasek) and workplace analysis, the method will be evaluated in terms of satisfaction of the volunteers, applicability (clinicians’ appreciation), and positive changing in the services (workers’ health, health prevention policies, organisational policies, retreat policies).

The WAI – Work Ability Index- is a clinical tool which was created by the Finnish Institute of Occupational Health, in order to help the occupational specialists in following the ageing workers. It is a sort of thermometer of the occupational health. It promises to be of good help for clinicians, but is relatively new in Switzerland (2005). One of the aims of our study is to assess this tool: applicability, acceptance, and reliability. Measuring the WAI anonymously and before any intervention may be a first step in assessing health risks, and may help with prioritising interventions.

Analysis of the factors influencing vocational rehabilitation in patients after renal or liver transplants performed between 1993-2003 at CHUV

Work is one of the most important measures of human existence, described in Abrams’ definition of Quality of Life (Qol) as one of the basic determinants of life satisfaction experienced by human beings. It is an essential factor for preserving psychological well-being, and a source of self-consciousness and self-realization. With organ transplantation patients obtain a new lease on life, both socially and professionally. Apart from the strictly medical aspects, organ transplantation changes the poor prognosis of the disease radically; the possibility of returning to work after transplantation not only enhances QoL, it is also an important rehabilitation factor and indicator of overall transplants success. It is therefore extremely important for healthcare professionals to appreciate the complex nature of the transplantation process, and to consider recipients in a wholistic fashion, encompassing the physical, social, psychological and vocational aspects.

This study explores vocational rehabilitation after renal and liver transplantation and will demonstrate the factors that influence return to work: for example renal or liver disease duration, time between stopping work and the transplantation; time between transplantation and return to work; economic and social difficulties; entitlement to disability insurance, etc.

The group being studied, renal or liver patients who received transplants at CHUV between 1993-2003 will respond to an extensive questionnaire about the medical, social, economic and vocational aspects of their cases.

European Working Conditions Survey (EWCS) – Swiss Data Analysis

In 2005 Switzerland was, for the first time, included in the European Working Conditions Survey (EWCS). The EWCS periodic is an important tool to evaluate the national Occupational Health situation in comparison with the other European countries. At the moment Switzerland has no “indicators of performance” related to occupational health so that the priority areas where research or interventions are needed are not known. EWCS should help us to detect where are the most important problems and which type of factors are the most relevant in this context.

This project aims to analyse the EWCS data at two levels: (1) national data will be analysed to assess the current Swiss situation (2) European data will be analysed to address research issues in regards of correlations between causal factors and subjective/objective occupational health outcomes.

Effets des particules sur la santé

In-vitro effects of natural mineral fibres from stone treatment processes

During stone treatment processes such as tunnel works or stone sculpturing, fibre-shaped particles (according WHO definition) may be released into the air. These particles are formed during the treatment, which is in contrast to those that are already present in the mineral (e.g. asbestos fibres). Fibre-shaped particles from the mineral-group of the amphiboles could be classified as asbestos or non-asbestos depending on slight differences in their chemistry (Si-Al). Fibres-shaped particles from amphibol minerals such as tremolite, actinolite, anthophyllite would be classified as asbestos (no or little Al), while chemically very close amphibol minerals such as hornblende which contains some percent of Al would be classified as non-asbestos, i.e. as not dangerous. Furthermore, some “non-suspicious” soapstones commonly used for sculpturing by artists and in school workshops were found to release asbestos fibres.

This projects aims at examining the effects of mineral fibres released during stone treatment processes on cell cultures. Specifically, fibre-shaped particles from amphibolitic stones (i.e. by definition asbestos), from chemically closely related stones (hornblende), fibres and particles from “non-suspicious” soapstones and (for comparison) “true” geologically formed asbestos fibres will be used to test their toxicity on human macrophage cells in an in-vitro system.

NanoHealthNet

Nanoparticles are particles smaller than 100 nm. Their chemical and physical characteristics are interesting for technical and medical applications. In spite of recent advances in medical and toxicological research, it is unclear, how exactly nanoparticles interact with biological targets and which particle metrics are driving these responses. This Network will promote research cooperation in four areas: 1) What types of particles are being produced in bulk, which of them present likelihood for large-scale human exposure and how can unwanted exposures be prevented? 2) How are particles taken up, translocated and distributed in cells, organs, and compartments? 3) How do particles interact with cells and organs? 4) How are the interactions manifested in animals and humans? Answering these questions will benefit medical sciences, will provide key knowledge for risk assessment, and will guide a safe and responsible production, use, and disposal of nanoparticles.

Properties and toxicity of brake nanoparticules

Fine particulate matter is associated with increased morbidity and mortality. Increased relative risks were observed for exposure to traffic particles. Major sources of traffic particles are combustion engines, brake and road wear. In a previous study, we (AJRCCM 2004, PFT 2005) observed in a population of highway patrol officers negative health effects to be mostly associated to a source characterized by components from engine emissions and brake wear.

Copper is an important component of vehicle brakes. During a braking process, large numbers of ultrafine particles will be released. These particles will have a large reactive surface. Copper has an inherent potential for the formation of reactive oxygene species. It is reasonable to assume that brake wear partices may contribute the the formation of ROS and cause damage to cells. To study this potential toxicity cells will be exposed to brake wear particles and afterwards tested for ROS.

Use of nanoparticules in industry: safe aspects

The principal aim of this study is to evaluate the risk for workers due to exposure to non-controlled emission of nanoparticules in industry. This information will be contributing to safer work conditons and to establish rules and strategies for protection in case of accident.

