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Objectives: Within the chemical legislation, REACH was implemented in order to improve safe working conditions with hazardous substances. Literature and real-life experiences by those concerned have shown that there are still gaps with a need for improved risk communication. This study elaborated on how information provided by REACH is understood and acted on by down- and upstream users, and how it can be further improved., Methods: An extensive literature study including 21 studies and 13 tools was carried out. The outcomes were discussed and further supplemented by means of 18 interviews concerning 37 internal safety and REACH documents to build six different use cases representing different Dutch downstream companies. For the upstream perspective also 2 sector organizations and 2 registrants were interviewed. Three online workshops were organized in order to share insights and gather input on international recognition, potential suggestions and further recommendations with 30 participants from nine different EU countries., Results: Although the methods to collect the data differed between the different stages of the study, the general results from all three stages elucidated similar themes in the data and each of the stages used the results from the previous stage as a starting point. Recurring themes concerned the (i) complexity of documents, (ii) deficiencies as experienced by SMEs in REACH, (iii) feedback and responsibilities in the supply chain, and (iv) the cooperation between REACH and OSH., Discussion: The study at hand revealed that even though there are currently several activities to improve communication on safe-use of chemicals, communication on safe-use in the scope of REACH should be improved. This includes e.g. the future involvement of actual end-users in activities and development related to communication of safe-use information in the scope of REACH including feedback, less complicated and complex documents and clear communication concerning legislations and updates of documents. Furthermore, the issues recognized in the Netherlands are mostly also recognized by international workshop participants, thereby indicating international benefits in various areas by means of improved communication., Conclusions: The study confirmed that many of our generic conclusions were already part of the shared knowledge in the REACH community, but that it is very valuable that this knowledge has been explicated, validated and reported in a structured way in the present project. Besides uncovering some crucial aspects that offer potential improvements regarding risk communication, this study offers possible solutions and next steps to be taken., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Occupational exposure to manufactured nano-objects and their agglomerates, and aggregates (NOAA) has been described in several workplace air monitoring studies. However, data pooling for general conclusions and exposure estimates are hampered by limited exposure data across the occupational life cycle of NOAA and a lack in comparability between the methods of collecting and analysing the data. By applying a consistent method of collecting and analysing the workplace exposure data, this study aimed to provide information about the occupational NOAA exposure levels across various life cycle stages of NOAA in the Netherlands which can also be used for multi-purpose use., Methods: Personal/near field task-based exposure data was collected using a multi-source exposure assessment method collecting real time particle number concentration, particle size distribution (PSD), filter-based samples for morphological, and elemental analysis and detailed contextual information. A decision logic was followed allowing a consistent and objective way of analysing the exposure data., Results: In total, 46 measurement surveys were conducted at 15 companies covering 18 different exposure situations across various occupational life cycle stages of NOAA. Highest activity-effect levels were found during replacement of big bags (<1000-76000 # cm(-3)), mixing/dumping of powders manually (<1000-52000 # cm(-3)) and mechanically (<1000-100000 # cm(-3)), and spraying of liquid (2000-800000 # cm(-3)) showing a high variability between and within the various exposure situations. In general, a limited change in PSD was found during the activity compared to the background., Conclusions: This broad-scale exposure study gives a comprehensive overview of the NOAA exposure situations in the Netherlands and an indication of the levels of occupational exposure to NOAA across various life cycle of NOAA. The collected workplace exposure data and contextual information will serve as basis for future pooling of data and modelling of worker exposure., (© The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Several studies showed that oncology nurses are exposed to antineoplastic drugs via the skin during daily activities. Several antineoplastic drugs (including cyclophosphamide) have been classified as carcinogenic to humans. This study aims to assess the leukemia risk of occupational exposure to cyclophosphamide. Average task frequencies from the population of oncology nurses in the Netherlands and task-based dermal exposure intensities were used to calculate oncology nurses' dermal exposure levels. A dermal absorption model in combination with a physiologically based pharmacokinetic model was used to assess the delivered dose of cyclophosphamide and its active metabolites in the bone marrow. This delivered dose was subsequently related to pharmacodynamic and epidemiological information from a longitudinal study with cyclophosphamide-treated patients to estimate the excess lifetime leukemia risk at age 80 for Dutch oncology nurses after 40 years of exposure to cyclophosphamide. The excess lifetime leukemia risk at age 80 of an exposed oncology nurse after 40 years of dermal exposure to cyclophosphamide was estimated to be 1.04 per million oncology nurses. This risk could potentially increase to a maximum of 154 per million if a nurse performs all cyclophosphamide-related tasks with the maximum frequency (as observed in this population) and is exposed to maximum exposure intensities for each task without using protective gloves for 40 years. This study indicates that the risk of an oncology nurse in a Dutch hospital with an average dermal exposure to cyclophosphamide is well below the maximum tolerable risk of one extra death from cancer per 250 deaths after 40 years of occupational exposure, and that this level is not exceeded in a worst-case scenario.

