Wouter Fransman

Publications of Wouter Fransman

• Stoffenmanager Nano Version 1.0: A Web-Based Tool for Risk Prioritization of Airborne Manufactured Nano Objects.

  Authors: Birgit Van Duuren-Stuurman, Stefan R Vink, Koen J M Verbist, Henri G A Heussen, Derk H Brouwer, Dinant E D Kroese, Maikel F J Van Niftrik, Erik Tielemans, Wouter Fransman

  The Annals of occupational hygiene. 01/2012;

  Stoffenmanager Nano (version 1.0) is a risk-banding tool developed for employers and employees to prioritize health risks occurring as a result of exposure to manufactured nano objects (MNOs) for aStoffenmanager Nano (version 1.0) is a risk-banding tool developed for employers and employees to prioritize health risks occurring as a result of exposure to manufactured nano objects (MNOs) for a broad range of worker scenarios and to assist implementation of control measures to reduce exposure levels. In order to prioritize the health risks, the Stoffenmanager Nano combines the available hazard information of a substance with a qualitative estimate of potential for inhalation exposure. The development of the Stoffenmanager Nano started with a review of the available literature on control banding. Input parameters for the hazard assessment of MNOs were selected based on the availability of these parameters in, for instance, Safety Data Sheets or product information sheets. The conceptual exposure model described by Schneider et al. (2011) was used as the starting point for exposure banding. During the development of the Stoffenmanager Nano tool, the precautionary principle was applied to deal with the uncertainty regarding hazard and exposure assessment of MNOs. Subsequently, the model was converted into an online tool (http://nano.stoffenmanager.nl), tested, and reviewed by a number of companies. In this paper, we describe the Stoffenmanager Nano. This tool offers a practical approach for risk prioritization in exposure situations where quantitative risk assessment is currently not possible. Updates of this first version are anticipated as more data become available in the future.

• Harmonization of measurement strategies for exposure to manufactured nano-objects; report of a workshop.

  Authors: Derk Brouwer, Markus Berges, Mohammed Abbas Virji, Wouter Fransman, Dhimiter Bello, Laura Hodson, Stefan Gabriel, Erik Tielemans

  The Annals of occupational hygiene. 12/2011; 56(1):1-9.

  The present paper summarizes the outcome of the discussions at the First International Scientific Workshop on Harmonization of Strategies to Measure and Analyze Exposure to (Manufactured)The present paper summarizes the outcome of the discussions at the First International Scientific Workshop on Harmonization of Strategies to Measure and Analyze Exposure to (Manufactured) Nano-objects in Workplace Air that was organized and hosted by the Netherlands Organization for Applied Scientific Research (TNO) and the Institute for Occupational Safety and Health of the German Social Accident Insurance (IFA) (Zeist, The Netherlands, December 2010). It reflects the discussions by 25 international participants in the area of occupational (nano) exposure assessment from Europe, USA, Japan, and Korea on nano-specific issues related to the three identified topics: (i) measurement strategies; (ii) analyzing, evaluating, and reporting of exposure data; and (iii) core information for (exposure) data storage. Preliminary recommendations were achieved with respect to (i) a multimetric approach to exposure assessment, a minimal set of data to be collected, and basic data analysis and reporting as well as (ii) a minimum set of contextual information to be collected and reported. Other issues that have been identified and are of great interest include (i) the need for guidance on statistical approaches to analyze time-series data and on electron microscopy analysis and its reporting and (ii) the need for and possible structure of a (joint) database to store and merge data. To make progress in the process of harmonization, it was concluded that achieving agreement among researchers on the preliminary recommendations of the workshop is urgent.

• Use of the MEGA Exposure Database for the Validation of the Stoffenmanager Model.

  Authors: Dorothea Koppisch, Jody Schinkel, Stefan Gabriel, Wouter Fransman, Erik Tielemans

  The Annals of occupational hygiene. 11/2011;