COST 633-Assessment of particulate exposure and surface characteristics in association with urinary/plasma levels of 8-hydroxy-2’-deoxyguanosine and relevant aldehydes, considered as markers of oxidative stress

A central hypothetical mechanism to explain the adverse effects of PM10 (particulate matter with aerodynamic diameter smaller than 10 µm) is the ability of some components of such a complex mixture to induce oxidative stress. Toxicologically relevant components are fine (<1 µm)/ultrafine (<0.1 µm) particles, organics like polycyclic aromatic hydrocarbons (PAH) and metals adsorbed on these particles. Diesel exhaust particulates (DEP) belong to the fine/ultrafine particles class and are a component of PM10. They might be a good “model” for studying such oxidative stress mechanism. When entering in contact with epithelial cell and alveolar macrophages, these components generate reactive oxygen species (ROS), leading to irritation, fibrosis and eventually cancer. The properties of particulate matter involved in such mechanisms are multiple but particle number and surface characteristics (reactivity) are important parameters to be considered. The aim of this research proposal is to quantify a few potential biomarkers in urine and plasma for oxidative stress caused by exposure to fine/ultrafine particulates. In a first step this evaluation will be done in real occupational situations, where exposure to DEP is expected to be high to medium. Mining activities where diesel equipments are in use (high exposure) and bus depot environments (moderate exposure) will be surveyed. Non-diesel exposed workers will be considered as control. Different physical and chemical exposure parameters such as particle number and mass, size distribution, adsorbed organics, surface functional groups and others will be measured for each population. Potentially interfering compounds in the gas phase like aldehydes from diesel exhaust will also be measured. Surface properties of the sampled particulates will be probed in order to gain insight into their reactivity. In urine and plasma, 8-hydroxy-2’-deoxyguanosine (8OHdG), considered as biomarker of free radical damage on DNA and n-aldehydes (C6 to C10), n-alkenals (C9 to C10) and 4-hydroxy-trans 2-nonenal (4HNE), all considered as biomarkers of lipid peroxidation, will be measured. Confounding factors such as tobacco smoke will be evaluated by measuring the nicotine/cotinine concentration in these matrices.

The obtained data will be used to investigate:

  • The differences in urinary/plasma concentrations of the selected biomarkers between control and exposed workers: a higher concentration of biomarkers is expected for exposed workers.
  • The correlations between the urinary/plasma biomarker concentrations and the particulate exposure variables, focussing particularly on the surface reactivity.

If aldehydes or 8OHdG are found to be good proxies for fine/ultrafine particulate exposure, these findings could be applied further in population studies like SAPALDIA or among groups with different health outcomes. The development of new and more sensitive biomarkers of PM exposure is of prime importance. Because the detectable health hazards of fine/ultrafine particulate in humans may have a long latency, the use of biomarkers for the early detection of relevant exposures or for surveillance of population groups at risk may become increasingly important. This project could also bring some insight into the relation between particulate surface characteristics as a source of ROS by-products.

Nanoinventory: manufactured nanoparticles in Swiss industries and the potential for human exposures

The principal aim of this study is to estimate the prevalence and extent of nanoparticle applications in the Swiss industry as well as the potential for exposure to manufactured nanoparticles of the Swiss working population. A representative questionnaire-based survey of Swiss companies will be used to create a nano-inventory that will contain the number of companies in different industrial branches using or producing nanoparticles, the type of particles used, and the number of potentially exposed employees. This information will be combined with data about protection measures for humans and the aquatic and atmospheric environment, and with exposure profiles of typical workplaces to estimate the potential exposure of the Swiss working population to nanoparticles. The data collected during this study will be useful for targeting prevention efforts, for designing research projects investigating the health of potentially exposed workers and for environmental risk assessments. Project status

In vitro reactivity of fine and ultrafine particles

Toxicity of particulates may be due to the reactivity of their surface when entering in contact with cells. Among other, their potential to generate reactive oxygen species seems to be very important.

This diploma work intends to use a simple method in order to determine the ability of some particles (ultrafine TiO2, crocidolite, diesel SRM 1650 and particles from real occupation situations) to catalyse the oxygen reduction by ascorbic acid.

The results obtained indicated that:

  • It is possible to detect such reaction with simple equipment (specific oxygen electrode)
  • In the experimental conditions, diesel SRM 1650 reacts about 10 times faster than crocidolite and that ultrafine TiO2 didn’t showed any reactivity.
  • Particles sampled in a bus depot indicated a very high reactivity. Heavy metals (Fe, Cu) could be potential important elements to explain this reactivity.
  • Experimental improvement has to be done mainly for getting a particulate suspension without artefacts.

Beryllium Surveillance Program in Switzerland

Occupational exposure to beryllium has recently become a topic of international interest in occupational health. Following recommendations made at the 2005 International Beryllium Research Conference in Montreal that it was urgent to evaluate the beryllium situation in industrialized countries, two research programs have been undertaken in Switzerland.

The first study aims at identifying the proportion of patients diagnosed with sarcoidosis in Switzerland who have, in fact, a chronic beryllium disease (CBD). Prevalent cases of sarcoidosis will be recruited from a registry maintained since 2002 by a network of 200 Swiss pulmonary physicians distributed nationwide, including all Swiss university centers, major non-university hospitals, and private practice pulmonary physicians. Incident cases will be recruited in pre-defined respiratory medicine centers from cases presenting for work-up of a suspected sarcoidosis. In sarcoidosis patients identified as potentially exposed to beryllium, different blood analyses (BeLPT, Be-ELISPOT, flow cytometry) will be performed in order to confirm or reject hypersensitivity to beryllium. Comparison of the different analyses for each subject should help determine the optimal method(s) and conditions to diagnose Be sensitization or Be disease.

The second study aims at identifying the population of Swiss workers exposed to beryllium, and at qualifying and quantifying the corresponding exposure levels. The preliminary phase of this study will rely on census data to estimate the working population and on available research results in other countries for the assessment of the fraction of the workers really exposed to Be. Based on the results of this study, industry specific survey might be elaborated to validate conclusions made from the literature.

