Models to Characterize Exposures to Manufactured Nanomaterials in OECD

by Vladimir Murashov, Ph.D. and John Howard, M.D.

Mosaic of imagesIntroduction

The early 2000s witnessed an explosive growth of  research investments into nanotechnology. This new technology promised enhanced products and new nanomaterials with improved performance, but also raised public concerns about how safe they were for the environment, workers and consumers. Initially, the main research efforts were directed at identifying  the hazards presented by nanomaterials, while investigations into the specifics of exposure risks lagged behind. Given the growing variety of exposure situations to nanomaterials of concern, a critical need for internationally-accepted exposure models for use in nanomaterial risk assessments became broadly recognized (OECD 2017). This need was addressed by recently completed international projects described in this article and conducted under the umbrella of the Organization for Economic Cooperation and Development (OECD).

Steering Group on Exposure Measurement and Mitigation of Nanomaterials

OECD was among first international organizations to address safety of manufactured nanomaterials. In 2006, it set up the Working Party on Manufactured Nanomaterials (WPMN) to promote safe and responsible introduction of manufactured nanomaterials into commerce. In 2007, WPMN formalized a Steering Group on Exposure Measurements and Exposure Mitigation (SG8). SG8 was tasked with handling the exposure component of the risk assessment and risk management program for manufactured nanomaterials (Murashov et al. 2009). 

Since then, the U.S. National Institute for Occupational Safety and Health (NIOSH) has led Steering Group 8 (SG8). SG8 initially focused on occupational exposure, since it is widely recognized that workers are at greater risk of exposure and suffer disproportionately from the adverse human health effects associated with emerging technologies. SG8 conducted a number of case-studies to characterize workplace exposures to select nanomaterials such as carbon nanotubes, nanoscale silver and nanoscale gold and developed recommended approaches for emission and exposure assessments. In 2014, SG8 expanded its activities into nanomaterial exposures in the environment and to  consumers. 

To date, SG8 has been one of the most productive WPMN steering groups. SG8 has authored eighteen OECD publications providing internationally accepted guidance on exposure characterization and exposure mitigation for manufactured nanomaterials and has hosted six workshops that brought together experts to  advance this field. One of those publications, Harmonised Tiered Approach to Measure and Assess the Potential Exposure to Airborne Emissions of Engineered Nano-objects and their Agglomerates at Workplaces (OECD 2015), is referenced in the OECD legal instrument on the Safety Testing and Assessment of Manufactured Nanomaterials as a recommended tool for exposure assessment (OECD 2013).

On December 2, 2021, the SG8 organized a webinar to present four recent publications on models to characterize exposures to manufactured nanomaterials (a video recording of the webinar can be found here and here). 

These four publications, numbered 98 through 101 in the OECD Series on the Safety of Manufactured Nanomaterials, describe results of SG8 projects aimed at evaluating existing models to characterize exposures for nanomaterials in three populations: (1) workers; (2) consumers; and (3) the environment. Experts from Health Canada, Environment and Climate Change Canada, the National Research Center for the Working Environment in Denmark and NIOSH led these projects. Many other OECD member countries actively contributed to the projects making this an international effort.

The need for exposure models, whose performance has been evaluated and which are internationally accepted for conducting risk assessments of manufactured nanomaterials, prompted these SG8 projects. For example, Scott-Fordsmand et al. (2021) highlighted the lack of consensus on exposure assessment and modeling approaches. Additionally, Nielsen et al. (2021) reviewed available test guidelines and models for compliance with technical data requirements for nanomaterials under European chemical safety regulations including REACH and concluded that a need exists for further development of nanomaterial-specific environmental exposure modeling. While several models have been developed to characterize exposure to manufactured nanomaterials, choosing and using specific models in risk assessments have remained a challenge due to the lack of studies confirming the performance of these models. Lack of environmental exposure data made it “impossible to validate either the material flow or environmental fate models, significantly limiting their utility” (Johnston et al. 2020).

Nanomaterial Exposure Models

Focusing on workers, consumers, and the environment, the SG8 exposure modeling projects had three goals. First was the compilation and prioritization of available models for nanomaterial exposure characterizations. Second was a functional assessment and statistical analysis of a prioritized selection of the models. Third was a performance assessment of the models. 