  OBJECTIVES: This paper explores the usefulness of the exposure database MEGA for model validation and evaluates the capability of two Stoffenmanager model equations (i.e. handling of powders/granulesOBJECTIVES: This paper explores the usefulness of the exposure database MEGA for model validation and evaluates the capability of two Stoffenmanager model equations (i.e. handling of powders/granules and machining) to estimate workers exposure to inhalable dust. METHODS: For the task groups, 'handling of powders and granules' (handling) and 'machining of wood and stone' (machining) measurements were selected from MEGA and grouped in scenarios depending on task, product, and control measures. The predictive capability of the model was tested by calculating the relative bias of the single measurements and the correlation between geometric means (GMs) for scenarios. The conservatism of the model was evaluated by checking if the percentage of measurement values above the 90th percentile estimate was ≤10%. RESULTS: From 22 596 personal measurements on inhalable dust within MEGA, 390 could be selected for handling and 1133 for machining. The relative bias for the task groups was -25 and 68%, respectively, the percentage of measurements with a higher result than the estimated 90th percentile 11 and 7%. Correlations on a scenario level were good for both model equations as well for the GM (handling: r(s) = 0.90, n = 15 scenarios; machining: r(s) = 0.84, n = 22 scenarios) as for the 90th percentile (handling: r(s) = 0.79; machining: r(s) = 0.76). CONCLUSIONS: The MEGA database could be used for model validation, although the presented analyses have learned that improvements in the database are necessary for modelling purposes in the future. For a substantial amount of data, contextual information on exposure determinants in addition to basic core information is stored in this database. The relative low bias, the good correlation, and the level of conservatism of the tested model show that the Stoffenmanager can be regarded as a useful Tier 1 model for the Registration, Evaluation, Authorisation and Restriction of Chemicals legislation.

• Advanced REACH Tool: development and application of the substance emission potential modifying factor.

  Authors: Martie van Tongeren, Wouter Fransman, Sally Spankie, Martin Tischer, Derk Brouwer, Jody Schinkel, John W Cherrie, Erik Tielemans

  The Annals of occupational hygiene. 11/2011; 55(9):980-8.

  The Advanced REACH Tool (ART) is an exposure assessment tool that combines mechanistically modelled inhalation exposure estimates with available exposure data using a Bayesian approach. TheThe Advanced REACH Tool (ART) is an exposure assessment tool that combines mechanistically modelled inhalation exposure estimates with available exposure data using a Bayesian approach. The mechanistic model is based on nine independent principal modifying factors (MF). One of these MF is the substance emission potential, which addresses the intrinsic substance properties as determinants of the emission from a source. This paper describes the current knowledge and evidence on intrinsic characteristics of solids and liquids that determine the potential for their release into workplace air. The principal factor determining the release of aerosols from handling or processing powdered, granular, or pelletized materials is the dustiness of the material, as well as the weight fraction of the substance of interest in the powder and the moisture content. The partial vapour pressure is the main intrinsic factor determining the substance emission potential for emission of vapours. For generation of mist, the substance emission potential is determined by the viscosity of the liquid as well as the weight fraction of the substance of interest in the liquid. Within ART release of vapours is considered for substances with a partial vapour pressure at the process temperature of 10 Pa or more, while mist formation is considered for substances with a vapour pressure ≤ 10 Pa. Relative multipliers are assigned for most of the intrinsic factors, with the exception of the weight fraction and the vapour pressure, which is applied as a continuous variable in the estimation of the substance emission potential. Currently, estimation of substance emission potential is not available for fumes, fibres, and gases. The substance emission potential takes account of the latest thinking on emissions of dusts, mists, and vapours and in our view provides a good balance between theory and pragmatism. Expanding the knowledge base on substance emission potential will improve the predictive power of occupational exposure models and thereby the accuracy and precision of the exposure estimates.

• Revisiting the effect of room size and general ventilation on the relationship between near- and far-field air concentrations.

  Authors: John W Cherrie, Laura Maccalman, Wouter Fransman, Erik Tielemans, Martin Tischer, Martie Van Tongeren

  The Annals of occupational hygiene. 11/2011; 55(9):1006-15.

  In 1999, Cherrie carried out a series of mathematical simulations to investigate dispersion of pollutants through two indoor zones: the near-field (NF) and the far-field (FF). The results of theseIn 1999, Cherrie carried out a series of mathematical simulations to investigate dispersion of pollutants through two indoor zones: the near-field (NF) and the far-field (FF). The results of these simulations were used to derive modifying factors for use in exposure modeling. However, in the original simulations, no account was taken of deposition on surfaces, either from sedimentation of aerosols or other mechanisms or the potential effects of intermittent or short duration sources. These factors may affect pollutant dispersion, particularly the relationship between NF and FF levels. The Advanced REACH Tool (ART) is based on a two-zone dispersion paradigm. Further simulations have been carried out to help ensure that the ART realistically reflects pollutant dispersion. Pollutant dispersion has been simulated using a two-compartment well-mixed box model to represent the NF and the FF. Simulations were repeated for a range of room sizes and ventilation conditions. Intermittent sources (e.g. batch processes) were simulated by having the source active for 1 h followed by a 1-h gap, while short duration work emissions were set to last for 10 min, 30 min, 1 h, or 4 h, within the working day. Deposition was modeled by adding an equivalent air exchange rate based on published research data. Simulations were undertaken for non-volatile, monodisperse aerosols of aerodynamic diameter: 0.3, 1, 3, 10, 30, and 100 μm and the results were then interpreted in terms of typical polydisperse industrial aerosols. Room size and general ventilation strongly influenced dispersion from the NF to the FF as Cherrie had originally found. When varying the duration of the simulation, the biggest difference from continuous work was seen in small poorly ventilated rooms, with the ratio of the NF to FF concentration for 1-h work in the smallest room and lowest air exchange rate being a fifth of that calculated for continuous work. For large rooms and high general ventilation rates, the duration of the activity made little difference to dispersion. The results suggest that for the purposes of dispersion intermittent batch work is equivalent to continuous work. For typical simulated poly-disperse aerosols, the main effect of aerosol deposition was to reduce the predicted high concentrations compared to vapours when working in confined spaces. Both short duration of source emissions and deposition of aerosols have an important effect on dispersion, and the results from this study have been reflected in the ART model.