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 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.

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 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.

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 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.

Background: Nurses and other hospital workers are exposed to antineoplastic drugs during daily activities. Previous studies suggest that antineoplastic drugs at occupational exposure levels may be toxic to reproduction, but these studies are not consistent or conclusive., Methods: Self-administered questionnaires were completed by 4393 exposed and nonexposed nurses employed between 1990 and 1997 (79% response). Questions were asked about pregnancy outcome, work-related exposures, and lifestyle. Exposure to antineoplastic drugs was estimated using task-based dermal exposure measurements and self-reported task frequencies. Time to pregnancy was modeled using survival analysis, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for other reproductive outcomes using multiple logistic regression analysis. Associations were further explored by nonparametric regression modeling., Results: Nurses highly exposed to antineoplastic drugs took longer to conceive than referent nurses (adjusted hazard ratio = 0.8; CI = 0.6-0.9). Exposure to antineoplastic drugs was associated with premature delivery (OR per unit increase in ln[exposure] = 1.08; CI = 1.00-1.17) and low birth weight (OR per unit increase in ln[exposure] = 1.11; 1.01-1.21). Penalized smoothed spline plots corroborated these log-linear relations. Spontaneous abortion, stillbirth, congenital anomalies, and sex of offspring appeared not to be related to exposure to antineoplastic drugs., Conclusion: Antineoplastic drugs may reduce fertility and increase poor neonatal outcomes among occupationally exposed oncology nurses.

Objectives: The objectives were (i) to identify occupational populations outside hospitals working with antineoplastic drugs, (ii) to determine the size of the populations 'at risk', (iii) to identify major determinants and routes of exposure outside hospitals and (iv) to estimate exposure levels and frequencies relative to levels found in hospitals., Methods: The survey consisted of two phases; (i) identification of activities with potential exposure to antineoplastic drugs by literature review, interviews, questionnaires and workplace visits, (ii) exploratory measurements of exposure and surface contamination in selected sectors., Results: Eight sectors were identified with potential exposure to antineoplastic drugs: pharmaceutical industry, pharmacies, universities, veterinary medicine, nursing homes, home care, laundry facilities, and waste treatment. Four sectors were of primary concern: veterinary medicine, home care, nursing homes and industrial laundries. The populations potentially exposed in these sectors vary considerably (from several tens to thousands of workers), as do their levels of exposure. Exposure measurements collected in the veterinary medicine sector showed that workers are indeed exposed to antineoplastic drugs and, in some cases (on gloves after administration), levels were 15 times higher than levels measured during administration in hospitals. Workers sorting contaminated hospital laundry in industrial laundry facilities were exposed to antineoplastic drugs through inhalation. For the home care and nursing homes sectors the highest exposure levels were found when cleaning toilets and washing treated patients. These two sectors are expected to have the largest exposed population (5,000-10,000 individuals)., Conclusions: This study has resulted in a comprehensive overview of populations with potential exposure to antineoplastic drugs. Exposure levels can potentially be high compared with the hospital environment, because exposure routes are complex and awareness of the hazard (and therefore use of protective measures) is low. The number of individuals outside hospitals in The Netherlands exposed to antineoplastic drugs is estimated to be between 5,000 and 15,000.

