The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry.

Background: The NORMAN Association (https://www.norman-network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https://zenodo.org/communities/norman-sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox.epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-network.com/nds/SLE/). Supplementary Information: The online version contains supplementary material available at 10.1186/s12302-022-00680-6.

IVIVE: Facilitating the Use of In Vitro Toxicity Data in Risk Assessment and Decision Making.

During the past few decades, the science of toxicology has been undergoing a transformation from observational to predictive science. New approach methodologies (NAMs), including in vitro assays, in silico models, read-across, and in vitro to in vivo extrapolation (IVIVE), are being developed to reduce, refine, or replace whole animal testing, encouraging the judicious use of time and resources. Some of these methods have advanced past the exploratory research stage and are beginning to gain acceptance for the risk assessment of chemicals. A review of the recent literature reveals a burst of IVIVE publications over the past decade. In this review, we propose operational definitions for IVIVE, present literature examples for several common toxicity endpoints, and highlight their implications in decision-making processes across various federal agencies, as well as international organizations, including those in the European Union (EU). The current challenges and future needs are also summarized for IVIVE. In addition to refining and reducing the number of animals in traditional toxicity testing protocols and being used for prioritizing chemical testing, the goal to use IVIVE to facilitate the replacement of animal models can be achieved through their continued evolution and development, including a strategic plan to qualify IVIVE methods for regulatory acceptance.

Exploring current read-across applications and needs among selected U.S. Federal Agencies.

Read-across is a well-established data gap-filling technique applied for regulatory purposes. In US Environmental Protection Agency's New Chemicals Program under TSCA, read-across has been used extensively for decades, however the extent of application and acceptance of read-across among U.S. federal agencies is less clear. In an effort to build read-across capacity, raise awareness of the state of the science, and work towards a harmonization of read-across approaches across U.S. agencies, a new read-across workgroup was established under the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). This is one of several ad hoc groups ICCVAM has convened to implement the ICCVAM Strategic Roadmap. In this article, we outline the charge and scope of the workgroup and summarize the current applications, tools used, and needs of the agencies represented on the workgroup for read-across. Of the agencies surveyed, the Environmental Protection Agency had the greatest experience in using read-across whereas other agencies indicated that they would benefit from gaining a perspective of the landscape of the tools and available guidance. Two practical case studies are also described to illustrate how the read-across approaches applied by two agencies vary on account of decision context.

Interpreting Mobile and Handheld Air Sensor Readings in Relation to Air Quality Standards and Health Effect Reference Values: Tackling the Challenges.

The US Environmental Protection Agency (EPA) and other federal agencies face a number of challenges in interpreting and reconciling short-duration (seconds to minutes) readings from mobile and handheld air sensors with the longer duration averages (hours to days) associated with the National Ambient Air Quality Standards (NAAQS) for the criteria pollutants-particulate matter (PM), ozone, carbon monoxide, lead, nitrogen oxides, and sulfur oxides. Similar issues are equally relevant to the hazardous air pollutants (HAPs) where chemical-specific health effect reference values are the best indicators of exposure limits; values which are often based on a lifetime of continuous exposure. A multi-agency, staff-level Air Sensors Health Group (ASHG) was convened in 2013. ASHG represents a multi-institutional collaboration of Federal agencies devoted to discovery and discussion of sensor technologies, interpretation of sensor data, defining the state of sensor-related science across each institution, and provides consultation on how sensors might effectively be used to meet a wide range of research and decision support needs. ASHG focuses on several fronts: improving the understanding of what hand-held sensor technologies may be able to deliver; communicating what hand-held sensor readings can provide to a number of audiences; the challenges of how to integrate data generated by multiple entities using new and unproven technologies; and defining best practices in communicating health-related messages to various audiences. This review summarizes the challenges, successes, and promising tools of those initial ASHG efforts and Federal agency progress on crafting similar products for use with other NAAQS pollutants and the HAPs. NOTE: The opinions expressed are those of the authors and do not necessary represent the opinions of their Federal Agencies or the US Government. Mention of product names does not constitute endorsement.

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.

Isocyanates and human health: multistakeholder information needs and research priorities.