• Advanced Reach Tool (ART): development of the mechanistic model.

  Authors: Wouter Fransman, Martie Van Tongeren, John W Cherrie, Martin Tischer, Thomas Schneider, Jody Schinkel, Hans Kromhout, Nick Warren, Henk Goede, Erik Tielemans

  The Annals of occupational hygiene. 11/2011; 55(9):957-79.

  This paper describes the development of the mechanistic model within a collaborative project, referred to as the Advanced REACH Tool (ART) project, to develop a tool to model inhalation exposure forThis paper describes the development of the mechanistic model within a collaborative project, referred to as the Advanced REACH Tool (ART) project, to develop a tool to model inhalation exposure for workers sharing similar operational conditions across different industries and locations in Europe. The ART mechanistic model is based on a conceptual framework that adopts a source receptor approach, which describes the transport of a contaminant from the source to the receptor and defines seven independent principal modifying factors: substance emission potential, activity emission potential, localized controls, segregation, personal enclosure, surface contamination, and dispersion. ART currently differentiates between three different exposure types: vapours, mists, and dust (fumes, fibres, and gases are presently excluded). Various sources were used to assign numerical values to the multipliers to each modifying factor. The evidence used to underpin this assessment procedure was based on chemical and physical laws. In addition, empirical data obtained from literature were used. Where this was not possible, expert elicitation was applied for the assessment procedure. Multipliers for all modifying factors were peer reviewed by leading experts from industry, research institutes, and public authorities across the globe. In addition, several workshops with experts were organized to discuss the proposed exposure multipliers. The mechanistic model is a central part of the ART tool and with advancing knowledge on exposure, determinants will require updates and refinements on a continuous basis, such as the effect of worker behaviour on personal exposure, 'best practice' values that describe the maximum achievable effectiveness of control measures, the intrinsic emission potential of various solid objects (e.g. metal, glass, plastics, etc.), and extending the applicability domain to certain types of exposures (e.g. gas, fume, and fibre exposure).

• Advanced REACH Tool (ART): overview of version 1.0 and research needs.

  Authors: Erik Tielemans, Nick Warren, Wouter Fransman, Martie Van Tongeren, Kevin McNally, Martin Tischer, Peter Ritchie, Hans Kromhout, Jody Schinkel, Thomas Schneider, John W Cherrie

  The Annals of occupational hygiene. 11/2011; 55(9):949-56.

  This paper provides an outline of the Advanced REACH Tool (ART) version 1.0 and a discussion of how it could be further developed. ART is a higher tier exposure assessment tool that combinesThis paper provides an outline of the Advanced REACH Tool (ART) version 1.0 and a discussion of how it could be further developed. ART is a higher tier exposure assessment tool that combines mechanistically modelled inhalation exposure predictions with available exposure data using a Bayesian approach. ART assesses exposure for scenarios across different plants and sites. Estimates are provided for different percentiles of the exposure distribution and confidence intervals around the estimate. It also produces exposure estimates in the absence of data, but uncertainty of the estimates will decrease when results of exposure measurements are included. The tool has been calibrated using a broad range of exposure data and provides estimates for exposure to vapours, mists, and dusts. ART has a robust and stable conceptual basis but will be refined in the future and should therefore be considered an evolving system. High-priority areas for future research are identified in this paper and include the integration of partially analogous measurement series, inclusion of company and site-specific assessments, user decision strategies linked to ART predictions, evaluation of validity and reliability of ART, exploring the possibilities for incorporating the dermal route and integration of ART predictions with tools for modelling internal dose. ART is initially developed in the scope of REACH but is equally useful for exposure assessment in other areas.

• Classification of occupational activities for assessment of inhalation exposure.

  Authors: Hans Marquart, Thomas Schneider, Henk Goede, Martin Tischer, Jody Schinkel, Nick Warren, Wouter Fransman, Suzanne Spaan, Martie Van Tongeren, Hans Kromhout, Erik Tielemans, John W Cherrie

  The Annals of occupational hygiene. 09/2011; 55(9):989-1005.

