Exposure Models for REACH and Occupational Safety and Health Regulations

Model tools for estimating hazardous substance exposure are an accepted part of regulatory risk assessments in Europe, and models underpin control banding tools used to help manage chemicals in workplaces. Of necessity the models are simplified abstractions of real-life working situations that aim to capture the essence of the scenario to give estimates of actual exposures with an appropriate margin of safety. The basis for existing inhalation exposure assessment tools has recently been discussed by some scientists who have argued for the use of more complex models. In our opinion, the currently accepted tools are documented to be the most robust way for workplace health and safety practitioners and others to estimate inhalation exposure. However, we recognise that it is important to continue the scientific development of exposure modelling to further elaborate and improve the existing methodologies

First order risk assessment for nanoparticle inhalation exposure during injection molding of polypropylene composites and production of tungsten-carbide-cobalt fine powder based upon pulmonary inflammation and surface area dose

AbstractInhalation exposure to low toxicity and biodurable particles has shown to induce polymorphonuclear neutrophilia (PMN) in the lungs, which is a strong indicator for lung inflammation. Recently, Schmid and Stoeger (2016; http://dx.doi.org/10.1016/j.jaerosci.2015.12.006) reviewed mice and rat intratracheal instillation studies and assessed the relation between particles dry powder BET surface area dose and PMN influx for granular biodurable particles (GBPs) and transition metal oxides. In this study, we measured workers alveolar lung deposited surface area (LDSA) concentrations (μm2 cm−3) during injection molding of polypropylene (PP) car bumpers and production of tungsten-carbide-cobalt (WCCo) fine grade powder using diffusion chargers. First order risk assessment was performed by comparing the doses calculated from measured LDSA concentrations during an 8-h work day with the NOEL1/100, the one hundredth of no observed effect level, assigned for GBPs (0.11cm2g−1) and transition metal oxide particles (9×10−3cm2g−1). During the injection molding of PP car bumpers, LDSA concentrations varied from 23 to 39.8μm2cm−3. During 8-h exposure PP, particle doses were at a maximum of 1.4×10−3cm2g−1, which was a factor 100 lower compared to the NOEL1/100 assigned for GBPs. In the WCCo fine powder production plant, the LDSA concentrations were below 18.7μm2cm−3, which corresponds to the 8-h dose of 2.7×10−3cm2g−1. This is 3 times lower than the NOEL1/100 assigned for transition metal oxide particles. The LDSA concentrations were generally low compared to urban background levels of 44.2μm2cm−3 in European cities

First order risk assessment for nanoparticle inhalation exposure during injection molding of polypropylene composites and production of tungsten-carbide-cobalt fine powder based upon pulmonary inflammation and surface area dose

AbstractInhalation exposure to low toxicity and biodurable particles has shown to induce polymorphonuclear neutrophilia (PMN) in the lungs, which is a strong indicator for lung inflammation. Recently, Schmid and Stoeger (2016; http://dx.doi.org/10.1016/j.jaerosci.2015.12.006) reviewed mice and rat intratracheal instillation studies and assessed the relation between particles dry powder BET surface area dose and PMN influx for granular biodurable particles (GBPs) and transition metal oxides. In this study, we measured workers alveolar lung deposited surface area (LDSA) concentrations (μm2 cm−3) during injection molding of polypropylene (PP) car bumpers and production of tungsten-carbide-cobalt (WCCo) fine grade powder using diffusion chargers. First order risk assessment was performed by comparing the doses calculated from measured LDSA concentrations during an 8-h work day with the NOEL1/100, the one hundredth of no observed effect level, assigned for GBPs (0.11cm2g−1) and transition metal oxide particles (9×10−3cm2g−1). During the injection molding of PP car bumpers, LDSA concentrations varied from 23 to 39.8μm2cm−3. During 8-h exposure PP, particle doses were at a maximum of 1.4×10−3cm2g−1, which was a factor 100 lower compared to the NOEL1/100 assigned for GBPs. In the WCCo fine powder production plant, the LDSA concentrations were below 18.7μm2cm−3, which corresponds to the 8-h dose of 2.7×10−3cm2g−1. This is 3 times lower than the NOEL1/100 assigned for transition metal oxide particles. The LDSA concentrations were generally low compared to urban background levels of 44.2μm2cm−3 in European cities

Theoretical Background of Occupational-Exposure Models-Report of an Expert Workshop of the ISES Europe Working Group "Exposure Models"

On 20 October 2020, the Working Group "Exposure Models" of the Europe Regional Chapter of the International Society of Exposure Science (ISES Europe) organised an online workshop to discuss the theoretical background of models for the assessment of occupational exposure to chemicals. In this report, participants of the workshop with an active role before and during the workshop summarise the most relevant discussion points and conclusions of this well-attended workshop. ISES Europe has identified exposure modelling as one priority area for the strategic development of exposure science in Europe in the coming years. This specific workshop aimed to discuss the main challenges in developing, validating, and using occupational-exposure models for regulatory purposes. The theoretical background, application domain, and limitations of different modelling approaches were presented and discussed, focusing on empirical "modifying-factor" or "mass-balance-based" approaches. During the discussions, these approaches were compared and analysed. Possibilities to address the discussed challenges could be a validation study involving alternative modelling approaches. The wider discussion touched upon the close relationship between modelling and monitoring and the need for better linkage of the methods and the need for common monitoring databases that include data on model parameters.Peer reviewe

Exposure modelling in Europe : how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.Peer reviewe

Occupational dermal exposure to cyclophosphamide in Dutch hospitals: a pilot study. Ann Occup Hyg

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

The Validity and Applicability of Using a Generic Exposure Assessment Model for Occupational Exposure to Nano-Objects and Their Aggregates and Agglomerates

BACKGROUND: Control banding can be used as a first-tier assessment to control worker exposure to nano-objects and their aggregates and agglomerates (NOAA). In a second tier, more advanced modelling approaches are needed to produce quantitative exposure estimates. As currently no general quantitative nano-specific exposure models are available, this study evaluated the validity and applicability of using a generic exposure assessment model (the Advanced REACH Tool-ART) for occupational exposure to NOAA. METHOD: The predictive capability of ART for occupational exposure to NOAA was tested by calculating the relative bias and correlations (Pearson) between the model estimates and measured concentrations using a dataset of 102 NOAA exposure measurements collected during experimental and workplace exposure studies. RESULTS: Moderate to (very) strong correlations between the ART estimates and measured concentrations were found. Estimates correlated better to measured concentration levels of dust (r = 0.76, P < 0.01) than liquid aerosols (r = 0.51, P = 0.19). However, ART overestimated the measured NOAA concentrations for both the experimental and field measurements (factor 2-127). Overestimation was highest at low concentrations and decreased with increasing concentration. Correlations seemed to be better when looking at the nanomaterials individually compared to combined scenarios, indicating that nanomaterial-specific characteristics are not well captured within the mechanistic model of the ART. DISCUSSION: Although ART in its current state is not capable to estimate occupational exposure to NOAA, the strong correlations for the individual nanomaterials indicate that the ART (and potentially other generic exposure models) have the potential to be extended or adapted for exposure to NOAA. In the future, studies investigating the potential to estimate exposure to NOAA should incorporate more explicitly nanomaterial-specific characteristics in their models

Occupational Exposure to Nano-Objects and Their Agglomerates and Aggregates Across Various Life Cycle Stages; A Broad-Scale Exposure Study

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