Suzanne Spaan

Publications of Suzanne Spaan

• 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.

• 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.

• Endotoxin exposure in sewage treatment workers: investigation of exposure variability and comparison of analytical techniques.

  Authors: Suzanne Spaan, Lidwien Smit, Wijnand Eduard, Lennart Larsson, Huib Arts, Inge Wouters, Dick Heederik

  Annals of agricultural and environmental medicine : AAEM. 01/2009; 15(2):251-61.

  Introduction: Objectives were to give an overview of endotoxin exposure and its determinants in sewage treatment workers, and to study exposure to culturable and non-culturable microorganisms and theIntroduction: Objectives were to give an overview of endotoxin exposure and its determinants in sewage treatment workers, and to study exposure to culturable and non-culturable microorganisms and the applicability of the LAL assay in this work environment. Material and methods: In 43 Dutch sewage treatment plants 470 full-shift, 123 task-based personal and 54 stationary inhalable dust samples were collected. Endotoxin concentration was determined with the LAL-assay. Mixed effects models were used to investigate possible determinants of exposure. Simultaneous parallel filter samples, impinger samples and viable total bacteria and Gram-negative bacterial samples were taken to compare analytical techniques. Filter and impinger samples were analyzed with the LAL-assay, gas chromatography-mass spectrometry (GC-MS) and fluorescence microscopy. Results: Endotoxin exposure levels were moderate to low (geometric mean personal exposure 27 EU/m(3), stationary 33 EU/m(3), task-based 64 EU/m(3)), yet differences between jobs and sources and some determinants of exposure were identified. Exposure varied more from day to day than between workers. Concentrations in filter samples were higher and more consistent than in impinger samples. Fungi and Gram-positive bacteria were found in higher levels than Gram-negative bacteria. The LAL assay and GC-MS showed comparable endotoxin levels. Discussion and conclusion: Endotoxin exposure in Dutch sewage treatment workers was relatively low. Comparison of sampling and analytical techniques suggests that the LAL-assay did not result in much exposure misclassification. It thus seems justified to perform filter measurements in combination with the LAL-assay to measure endotoxin exposure in sewage treatment plants.

• Variability in endotoxin exposure levels and consequences for exposure assessment.

  Authors: Suzanne Spaan, Jody Schinkel, Inge M Wouters, Liesbeth Preller, Erik Tielemans, Evelyn Tjoe Nij, Dick Heederik

  The Annals of occupational hygiene. 07/2008; 52(5):303-16.

  OBJECTIVES: Workers in many industries are exposed to endotoxins, which may cause adverse health effects. In exposure assessment, information about exposure variability is essential. However,OBJECTIVES: Workers in many industries are exposed to endotoxins, which may cause adverse health effects. In exposure assessment, information about exposure variability is essential. However, variability in exposure has rarely been investigated for biological agents and more specifically for endotoxin. Therefore, variance components and determinants of exposure were studied in a large database with >2000 endotoxin measurements. METHODS: Data from 10 individual studies were combined to create a database with 2010 personal inhalable dust and endotoxin measurements, of which 1650 were repeated measurements. Exposure groups were defined based on job codes. Between- and within-worker variance components were estimated for different grouping strategies, and determinants of exposure were studied using mixed effects models. RESULTS: Inhalable dust and endotoxin exposure levels are summarized for 46 industries and 4 broadly defined sectors. The between-worker variability exceeded the within-worker variability overall and within sectors and subsectors, and variance components were larger for endotoxin than for dust. Between-worker variability also exceeded within-worker variability in nearly half of the exposure groups based upon industries or job code within industries for endotoxin exposure and in 10% of the groups for dust exposure. Among other things, dustiness of the process, contact with animals, bulk production, presence of plant material or a cyclic process appeared as determinants of exposure, which largely explained the between-worker variability. CONCLUSIONS: Exposure groups were much less homogeneous for endotoxin exposure than for dust exposure. This is distinctly different than for chemical exposure. Large variability in measured exposure levels is inherent to endotoxin exposure, which is caused in part by determinants that influence growth of microorganisms. These findings have major consequences for the design of future occupational intervention and epidemiological studies. The measurement effort needs to be greater than exposure assessment for chemical agents which demonstrate lower exposure variability, especially when evaluating endotoxin exposure for compliance testing. The established determinants of exposure give direction for potential exposure control, although more information about determinants of day-to-day variability in exposure is still needed to be able to effectively control endotoxin exposure.

• Effect of extraction and assay media on analysis of airborne endotoxin.

  Authors: Suzanne Spaan, Gert Doekes, Dick Heederik, Peter S Thorne, Inge M Wouters

  Applied and environmental microbiology. 07/2008; 74(12):3804-11.