  There is a large variety of activities in workplaces that can lead to emission of substances. Coding systems based on determinants of emission have so far not been developed. In this paper, a systemThere is a large variety of activities in workplaces that can lead to emission of substances. Coding systems based on determinants of emission have so far not been developed. In this paper, a system of Activity Classes and Activity Subclasses is proposed for categorizing activities involving chemical use. Activity Classes share their so-called 'emission generation mechanisms' and physical state of the product handled and the underlying determinants of emission. A number of (industrial) stakeholders actively participated in testing and fine-tuning the system. With the help of these stakeholders, it was found to be relatively easy to allocate a large number of activities to the Activity Classes and Activity Subclasses. The system facilitates a more structured classification of activities in exposure databases, a structured analysis of the analogy of exposure activities, and a transparent quantification of the activity emission potential in (new) exposure assessment models. The first use of the system is in the Advanced REACH Tool.

• Validation of the inhalable dust algorithm of the Advanced REACH Tool using a dataset from the pharmaceutical industry.

  Authors: Patricia E Mc Donnell, Jody M Schinkel, Marie A Coggins, Wouter Fransman, Hans Kromhout, John W Cherrie, Erik L Tielemans

  Journal of environmental monitoring : JEM. 06/2011; 13(6):1597-606.

  As it is often difficult to obtain sufficient numbers of measurements to adequately characterise exposure levels, occupational exposure models may be useful tools in the exposure assessment process.As it is often difficult to obtain sufficient numbers of measurements to adequately characterise exposure levels, occupational exposure models may be useful tools in the exposure assessment process. This study aims to refine and validate the inhalable dust algorithm of the Advanced REACH Tool (ART) to predict airborne exposure of workers in the pharmaceutical industry. The ART was refined to reflect pharmaceutical situations. Largely task based workplace exposure data (n = 192) were collated from a multinational pharmaceutical company with exposure levels ranging from 5 × 10(-5) to 12 mg m(-3). Bias, relative bias and uncertainty around geometric mean exposure estimates were calculated for 16 exposure scenarios. For 12 of the 16 scenarios the ART geometric mean exposure estimates were lower than measured exposure levels with on average, a one-third underestimation of exposure (relative bias -32%). For 75% of the scenarios the exposure estimates were, within the 90% uncertainty factor of 4.4, as reported for the original calibration study, which may indicate more uncertainty in the ART estimates in this industry. While the uncertainty was higher than expected this is likely due to the limited number of measurements per scenario, which were largely derived from single premises.

• Assessment of dermal exposure to bitumen condensate among road paving and mastic crews with an observational method.

  Authors: Michela Agostini, Wouter Fransman, Frank De Vocht, Berna Van Wendel de Joode, Hans Kromhout

  The Annals of occupational hygiene. 05/2011; 55(6):578-90.

  To assess dermal exposure to bitumen condensate among road pavers and indoor mastic workers in multiple crews using a semi-quantitative observational method [DeRmal Exposure Assessment MethodTo assess dermal exposure to bitumen condensate among road pavers and indoor mastic workers in multiple crews using a semi-quantitative observational method [DeRmal Exposure Assessment Method (DREAM)]. Two skilled observers assessed dermal exposure to bitumen condensate among 85 asphalt workers from 12 crews from nine companies active within four European countries using the DREAM methodology, which produces an estimate of exposure expressed in dimensionless DREAM units. Both observers independently evaluated each crew member's job (N = 14 jobs) for road paving and mastic applications. Potential and actual dermal exposures were estimated for hands and for the rest of the body separately, taking into account the effect of protective clothing. To evaluate the reproducibility of the observational method intra-class correlation coefficients (ICCs) were estimated. The exposures in DREAM units were modelled using linear mixed models to estimate average relative scores for each job. Correlations between dermal exposure parameters were evaluated by estimating Pearson correlation coefficients. A total of 170 observations were completed by two observers independently (n = 118 and n = 52 for 59 road pavers and 26 mastic workers, respectively) in 11 days. The mean ICCs (for potential and actual exposure in DREAM units) varied between 0.74 and 0.80 with values for actual units being slightly higher. Geometric mean potential dermal exposure units of mastic workers were higher than for road pavers (factor 3 for hands and factor 4 for rest of the body). Differences for actual dermal exposure units were smaller for hands (factor 2) and larger for actual exposure units of rest of the body (factor 5). Differences in dermal exposure at the hands between jobs within a paving crew were much larger than between jobs within a mastic crew. Within paving crews, a consistent pattern for all exposure units emerged with 'screed man' and 'raker' as the two highest exposed jobs. Within mastic crews, 'driver dumper truck' and 'spreader of mastic' were scored as the two jobs with the highest exposure units. Potential and actual exposure units were highly correlated. Hands were more profoundly exposed than the rest of the body, with transfer from contaminated surface to the hands as the most important route. DREAM observations were reproducible and showed a consistent dermal exposure pattern among the observed crews. The study provided a clear picture of dermal exposure among road pavers and indoor mastic workers, with the mastic workers being considerably more highly exposed. The most important route of exposure appeared to be transferred from contaminated surfaces to the hands.

