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Featuring:

Prachi Pradeep, PhD: “NAM-based Assessment to Classify Chemicals for Systemic Toxicity Effects"

ASCCT 14th Annual Meeting Ed Carney Predictive Toxicology Award Recipient

Kenzie Pereira, PhD: “Predictivity Assessment of the Human Thyroid Microtissue Assay”

ASCCT 14th Annual Meeting Suzanne Fitzpatrick Student Travel Award Recipient

Raymond Hu: “Development of a curated database of skin sensitizers released from medical devices”

ASCCT 14th Annual Meeting Poster Award Recipient

A brief Q&A session will follow each presentation.

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ABSTRACTS

NAM-based Assessment to Classify Chemicals for Systemic Toxicity Effects
Authors: Prachi Pradeep, Matthias Herzler, Ralph Pirow, Sebastian Schmeisser
Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany
The EPAA–JRC NAMs Designathon is a joint initiative by the European Partnership for Alternative Approaches to Animal Testing (EPAA) and the EU’s Joint Research Centre (JRC). It explores how New Approach Methodologies (NAMs) can support future systemic toxicity classification. Participants were invited to assign high, medium, or low concern levels to 150 reference chemicals using a transparent, reproducible process.
Here, we propose a stepwise screening workflow integrating NAM-based toxicodynamics (TD) and toxicokinetics (TK). Curated in vitro bioactivity data from high-throughput screening (HTS) assays were used to characterize chemical potency for systemic, repeated dose toxicity. In silico QSAR-predicted points of departure (PoDs) provided additional hazard information. Chemicals without sufficient TD data were assessed using read-across. TK modelling was used to estimate systemic availability following oral exposure. Chemicals were categorized into three concern levels for TD and TK separately, then combined using a classification matrix. Finally, a confidence score was assigned based on data type.

Of 150 chemicals, 98% were assessed using multiple lines of evidence demonstrating the feasibility of combining diverse NAMs within a single framework. This workflow serves as a proof-of-concept for early chemical hazard prioritization, while also highlighting current limitations, including data gaps, variability across evidence streams, and the need for continued methodological development and collaboration to support future regulatory applications.

Predictivity Assessment of the Human Thyroid Microtissue Assay 

Authors: Kenzie Pereira, Briana Foley, Scott G. Lynn, Chad Deisenroth
The US EPA aims to validate and adopt new approach methods (NAMs) into hazard screening for endocrine-disrupting chemicals. The human thyroid microtissue (hTMT) assay is a medium throughput in vitro assay that utilizes primary human thyrocytes to evaluate chemical effects on thyroid hormone synthesis. Previous work has provided detailed characterization of the hTMT model, including qualification criteria for human thyrocyte selection, acceptance criteria for assay performance, and benchmark potency ranges of reference chemicals for proficiency testing. While an interlaboratory validation study has assessed the relevance, reliability, and transferability of the assay using a small reference chemical set, additional validation is needed to evaluate the predictive accuracy of the assay using a broader chemical test set. Here, 49 chemicals were tested across 6 concentrations (0.001 – 100 µM) with the standardized hTMT assay to assess chemical-induced cytotoxicity and disruption of thyroxine (T4) synthesis (n = 4). The chemical test set comprised four previously evaluated reference chemicals, and 45 additional chemicals curated by subject matter experts. These included known inhibitors of molecular initiating events (MIEs) within the thyroid adverse outcome pathway (AOP) network, as well as inactive chemicals. Initial results demonstrate a range of chemical-induced T4 disruption, consistent with previously published data on chemical-specific inhibition of thyroid MIEs. The final assessment of sensitivity and specificity will support EPA initiatives toward the implementation of NAMs to improve chemical hazard assessment strategies while reducing reliance on animal testing. This abstract does not reflect US EPA policy.

Development of a curated database of skin sensitizers released from medical devices
Authors: Raymond Hu, Amel Mohamed, Brennan Lawless, Anh Nguyen, Jenna Glockner, Ron Brown
The qualification of New Approach Methods (NAMs) for regulatory use requires the use of methods that are fit-for-purpose and qualified within a context of use that is specific for a narrowly defined group of regulated products (e.g., food additives, agrochemicals, medical devices). Therefore, when used for the safety assessment of medical devices, the NAM should be validated using compounds known to be released from materials used to manufacture medical devices. Doing so requires developing a carefully curated list of device-related skin sensitizers. An initial list of these compounds was compiled during development of the ISO Technical Specification, ISO/TS 11796:2023 (Biological evaluation of medical devices — Requirements for inter-laboratory studies to demonstrate the applicability of validated in vitro methods to assess the skin sensitization of medical devices); however, concerns have been expressed by at least one regulatory agency that this list does not fully represent the universe of sensitizers that can be released from devices. To address this concern, an effort was undertaken to develop a comprehensive, curated list of skin sensitizers released from device materials. Following a systematic review of the data, a preliminary list of around 130 compounds that are both known to be sensitizers and also known to be released from device materials was compiled. This list can be used to qualify in vitro and in silico NAMs for the safety assessment of medical devices within a defined context of use.

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ABOUT THE PRESENTERS

Dr. Prachi Pradeep is a Computational Toxicologist in the Department of Chemicals and Product Safety at the German Federal Institute for Risk Assessment (BfR). With over a decade of experience in cheminformatics and bioinformatics, she brings a strong data science perspective to chemical safety assessment. Her research focuses on the development and validation of predictive models, the regulatory integration of new approach methodologies (NAMs), and the characterization of data variability and uncertainty to support robust, science-based risk assessment. She holds a Master’s degree in Bioinformatics and a PhD in Computational Sciences, completed in collaboration with the U.S. Food and Drug Administration’s Center for Devices and Radiological Health, and undertook postdoctoral training at the U.S. EPA’s Center for Computational Toxicology and Exposure.

Dr. Kenzie Pereira is an ORISE postdoctoral participant within the U.S. EPA Office of Chemical Safety and Pollution Prevention in the Endocrine Disruptor Screening Program. She is a Louisiana native and earned her Ph.D. from Duquesne University. Her background includes integrative research on vertebrate immunity, stress physiology, disease, and environmental drivers of health. Her current work focuses on evaluating the predictive capacity of an in vitro human thyroid microtissue (hTMT) assay as part of new approach method (NAM) prevalidation, supporting human-relevant, mechanistically informed screening for endocrine-disrupting chemicals.

Raymond Hu, is a master’s student in Toxicology at Johns Hopkins University, with academic training in occupational health and computational toxicology. His research interests focus on chronic disease-related consumer products, integrating computational approaches with clinical evidence to improve product safety and risk assessment.
He holds a BSN degree and has prior bedside clinical experience, bringing a clinically grounded perspective to toxicological risk assessment and exposure-related health outcomes. He is currently working with Risk Science Consortium, LLC, and JHU-affiliated clinics to develop a curated database of skin sensitizers released from medical devices.

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The recording and select materials from this webinar will be posted on the ASCCT webinar archive: https://ASCCTox.org/Webinar-Archive

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