Quantitative prediction of toxicological points of departure using two-stage machine learning models: A new approach methodology (NAM) for chemical risk assessment

Journal of Hazardous Materials, Год журнала: 2025, Номер 487, С. 137071 - 137071

Опубликована: Янв. 10, 2025

Язык: Английский

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Incorporating new approach methods (NAMs) data in dose–response assessments: The future is now!

Journal of Toxicology and Environmental Health Part B, Год журнала: 2024, Номер unknown, С. 1 - 35

Опубликована: Окт. 10, 2024

Regulatory dose–response assessments traditionally rely on in vivo data and default assumptions. New Approach Methods (NAMs) present considerable opportunities to both augment traditional accelerate the evaluation of new/data-poor chemicals. This review aimed determine potential utilization NAMs through a unified conceptual framework that compartmentalizes derivation toxicity values into five sequential Key Dose–response Modules (KDMs): (1) point-of-departure (POD) determination, (2) test system-to-human (e.g. inter-species) toxicokinetics (3) toxicodynamics, (4) human population (intra-species) variability (5) toxicokinetics. After using several "traditional" dose-response illustrate this framework, is presented where existing NAMs, including silico, vitro, approaches, might be applied across KDMs. Further, false dichotomy between NAMs-derived sources broken down by organizing matrix each KDM has Tiers increasing precision confidence: Tier 0: Default/generic values, 1: Computational predictions, 2: Surrogate measurements, 3: Direct measurements. These findings demonstrated although many publications promote use KDMs for POD determination toxicokinetics, proposed reveals additional immediate integrated other critical needs were identified developing improve vitro dosimetry quantify system toxicodynamics. Overall, broadening integration steps assessment promises yield higher throughput, less animal-dependent, more science-based protecting health.

Язык: Английский

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Application of new approach methodology-derived points of departure with predicted or regulatory exposures to estimate bioactivity to exposure ratios (BER) for risk assessment

Human and Ecological Risk Assessment An International Journal, Год журнала: 2025, Номер unknown, С. 1 - 39

Опубликована: Янв. 26, 2025

Язык: Английский

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Developmental toxicity: artificial intelligence-powered assessments

Trends in Pharmacological Sciences, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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