Tiered Exposure Assessment Research Articles

The Path to UVCBEcological Risk Assessment: Grappling with Substance Characterization.

Substances of unknown or variable composition, complex reaction products, and biological materials (UVCBs) pose a unique challenge to regulators and to product registrants, who are required to characterize their fate, exposure, hazard, and potential risks to human health and the environment. To address these challenges and ensure an efficient and fit-for-purpose process, it is proposed that the ecological risks of UVCBs be assessed following a tiered strategy. The development of this approach required exploring how substance composition ties into hazard and exposure information and determining the extent to which a UVCB needs to be characterized to ensure a robust risk assessment. The present study highlights the key aspects of this new method. It presents how a tiered substance characterization approach can be integrated into broader UVCB risk-assessment schemes to encourage an examination of data needs before a full substance characterization is performed. The first tier of the characterization process, Tier 0, is a fundamental step that includes data from basic, lower-resolution compositional analyses. Tier 0 assessments can be used to inform hazard and exposure for any substance of interest. The need for more sophisticated, higher-tier characterization is determined by the level of uncertainty of the risk assessment. The next step will integrate a tiered exposure assessment into the characterization scheme featured in the present study, to create a more complete risk-assessment framework. Environ Toxicol Chem 2022;41:2649-2657. © 2022 Her Majesty the Queen in Right of Canada, Health and Environmental Sciences Institute and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. Reproduced with the permission of the Minister of Environment and Climate Change Canada.

Characterizing and quantifying chemical ingredient use in consumer products between two separate databases and implications for environmental and human health exposure

Assessing chemical exposure in home and personal care products (HPCPs) represents an important data need. Key challenges to the assessment are related to limited knowledge in quantifying and characterizing the weight-fraction inclusion level and functionality of chemicals in HPCPs. Publicly available tools have been developed to address these challenges, such as the Chemical and Products database (CPDat). This study aims to evaluate the relative performance of CPDat by comparing estimates of weight-fraction inclusion level and functionality to other relevant data sources. Specifically, estimates obtained from CPDat are evaluated and compared with estimates obtained from marketing analytic data, using Euromonitor Passport for 31 commonly used chemicals found in HPCPs. The results obtained from this exercise suggest relatively good agreement between each of the methods for 10 chemicals (ρ = 0.92; P-value =0.02). When considering all 31 chemical ingredients, however, the correlation observed is generally poor (ρ = 0.46; P-value = 0.1), which is attributed to differences in how the underlying data are obtained for each method. With an emphasis on obtaining data based on mining datasheets for individual products, the application of CPDat is suggested to be useful for higher tiers of assessment, with data obtained from marketing analytics providing valuable input to exposure-based screening models. The insight gained from this study can be used to help guide the appropriate use of data obtained from different sources within a tiered exposure assessment.

A risk assessment framework for self-management of poorly soluble low toxic nanomaterials

The safety of nanomaterials is still being debated and the risk should be assessed using the latest available information. As for poorly soluble low toxic (PSLT) nanomaterials, the US National Institute for Occupational Safety and Health estimated the occupational exposure limit (OEL) for titanium dioxide (TiO2) based on a particle surface area (SA) metric. The Organisation for Economic Co-operation and Development (OECD) suggested a tiered exposure assessment approach. This article proposes a risk assessment framework for self-management of PSLT particles. Lung burden (described in SA units), which had positive correlation with low observed adverse effect levels for PSLT particles, is chosen as the dose metric. In-house OEL is determined for individual workplaces. For materials with limited data, we suggest evaluating in-house OEL by utilizing the no observed adverse effect level (NOAEL) for TiO2, as a representative PSLT nanomaterial. As for the exposure assessment, workplace concentration is first measured with simple equipment (ex. optical particle counter, OPC), and respirator performance is taken into account if it is unavoidable as a last resort. This framework enables efficient risk assessment for PSLT particles by assuming worst cases for each step, and considering the particle characteristics and operational conditions in each workplace.

Evaluation of Exposure Assessment Tools under REACH: Part II-Higher Tier Tools.