These two programs mark the beginning of the implementation of a long-term strategy to appropriately detect and manage future cases of CBD in Switzerland.

Personal exposure to endotoxin among household waste collectors from Zurich city

Collections of household waste generate organic dust, which may contain high amounts of endotoxin. Endotoxin exposure may be correlated with several factors including the season of the year. In summer, high temperature should favour the growth of microorganism over the low temperature encountered in winter. The purpose of this study was to assess the influence of season on endotoxin level and to correlate it with health symptoms (collaboration with IUMSP ZH, P. Hotz).

Helicobacter pylori and Campylobacter sp: a source of occupational risk in sewage workers?

Contaminated water is recognised as an important vehicle for the transmission of several viral and bacterial diseases. The kind and quantity of microorganisms present in sewage reflect both clinical and sub-clinical infections prevalent in the community (Vaidya et al. 2002).

Helicobacter pylori is the causative agent of gastritis and duodenal ulcer and plays a role in the development of gastric cancer (Cover & Blaser 1995, Parsonnet et al. 1994). It is considered a class I carcinogen by the International Agency for research on cancer. The transmission of H.pylori remains unclear (Megraud & Broutet, 2000), but the ability to culture H. pylori from stools suggests that it is viable in sewage systems.

Campylobacter sp. causes enteritis. Results from several countries have shown that this bacteria are ubiquitous in sewage and that human and animal waste from abattoirs and animal livestock are the major sources (Jones 2001, Corry & Atabay 2001).

He aim of this study is to develop a reliable PCR-based method to detect those two microorganisms in aerosols and water.

Caractérisation de l’exposition et gestion du risque

Solid-Phase Microextraction as Short-Term Sampling Technique for BTEX Occupational Exposure

The potential of SPME as alternative to convential method was confirmed. Charcoal tubes as air sampling method are generally insufficiently sensitive to allow the determination of the analytes in short exposures, and to comply with the new requirement of 15-minute TLVSTEL for benzene (8 mg/m3). In contrast, SPME technique with good calibration facilities using permeation device for individual fiber calibration can be succefully used for BTEX survey in occupational field and environmental studies. SPME technique has many advantages: sensitivity, simplicity, cheap, solvent-free, fast, short sampling time, no sample preparation and accuracy. However, the use of SPME fiber under non-equilibrium conditions required to determine the equivalent uptake rate of each individual fiber for every analyte of interest. A special care has to be taken over the influence of air velocity. But this latter is not so critical in normal calm air situations. In these conditions, SPME method for air sampling is a very sensitive technique allowing fulfilling the performance criteria required for 15-minute TLV-STEL for benzene.

Occupational exposure of parquet floor sander to polycyclic aromatic hydrocarbons (PAH) in the generated wood dust

Malignant naso-sinusalcavity (NSC) tumours represent approximately 3% of ORL cancers. NSC adenocarcinomas an occupational disease acknowledged in certain specialist workers such as joiners and cabinet makers. Great Britain in 1969 and France in 1981 recognize its professional aetiology based on statistical observations. The high proportion of woodworkers contracting a NSC adenocarcinoma, subjected to an estimated risk 50 to 100 times higher at that affecting the general population, has suggested various study paths to some possible causes, such as the tannin in hardwood, formaldehyde in plywood and benzo(a)pyreneproduced by overheated wood by cutting tools. Specific tasks, such as sanding, cause the emission of fine dust, which can remain in suspension in air for many hours in badly ventilated locations. These hypotheses have not been confirmed to date by practical measurements, and the issue remains open. It is acknowledged that tannin does not cause cancer under exposure to tea dust. Formaldehyde is an irritant, but it is also classed carcinogenic. The path involving carcinogenic Polycyclic Aromatic Hydrocarbons (PAH) emitted by overheated wood is attractive. In this study, we have studied their content in relation to operations performed on wood in an experimental chamber and we have measured the particle size of the generated dust.

The wood dust contains carcinogenic PAH at the level of g/g or ppm. The PU canish-impregnated wood produces 100 times more PAH than the unfinished wood during sanding operations. The woodworking tools such as sander, circular saw or plane create dusts with particle size distribution centred around 10mm or more, thereby resulting in a prevailing dust deposit of dust in the naso-sinusal cavity and less in the lung. Swiss regulated TLV of 2mg/m3 of inhaled dust would appear to protect effectively workers, as long as PAH contents do not exceed the ppm level. The PAH are produced by excessive heating of the sanding or cutting tools at the surface level of the wood which induces a partial combustion of the organic matter in wood or the PU varnish. There are no notable difference in PAH content of tender wood (fir tree) and hard wood (oak).

It is important that the concerned workers are aware of the danger of wood dust exposure and that they adopt adequate protection measures, such as wearing a dust protection mask or workshop ventilation. Tools fitted with dust collection bags produce less airborne dust and contribute to a better protection. Coud the presence of PAHs in wood dust be a cause of adenocarcinoma in joiners and cabinetmakers? Additonal investigations are necessary to better determine the woodworker exposure to the PAHs and its health effects.

Indoor Air Quality in a Public Building following Smoking Bans

Indoor air quality in a university large building of 450’000 m3 of total volume was studied before and a smoking ban had been applied. Several selected environmental tobacco smoke (ETS) tracers were used during this study: total dust, condensate, polycyclic aromatic hydrocarbons (PAHs) monitor and nicotine. Measurements of real time monitors were collected with data-logging instrumentation. Before the decision to ban smoking in June 2004, the level of the concentrations of dust was higher, with a daily average of 320 μ g/m3, range 80-1000 μ g/m3 and peaks of more than 1000 μ g/m3, compared with outdoor air values, mean 22 μ g/m3, range 22-30 μ g/m3 . For the condensate, the mean was 96 μg/m3, range 37-224 μg/m3 before. The nicotine level is definitely more important before, mean 5.53 μ g/m3, range 1.5-17.9 μ g/m3. Once the smoking bans inside the building were applied, beginning in October 2004, we observed a clear improvement in terms of concentrations of pollutants. For dust, the concentration fell by 3 times, mean 120 μ g/m3, range 40-160 μ g/m3, for condensate 2 times, mean 57 μ g/m3, range 30-100 μ g/m3, and that of the nicotine by 10 times, mean 0.53 μ g/m3, range 0-1.69 μ g/m3 compared to that found before the smoking bans.