• Conceptual model for assessment of inhalation exposure to manufactured nanoparticles.

  Authors: Thomas Schneider, Derk Henri Brouwer, Ismo Kalevi Koponen, Keld Alstrup Jensen, Wouter Fransman, Birgit Van Duuren-Stuurman, Martie Van Tongeren, Erik Tielemans

  Journal of exposure science & environmental epidemiology. 03/2011; 21(5):450-63.

  As workplace air measurements of manufactured nanoparticles are relatively expensive to conduct, models can be helpful for a first tier assessment of exposure. A conceptual model was developed toAs workplace air measurements of manufactured nanoparticles are relatively expensive to conduct, models can be helpful for a first tier assessment of exposure. A conceptual model was developed to give a framework for such models. The basis for the model is an analysis of the fate and underlying mechanisms of nanoparticles emitted by a source during transport to a receptor. Four source domains are distinguished; that is, production, handling of bulk product, dispersion of ready-to-use nanoproducts, fracturing and abrasion of end products. These domains represent different generation mechanisms that determine particle emission characteristics; for example, emission rate, particle size distribution, and source location. During transport, homogeneous coagulation, scavenging, and surface deposition will determine the fate of the particles and cause changes in both particle size distributions and number concentrations. The degree of impact of these processes will be determined by a variety of factors including the concentration and size mode of the emitted nanoparticles and background aerosols, source to receptor distance, and ventilation characteristics. The second part of the paper focuses on to what extent the conceptual model could be fit into an existing mechanistic predictive model for ''conventional'' exposures. The model should be seen as a framework for characterization of exposure to (manufactured) nanoparticles and future exposure modeling.

• Advanced REACH Tool (ART): calibration of the mechanistic model.

  Authors: Jody Schinkel, Nicholas Warren, Wouter Fransman, Martie van Tongeren, Patricia McDonnell, Eef Voogd, John W Cherrie, Martin Tischer, Hans Kromhout, Erik Tielemans

  Journal of environmental monitoring : JEM. 03/2011; 13(5):1374-82.

  The mechanistic model of the Advanced Reach Tool (ART) provides a relative ranking of exposure levels from different scenarios. The objectives of the calibration described in this paper areThe mechanistic model of the Advanced Reach Tool (ART) provides a relative ranking of exposure levels from different scenarios. The objectives of the calibration described in this paper are threefold: to study whether the mechanistic model scores are accurately ranked in relation to exposure measurements; to enable the mechanistic model to estimate actual exposure levels rather than relative scores; and to provide a method of quantifying model uncertainty. Stringent data quality guidelines were applied to the collated data. Linear mixed effects models were used to evaluate the association between relative ART model scores and measurements. A random scenario and company component of variance were introduced to reflect the model uncertainty. Stratified analyses were conducted for different forms of exposure (abrasive dust, dust, vapours and mists). In total more than 2000 good quality measurements were available for the calibration of the mechanistic model. The calibration showed that after calibration the mechanistic model of ART was able to estimate geometric mean (GM) exposure levels with 90% confidence for a given scenario to lie within a factor between two and six of the measured GM depending upon the form of exposure.

• Variability of biomarkers in volunteer studies: The biological component.

  Authors: Suzanne Spaan, Wouter Fransman, Nick Warren, Richard Cotton, John Cocker, Erik Tielemans

  Toxicology letters. 10/2010; 198(2):144-51.

