Quantitative Structure Use Relationships: Highlights from a technical summit meeting.

The Quantitative Structure Use Relationship (QSUR) Summit, held on November 2-4, 2022, focused on advancing the development, refinement, and use of QSURs to support chemical substance prioritization and risk assessment and mitigation. QSURs utilize chemical structures to predict the function of a chemical within a formulated product or an industrial process. This presumed function can then be used to develop chemical use categories or other information necessary to refine exposure assessments. The invited expert meeting was attended by 38 scientists from Canada, Finland, France, the UK, and the USA, representing government, business, and academia, with expertise in exposure science, chemical engineering, risk assessment, formulation chemistry, and machine learning. Workshop discussions emphasized the importance of collection and sharing of data and quantification of relative chemical quantities to progress QSUR development. Participants proposed collaborative approaches to address key challenges, including mechanisms for aggregating information while still protecting proprietary product composition and other confidential business information. Discussions also led to proposals for applications beyond exposure and risk modeling, including sustainable formulation discovery. In addition, discussions continue to construct, conduct, and circulate case studies tied to various specific problem formulations in which QSURs supply or derive information on chemical functions, concentrations, and exposures.

An assessment of the ECETOC TRA Consumer tool performance as a screening level tool.

BACKGROUND: The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) Consumer tool was developed to fill in a methodology gap for a high throughput, screening level tool to support industry compliance with the European Union's Registration, Evaluation, Authorization, and Restriction of Chemicals (REACH) regulation. OBJECTIVE: To evaluate if the TRA Consumer tool has met its design of being a screening level tool (i.e., one which does not under-predict potential exposures). METHODS: The TRA Consumer tool algorithms and defaults were reviewed and performance benchmarked vs. other consumer models and/or empirical data. Findings from existing reviews of the TRA consumer tool were also considered and addressed. RESULTS: TRA predictions based on its default inputs exceeded measured exposures when available, typically by orders of magnitude, and were generally greater than or similar to those of other consumer exposure tools. For dermal exposure from articles, there was no evidence that a diffusivity approach would provide more appropriate exposure estimates than those of the TRA. When default values are refined using more specific data, the refined values must be considered holistically to reflect the situation being modeled as some parameters may be correlated. SIGNIFICANCE: This is the first evaluation of the ECETOC TRA consumer tool in its entirety, considering algorithms, input defaults, and associated predictions for consumer products and articles. The evaluation confirmed its design as a screening level tool. IMPACT STATEMENT: The ECETOC TRA Consumer tool has been widely applied to generate exposure estimates to support chemical registrations under the EU REACH regulation. This evaluation supports the appropriateness of the TRA as a screening level exposure assessment tool. It also warrants additional measurements of consumer exposure, especially for article use scenarios, to aid the development of consumer exposure tools and chemical risk assessment.

Exploring the utility of robots in exposure studies.

Obtaining valid, reliable quantitative exposure data can be a significant challenge for industrial hygienists, exposure scientists, and other health science professionals. In this proof-of-concept study, a robotic platform was programmed to perform a simple task as a plausible alternative to human subjects in exposure studies for generating exposure data. The use of robots offers several advantages over the use of humans. Research can be completed more efficiently and there is no need to recruit, screen, or train volunteers. In addition, robots can perform tasks repeatedly without getting tired allowing for collection of an unlimited number of measurements using different chemicals to assess exposure impacts from formulation changes and new product development. The use of robots also eliminates concerns with intentional human exposures while removing health research ethics review requirements which are time consuming. In this study, a humanoid robot was programmed to paint drywall, while volatile organic compounds were measured in air for comparison to model estimates. The measured air concentrations generally agreed with more advanced exposure model estimates. These findings suggest that robots have potential as a methodology for generating exposure measurements relevant to human activities, but without using human subjects.

Perspectives on advancing consumer product exposure models.

