Community-Engaged Research and the Use of Open Access ToxVal/ToxRef In Vivo Databases and New Approach Methodologies (NAM) to Address Human Health Risks From Environmental Contaminants.

The paper analyzes opportunities for integrating Open access resources (Abstract Sifter, US EPA and NTP Toxicity Value and Toxicity Reference [ToxVal/ToxRefDB]) and New Approach Methodologies (NAM) integration into Community Engaged Research (CEnR). CompTox Chemicals Dashboard and Integrated Chemical Environment with in vivo ToxVal/ToxRef and NAMs (in vitro) databases are presented in three case studies to show how these resources could be used in Pilot Projects involving Community Engaged Research (CEnR) from the University of California, Davis, Environmental Health Sciences Center. Case #1 developed a novel assay methodology for testing pesticide toxicity. Case #2 involved detection of water contaminants from wildfire ash and Case #3 involved contaminants on Tribal Lands. Abstract Sifter/ToxVal/ToxRefDB regulatory data and NAMs could be used to screen/prioritize risks from exposure to metals, PAHs and PFAS from wildfire ash leached into water and to investigate activities of environmental toxins (e.g., pesticides) on Tribal lands. Open access NAMs and computational tools can apply to detection of sensitive biological activities in potential or known adverse outcome pathways to predict points of departure (POD) for comparison with regulatory values for hazard identification. Open access Systematic Empirical Evaluation of Models or biomonitoring exposures are available for human subpopulations and can be used to determine bioactivity (POD) to exposure ratio to facilitate mitigation. These resources help prioritize chemical toxicity and facilitate regulatory decisions and health protective policies that can aid stakeholders in deciding on needed research. Insights into exposure risks can aid environmental justice and health equity advocates.

Silva M ，Capps S ，London JK 《Birth Defects Research》

Sourcing data on chemical properties and hazard data from the US-EPA CompTox Chemicals Dashboard: A practical guide for human risk assessment.

For the past six decades, human health risk assessment of chemicals has relied on in vivo data from human epidemiological and experimental animal toxicological studies to inform the derivation of non-cancer toxicity values. The ongoing evolution of this risk assessment paradigm in an environmental landscape of data-poor chemicals has highlighted the need to develop and implement non-testing methods, so-called New Approach Methodologies (NAMs). NAMs include a growing number of in silico and in vitro data streams designed to inform hazard properties of chemicals, including kinetics and dynamics at different levels of biological organization, environmental fate and transport, and exposure. NAMs provide a fit-for-purpose science-basis for human hazard and risk characterization of chemicals ranging from data-gap filling applications to broad evidence-based decision-making. Systematic assembly and delivery of empirical and predicted data for chemicals are paramount to advancing chemical evaluation, and software tools serve an essential role in delivering these data to the scientific community. The CompTox Chemicals Dashboard (from here on referred to as the "Dashboard") is one such tool and is a publicly available web-based application developed by the US Environmental Protection Agency to provide access to chemistry, toxicity and exposure information for ~900,000 chemicals. The Dashboard is increasingly becoming a valuable resource for assessors tasked with the evaluation of potential human health risks associated with chemical exposures. In this context, the significant amount of information present in the Dashboard facilitates: 1) assembly of information on physicochemical properties and environmental fate and transport and exposure parameters and metrics; 2) identification of cancer and non-cancer health effects from extant human and experimental animal studies in the public domain and/or information not available in the public domain (i.e., "grey literature"); 3) systematic literature searching and review for developing cancer and non-cancer hazard evidence bases; and 4) access to mechanistic information that can aid or augment the analysis of traditional toxicology evidence bases, or potentially, serve as the primary basis for informing hazard identification and dose-response when traditional bioassay data are lacking. Finally, in silico predictive tools developed to conduct structure-activity or read-across analyses are also available within the Dashboard. This practical tutorial is intended to address key questions from the human health risk assessment community dealing with chemicals in both food and in the environment. Perspectives for future development or refinement of the Dashboard highlight foreseen activities to further support the research and risk assessment community in cancer and non-cancer chemical evaluations.

Williams AJ ，Lambert JC ，Thayer K ，Dorne JCM ... -  《-》

Sources, pathways, and relative risks of contaminants in surface water and groundwater: a perspective prepared for the Walkerton inquiry.

Ritter L ，Solomon K ，Sibley P ，Hall K ，Keen P ，Mattu G ，Linton B ... -  《journal of toxicology and environmental health》

Computational toxicology as implemented by the U.S. EPA: providing high throughput decision support tools for screening and assessing chemical exposure, hazard and risk.

Kavlock R ，Dix D 《-》

Profiling chemicals based on chronic toxicity results from the U.S. EPA ToxRef Database.

Martin MT ，Judson RS ，Reif DM ，Kavlock RJ ，Dix DJ ... -  《-》