Stoffenmanager®v4.5 and Advanced REACH Tool (ART) v1.5, two higher tier exposure assessment tools for use under REACH, were evaluated by determining accuracy and robustness. A total of 282 exposure measurements from 51 exposure situations (ESs) were collected and categorized by exposure category. In this study, only the results of liquids with vapor pressure (VP) > 10 Pa category having a sufficient number of exposure measurements (n = 251 with 42 ESs) were utilized. In addition, the results were presented by handling/activity description and input parameters for the same exposure category. It should be noted that the performance results of Stoffenmanager and ART in this study cannot be directly compared for some ESs because ART allows a combination of up to four subtasks (and nonexposed periods) to be included, whereas the database for Stoffenmanager, separately developed under the permission of the legal owner of Stoffenmanager, permits the use of only one task to predict exposure estimates. Thus, it would be most appropriate to compare full-shift measurements against ART predictions (full shift including nonexposed periods) and task-based measurements against task-based Stoffenmanager predictions. For liquids with VP > 10 Pa category, Stoffenmanager®v4.5 appeared to be reasonably accurate and robust when predicting exposures [percentage of measurements exceeding the tool's 90th percentile estimate (%M > T) was 15%]. Areas that could potentially be improved include ESs involving the task of handling of liquids on large surfaces or large work pieces, allocation of high and medium VP inputs, and absence of local exhaust ventilation input. Although the ART's median predictions appeared to be reasonably accurate for liquids with VP > 10 Pa, the %M > T for the 90th percentile estimates was 41%, indicating that variance in exposure levels is underestimated by ART. The %M > T using the estimates of the upper value of 90% confidence interval (CI) of the 90th percentile estimate (UCI90) was considerably reduced to 18% for liquids with VP > 10 Pa. On the basis of this observation, users might be to consider using the upper limit value of 90% CI of the 90th percentile estimate for predicting reasonable worst case situations. Nevertheless, for some activities and input parameters, ART still shows areas to be improved. Hence, it is suggested that ART developers review the assumptions in relation to exposure variability within the tool, toward improving the tool performance in estimating percentile exposure levels. In addition, for both tools, only some handling/activity descriptions and input parameters were considered. Thus, further validation studies are still necessary.

Modelling ecological and human exposure to POPs in Venice lagoon – Part II: Quantitative uncertainty and sensitivity analysis in coupled exposure models

The study is focused on applying uncertainty and sensitivity analysis to support the application and evaluation of large exposure models where a significant number of parameters and complex exposure scenarios might be involved. The recently developed MERLIN-Expo exposure modelling tool was applied to probabilistically assess the ecological and human exposure to PCB 126 and 2,3,7,8-TCDD in the Venice lagoon (Italy). The ‘Phytoplankton’, ‘Aquatic Invertebrate’, ‘Fish’, ‘Human intake’ and PBPK models available in MERLIN-Expo library were integrated to create a specific food web to dynamically simulate bioaccumulation in various aquatic species and in the human body over individual lifetimes from 1932 until 1998. MERLIN-Expo is a high tier exposure modelling tool allowing propagation of uncertainty on the model predictions through Monte Carlo simulation. Uncertainty in model output can be further apportioned between parameters by applying built-in sensitivity analysis tools. In this study, uncertainty has been extensively addressed in the distribution functions to describe the data input and the effect on model results by applying sensitivity analysis techniques (screening Morris method, regression analysis, and variance-based method EFAST). In the exposure scenario developed for the Lagoon of Venice, the concentrations of 2,3,7,8-TCDD and PCB 126 in human blood turned out to be mainly influenced by a combination of parameters (half-lives of the chemicals, body weight variability, lipid fraction, food assimilation efficiency), physiological processes (uptake/elimination rates), environmental exposure concentrations (sediment, water, food) and eating behaviours (amount of food eaten). In conclusion, this case study demonstrated feasibility of MERLIN-Expo to be successfully employed in integrated, high tier exposure assessment.

Airborne engineered nanomaterials in the workplace—a review of release and worker exposure during nanomaterial production and handling processes

For exposure and risk assessment in occupational settings involving engineered nanomaterials (ENMs), it is important to understand the mechanisms of release and how they are influenced by the ENM, the matrix material, and process characteristics. This review summarizes studies providing ENM release information in occupational settings, during different industrial activities and using various nanomaterials. It also assesses the contextual information — such as the amounts of materials handled, protective measures, and measurement strategies — to understand which release scenarios can result in exposure. High-energy processes such as synthesis, spraying, and machining were associated with the release of large numbers of predominantly small-sized particles. Low-energy processes, including laboratory handling, cleaning, and industrial bagging activities, usually resulted in slight or moderate releases of relatively large agglomerates. The present analysis suggests that process-based release potential can be ranked, thus helping to prioritize release assessments, which is useful for tiered exposure assessment approaches and for guiding the implementation of workplace safety strategies. The contextual information provided in the literature was often insufficient to directly link release to exposure. The studies that did allow an analysis suggested that significant worker exposure might mainly occur when engineering safeguards and personal protection strategies were not carried out as recommended.

Potential for MERLIN-Expo, an advanced tool for higher tier exposure assessment, within the EU chemical legislative frameworks

MERLIN-Expo merges and integrates advanced exposure assessment methodologies, allowing the building of complex scenarios involving several pollution sources and targets. The assessment of exposure and risks to human health from chemicals is of major concern for policy and ultimately benefits all citizens. The development and operational fusion of the advanced exposure assessment methodologies envisaged in the MERLIN-Expo tool will have a significant impact in the long term on several policies dealing with chemical safety management. There are more than 30 agencies in Europe related to exposure and risk evaluation of chemicals, which have an important role in implementing EU policies, having especially tasks of technical, scientific, operational and/or regulatory nature. The main purpose of the present paper is to introduce MERLIN-Expo and to highlight its potential for being effectively integrated within the group of tools available to assess the risk and exposure of chemicals for EU policy. The main results show that the tool is highly suitable for use in site-specific or local impact assessment, with minor modifications it can also be used for Plant Protection Products (PPPs), biocides and REACH, while major additions would be required for a comprehensive application in the field of consumer and worker exposure assessment.

