{"title":"Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!","authors":"En-Hsuan Lu, Ivan Rusyn, Weihsueh A Chiu","doi":"10.1080/10937404.2024.2412571","DOIUrl":null,"url":null,"abstract":"<p><p>Regulatory dose-response assessments traditionally rely on <i>in vivo</i> data and default assumptions. New Approach Methods (NAMs) present considerable opportunities to both augment traditional dose-response assessments and accelerate the evaluation of new/data-poor chemicals. This review aimed to determine the potential utilization of NAMs through a unified conceptual framework that compartmentalizes derivation of 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 and (3) toxicodynamics, (4) human population (intra-species) variability in toxicodynamics, and (5) toxicokinetics. After using several \"traditional\" dose-response assessments to illustrate this framework, a review is presented where existing NAMs, including <i>in silico</i>, <i>in vitro</i>, and <i>in vivo</i> approaches, might be applied across KDMs. Further, the false dichotomy between \"traditional\" and NAMs-derived data sources is broken down by organizing dose-response assessments into a matrix where each KDM has Tiers of increasing precision and confidence: Tier 0: Default/generic values, Tier 1: Computational predictions, Tier 2: Surrogate measurements, and Tier 3: Direct measurements. These findings demonstrated that although many publications promote the use of NAMs in KDMs (1) for POD determination and (5) for human population toxicokinetics, the proposed matrix of KDMs and Tiers reveals additional immediate opportunities for NAMs to be integrated across other KDMs. Further, critical needs were identified for developing NAMs to improve <i>in vitro</i> dosimetry and quantify test system and human population toxicodynamics. Overall, broadening the integration of NAMs across the steps of dose-response assessment promises to yield higher throughput, less animal-dependent, and more science-based toxicity values for protecting human health.</p>","PeriodicalId":49971,"journal":{"name":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","volume":null,"pages":null},"PeriodicalIF":6.4000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Toxicology and Environmental Health-Part B-Critical Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10937404.2024.2412571","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Regulatory dose-response assessments traditionally rely on in vivo data and default assumptions. New Approach Methods (NAMs) present considerable opportunities to both augment traditional dose-response assessments and accelerate the evaluation of new/data-poor chemicals. This review aimed to determine the potential utilization of NAMs through a unified conceptual framework that compartmentalizes derivation of 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 and (3) toxicodynamics, (4) human population (intra-species) variability in toxicodynamics, and (5) toxicokinetics. After using several "traditional" dose-response assessments to illustrate this framework, a review is presented where existing NAMs, including in silico, in vitro, and in vivo approaches, might be applied across KDMs. Further, the false dichotomy between "traditional" and NAMs-derived data sources is broken down by organizing dose-response assessments into a matrix where each KDM has Tiers of increasing precision and confidence: Tier 0: Default/generic values, Tier 1: Computational predictions, Tier 2: Surrogate measurements, and Tier 3: Direct measurements. These findings demonstrated that although many publications promote the use of NAMs in KDMs (1) for POD determination and (5) for human population toxicokinetics, the proposed matrix of KDMs and Tiers reveals additional immediate opportunities for NAMs to be integrated across other KDMs. Further, critical needs were identified for developing NAMs to improve in vitro dosimetry and quantify test system and human population toxicodynamics. Overall, broadening the integration of NAMs across the steps of dose-response assessment promises to yield higher throughput, less animal-dependent, and more science-based toxicity values for protecting human health.
期刊介绍:
"Journal of Toxicology and Environmental Health: Part B - Critical Reviews" is an academic journal published by Taylor & Francis, focusing on the critical examination of research in the areas of environmental exposure and population health. With an ISSN identifier of 1093-7404, this journal has established itself as a significant source of scholarly content in the field of toxicology and environmental health.
Since its inception, the journal has published over 424 articles that have garnered 35,097 citations, reflecting its impact and relevance in the scientific community. Known for its comprehensive reviews, the journal also goes by the names "Critical Reviews" and "Journal of Toxicology & Environmental Health, Part B, Critical Reviews."
The journal's mission is to provide a platform for in-depth analysis and critical discussion of the latest findings in toxicology, environmental health, and related disciplines. By doing so, it contributes to the advancement of knowledge and understanding of the complex interactions between environmental factors and human health, aiding in the development of strategies to protect and improve public health.