OBJECTIVES: To outline the knowledge gaps and research priorities identified by a broad base of stakeholders involved in the planning and participation of an international conference and research agenda workshop on isocyanates and human health held in Potomac, Maryland, in April 2013. METHODS: A multimodal iterative approach was used for data collection including preconference surveys, review of a 2001 consensus conference on isocyanates, oral and poster presentations, focused break-out sessions, panel discussions, and postconference research agenda workshop. RESULTS: Participants included representatives of consumer and worker health, health professionals, regulatory agencies, academic and industry scientists, labor, and trade associations. CONCLUSIONS: Recommendations were summarized regarding knowledge gaps and research priorities in the following areas: worker and consumer exposures; toxicology, animal models, and biomarkers; human cancer risk; environmental exposure and monitoring; and respiratory epidemiology and disease, and occupational health surveillance.

The National Library of Medicine's (NLM) Hazardous Substances Data Bank (HSDB): background, recent enhancements and future plans.

The National Library of Medicine's (NLM) Division of Specialized Information Services (SIS) Toxicology and Environmental Health Information Program is responsible for the management of the online Hazardous Substances Data Bank (HSDB). HSDB, a part of NLM's Toxicology Data Network (TOXNET(®)), is a file of chemical/substance information with one record for each specific chemical or substance, or for a category of chemicals or substances. Like the rest of TOXNET's databases and other resources, HSDB is available online at no cost to global users. HSDB has approximately 5600 chemicals and substances, with a focus on toxicology information and also on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, and related areas of likely interest to HSDB users. All data are from a core set of books, government documents, technical reports, selected primary journal literature, and other online sources of information, with a goal of linking the HSDB content to as much publicly available information as possible. HSDB's content is peer-reviewed by the Scientific Review Panel, a group of experts in the areas covering the scope of HSDB content. Recent enhancements include the addition of chemical structures to HSDB records, the addition of new subfields such as age groups for human data, more occupational exposure standards, and the addition of information on numerous nanomaterials. Examples of future plans include providing more exposure-related information, e.g., uses of a chemical or substance in consumer products; the addition of information summaries aimed towards consumers and other members of the public wanting to learn about a chemical or substance; more visual content such as diagrams (images) of the pathways of metabolism of a substance; and enhanced search features and navigation.

Emerging methods and tools for environmental risk assessment, decision-making, and policy for nanomaterials: summary of NATO Advanced Research Workshop.

Nanomaterials and their associated technologies hold promising opportunities for the development of new materials and applications in a wide variety of disciplines, including medicine, environmental remediation, waste treatment, and energy conservation. However, current information regarding the environmental effects and health risks associated with nanomaterials is limited and sometimes contradictory. This article summarizes the conclusions of a 2008 NATO workshop designed to evaluate the wide-scale implications (e.g., benefits, risks, and costs) of the use of nanomaterials on human health and the environment. A unique feature of this workshop was its interdisciplinary nature and focus on the practical needs of policy decision makers. Workshop presentations and discussion panels were structured along four main themes: technology and benefits, human health risk, environmental risk, and policy implications. Four corresponding working groups (WGs) were formed to develop detailed summaries of the state-of-the-science in their respective areas and to discuss emerging gaps and research needs. The WGs identified gaps between the rapid advances in the types and applications of nanomaterials and the slower pace of human health and environmental risk science, along with strategies to reduce the uncertainties associated with calculating these risks.

Issues in consumer exposure modeling: towards harmonization on a global scale.

Understanding where and how chemicals are used throughout their life cycle is becoming increasingly important. In 2003, within the context of REACH and GPSD legislation, the European Commission started developing a European and global infrastructure of exposure methods and tools. The infrastructure aims (1) to link modeling tools and exposure-related data and scenarios in a single framework so that harmonized exposure assessment procedures can be developed for consumer products in the EU and (2) to make this framework flexible enough to allow global application. A number of issues are raised by a global infrastructure of consumer exposure modeling that answers to multi-legislative mandates. These include transparency, consistency, usability, and defensibility of the models, including the relevant degree of complexity for priority setting versus assessment. As part of the initiative to set up a harmonized global infrastructure on consumer exposure assessment, these issues were presented, discussed, and further developed in a series of European Commission-sponsored workshops organized in October 2004 and June 2005 as part of the "Harmonization of Consumer Exposure Models on a Global Scale" project. The project focused on development, harmonization, and validation of consumer exposure modeling approaches. The workshops included experts from the EU, USA, Japan, and Canada. The conclusions and recommendations made on the basis of this work are described. To help achieve harmonization of approaches, the European Commission's Joint Research Centre is proposing a framework (1) to compare information on elements of chemical risk assessment to understand exposure regulations in different countries, (2) to save time and expense by sharing information and models, and (3) to promote credible science through better communication among organizations and by peer review of assessments and assessment procedures.