This confirms that the indoor pollution observed has cigarette smoke as its origin. Nicotine is proposed as the best tracer for indoor air quality monitoring against pollution by ETS.

Laboratory Generated Bitumen Fumes Under Standardized Conditions

Clean-up Scheme and Ion Trap GC-MS Analysis of VOC, Semi-Volatile and Particulate PAH and PASH

This project aims at evaluating the applicability of an efficient clean-up and enrichment procedure for the determination of polycyclic aromatic compounds (PAC) including polycyclic aromatic hydrocarbons (PAH) and polycyclic aromatic sulfur heterocyclic hydrocarbons (PASH) in the gas and particulate phases in raw bitumen and bitumen fumes by gas chromatography-ion trap mass spectrometry. The scheme includes a liquid-liquid partition to eliminate the aliphatics, a solid phase extraction on SiO2 cartridge to remove the polar compounds and an HPLC fractionation to isolate the aromatic fraction. The purified extract enables the determination of PAH profile from 2 to 7 rings including their methyl derivatives and 3 carcinogenic benzonaphthothiophene isomers. The reproducibility of the method was estimated by analyzing 6 bitumen replicates and is around the 30% overall uncertainty or less. In bitumen fumes generated at 170°C under standardized conditions, VOC and semi-volatile PAH were sampled with XAD-2 tubes and were also determined in six replicates. The VOCs are mainly monoaromatic derivatives (4% of fumes) and aliphatics essentially from C6 to C17 (27%). With regards to the particulate phase PAC, the coefficients of variation from 6 replicates are 5-24 % for PAH and 6-10% for PASH. Data on VOC and PASH represent new contribution in the characterization of bitumen fumes.

Identification and quantification of PAH in bitumen by GC-ion trap MS and HPLC-fluorescent detectors

Bitumen is a complex product with a large matrix of heavy aliphatic/naphthenic/aromatic hydrocarbons as well as a large number of isomeric compounds such as polycyclic aromatic compounds (PACs). Some PACs and derivatives are known to have a mutagenic and carcinogenic activity, and there is no generally satisfactory clean-up method for separating PACs from this very complex hydrocarbon matrix. Moreover, from an analytical point of view, the isomeric compounds usually co-elute in the same gas chromatography (GC) retention range, GC being one of the most widely used techniques in this area. However, the use of a suitable clean-up procedure for isolating the aromatic fractions, combined with two selective detection techniques such as mass spectrometry (GC-Ion Trap MS) and HPLC-Florescent detector (HPLC-FL), is expected to provide an effective tool for accurately determining certain PAC species in bitumen.

Occupational exposure to mineral oil Metalworking Fluid (MWFs). Mist: development of new methodologies for mist sampling and analysis

Metalworking Fluids (MWFs) are largely used in the sector of undercutting, a large professional activity in Switzerland, in particular in the fine mechanic and watch making industry. France proposes a permissible exposure limit (PEL) of 1 mg/m3 of aerosol. The American Conference of Governmental Industrial Hygienists (ACGIH) sets its value at 5 mg/m3 but a proposal to lower the standard (“intended changes”) to 0.2 mg/m3 of aerosol is pending since 2001. However, it has not become a recognized threshold limit value for exposure. Since 2003, the new Swiss PEL (MAK) recommendations would be 0.2 mg/m3 of aerosol (oil with boiling point > 350°C without additives) and/or 20 mg/m3 of oil aerosol + vapour.

To evaluate evaporative losses of sampled oil, the German Berufsgenossenschaftliches Institut für Arbeitssicherheit (BGIA) recommends the use of a XAD-2 cartridge behind the filter. The method seems to work perfectly for MWFs in a clean occupational atmosphere free from interference of light vapour cleaning solvent such as “White Spirit”. Yet, in machine shops atmosphere contaminated with traces of White Spirit, the BGIA method failed to estimate the MWFs levels (overestimation). In this project, we propose a new approach meant to measure both oil vapours and aerosols. Inter-laboratory comparisons will be organized, based on the production of oil mist in an experimental chamber under controlled conditions.

OHBaP by HPLC-Column Switching

IST has been interested in the analysis of polycyclic aromatic hydrocarbons (PAH) for many years because of their potential carcinogenicity. These substances are found in many workplaces such as coke ovens, aluminium plants, during paving roads activities. In the human body PAH are oxidised and partly eliminated in the urine in a hydroxylated form. Urinary 1-hydroxypyrene (1-OHP) has been widely used as a biomarker of exposure to PAH. However, neither pyren nor its metabolites are carcinogens and their presence is not a proof of exposure to carcinogenic hydrocarbons. Benzo[a]pyren (BaP) is known to cause cancer; after metabolisation, it is eliminated in the form of two isomers, 1 and 3-hydroxybenzo[a]pyrene (1 and 3-OHBaP). The analysis of PAH mixtures is commonly done by HPLC-FL, but an efficient separation of 1 and 3-OHBaP is problematic as they elute together. The project aimed at building an HPLC switching system and analyse 3-OHBaP in urines of smokers and possibly non-smokers. The switching system has been ultimated and it can be applied to any HPLC system, and of course, to the LC-MS/MS facility.

