GENETIC TOXICOLOGY SUPPORT FOR THE NTP AND THE NIEHS

NTP 和 NIEHS 的遗传毒理学支持

• 批准号: 10918014
• 负责人: LESLIE RECIO
• 金额: $ 75.47万
• 依托单位: INTEGRATED LABORATORY SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-06 至 2024-09-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10918014
• 关键词: Adopted; Adult; Adverse effects; Aging; Animal Model; Animal Testing; Animals; Biological; Biological Assay; Biological Monitoring; Biotechnology; Birth; Blood specimen; Botanicals; Brain; Carcinogens; Cells; Chemical Exposure; Chemicals; Clinic; Clinical; Clinical Research; Colon; Comet Assay; Complication; Contracts; DNA Damage; DNA sequencing; Data; Development; Diagnosis; Disasters; Disease; Early Diagnosis; Economics; Environment; Environmental Exposure; Erythrocytes; Event; Evolution; Exposure to; Family suidae; Frequencies; Future; Gene Expression; Gene Mutation; Generations; Genes; Genetic; Genetic Induction; Genomics; Guidelines; Health; Human; In Vitro; Induced Mutation; International; Kidney; Laboratories; Life; Link; Liver; Malignant Neoplasms; Mammalian Cell; Methods; Micronucleus Tests; Mission; Monitor; Mus; Mutagenicity Tests; Mutation; Mutation Detection; Mutation Spectra; National Institute of Environmental Health Sciences; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neurologic; Oncology; Participant; Pesticides; Pharmaceutical Preparations; Pharmacologic Substance; Process; Protocols documentation; Rattus; Resources; Rodent; Sampling; Source; Stomach; Study models; Symptoms; System; Technology; Testing; Tissues; Toxic effect; Toxicity Tests; Toxicogenetics; Toxicology; Translating; United States Environmental Protection Agency; United States Food and Drug Administration; Update; West Virginia; carcinogenicity; contaminated water; dietary supplements; early life exposure; environmental chemical; exposed human population; flexibility; genotoxicity; human study; in vitro testing; in vivo; innovation; interest; micronucleus; multiplex assay; mutation assay; novel strategies; peripheral blood; response; treatment response; tumor

This genetic toxicology testing contract has supported the overall mission of the Division of Translational Toxicology (DTT) to provide detailed toxicological profiles, including potential for carcinogenicity, of compounds of interest for over 30 years. Assessment of genetic damage, an important factor in the initiation and development of cancer, birth defects, aging processes, and other adverse human health effects, is a critical component of any in-depth toxicological profile of a chemical or product. An important complication in assessing the impact of environmentally induced genetic damage is that genetic damage induced early in life, even prior to birth, may not manifest as an adverse health effect until decades later, during adulthood. This delay in manifestation, along with a lack of any immediate symptoms of genetic damage, makes it difficult to link early life exposures that cause genetic damage with adult disease. Because of the importance in understanding potential for induced genetic damage, a detailed characterization of the genotoxic potential of new pharmaceutical and pesticide products, as well as other types of products for which human exposure is a concern, is required by regulatory agencies such as the Food and Drug Administration and the Environmental Protection Agency prior to approval for use. This Genetic Toxicity Testing contract provides information to the DTT on various types of exposure-related genetic damage using globally accepted standard testing protocols as well as innovative approaches, when necessary and applicable, to supplement the information obtained from standard tests. Testing systems employed under this contract include both in vitro (animal and human cell-based, and bacterial) and in vivo (rats and mice) assays. The capabilities of this genetic toxicity testing contract are continuously updated to remain current with the latest scientific approaches in the field and consistent with international guidelines for conducting these kinds of tests. The field is currently undergoing rapid evolution with the many dramatic changes in technological capabilities that are occurring today.

这份遗传毒理学测试合同支持了转化毒理学(DTT)司的总体使命，即提供有关化合物30多年来的详细毒理学概况，包括潜在的致癌能力。基因损伤评估是癌症、出生缺陷、衰老过程和其他对人类健康不利影响的发生和发展的重要因素，是任何深入的化学品或产品毒理学概况的关键组成部分。在评估环境引起的遗传损害的影响时，一个重要的复杂问题是，在生命早期造成的遗传损害，甚至在出生之前，可能要到几十年后，也就是成年期间，才会表现出对健康的不利影响。这种表现的延迟，加上缺乏任何直接的基因损伤症状，使得人们很难将导致基因损伤的早期生命暴露与成人疾病联系起来。由于了解潜在的诱发遗传损害的重要性，在批准使用之前，食品和药物管理局和环境保护局等监管机构要求对新的药物和农药产品以及其他类型的产品的遗传毒性潜力进行详细的表征，因为人类暴露在这些产品中是一个令人担忧的问题。这份遗传毒性测试合同使用全球公认的标准测试协议，以及在必要和适用时的创新方法，向DTT提供与暴露相关的各种遗传损害的信息，以补充从标准测试中获得的信息。根据该合同采用的检测系统包括体外(基于动物和人类细胞，以及细菌)和体内(大鼠和小鼠)检测。这份遗传毒性测试合同的能力不断更新，以与该领域的最新科学方法保持同步，并与进行这类测试的国际准则保持一致。该领域目前正在经历快速发展，当今技术能力发生了许多戏剧性的变化。