2024年国际毒理学病理学会 (IATP) 卫星研讨会:神经毒性评估和监管前景的新方法方法 (NAMs)
Helena T Hogberg1, Ellen Fritsche2, Sibylle Gröters3
1National Institute of Environmental Health Sciences, Durham, North Carolina, USA.
Toxicologic pathology
|May 15, 2025
概括
新方法方法 (NAMs) 为化学品和药物提供更快,更具成本效益的神经毒性评估. 将NAM与AOP和IATA等框架相集成,支持监管机构使用以改善安全评估.
科学领域:
- 毒理学 毒理学 毒理学
- 神经科学是一个神经科学.
- 监管科学 监管科学
背景情况:
- 对于大量的环境化学物质和早期药物开发,传统的体内动物对神经毒性的研究是不切实际的.
- 越来越需要改进,高效的方法来评估神经毒性.
- 新方法方法 (NAM) 正在作为传统方法的替代品出现.
研究的目的:
- 讨论NAM在神经毒性评估和监管决策中的作用和整合.
- 探索NAM所需的科学验证和技术表征.
- 介绍关于在化学和药物安全方面应用NAM的案例研究.
主要方法:
- 使用人体体外试验和小型模型生物进行神经毒性评估.
- 应用不良结果途径 (AOP) 框架,将细胞结果与神经病理发现联系起来.
- 采用综合测试和评估方法 (IATA) 进行监管应用.
- 介绍了关于发育神经毒性 (DNT),帕金森病和药物诱导的发作的案例研究.
主要成果:
- NAMs提供了更快,更具成本效益,更具机械洞察力的神经毒性评估.
- AOP和IATA框架有助于NAM数据的验证和监管接受.
- 案例研究表明,在化学和药物安全评估中,NAMs的成功应用.
- 与体内研究相结合,NAM可加强危险识别和药物查.
结论:
- 在推进化学品和药物毒性评估方面,NAM至关重要,它提供了实用和高效的替代方案.
- 强大的验证和整合策略,包括AOP和IATA,对于NAM的监管采用至关重要.
- 通过改进的毒性测试,NAM代表了通过改进的毒性测试来确保公共健康和安全的重大进步.
更多相关视频
17:28Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
12.5K
09:02Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
Published on: June 9, 2017
23.0K
相关概念视频
01:26Toxic Reactions: Overview
When toxic substances penetrate the human body, they disseminate to various tissues, undergoing metabolic changes. This process yields reactive metabolites that may covalently bind with specific target molecules, resulting in toxicity.
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
Toxicity falls into two primary categories: local and systemic.
Local toxicity appears at the exposure site, such as protein denaturation caused by caustic substances.
In contrast, systemic toxicity requires the toxic agent's absorption and distribution,...
01:28Preclinical Development: Overview
Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
01:15Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).
01:21Toxicokinetics: Overview
Studies that assess how a drug is absorbed, distributed, metabolized, and excreted (ADME) at toxic doses are termed toxicokinetics. Understanding toxicokinetics helps predict adverse drug reactions (ADRs) and manage toxicity in humans.Toxicokinetics differs from pharmacokinetics mainly in the dose levels studied, with toxicokinetics focusing on higher toxic doses. The kinetics at these levels can be non-linear due to altered physiological processes. Toxicodynamics examines the relationship...
01:23Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...