Analysis of urinary PAHs metabolites by HPLC-FL and LC-MS/MS

IST has been interested in the analysis of polycyclic aromatic hydrocarbons (PAH) for many years because of their potential carcinogenicity. These substances are found in many workplaces such as coke ovens, aluminium plants, paving roads activities or passive tobacco smoke. It is thus clear that the analysis of PAH in the work environment and in the workers themselves (biological monitoring) is of primary importance. In the human body PAH are oxidised and partly eliminated in the urine in a hydroxylated form. The oxidised forms of some PAH are carcinogenic as they can fit in the base pairs of DNA double helix and bind to it. As pyrene is very often present in PAH mixture, its metabolite 1-hydroxypyrene (1-OHP), which is excreted in urines, has been used several times as a biological indicator of exposure to PAHs. However, nor pyrene nor its metabolites are carcinogens and their presence is not a proof of exposure to carcinogenic hydrocarbons. Benzo[a]pyrene (BaP) is known to cause cancer; after metabolisation, it is eliminated in the form of two isomers, 1 and 3-hydroxybenzo[a]pyrene (1 and 3-OHBaP). It seems that the second metabolite is the most carcinogenic form so that the analysis of this isomer is very important for proving a workplace dangerous for the workers’ health. 3-OHBaP is present in the human urine in quantities near the limit of detection of the most usual analytical techniques so that great care must be given to the choice of the extraction method in order to recover the most part of the analytes.

Aims

The objectives of the present research project are to evaluate PAHs urinary metabolite levels (particularly the 1-hydroxypyrene (1-OHP), 6-hydroxychrysen (6-OHC), 1- and 3-hydroxybenzo(a)pyrene (1- and 3-OHBaP)) in few urine samples, from smokers and non-smokers, occupational PAHs exposed and non-exposed workers.

Methods

  • Develop a quantitative method to characterize the PAHs urinary metabolites by HPLC-FL and LC-MS/MS, particularly the 1-hydroxypyrene (1-OHP), 6-hydroxychrysen (6-OHC), 1- and 3-hydroxybemzo(a)pyrene (1- and 3-OHBaP).
  • Confirm by LC-MS/MS the presence of 1-OHP and OHBaP in human urine.
  • Development of extraction techniques, clean-up scheme, recovery studies : SPE cartridges, Liquid-liquid extraction and “Blue-Rayon” (copper phthalocyanine) enrichment.
  • Apply the method to evaluate PAHs urinary metabolite levels in few urine samples, from smokers and non-smokers, occupational PAHs exposed and non-exposed workers.

Expected results

This work should contribute to the validation of a new analytical method for the urinary PAHs metabolites as a tool to evaluate the occupational exposure to the carcinogenic members of the PAHs family.

“Comet Assay”, in vitro testing and in vivo application

Single cell gel (SCG) electrophoresis or “Comet assay” is a rapid and very sensitive microscopic method to examine DNA damage and repair at individual cell level. Actually, the comet assay has become one of the standard methods for assessing DNA damage, with applications in genotoxicity testing, human biomonitoring and molecular epidemiology, as well as fundamental research in DNA damage and repair. The assay is attractive because of its simplicity, sensitivity, versatility, speed, and economy.

The first objective of the present project is to develop and validate the comet assay on finger-prick blood samples.

The final goal is to screen a wide variety of occupational situations to evaluate the DNA damaging risk in relation with other air and biomonitoring indicators.

Mercury exposure assessment associated with gold mining activities

Artisanal gold-mining activities are in full rise in Burkina Faso with about 200 active sites spread in the entire country. The mining process involves the extraction of gold from the ore by mercury amalgamation, followed by roasting the resulting product to vaporize mercury out of the amalgam. A health survey was conducted among the working population of several sites by the OST. As part of this survey, biomonitoring was used to assess mercury exposure in the various mining sites, and associated with the various activities. Mercury excretion in urine was used as indicator of current exposure.

Methods

Forty-six subjects associated with gold mining activities in 5 sites participated in this pilot study. Biomonitoring was performed by mercury determination in spot urine samples collected before shift in a metal-free polystyrene flask. Samples were frozen at -20°C the same day and delivered in a cold state to the IST laboratory in Switzerland. Analysis was carried out by cold vapour atomic absorption spectrometry for mercury, and colorimetry for creatinine. Occupational history and medical status were assessed by local medical personnel using a standard questionnaire.

Results

From the 46 urine samples collected, 31 came from “unrefined gold” dealers (group A) who are also doing amalgam roasting, 13 from workers involved in ore washing and the amalgamation process (group B), and 2 from workers concerned with crushing, brinding and washing stages (group C). Urinary mercury excretion ranged from 5 to 1707 mg/g creatinine with a global average of 146 mg/g. Seventy percent of the urinary results are above the BEI of 35 mg/g creatinine recommended by ACGIH. Mean urinary concentrations were respectively for each group A, B, and C of 204, 28.7 and 15.6 mg/g, indicating a very high exposure for “unrefined gold” dealers due to their roasting activity. Analysis of the results by sites shows a very high variability with averages by sites ranging from 26.1 mg/g up to 298.8 mg/g.

Results obtained can be used to target prevention programs and activities in order to reduce mercury exposure in the concerned population.

Biological monitoring of occupational exposure.

Toxicokinetic differences due to age and gender

Biological monitoring is a widely used method among occupational physicians to estimate chemical exposure. Recommended biological limits are published periodically in Switzerland and in other countries for interpretation and decision-making. A large variability is associated with biological monitoring, making interpretation less efficient than foreseen. In order to improve applicability of biological monitoring, specific factors responsible for this variability should be identified and their contribution quantified. Among these factors, age and gender are easily identifiable, and present knowledge about pharmaceutical chemicals suggests that they play an important role on the toxicokinetics of occupational chemical agents, and therefore on the biological monitoring results.