  The measurement of airborne endotoxins is thus far not standardized. Earlier studies reported higher endotoxin yields when Tween 20 was added to the media used for filter extraction and in theThe measurement of airborne endotoxins is thus far not standardized. Earlier studies reported higher endotoxin yields when Tween 20 was added to the media used for filter extraction and in the Limulus amebocyte lysate (LAL) assay. This study compared four common media and assessed the effects of Tween during extraction and analysis separately. Parallel airborne dust samples from five work environments (n = 250) were used to compare the four media (pyrogen-free water [PFW], PFW-Tween 20, PFW-Tris, and PFW-triethylamine-phosphate [TAP]) and an extraction time of 10 or 60 min. A subset of the extracts in PFW or PFW-Tween (n = 40) were analyzed in parallel LAL assays with PFW or PFW-Tween as the assay medium. The results produced by a shorter extraction time or the presence of Tris were similar to the results for the reference procedure (PFW and 60 min of shaking). The use of PFW-TAP showed overall lower yields and a deviant calibration curve. The presence of Tween in the extraction medium resulted in significantly (P < 0.05) higher endotoxin yields from all dust types, independent of the effect of Tween in the assay. Tween in the LAL assay, however, also strongly inhibited the reactivity of the lipopolysaccharide (LPS) standard, thus shifting the calibration curve to higher values. The inhibition of LPS in test samples was less pronounced and varied between dust sources, resulting in enhanced calculated concentrations. This assay effect could be circumvented by diluting extracts at least 50-fold before the LAL assay. In conclusion, of the media tested, only Tween enhances the efficiency of endotoxin extraction from airborne dust samples in a consistent manner. We recommend extraction in PFW-Tween combined with dilution and LAL analysis in PFW.

• Optimization of airborne endotoxin exposure assessment: effects of filter type, transport conditions, extraction solutions, and storage of samples and extracts.

  Authors: Suzanne Spaan, Dick J J Heederik, Peter S Thorne, Inge M Wouters

  Applied and environmental microbiology. 11/2007; 73(19):6134-43.

  Endotoxin exposure occurs in homes and occupational environments and is known to cause adverse health effects. In order to compare results from different studies and establish standards, airborneEndotoxin exposure occurs in homes and occupational environments and is known to cause adverse health effects. In order to compare results from different studies and establish standards, airborne endotoxin exposures should be assessed using standardized methods. Although the European Committee for Standardization (CEN) developed guidelines for endotoxin exposure assessment, these leave room for individual interpretation. The influence of methods of sampling, extraction, and analysis has never been investigated in a full experimental design. Thus, we sought to fully elucidate the importance of all facets of endotoxin assessment. Inhalable dust samples collected simultaneously were used to investigate the effects on and interactions with airborne endotoxin concentration in two working environments of filter type (glass fiber or Teflon), transport conditions (with/without desiccant), sample storage (-20 or 4 degrees C), extraction solution (pyrogen-free water [PFW] or PFW plus 0.05% Tween 20), extract storage (-20 or 4 degrees C), and assay solution (PFW or PFW plus 0.05% Tween 20). Four hundred samples were collected and randomly distributed over the 20 combinations of treatments. There were no differences found for transport conditions and storage temperature of extracts. Also, no interactions between study variables existed. Sampling on glass-fiber filters, storage of samples in the freezer, and extraction in PFW plus 0.05% Tween 20 resulted in 1.3-, 1.1-, and 2.1-fold-higher estimated endotoxin concentrations, respectively. Use of PFW plus 0.05% Tween 20 in the assay solution had an additive effect. Thus, this study investigated gaps in the CEN protocol and provides data with which to fully specify a protocol for standardization of endotoxin exposure assessment.

• Exposure to inhalable dust and endotoxins in agricultural industries.

  Authors: Suzanne Spaan, Inge M Wouters, Isabella Oosting, Gert Doekes, Dick Heederik

  Journal of environmental monitoring : JEM. 02/2006; 8(1):63-72.