Advanced REACH Tool (ART): Overview of Version 1.0 and Research Needs

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 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.

Use of read-across and tiered exposure assessment in risk assessment under REACH – A case study on a phase-in substance

REACH requests the exploration of alternative strategies for hazard identification before resorting to ( in vivo) testing. Here, we combined read-across as non-testing strategy with a tiered exposure assessment for the risk characterisation of 1-methoxypropan-2-ol (PGME) as a representative for phase-in substances to be registered under REACH. Read-across from the selected source substances provided data which were comparable with experimental data available for target substance PGME, resulting in a realistic starting point for both qualitative and quantitative risk assessment. Greater variability was observed in the exposure estimates from a first Tier model (ECETOC TRA) or less conservative further Tier models (Stoffenmanager; RISKOFDERM), when these results were compared with results from a data-rich approach using measured data. When safe use of chemicals cannot be demonstrated with these approaches, refinement can be introduced in the estimation of hazard and exposure, or both. In view of the variability associated with exposure modeling, it may often add more value to invest in realistic exposure data than in toxicity studies, apart from animal welfare considerations.

Protection of non-human biota against radiation in freshwater—Effect of time dependence in tiered exposure assessment

The ERICA's European framework that have been proposed to assess the exposure of biota to radionuclides is based on tiered approach: the Tier 1 assessment is based on equilibrium assumptions (constant radioactive releases over time, equilibrium at the interfaces water-suspended matter and water-biota); the Tier 2 assessment allows to use time-dependent and site-specific data to perform a more precise evaluation. The objective of this paper was to compare these two tiers in the context of routine releases from nuclear power plants in freshwater ecosystem. The Loire River where 14 nuclear power plants (NPPs) operate was chosen as a case study and the transport of 60Co in the river, its partition between water and suspended particles and its bioaccumulation was calculated under equilibrium and time-dependent assumptions respectively. Using this case study allowed to quantify the overpredictions linked to conservatisms assumed in Tier 1. Recommendations were identified on when a Tier 2 approach is actually needed.

Evaluation of a Lower Tier Exposure Assessment Model for Veterinary Medicines

Veterinary antibiotics are used in large quantities in the European Union, and one of the key environmental exposure routes is via the application of manure containing excreted antibiotics to arable land as fertilizer. It is a legal requirement to assess the environmental risk of veterinary medicines, and this is done in two stages. A key decision parameter in phase I of these assessments is the predicted environmental concentration (PEC) in soil, and if a trigger value of 100 microg/kg is exceeded, then further phase II studies on the fate, behavior, and effects are carried out. A widely used model to calculate manure and soil PECs is the Uniform Approach. This study evaluated the Uniform Approach in two ways: first, by reviewing existing data, addressing data gaps by performing degradation studies, and then calculating soil and manure PECs for the veterinary antibiotics sulfachloropyridazine, oxytetracycline, and tylosin applied to arable land via liquid pig manure and comparing these data with the results from two field-scale fate studies; second, by collating monitoring data and making a comparison with modeled data. The data comparisons indicated that the Uniform Approach model performed conservatively, with initial PECs being up to 2 orders of magnitude greater than measured environmental concentrations, providing confidence in the use of the model in the risk assessment process, although the assumption of first-order degradation kinetics in the model may underestimate the environmental persistence of veterinary antibiotics.

Exposure assessment for terrestrial non-target arthropods

Concerns regarding the potential of pesticides to harm terrestrial non-target arthropod populations have led to the increased use of ecotoxicological test systems for terrestrial Non-target Arthropod risk assessment. Whilst some useful guidance on terrestrial invertebrate test systems is available, there are significant gaps in guidance for terrestrial non-target arthropod exposure estimates. The typical exposure in the standard test systems is by application of the test substance at the field rate (i. e. gram substance per hectare field) on to a two dimensional surface. However, under field conditions such a spray deposit will be diluted over the total available 3-Dimensional plant and soil surface. The recommendation is to use published leaf area index and crop interception values to standardize terrestrial dilution factors, which can then be used to predict exposure on a 3-Dimensional plant surface. Based on average crop/time specific LAI data for 26 crops, a surrogate off-crop dilution factor of 12 was calculated which can be used to convert 2-Dimensional spray drift exposure to 3-Dimensional off-crop plant surface exposure. Another significant terrestrial exposure guidance gap is how to calculate predicted environmental concentrations (PECs) for multiple application products. Based on spray interval and half-life data from 32 representative multiple application plant protection products, the typical worst-case PECs for accumulation of residues were calculated after up to 8 applications. These data showed that Multiple Application Factors (MAFs = accumulated PEC/initial PEC), increased from 1 to 3.5 after 1 to 8 applications, respectively. Finally, overall 90th percentile spray deposit values have been proposed for deriving off-crop multiple applications PECs (1 to 8 applications) based on published spray drift data. The recommended equations for terrestrial exposure assessment include the use of:-application rate, the 90th percentile drift value, the multiple application factors (MAF) and the standard dilution factor (for 3-Dimensional plant surface). This proposed terrestrial non-target arthropod exposure scheme is comparable with other first tier exposure assessment schemes eg aquatic exposure assessment.