The objective of the present research project is to quantify the influence of age and gender on biological levels of some important chemicals and their metabolites in the human body. This will be done experimentally, by observation, and by toxicokinetic computer simulation.

Controlled human exposures to methyl ethyl ketone (MEK), 1,1,1-trichloroethane, styrene and propylene glycol monomethyl ether (PGME) will be performed in an exposure chamber and the kinetics of the parent compounds (organic volatiles) and their metabolite(s) followed in blood, urine and expired air over time. Extrapolation to other chemicals will be done by physiologically based pharmacokinetic (PBPK) models and by compartmental toxicokinetic (TK) models after validation.

The proposed project will improve our understanding of the influence of age and gender on biological indicators of exposure. It is expected that the results obtained will make it possible to improve recommended limits and the associated decision process to avoid undue costs and unacceptable risks to the employees.

Occupational health: molecular approaches to assess risk of bioaerosol exposure in workplaces

The presence of micro-organisms (bacteria, fungi and their by-products) in the work environment may compromise the quality of work material and/or the health and well being of the exposed workers. There are many occupations, which involve the handling of organic matter, and this may be an optimal medium for multiplication of microorganisms. Some populations of workers are, therefore, exposed to high levels of airborne microorganisms, which have been recognised as a cause of respiratory symptoms. In particular, inhalation of endotoxins (a toxic component of the cell wall of Gram-negative bacteria) is associated with many symptoms such as acute airway obstruction, a decline of pulmonary function, acute fever, extrinsic allergic alveolitis, chronic bronchitis and organic dust toxic syndrome.

Traditional culture-dependent methods to quantify and identify airborne microorganisms are limited by different factors (short-duration sampling times, difficulties in personal sampling and inability to enumerate non-culturable or non-viable bacteria). Consequently, assessment of bioaerosols is often underestimated. With the advent of PCR technology it is now possible to overcome these limitations. The goal of this project is to focus our research on a molecular approach to assess and monitor bioaerosol exposure at work in respect to their health effects. This will include the setting up of new experimental designs, the development of robust identification protocols (including the detection of specific airborne micro-organisms using DNA analysis), the use of PCR for bioaerosol quantification and monitoring (quantitative PCR). This study will be the only project involving a molecular approach to bioaerosol analysis and occupational health in Switzerland. Results could improve quality of life and reduce health costs.

Application of real-time PCR method for total airborne bacterial assessment, comparison with epifluorescence microscopic method

Traditional culture-dependent methods to quantify and identify airborne microorganisms are limited by different factors (short-duration sampling times, inability to enumerate non-cultivable or non-viable bacteria). Consequently, the assessment of bioaerosols is often underestimated. To overcome this problem, the real-time quantitative polymerase chain reaction (real-time Q-PCR) has been used to quantify bacteria in environmental samples. The aim of this study was to evaluate the performance of a real-time Q-PCR method to quantify the bacterial load in indoor air of poultry houses and sewage treatment plants and to compare it with epifluorescence microscopy (collaboration with INRS, P. Duquenne) and culture-dependent methods.

Quantification of biological variability. Contribution of air exposure variations

The objective of the present project is to document and quantify the contribution of variability of air exposures to the total variability observed in biological indicators. The objective is also to propose a mathematical model to describe total variability in biological monitoring by including the different sources of variability.

Compartmental and PBPK models are used together with a priori distributions of physiological and metabolic parameters, and distributions of exposure levels to estimate variability in 30 biological indicators. Results obtained are presented in a form which can be helpful for practitioners to interpret biological monitoring results.

The present research in carried out in collaboration with University of Montreal and the IRSST of Quebec.

Biological monitoring for the evaluation of occupational health risks for workers exposed to fungicides in arboriculture

Arboriculture represents about 20% of the agricultural activity in Valais. Fruit trees undergo numerous fungicides treatments despite ecological requirements. Captan and Folpet, two important fungicides, are used for treatment in spring and in autumn. Potential dermal, oral and respiratory exposure of workers can occur during these treatment.

The objective of the present research is to develop a toxicokinetic model in order to establish reference biological values for Captan and Folpet. The model should describe the parent compound and its metabolites in the human body.

Three aspects are considered in this research: exposure of human volunteers, development of a toxicokinetic model, field investigations in exposed workers including urine and blood measurements of metabolites and exposure (dermal, inhalation) investigations.

The biological monitoring tools developed here will serve to better assess the exposure of workers to Captan and Folpet under various circumstances. Extrapolation to other fungicides will also be considered for application.

Emission factors integrated method for airborne pollutants assessment at workplaces

The proposed project aims, by providing adequate tools for the practitioners (OH&S specialists), to improve the conditions in which the “expert judgments” take place. It is assumed that, an implementation of the existing models with emission and near-field considerations may not only enhance significantly the tools itself but also the overall expert judgement performance.

In a first step a survey was made among professionals to better define their expectations about modelling tools (what types of results, models and potential observable parameters).

Experimental and modelling work was performed in some specific cases to identify difficulties with existing tools. Further exposure to waterproofing sprays was studied as part of an epidemiological study on a Swiss cohort.

Experiments were then carried out in 2 experimental chambers to better understand the processes of emission and dispersion for tracer compounds. In a further step the experimental data were completed by observations made in about 100 different workplaces, including exposure measurements and observation of predefined determinants. The various data obtained have been used to improve an existing two-compartment exposure model.

Evaluation of chemical exposure: combining exposure measurements and determinants to make better decisions

Occupational exposure to chemicals is influenced by numerous factors associated with characteristics of the workplaces and activities of the workers. In most cases exposure is estimated by direct measurements of air concentrations or of levels in biological fluids. An other approach consists of predicting exposure with physical models of emission and dispersion, taking into account some exposure determinants. Still an other approach would consist in a Bayesian combination of the 2 types of results (measurements and determinants). This combination would allow generally a reduction of the variability associated with direct occupational exposure measurements. This would make decision more efficient when comparing results with occupational exposure limits for example.