  Biological monitoring has become one of the methods to measure exposure, with the advantage that it gives information about the concentration of a substance that actually enters the body and reflectsBiological monitoring has become one of the methods to measure exposure, with the advantage that it gives information about the concentration of a substance that actually enters the body and reflects the inter-individual differences in uptake and metabolic variation. However, limited information is available on inter- and intra-individual variability of biomarkers. The aim of this study was to gather information about the biological component of inter-individual variation in biomarkers using results from volunteer studies. Open literature and other (internal) sources were searched to find human volunteer studies utilizing biological monitoring. Ultimately 41 studies were included in our analysis, with a total of 6747 observations for one or more biomarkers from 223 volunteers. The data from these studies were grouped on the basis of study, substance under investigation, exposure route, biological matrix, exposure duration, dose and number of exposure events to obtain 278 homogeneous groups (strata) for statistical analysis. Variability was assessed in two ways. Firstly, estimates of biomarker half-life were calculated for each individual, thereby allowing the estimation of inter-individual variability in half-lives within the homogeneous groups. Secondly, variation in biomarker concentrations at a given time point was estimated. For estimated half-lives the GSDs ranged from 1.0 to 6.8. The variability in estimated half-lives did not differ much for the different types of substances. For concentrations at a given time point the average GSDs within strata ranged from 1.0 to 5.6. Again, variability did not differ much for different groups (e.g., type of substance). The median variability component was 0.11 (range 0-3.0). In conclusion, volunteer studies enable the estimation of both variation in half-lives and variation in biomarker levels in the well-defined homogeneous groups. Comparison of our results with other studies indicates that variation due to biological differences within and between people is quite substantial in homogeneous exposure groups. The relative contribution of this biological component to the total variation will be smaller when variance components are estimated in less homogeneous groups, such as those in occupational and environmental settings.

• A graphical tool to evaluate temporal coverage of occupational history by exposure measurements.

  Authors: Jelle Vlaanderen, Wouter Fransman, Brian Miller, Igor Burstyn, Dick Heederik, Fintan Hurley, Roel Vermeulen, Hans Kromhout

  Occupational and environmental medicine. 09/2010; 67(9):636-8.

  In occupational epidemiology, differences in the temporal coverage of the exposure history by available exposure measurement data may affect the uncertainty of exposure estimates. In the reporting ofIn occupational epidemiology, differences in the temporal coverage of the exposure history by available exposure measurement data may affect the uncertainty of exposure estimates. In the reporting of results of studies, greater attention should be paid to the extent to which exposure assessments require extrapolation outside the timeframe for which exposure measurements are available. We propose a simple graphical method that can be used to visualise the temporal coverage of exposure history with exposure measurements and the extent of temporal extrapolation needed. We construct a graph that displays the accumulated work history years for which exposure had to be assessed in each calendar year. Years for which exposure measurements were available are shaded. The proportion of work history years covered by exposure measurements and the proportion of work history years accrued before the first measurements are summarised. When available, the actual number of measurements available in each calendar year is shown. We demonstrate the application of the graphical tool in three nested case-control studies that reported on leukaemia in relation to low-level benzene exposures in the petroleum industry. Considerable differences in temporal coverage between the studies were illustrated, which may have resulted in differences in the reliability of the retrospective exposure estimates derived for these studies. We introduce a graphical tool for visualising the temporal coverage by available exposure measurement data in epidemiological studies and encourage others to use similar graphs to derive and share better qualitative insights into the uncertainty in exposure assessment.

• Stoffenmanager exposure model: company-specific exposure assessments using a Bayesian methodology.

  Authors: Peter van de Ven, Wouter Fransman, Jody Schinkel, Carina Rubingh, Nicholas Warren, Erik Tielemans

  Journal of occupational and environmental hygiene. 04/2010; 7(4):216-23.

  The web-based tool "Stoffenmanager" was initially developed to assist small- and medium-sized enterprises in the Netherlands to make qualitative risk assessments and to provide advice on control atThe web-based tool "Stoffenmanager" was initially developed to assist small- and medium-sized enterprises in the Netherlands to make qualitative risk assessments and to provide advice on control at the workplace. The tool uses a mechanistic model to arrive at a "Stoffenmanager score" for exposure. In a recent study it was shown that variability in exposure measurements given a certain Stoffenmanager score is still substantial. This article discusses an extension to the tool that uses a Bayesian methodology for quantitative workplace/scenario-specific exposure assessment. This methodology allows for real exposure data observed in the company of interest to be combined with the prior estimate (based on the Stoffenmanager model). The output of the tool is a company-specific assessment of exposure levels for a scenario for which data is available. The Bayesian approach provides a transparent way of synthesizing different types of information and is especially preferred in situations where available data is sparse, as is often the case in small- and medium sized-enterprises. Real-world examples as well as simulation studies were used to assess how different parameters such as sample size, difference between prior and data, uncertainty in prior, and variance in the data affect the eventual posterior distribution of a Bayesian exposure assessment.

• Cross-validation and refinement of the Stoffenmanager as a first tier exposure assessment tool for REACH.