Risk management measures for chemicals in consumer products: documentation, assessment, and communication across the supply chain.

This paper analyzes the way risk management measures (RMMs) for consumer products have been used to date in authority and industry risk assessments. A working concept for consumer product RMMs is developed, aimed at controlling, limiting or avoiding exposures, and helping to insure the safe use (or handling) of a substance as part of a consumer product. Particular focus is placed on new requirements introduced by REACH (registration, evaluation, and authorization of chemicals). A RMMs categorization approach is also developed, dividing consumer product RMMs into those that are product integrated and those that are communicated to consumers. For each of these categories, RMMs for normal use, accidental use or misuse need to be distinguished. The level of detail for documenting, assessing and communicating RMMs across supply chains can vary, depending on the type of the assessment (tiered approach). Information on RMMs was collected from published sources to demonstrate that a taxonomical approach using standard descriptors for RMMs libraries is needed for effective information exchange across supply chains.

Communicating exposure and health effects results to study subjects, the community and the public: strategies and challenges.

The Mickey Leland National Urban Air Toxics Research Center sponsored a Symposium in August 2002 that focused on the communication of health effects results from community studies involving exposure to hazardous substances in the environment. Some of the audiences identified for presentation of study results were the study subjects, the community, and the general public. Principles and approaches to communicating findings were discussed, as were the challenges that may confront researchers in developing and implementing a communication plan. The Symposium included four sessions. The first was an overview session where Timothy McDaniels (University of British Columbia) described risk communication as a decision-aiding process. In the second session, case studies were presented by Timothy Buckley (Johns Hopkins University), Jane Hoppin (National Institute of Environmental Health Sciences), and Anne-Marie Nicol (University of British Columbia). Approaches and strategies used by different stakeholders to communicate study results was the topic for a panel discussion at the third session. Panelists included: James Collins (The Dow Chemical Company), Mary White (Agency for Toxic Substances and Disease Registry), Richard Clapp (Boston University), Valerie Zartarian (Environmental Protection Agency), Pamela Williams (Chemrisk), and Tina Bahadori (American Chemistry Council). The final session was a summary presentation on lessons learned given by Rebecca Parkin of George Washington University, in which she synthesized the preceding presentations and formulated guidelines for effective risk communication in community research studies.

Human exposure assessment resources on the World Wide Web.

Human exposure assessment is frequently noted as a weak link and bottleneck in the risk assessment process. Fortunately, the World Wide Web and Internet are providing access to numerous valuable sources of human exposure assessment-related information, along with opportunities for information exchange. Internet mailing lists are available as potential online help for exposure assessment questions, e.g. RISKANAL has several hundred members from numerous countries. Various Web sites provide opportunities for training, e.g. Web sites offering general human exposure assessment training include two from the US Environmental Protection Agency (EPA) and four from the US National Library of Medicine. Numerous other Web sites offer access to a wide range of exposure assessment information. For example, the (US) Alliance for Chemical Awareness Web site addresses direct and indirect human exposures, occupational exposures and ecological exposure assessments. The US EPA's Exposure Factors Program Web site provides a focal point for current information and data on exposure factors relevant to the United States. In addition, the International Society of Exposure Analysis Web site provides information about how this society seeks to foster and advance the science of exposure analysis. A major opportunity exists for risk assessors and others to broaden the level of exposure assessment information available via Web sites. Broadening the Web's exposure information could include human exposure factors-related information about country- or region-specific ranges in body weights, drinking water consumption, etc. along with residential factors-related information on air changeovers per hour in various types of residences. Further, country- or region-specific ranges on how various tasks are performed by various types of consumers could be collected and provided. Noteworthy are that efforts are underway in Europe to develop a multi-country collection of exposure factors and the European Commission is in the early stages of planning and developing a Web-accessible information system (EIS-ChemRisks) to serve as a single gateway to all major European initiatives on human exposure to chemicals contained and released from cleaning products, textiles, toys, etc.