Environment Models. A search of environment exposure models found 24 models, including: Material Flow Analysis (MFA) models, Environmental Fate Models (EFM), and spatially explicit river models (OECD 2021, No. 98). Project leaders organized the models based on set priority criteria including appropriate model domain, scope, time range and availability of default values and user-overrides. The top ten environmental models were further assessed based on installation, user requirements, data requirements, input parameters, model outputs, assumptions made, algorithms used, statistical uncertainty, and systematic sensitivity analyses. Based on these assessments, the data supports use of three models for the environment (OECD 2021, No. 98). These are as follows: (1) Dynamic Probabilistic Material Flow Analysis, which is a Material Flow Analysis model suitable to estimate nanomaterial flows from the techno-sphere to environmental compartments for a variety of scenarios; (2) SimpleBox4Nano, which is an Environmental Fate Model suitable to estimate screening level estimates of nanomaterial concentrations in environmental compartments based on several nanomaterial specific pseudo-first order kinetic processes; and (3) NanoDUFLOW, which is a river model implementation of a specific river system, but could be modified to model any river system and could be used in cases where the risk of exposure is high to provide more reliable site-specific estimations of nanomaterial concentrations in river systems. Major benefits of using these exposure models in risk assessments of nanomaterials include their user-friendliness, reasonable level of output variance, predictable sensitivity response and transparency with respect to input parameters and calculations which facilitates implementation of new scenarios and compartments. Furthermore, a report on the assessment highlighted the need to generate experimental data about all input parameters. In addition, it identifies the need to use several scenarios to conduct more in-depth uncertainty and sensitivity analyses of environmental exposure models and to evaluate their performance.

Worker and Consumer Models. A search of exposure models for worker and consumer exposures found 32 models (OECD 2021, No. 99), of which fourteen models can be applied to both worker and consumer scenarios. Five models were eliminated because they were not nano-specific. After functional analyses, only nineteen models underwent sensitivity analysis (eight models were not suitable for sensitivity analysis). Based on the sensitivity analysis results, project leaders completed performance testing on the models to assess the predictive capability by comparing the outputs with exposure measurement data. 

Worker Models. For worker exposures, fifteen models were tested. Eight out of fifteen occupational exposure models were adequate and followed the two main project criteria (Spearman correlation between output and measured exposure > 0.6 and underprediction < 10% of the total comparisons). These tools are BIORIMA, Stoffenmanager Nano, ENAE-CPSC, LiCARA nanoSCAN, NanoSafer, GUIDEnano, Swiss Precautionary Matrix and ConsExpo Nano (OECD 2021, No. 100). 

Consumer Models. For consumer exposures, seven models were tested. Among the seven consumer exposure models, only four (ENAE-CPSC, Boxall et al. 2007, GUIDEnano, and ConsExpo Nano) were found suitable for quantifying the exposure of manufactured nanomaterials in consumer spray scenarios such as use or application of products containg nanomaterials that could be aerosolized (e.g. paint or sunscreen) (OECD 2021, No 101). Stoffenmanager Nano and Swiss Precautionary Matrix can be applied to rank different manufactured nanomaterials based on their exposure potential, but not to perform quantitative predictions. NanoSafer can be used to estimate acute air concentration for consumer spray scenarios. The report on the performance of consumer exposure models identifies a lack of measurement data for scenarios resulting from a lack of research studies and supports using measured data in developing, evaluating, and implementing models to estimate exposure to manufactured nanomaterials for consumer exposure scenarios. 

Next Steps

The results of these SG8 projects can help guide private and public sector risk assessment and risk management professionals to choose adequate models to identify exposure to manufactured nanomaterials. However, some challenges remain and include: (1) there is a paucity of high-quality experimental exposure data and a very limited number of exposure scenarios hindering model performance testing;  (2) most existing models tend to overestimate exposure due to the application of the precautionary approach in the absence of sufficient data; and (3) existing models do not account for agglomeration and aggregation of nanomaterials. Addressing these challenges will require effective international collaborations, and OECD SG8 continues to provide a unique platform for such collaborations. SG8 plans to continue with its activities, building on the outputs of exposure model projects and providing further authoritative guidance on the use of exposure models for specific exposure situations. It also initiated two new projects aimed at identification of factors that can be measured to evaluate exposure to nanomaterials in the workplace and at developing guidance on release tests for nanomaterials.