The present research project proposes to integrate exposure a priori with direct measurements in order to reach a better estimation of past (epidemiology) and current exposure (surveillance). A Bayesian integration framework will be developed based on existing exposure data. This research consists of the following parts:

  • Identification of existing exposure data in France and Switzerland, taking into account not only exposure itself but also the availability of exposure determinants,
  • Processing of existing data following the norm EN 689 in order to put every chemical agent on the same scale
  • Building of empirical models using neuronal networks to integrate information on exposure determinants,
  • Application of Bayesian statistics to combine direct measurements and information of determinants, to reduce estimation uncertainty,
  • Development of a strategy for decision making on the combined information.

This approach has already been tried at several occasions for the retrospective estimation of occupational exposure to chemicals, in one case by one of our research groups. It has however not yet been considered for current or prospective occupational exposure estimation. The decision making strategy presently used in occupational health is described in the norm EN 689. Present research work tends to integrate this strategy, notably decreasing variability of exposure assessment.

Occupational exposure database

Assessment of occupational exposure to chemical and physical agents is often done based on an “expert judgment” in Switzerland. A database is created with actual measurements in order to help practitioners. Direct measurements are costly and when done they should be shared between professionals so that more then one situation benefit from them.

Exposure measurements done by IST and other partners are stored in a database according to the format recommended by international experts. Apart from measurement of specific variables, the type of industry (NOGA) and of profession (OFS) are recorded. The database is accessible online on www.i-s-t.ch and can be search either by NOGA, OFS or danger (chemical, physical, biological). It contains (2007) more than 10’000 records.

It is expected that data form other Swiss institutions than IST will be available in the database shortly. The format of the database has been updated to include physical contextual determinants. This is an ongoing project.

Occupational skin exposure to chemicals. Towards an improved skin notation

The Skin Notation, indicating possible uptake via the skin, are based on varying databases and assumptions.

Both, the fact that they vary from country to country, and the number of chemicals notified with a Skin Notation (1/3 of the OEL list) indicate the unsatisfactory of the criteria and databases used for their establishment.

The objectives are to propose qualitative criteria to characterize the risks of the different chemicals for the skin and to propose quantitative criteria for the establishment of a reliable Skin Notation to be applied to the entire OEL list.

Preliminary contacts with the Swiss OEL Committee have shown a clear interest for a collaboration and the OEL Commission is expected results for the 2009 edition of OEL.

Assessing UV exposure: measurements and prediction of individual exposure

Excessive exposure to solar UV light is the main cause of skin cancers in humans. Factors such as the increase of solar irradiation at ground level, the rise in standard of living and the development of outdoor activities have contributed to increase exposure. Thus, unsurprisingly, incidence of skin cancers has increased over the last decades more than that of any other cancer. Switzerland is among the European countries the most affected by this public health problem.

UV exposure depends on ambient irradiation level and individual factors related to activity (position to sun, clothing, duration of exposure, other forms of sun protection). The risk of skin cancer varies according to the skin type and the exposure of anatomical parts of the body. The neck, shoulders and head are usually the most irradiated parts.

This research project aims at developing and validating a predictive tool of individual exposure to solar UV. Exposure levels of body parts will be predicted on basis of ambient irradiation levels and information about postural activity. The tool will use existing techniques in the field of 3D numeric simulation and will be validated against individual dose measurements.

The use of a numeric method should facilitate assessment of individual exposure and allow predictive scenarios (either prospective or retrospective). In the long run, a better quantification of exposures for specific occupational and leisure activities should assist in better targeting preventive actions.

Strategy development for retrospective exposure assessment

Most of the time, exposure assessment in occupational hygiene and ergonomic is prospective. In epidemiology and in patient’s exposure assessment, qualitative and quantitative tool are require to study past exposures.

The first objective of the present research is to develop strategies and tools for retrospective exposure assessment of patients presenting identified and developed pathologies. This project relies on systemic investigations of cases presented to the out-patient clinic of IST. A second objective is to make recommendation for improvement of workplaces to avoid further cases.

This research is based on the following methodologies: interview of patients, co-workers and supervisors, observation of work-processes, modelling of past exposures, measurement of reconstructed exposures.

For each case studied, a short report is made to the occupational physician and the employer (when applicable). Cases will be review and discussed in a general scientific report aimed at establishing an investigation strategy.

Cutaneous resorption of chemicals : Creation of a quantitative tool for risk analysis

The main purpose of the current project is to propose a computer-based tool that will help IH professionals identifying situations where the dermal exposure pathway might increase the health risk posed by a chemical substance. This tool will provide a quantitative and systematic alternative to the traditional skin notation.

Several approaches have been described in the literature that compared internal dose or blood levels of a chemical caused by dermal exposure to those caused by inhalation at the OEL. Based on these methods, we intend to create quantitative indices measuring the relative contribution of the dermal pathway to total internal dose. Existing OELs will be used to derive internal reference doses. Several indices will be created to allow for a variety of exposure scenarios, including different combinations of dermal exposure duration and proportion of body surface exposed. The calculation of the indices requiring values of transdermal penetration constants, they will be estimated using already available and validated quantitative structure-activity relationships (QSAR). All necessary physico-chemical constants and toxicological values for the substances in the Swiss OEL list have already been formatted into a database during a related research project at IST. The created approach will take the form of a decision tree guiding the user through the scenario selection process to the final index calculation. The procedure will be implemented in the form of a software available through download at the IST internet website.

This project will lead to the availability to IH professionals of a computer-based tool for assessing the contribution of the dermal exposure pathway to the overall risk posed by chemicals in the workplace. This should improve the specificity in selecting situations requiring detailed dermal exposure assessment.