  Authors: Jody Schinkel, Wouter Fransman, Henri Heussen, Hans Kromhout, Hans Marquart, Erik Tielemans

  Occupational and environmental medicine. 09/2009;

  OBJECTIVES: For regulatory risk assessment under REACH a tiered approach is proposed in which the first tier models should provide a conservative exposure estimate that can discriminate betweenOBJECTIVES: For regulatory risk assessment under REACH a tiered approach is proposed in which the first tier models should provide a conservative exposure estimate that can discriminate between scenarios of concern and those which are not. The Stoffenmanager is mentioned as first tier approach in the REACH guidance. In an attempt to investigate the validity of the Stoffenmanager algorithms a cross-validation study was performed. METHODS: Exposure estimates using the Stoffenmanager algorithms were compared with exposure measurement results (n=254). Correlations between observed and predicted exposures, bias and precision were calculated. Stratified analyses were performed for the scenarios "handling of powders and granules" (n=82), "handling solids resulting in comminuting" (n=60), "handling of low-volatile liquids" (n=40) and for "handling of volatile liquids" (n=72). RESULTS: The relative bias of the 4 algorithms ranged between -9% and -77% with a precision of approximately 1.7. The 90-percentile estimate of 1 out of 4 algorithms was not conservative enough. Based on these statistics and analyses of residual plots the underlying algorithm was adapted. Subsequently, the calibration and the cross-validation dataset were merged to one dataset (n=952) used for calibrating the adapted Stoffenmanager algorithms. This new calibration resulted in new exposure algorithms for the 4 scenarios. CONCLUSIONS: The Stoffenmanager is capable of discriminating among exposure levels mainly between scenarios in different companies. The 90-percentile estimates of the Stoffenmanager are verified to be sufficiently conservative. Therefore, the Stoffenmanager could be a useful Tier 1 exposure assessment tool for REACH.

• Development and Evaluation of an Exposure Control Efficacy Library (ECEL).

  Authors: Wouter Fransman, Jody Schinkel, Tim Meijster, Joop Van Hemmen, Erik Tielemans, Henk Goede

  The Annals of occupational hygiene. 09/2008;

  OBJECTIVES: This paper describes the development and evaluation of an evidence database on the effectiveness of risk management measures (RMMs) to control inhalation exposure. This database isOBJECTIVES: This paper describes the development and evaluation of an evidence database on the effectiveness of risk management measures (RMMs) to control inhalation exposure. This database is referred to as Exposure Control Efficacy Library (ECEL). METHODS: A comprehensive review of scientific journals in the occupational hygiene field was undertaken. Efficacy values for RMMs in conjunction with contextual information on study design, sampling strategy and measurement type (among other parameters) were stored in an MS Access database. In total, 433 efficacy values for six RMM groups (i.e. enclosure, local exhaust ventilation, specialized ventilation, general ventilation, suppression techniques and separation of the worker) were collected from 90 peer-reviewed publications. These RMM categories were subdivided into more specific categories. RESULTS: Estimated average efficacy values ranged from 87% for specialized ventilation to 43% for general ventilation. Substantial variation in efficacy values was observed within RMM categories based on differences in selected covariables within each study (i.e. study design, sampling strategy, measurement type and others). More contrast in efficacy values was observed when evaluating more detailed subcategories. CONCLUSIONS: It is envisaged that ECEL will contribute to exposure modelling, but should be supplemented with expert opinion, preferably in a formal expert elicitation procedure. The work presented here should be considered as a first attempt to collate and analyse RMM efficacy values and inclusion of additional (unpublished) exposure data is highly warranted.

• Stoffenmanager Exposure Model: Development of a Quantitative Algorithm.

  Authors: Erik Tielemans, Dook Noy, Jody Schinkel, Henri Heussen, Doeke Van Der Schaaf, John West, Wouter Fransman

  The Annals of occupational hygiene. 07/2008;

  In The Netherlands, the web-based tool called 'Stoffenmanager' was initially developed to assist small- and medium-sized enterprises to prioritize and control risks of handling chemical products inIn The Netherlands, the web-based tool called 'Stoffenmanager' was initially developed to assist small- and medium-sized enterprises to prioritize and control risks of handling chemical products in their workplaces. The aim of the present study was to explore the accuracy of the Stoffenmanager exposure algorithm. This was done by comparing its semi-quantitative exposure rankings for specific substances with exposure measurements collected from several occupational settings to derive a quantitative exposure algorithm. Exposure data were collected using two strategies. First, we conducted seven surveys specifically for validation of the Stoffenmanager. Second, existing occupational exposure data sets were collected from various sources. This resulted in 378 and 320 measurements for solid and liquid scenarios, respectively. The Spearman correlation coefficients between Stoffenmanager scores and exposure measurements appeared to be good for handling solids (r(s) = 0.80, N = 378, P < 0.0001) and liquid scenarios (r(s) = 0.83, N = 320, P < 0.0001). However, the correlation for liquid scenarios appeared to be lower when calculated separately for sets of volatile substances with a vapour pressure >10 Pa (r(s) = 0.56, N = 104, P < 0.0001) and non-volatile substances with a vapour pressure </=10 Pa (r(s) = 0.53, N = 216, P < 0.0001). The mixed-effect regression models with natural log-transformed Stoffenmanager scores as independent parameter explained a substantial part of the total exposure variability (52% for solid scenarios and 76% for liquid scenarios). Notwithstanding the good correlation, the data show substantial variability in exposure measurements given a certain Stoffenmanager score. The overall performance increases our confidence in the use of the Stoffenmanager as a generic tool for risk assessment. The mixed-effect regression models presented in this paper may be used for assessment of so-called reasonable worst case exposures. This evaluation is considered as an ongoing process and when more good quality data become available, the analyses described in this paper will be expanded. Based on these analyses, the algorithm will be refined in the near future.