Objective: The main goal was to investigate the potential of a probabilistic approach for exposure assessment and use this information to evaluate the impact of a complex of policy actions/interventions on dermal exposure to antineoplastic agents among oncology nurses. The central theme of this study was to make optimal use of existing data, supplemented only with limited additional information from a questionnaire survey., Methods: A task based exposure model was used to estimate dermal exposure of the hands among oncology nurses in non-academic hospitals in the Netherlands. Monte Carlo simulation was used to integrate information from available (exposure) studies and generate exposure distributions for the total population of oncology nurses in both pre- and post-intervention situation. Graphs and descriptive statistics of the simulated exposure distributions were used to evaluate trends in population exposure., Results: The inventory showed that important intervention occurred in the preparation and administering of antineoplastic agents and in the handling of urine. Hardly any changes were identified in de nursing tasks. The use of gloves seemed to have decreased for a number of tasks. The results of the analysis show that the interventions did not affect the median exposure. However frequencies of occurrence of individuals with very high and very low total dermal exposures decreased substantially in the post-intervention situation. Analysis of the effect of pregnancy showed that pregnancy is very unlikely to influence exposure or any of the key input variables., Conclusions: The present study shows that the probabilistic approach adds valuable information to deterministic exposure assessment, especially when extrapolating data on a subpopulation to populations of individuals at large. The results show that the identified changes in the past decade in Dutch non-academic hospitals resulted in changes in the exposure distribution of antineoplastic agents among oncology nurses.

Introduction: Several studies have shown that exposure to antineoplastic drugs can cause reproductive toxic effects as well as carcinogenic effects. Presence of these drugs in the urine of hospital personnel has been widely studied and some work has been done on exposure by inhalation. So far, assessment of dermal exposure to antineoplastic drugs has not been extensively studied. In this pilot study we assessed potential and actual dermal exposure for several common hospital tasks. Results were used to derive an optimal measurement strategy for a currently ongoing exposure survey., Methods: Dermal exposure to cyclophosphamide was determined in three Dutch hospitals during five tasks (preparation, decanting urine, washing the patient, removing bed sheets and cleaning the toilet) using pad samples on 10 body locations. In addition, protective medical gloves (worn during the performance of these activities) were collected to estimate potential exposure of the hands. Subsequently, hands were washed to measure actual exposure of the hands. Bulk samples (i.e. application and body fluids) were collected and possible contact surfaces were monitored to assess the amount of cyclophosphamide potentially available for exposure., Results: The results show that hospital personnel (i.e. pharmacy technicians and oncology nurses) are dermally exposed to cyclophosphamide during performance of their daily duties. Exposure occurred predominantly on the hands and sporadically on other body locations (i.e. forehead and forearms). Gloves used during preparation of cyclophosphamide were more contaminated than gloves used in other tasks, however, actual exposure of the hands (underneath the gloves) was highest during decanting of urine of treated patients. Glove samples correlated significantly with handwash samples (r = 0.57, P = 0.03, n = 15). The level of protection from gloves varied between tasks, being highest for gloves used during preparation (median = 98%) and lowest for gloves used during decanting urine (median = 19%)., Conclusion: This pilot study demonstrated that dermal exposure to cyclophosphamide is common among hospital personnel. The results showed that hands, forearms and forehead accounted for 87% of the cyclophosphamide total body exposure. Glove samples together with handwash samples enabled estimation of glove efficiency, which appeared to vary strongly between tasks observed.