Predictive models are used to estimate exposures from consumer products to support risk management decision-making. These model predictions may be used alone in the absence of measured data or integrated with available exposure data. When different models are used, the resulting estimates of exposure and conclusions of risk may be disparate and the origin of these differences may not be obvious. This Perspectives Paper provides recommendations that could promote more systematic evaluation and a wider range of applicability of consumer product exposure models and their predictions, improve confidence in model predictions, and result in more accurate communication of consumer exposure model estimates. Key insights for the exposure science community to consider include: consistency in product descriptions, exposure routes, and scenarios; consistent and explicit definitions of exposure metrics; situation-dependent benefits from using one or multiple models; distinguishing between model algorithms and exposure factors; and corroboration of model predictions with measured data.

A review of measured bioaccumulation data on terrestrial plants for organic chemicals: Metrics, variability, and the need for standardized measurement protocols.

Quantifying the transfer of organic chemicals from the environment into terrestrial plants is essential for assessing human and ecological risks, using plants as environmental contamination biomonitors, and predicting phytoremediation effectiveness. Experimental data describing chemical uptake by plants are often expressed as ratios of chemical concentrations in the plant compartments of interest (e.g., leaves, shoots, roots, xylem sap) to those in the exposure medium (e.g., soil, soil porewater, hydroponic solution, air). These ratios are generally referred to as "bioconcentration factors" but have also been named for the specific plant compartment sampled, such as "root concentration factors," "leaf concentration factors," or "transpiration stream (xylem sap) concentrations factors." We reviewed over 350 articles to develop a database with 7049 entries of measured bioaccumulation data for 310 organic chemicals and 112 terrestrial plant species. Various experimental approaches have been used; therefore, interstudy comparisons and data-quality evaluations are difficult. Key exposure and plant growth conditions were often missing, and units were often unclear or not reported. The lack of comparable high-confidence data also limits model evaluation and development. Standard test protocols or, at a minimum, standard reporting guidelines for the measurement of plant uptake data are recommended to generate comparable, high-quality data that will improve mechanistic understanding of organic chemical uptake by plants. Environ Toxicol Chem 2018;37:21-33. © 2017 SETAC.

A quantitative screening-level approach to incorporate chemical exposure and risk into alternative assessment evaluations.

As the general public and retailers ask for disclosure of chemical ingredients in the marketplace, a number of hazard screening tools were developed to evaluate the so-called "greenness" of individual chemical ingredients and/or formulations. The majority of these tools focus only on hazard, often using chemical lists, ignoring the other part of the risk equation: exposure. Using a hazard-only focus can result in regrettable substitutions, changing 1 chemical ingredient for another that turns out to be more hazardous or shifts the toxicity burden to others. To minimize the incidents of regrettable substitutions, BizNGO describes "Common Principles" to frame a process for informed substitution. Two of these 6 principles are: "reduce hazard" and "minimize exposure." A number of frameworks have emerged to evaluate and assess alternatives. One framework developed by leading experts under the auspices of the US National Academy of Sciences recommended that hazard and exposure be specifically addressed in the same step when assessing candidate alternatives. For the alternative assessment community, this article serves as an informational resource for considering exposure in an alternatives assessment using elements of problem formulation; product identity, use, and composition; hazard analysis; exposure analysis; and risk characterization. These conceptual elements build on practices from government, academia, and industry and are exemplified through 2 hypothetical case studies demonstrating the questions asked and decisions faced in new product development. These 2 case studies-inhalation exposure to a generic paint product and environmental exposure to a shampoo rinsed down the drain-demonstrate the criteria, considerations, and methods required to combine exposure models addressing human health and environmental impacts to provide a screening level hazard and exposure (risk) analysis. This article informs practices for these elements within a comparative risk context to improve alternatives assessment evaluation and decision making. Integr Environ Assess Manag 2017;13:1007-1022. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Exploring Global Exposure Factors Resources for Use in Consumer Exposure Assessments.