• Inhalation and dermal exposure to eight antineoplastic drugs in an industrial laundry facility.

  Authors: Wouter Fransman, Daan Huizer, Jochen Tuerk, Hans Kromhout

  International archives of occupational and environmental health. 05/2007; 80(5):396-403.

  OBJECTIVES: The aims of the study were to quantify levels of dermal and inhalation exposure to antineoplastic drugs in an industrial laundry service in the Netherlands and to test the removalOBJECTIVES: The aims of the study were to quantify levels of dermal and inhalation exposure to antineoplastic drugs in an industrial laundry service in the Netherlands and to test the removal efficiency of the washing procedure for removal of antineoplastic drugs. METHODS: During four workdays dermal and inhalation exposure to eight frequently used antineoplastic drugs (cyclophosphamide, ifosfamide, methotrexate, 5-fluorouracil, etoposide, cytarabine, gemcitabine and chlorambucil) were measured for all job titles involved in handling unwashed laundry. To test the removal efficiency of the washing procedure, 10 x 10 cm sections were excised before and after the washing procedure. These sections were taken from 15 bed sheets that were collected in hospitals of patients who were treated with one of the selected antineoplastic drugs. RESULTS: During none of the four measurement days, detectable levels of any of the eight antineoplastic drugs (cyclophosphamide, ifosfamide, methotrexate, 5-fluorouracil, etoposide, cytarabine, gemcitabine, or chlorambucil) were found on workers' skin of hands or in any of the air samples. Only four out of the 15 bed sheets from patients that were treated with antineoplastic drugs appeared to be contaminated with detectable levels of antineoplastic drugs before the washing procedure (range 13.0-3,060 ng/100 cm(2)). After the pre-washing and after the complete washing procedure, no detectable levels of any of the eight antineoplastic drugs were found anymore in the selected bed sheets. CONCLUSIONS: The implementation of guidelines for working with antineoplastic drugs seems to be successful in reducing exposure to antineoplastic drugs of workers in this laundry facility to an acceptable, non-detectable level and to remove antineoplastic drug contamination from bed linen.

• A pooled analysis to study trends in exposure to antineoplastic drugs among nurses.

  Authors: Wouter Fransman, Susan Peelen, Simone Hilhorst, Nel Roeleveld, Dick Heederik, Hans Kromhout

  The Annals of occupational hygiene. 05/2007; 51(3):231-9.

  OBJECTIVES: Several studies have shown that exposure to antineoplastic drugs can cause toxic effects on reproductive health as well as carcinogenic effects. Numerous studies have corroborated thatOBJECTIVES: Several studies have shown that exposure to antineoplastic drugs can cause toxic effects on reproductive health as well as carcinogenic effects. Numerous studies have corroborated that hospital workers are exposed to these drugs. This study focused on trends in exposure to antineoplastic drugs since the introduction of guidelines in The Netherlands. METHODS: Data from three cross-sectional exposure surveys conducted in The Netherlands were pooled to examine trends in occupational exposure to cyclophosphamide. Nurses' 24 h urine samples were analyzed in separate fractions, surface contamination was determined and gloves used during preparation or while handling patient urine were collected. The difference in detectable urine samples between 1997 and 2000 was determined by a generalized estimating equations (GEE) binomial regression model. Mixed models were used to study the time trend in surface and glove contamination levels. RESULTS: The percentage of nurses' urine samples with detectable cyclophosphamide had decreased 4-fold between 1997 and 2000. Median cyclophosphamide levels in the positive urine samples were 3-fold lower in 2000 than in 1997. Surface and glove contamination had statistically significantly decreased between 1997 and more recent years. CONCLUSIONS: Nurses working at outpatient clinics or oncology wards are still being exposed to cyclophosphamide, but their exposure decreased considerably between 1997 and 2000, presumably due to the introduction of detailed guidelines and regulations in The Netherlands, the subsequent increased use of LuerLock connections and infusion systems prefilled with saline, and growing hazard awareness of nurses working with antineoplastic drugs.