Facteurs psychosociaux

Cardiorespiratory Reactivity, Visual Attention and Metabolic Balance During Affective Picture Viewing

Picture series of different contents were shown to 41 young adults while cardiorespiratory parameters, skin conductance, spontaneous eye-blinking and judgments of valence and arousal were recorded. The analyses reveal several relationships between self-rated valence and arousal and the physiological measures which extend and enrich our knowledge of emotional processing.

Diseases and reasons for absences in the road maintenance services (project ASTRA 2004/019)

The objective of this study is to get a better understanding of characteristic health problems that are prevalent among the employees of the road maintenance services. This study will focus on aspects regarding occupational medicine, ergonomics and occupational hygiene to understand the causes of diseases and absences in the road maintenance services. Studying work activities, physical and psychological stress, postures, tool handling, dangerous substances, and air pollutants will help identify potential risks for the workers’ health. The results of this study will allow proposing measures for adjusting work conditions and for defining future occupational medical services.

Médecins pour médecins: une antenne au service de la santé des médecins

Médecins pour Médecins est un projet d’entraide pour les médecins en difficulté, inspiré des connaissances en médecine du travail. Il comprend en particulier la mise sur pied d’une antenne téléphonique avec capacité d’accueil, d’écoute et de conseil par un médecin. Appuyé par un réseau de thérapeutes de toute la Romandie prêts à recevoir un collègue, l’antenne sera à même de proposer un choix de prise en charge spécialisée en fonction du problème évoqué.

Le projet a aussi pour ambition de proposer un pool de médecins pour des remplacements urgents en cabinet, et de promouvoir une culture de santé au travail au sein de la corporation médicale, avec une remise en questions de certaines tendances défavorables inhérentes à sa tradition et à un système de croyances bien ancré.

Réinsertion professionnelle des opérateurs absents pour cause de troubles musculosquelettiques dorsaux

Les troubles musculosquelettiques sont des pathologies multifactorielles. Des facteurs de risque, tant psychosociaux (insatisfaction au travail, manque de reconnaissance et de soutien social, insécurité de l’emploi), qu’organisationnels (manque d’autonomie, pression tempo­relle, répartition des tâches) et biomécaniques (répétitivité, postures contraignantes) sont en cause. Pour favoriser le retour au travail d’opérateurs absents suite à ce type de pathologie, une intervention sur l’individu et sur les conditions de travail est indispensable.

Un programme intensif de rééducation, axé sur l’activité professionnelle, a été organisé pour restaurer les capacités fonctionnelles et professionnelles de l’individu. Parallèlement, une ana­lyse ergonomique de la situation de travail permettra une adaptation des conditions de travail. Plu­sieurs outils utilisés lors de l’analyse ergonomique du travail (Siegrist, Karasek) mettent en évidence des corrélations entre les facteurs psychosociaux et le développement de patho­lo­gies, dont les troubles musculosquelettiques.

Factors and strategies affecting health in ambulance personnel

This study aims at identifying and better understanding protective and risk factors affecting health in ambulance personnel. Both mental and musculoskeletal health issues will be addressed. A closer look will be given to individual and collective strategies contributing to prevent health hazards. This study consists of two steps. Step 1:  A questionnaire will be used to assess working conditions, as well as musculoskeletal and mental health in a population of ambulance personnel. Risk factors, as well as their protective counterparts will be identified. Step 2: A qualitative study of work activity in real prehospital emergency interventions will be performed. The focus of this qualitative analysis will be on strategies (individual and collective) enabled by protecting factors. The acquired knowledge regarding these strategies will be used as new educational and training content for ambulance personnel.

Emotion across the adult lifespan : A psychophysiological investigation

A growing literature suggests that older adults experience emotion differently than younger adults in a way that may promote well-being. The aim of this research project is to extend our knowledge on the relation between age and emotion across adulthood. More specifically, we aim to examine age-related differences in emotional reactivity (i.e., the phase when processing an affective stimulus) and in emotional recovery (i.e., the phase after offset of the affective stimulus) by assessing the basic components of emotion: the feelings, the facial-expressive behavior, and the physiological activation (e.g., respiration, cardiovascular system). We are particularly interested in examining how the direction and intensity of the responses as well as the relationships among these components are modulated by age. Further, the role of two emotion regulation processes, attention resource allocation and memory for emotional stimuli, are investigated.

La gêne

Effects of F.M. Alexander Intervention on subjective and cardio-respiratory measures during daily activities – a pilot study

Scientific research on the psychophysiological effects of the F:M. Alexander Technique are scant. Put simply, the Technique is a means to re-educate how we use ourselves in our everyday life. By becoming more aware of the habits that tend to drive our lives we can learn to make conscious decisions both about how we organize our physical selves when lifting, speaking, handling objects, sitting etc. and in how we react to the stimuli that we meet during our every waking moment. This pilot study investigates how cardio-respiratory parameters and subjective feelings of nine adults are modified by a brief intervention with the F.M. Alexander Technique while sitting and standing both with and without the help of a trained person.

Music performance anxiety in professional music students

This study aims to determine if music performance anxiety (MPA) is physiologically associated with specific correlates of breathing disturbance and hyperventilation and to determine how tightly response systems (affective experience, self-perceived physiological activation, actual physiological activation) are coupled in MPA. Further, it surveys the occurrence, experience, and management of MPA. The findings will permit to reject or support a theory of anxiety that postulates that increased levels of peripheral physiological responding always co-occur with higher levels of anxiety experience and higher levels of self-perceived physiological symptoms. This research will also have consequences for the use of ambulatory monitoring of respiration as an additional tool for the diagnostic assessment and the therapy outcome assessment of anxiety as well as implications relating to the development and implementation of treatments for MPA.