For its part, NIOSH supports international activities aimed at improving safety and health of workers handling manufactured nanomaterials and nano-enabled products. In its strategic plan for 2018-2025 (NIOSH 2019) Activity Goal 3.4.3 calls for NIOSH to “participate in and lead the development of ISO and WPMN activities and global standards on occupational safety and health for nanotechnology”. The plan also describes NIOSH support of exposure modeling activities by SG8 through a multi-pronged approach. In addition, the NIOSH plan identifies three activity goals directly contributing to advancing exposure models: (1) Activity Goal 2.4.4 “Develop and improve methods and approaches (including direct-reading and time-integrated sampling) for assessing workplace exposures to [engineered nanomaterials]” will generate real world exposure data for exposure model evaluations; (2) Activity Goal 2.4.7 “Conduct research to quan¬tify (correlate) the influence of dustiness on the potential for worker inhalation exposure for a range of nanoscale powders and handling tasks” will refine contribution of the dustiness component in exposure models; and (3) Activity Goal 2.6.1 “Create a harmonized data¬base to share exposure measurement, control, and epidemiologic data” will facilitate evaluation of exposure models. 

Ongoing and combined efforts by the international community for developing and recommending specific models for specific nanomaterial exposure situations will continue to contribute to the safety and health of workers, consumers, and the environment both now and in the future.

Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health.

References

  • Boxall et al., Current and future predicted environmental exposure to engineered nanoparticles, Central Science Laboratory, 2007.
  • Johnston et al., NanoImpact 2020, 18, 100219.
  • Murashov et al., J. Nanopart. Res. 2009, 11, 1587.
  • Nielsen et al., Environ. Sci.: Nano 2021, 8, 731.
  • NIOSH, Continuing to protect the nanotechnology workforce: NIOSH nanotechnology research plan for 2018–2025, DHHS (NIOSH) Publication 2019-116, 2019.
  • OECD, Consumer and Environmental Exposure to Manufactured Nanomaterials. Information used to characterize exposures: Analysis of a Survey, Series on the Safety of Manufactured Nanomaterials No 84, 2017.
  • OECD, Evaluation of Tools and Models for Assessing Environmental Exposure to Manufactured Nanomaterials - Functional Assessment and Statistical Analysis of Nano-Specific Environmental Exposure Tools and Models, Series on the Safety of Manufactured Nanomaterials No 98, 2021.
  • OECD, Evaluation of Tools and Models for Assessing Occupational and Consumer Exposure to Manufactured Nanomaterials - Part I:  Compilation of tools/models and analysis for further evaluation, Series on the Safety of Manufactured Nanomaterials No 99, 2021.
  • OECD, Evaluation of Tools and Models for Assessing Occupational and Consumer Exposure to Manufactured Nanomaterials - Part II: Performance testing results of tools/models for occupational exposure, Series on the Safety of Manufactured Nanomaterials No 100, 2021.
  • OECD, Evaluation of Tools and Models for Assessing Occupational and Consumer Exposure to Manufactured Nanomaterials - Part III: Performance testing results of tools/models for consumer exposure, Series on the Safety of Manufactured Nanomaterials No 101, 2021.
  • OECD, Harmonised Tiered Approach to Measure and Assess the Potential Exposure to Airborne Emissions of Engineered Nano-objects and their Agglomerates at Workplaces, Series on the Safety of Manufactured Nanomaterials No 55, 2015.
  • OECD, Recommendation of the Council on the Safety Testing and Assessment of Manufactured
  • Nanomaterials, OECD/LEGAL/0400, 2013.
  • Scott-Fordsmand et al., Nature Nanotech. 2021, 16, 608.
     

Biographies of the authors

Vladimir Murashov is a Senior Scientist in the Office of the Director of the U.S. National Institute for Occupational Safety in Washington, D.C., USA. He received his Ph.D. in Chemistry from Dalhousie University in Halifax, Canada in 1998. He completed his postdoctoral research in University of British Columbia in Vancouver, Canada in 2001. He leads nanotechnology safety groups in International Organization for Standardization and Organization for Economic Cooperation and Development.

John Howard is the Director of the National Institute for Occupational Safety and Health, and the Administrator of the World Trade Center Health Program in the U.S. Department of Health and Human Services. Prior to his appointment as NIOSH Director and WTC Health Program Administrator, Dr. Howard served as Chief of the Division of Occupational Safety and Health in the State of California’s Labor and Workforce Development Agency from 1991 through 2002.

 

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