  Endotoxin is a well-known bacterial toxin that causes several health effects. Animal faeces and plant materials contaminated with bacteria have been identified as important determinants of organicEndotoxin is a well-known bacterial toxin that causes several health effects. Animal faeces and plant materials contaminated with bacteria have been identified as important determinants of organic dust related endotoxin exposure. Although high exposure to organic dust and endotoxins has been described regularly in agricultural industries, a detailed overview of levels of airborne exposure to endotoxins in the agricultural industry, as well as a systematic comparison between several specific branches using the same exposure assessment protocols are lacking. In this study, personal endotoxin exposure in a broad spectrum of agricultural industries was investigated and possible determinants of exposure were explored. 601 personal inhalable dust samples were taken in 46 companies of three agricultural industrial sectors: grains, seeds and legumes sector (GSL), horticulture sector (HC) and animal production sector (AP), with 350 participating employees. Dust and endotoxin levels were determined gravimetrically and by using the Limulus Amoebocyte Lysate (LAL) assay, respectively. Basic descriptive analysis and elaborate analysis of variance were performed. Mean exposure levels were high, with large differences between sectors and between companies within the sectors. Highest dust and endotoxin exposures were found in companies of the GSL sector. In all three sectors exposure was higher in the primary production part compared to the (industrial) products processing part of the sector. The Dutch proposed health based occupational exposure limit (50 EU m(-3)) and temporary legal limit (200 EU m(-3)) for endotoxin were often exceeded. Differences in exposure between workers were larger than the day-to-day variability. Identified determinants increasing exposure levels were company, dustiness of the product and contact with animals/faeces. 'Wet' processes resulted in less dusty working environments and thus lowered endotoxin exposure. Overall, exposure to endotoxins over the whole range of agricultural industries is high. A 10-1,000 fold reduction in exposure is needed to reduce endotoxin related health risks.

• Overview of personal occupational exposure levels to inhalable dust, endotoxin, beta(1-->3)-glucan and fungal extracellular polysaccharides in the waste management chain.

  Authors: Inge M Wouters, Suzanne Spaan, Jeroen Douwes, Gert Doekes, Dick Heederik

  The Annals of occupational hygiene. 02/2006; 50(1):39-53.

  INTRODUCTION: In the past decade, we studied occupational bioaerosol exposures in various sites of the waste management chain. In this paper we present an overview of exposure levels of inhalableINTRODUCTION: In the past decade, we studied occupational bioaerosol exposures in various sites of the waste management chain. In this paper we present an overview of exposure levels of inhalable dust, endotoxin, beta(1-->3)-glucan (known or probable inducers of airways inflammation), and extracellular polysaccharide antigens of Aspergillus and Penicillium species (EPS-Pen/Asp; a common and probably more specific marker of fungal exposure). METHODS: Over 450 personal bioaerosol samples were taken. Mixed regression analyses were performed to estimate exposure determinants, between- and within-worker variance of exposure, and determinants of these variances. Furthermore, we explored whether the type of waste affected the bioaerosol composition of the dust. RESULTS: Endotoxin and glucan exposure levels were relatively low and comparable for waste collection and transferral, green waste composting and use of biomass in power plants. Exposure levels were 5-20 times higher in domestic waste transferral with sorting, and composting of both domestic and domestic and green waste ( approximately 300-1000 EU m(-3) for endotoxin, and 5-10 mug m(-3) for glucan). Observed exposure exceeded Dutch occupational exposure limits at all sites. EPS-Pen/Asp exposure was detected in 20% of waste collectors and 49% of compost workers. Exposure variability within tasks was large (geometric standard deviation > 2), with smaller between-worker than within-worker variance. Type of company and waste largely explained between-worker variance (40-90%), although within companies no major task-related determinants could be established. Markers of exposure correlated moderately to strongly. Relative endotoxin and glucan content in the dust was only weakly associated with handled waste. CONCLUSIONS: Occupational bioaerosol exposure in the waste management chain is lowest for outdoor handling of waste and highest when waste is handled indoors. However, exposure variability is large, with greater within-worker than between-worker variance. Occupational exposure limits for organic dust and endotoxins are frequently exceeded, suggesting workers are at risk of developing adverse health effects.

• Endotoxin exposure and symptoms in wastewater treatment workers.

  Authors: Lidwien A M Smit, Suzanne Spaan, Dick Heederik

  American journal of industrial medicine. 08/2005; 48(1):30-9.

  BACKGROUND: Wastewater treatment workers can be exposed to biological and chemical agents resulting in work-related health effects. The aim of this study was to investigate work-related symptoms inBACKGROUND: Wastewater treatment workers can be exposed to biological and chemical agents resulting in work-related health effects. The aim of this study was to investigate work-related symptoms in these workers. METHODS: Questionnaire data of 468 employees from 67 sewage treatment plants is evaluated. Personal endotoxin exposure (8 hr measurements; n = 460) was measured in a sample of workers in three different periods over 1 year. RESULTS: Endotoxin exposure ranged from 0.6 to 2093 endotoxin units (EU)/m(3), the geometric mean exposure was low (27 EU/m(3)). Factor analysis yielded three clusters of correlated symptoms: "lower respiratory and skin symptoms," "flu-like and systemic symptoms," and "upper respiratory symptoms." Symptoms appeared to be more prevalent in workers exposed to endotoxin levels higher than 50 EU/m(3). A significant dose-response relationship was found for "lower respiratory and skin symptoms" and "flu-like and systemic symptoms" (P < 0.05). CONCLUSIONS: Wastewater treatment workers reported a wide range of symptoms that may be work-related. Microbial exposures such as endotoxin seem to play a causal role.