This publication serves as a global comprehensive resource for readers seeking exposure factor data and information relevant to consumer exposure assessment. It describes the types of information that may be found in various official surveys and online and published resources. The relevant exposure factors cover a broad range, including general exposure factor data found in published compendia and databases and resources about specific exposure factors, such as human activity patterns and housing information. Also included are resources on exposure factors related to specific types of consumer products and the associated patterns of use, such as for a type of personal care product or a type of children's toy. Further, a section on using exposure factors for designing representative exposure scenarios is included, along with a look into the future for databases and other exposure science developments relevant for consumer exposure assessment.

Assessment of chemical coexposure patterns based upon phthalate biomonitoring data within the 2007/2008 National Health and Nutrition Examination Survey.

As regulatory initiatives increasingly call for an understanding of the cumulative risks from chemical mixtures, evaluating exposure data from large biomonitoring programs, which may inform these cumulative risk assessments, will improve the understanding of occurrence and patterns of coexposures. Here we have analyzed the urinary metabolite data for six phthalates (di-butyl phthalate; di-isobutyl phthalate; butyl-benzyl phthalate; bis(2-ethylhexyl) phthalate; di-isononyl phthalate; and di-isodecyl phthalate) in the 2007/2008 National Health and Nutrition Examination Survey (NHANES) data set. For the total data set (N=2604), the co-occurrence of multiple phthalates at the upper percentile of exposure was infrequent. There were no individuals in the NHANES sample who were exposed to >95th percentiles for all six phthalates. For 75% of individuals, none of the six phthalates were above the 95th percentile of their respective exposure distributions. These data suggest that high exposure to multiple phthalates is infrequent in the NHANES population. This analysis solely focused on the pattern of contribution of individual phthalates to total exposure. It did not address the pattern of contribution to potential risk. The approach presented could potentially be used to provide insight into understanding the coexposure patterns for other chemicals.

European solvent industry group generic exposure scenario risk and exposure tool.

The European Solvents Industry Group (ESIG) Generic Exposure Scenario (GES) Risk and Exposure Tool (EGRET) was developed to facilitate the safety evaluation of consumer uses of solvents, as required by the European Union Registration, Evaluation and Authorization of Chemicals (REACH) Regulation. This exposure-based risk assessment tool provides estimates of both exposure and risk characterization ratios for consumer uses. It builds upon the consumer portion of the European Center for Ecotoxicology and Toxicology of Chemicals (ECETOC) Targeted Risk Assessment (TRA) tool by implementing refinements described in ECETOC TR107. Technical enhancements included the use of additional data to refine scenario defaults and the ability to include additional parameters in exposure calculations. Scenarios were also added to cover all frequently encountered consumer uses of solvents. The TRA tool structure was modified to automatically determine conditions necessary for safe use. EGRET reports results using specific standard phrases in a format consistent with REACH exposure scenario guidance, in order that the outputs can be readily assimilated within safety data sheets and similar information technology systems. Evaluation of tool predictions for a range of commonly encountered consumer uses of solvents found it provides reasonable yet still conservative exposure estimates.

Multimedia modeling of human exposure to chemical substances: the roles of food web biomagnification and biotransformation.

The Risk Assessment IDentification And Ranking (RAIDAR) model is refined to calculate relative human exposures as expressed by total intake, intake fraction (iF), and total body burden (TBB) metrics. The RAIDAR model is applied to three persistent organic pollutants (POPs) and six petrochemicals using four mode-of-entry emission scenarios to evaluate the effect of metabolic biotransformation estimates on human exposure calculations. When biotransformation rates are assumed to be negligible, daily intake and iFs for the nine substances ranged over six orders of magnitude and TBBs ranged over 10 orders of magnitude. Including biotransformation estimates for fish, birds, and mammals reduced substance-specific daily intake and iF by up to 4.5 orders of magnitude and TBB by more than eight orders of magnitude. The RAIDAR iF calculations are compared to the European Union System for the Evaluation of Substances (EUSES) model iF calculations and differences are discussed, especially the treatment of food web bioaccumulation. Model selection and application assumptions result in different rankings of human exposure potential. These results suggest a need to critically consider model selection and to include reliable biotransformation rate estimates when assessing relative human exposure and ranking substances for priority setting. Recommendations for further model evaluations and revisions are discussed.