PATHOLOGY SUPPORT FOR THE NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

为国家环境健康科学研究所提供病理学支持

• 批准号: 8328466
• 负责人: JAMES A MORRISON
• 金额: $ 154.65万
• 依托单位: CHARLES RIVER LABORATORIES INTNTL, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-06 至 2015-06-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8328466
• 关键词: American; Anatomy; Animal Model; Animals; Apoptosis; Biological Assay; CDKN2A gene; Cell Proliferation; Cells; Chemical Agents; Chemicals; Chronic; Clinical Pathology; Collaborations; Communities; Data; Diagnosis; Documentation; Dose; Electron Microscopy; Ensure; Environment; Evaluation; Evaluation Studies; Exposure to; Generations; Goals; Hazardous Chemicals; Health; Health protection; Housing; Human; Hybrids; Immunohistochemistry; Inbred F344 Rats; Knockout Mice; Lesion; Literature; Measurement; Medical; Molecular; Mouse Strains; Mus; Mutation; National Cancer Institute; National Institute for Occupational Safety and Health; National Institute of Environmental Health Sciences; National Toxicology Program; Nature; Organ; Pathologist; Pathology; Phase; Private Sector; Procedures; Protocols documentation; Publishing; Qualifying; Reporting; Research; Research Personnel; Rodent; Role; Science; Slide; System; Terminology; Testing; Tissues; Toxic effect; Toxicology; Transgenes; Transgenic Mice; United States Dept. of Health and Human Services; United States Public Health Service; Work; animal resource; base; carcinogenesis; carcinogenicity; diagnostic accuracy; high standard; improved; programs; sex; working group

The goal of this contract is to provide support of National Toxicology Program (NTP) hazard identification activities targeted toward the prevention of diseases or adverse effects caused by environmental exposure to chemical or physical agents. The subject contract was established to provide a broad range of routine and specialized pathology services in support of studies conducted under contract by the NTP and for supplemental studies on pathology specimens generated through these studies. The contract also provides critical pathology support for studies conducted by in-house investigators at NIEHS and other NIEHS contract studies. The NTP evaluates the toxicity and carcinogenicity of agents (chemicals, physical or biological) of environmental concern by exposing rodents (usually rats and mice) to test materials by one of several different routes of administration, which include feed, gavage, inhalation, dermal application, and intraperitoneal injection. Studies designed to characterize the toxicity and carcinogenicity of these agents are conducted either at a number of testing laboratories under contract with the Environmental Toxicology Program (ETP), or at NIEHS under the auspices of the National Toxicology Program. These studies provide important data for risk assessment relating to potential human exposure to toxic substances in the environment. Pathology assessments, particularly tissue histopathological evaluations, are critical and integral components of all studies. Important goals in the complete pathological evaluation of studies performed by the NTP and NIEHS are to: 1) improve the understanding of the nature of chemically induced lesions in rodents, and 2) develop criteria and standardized terminology to facilitate consistent diagnosis, documentation and interpretation of the lesions observed, and 3) ensure uniformity, consistency, and accuracy of the diagnostic criteria and pathology procedures used. Routinely, this is accomplished through a variety of pathology tasks that are performed by qualified professionals (anatomic pathologists, molecular biologists) and technical staff (pathology assistants, histotechnologists), prior to, during, and after study completion as part of the Pathology Quality Assessment, Pathology Working Group (PWG) Coordinator and PWG panel reviews of studies, or in reviews subsequent to the PWG reviews. Furthermore, as study results become available, there is often the need to perform additional studies to further define the toxicity and/or carcinogenicity of the chemical under study, and the mechanisms that may be involved. Such studies may include additional routine gross and/or histopathological evaluations, the application of specialized procedures such as immunohistochemistry, electron microscopy, morphometrics, or the measurement of cell replication and apoptosis. In addition, studies conducted by in-house NIEHS investigators frequently require routine and/or specialized pathological support and evaluations before the studies can be completed and the results reported. These activities also require large amounts of professional and technical pathology support, and the same high standards of uniformity, consistency, and accuracy of the diagnostic criteria and pathology procedures used for generation of the data.

该合同的目的是为国家毒理学计划（NTP）的危害识别活动提供支持，这些活动旨在预防因环境暴露于化学或物理制剂而引起的疾病或不良影响。建立受试者合同是为了提供广泛的常规和专业病理学服务，以支持NTP根据合同进行的研究，并对通过这些研究生成的病理学标本进行补充研究。该合同还为NIEHS的内部研究人员和其他NIEHS合同研究提供关键病理学支持。 NTP通过将啮齿动物（通常为大鼠和小鼠）暴露于试验材料，通过几种不同的给药途径之一（包括饲料、灌胃、吸入、皮肤应用和腹膜内注射），评价环境关注物质（化学、物理或生物）的毒性和致癌性。在与环境毒理学计划（ETP）签订合同的多个测试实验室或在国家毒理学计划的主持下在NIEHS进行了旨在表征这些物质的毒性和致癌性的研究。这些研究为人类可能接触环境中有毒物质的风险评估提供了重要数据。 病理学评估，特别是组织病理学评价，是所有研究的关键组成部分。对NTP和NIEHS进行的研究进行完整病理学评价的重要目标是：1）提高对啮齿动物化学诱导病变性质的了解，2）制定标准和标准化术语，以促进对观察到的病变的一致诊断、记录和解释，以及3）确保所使用的诊断标准和病理学程序的统一性、一致性和准确性。然而，这是通过由合格的专业人员（解剖病理学家、分子生物学家）和技术人员（病理学助理、组织技术学家）在研究完成之前、期间和之后执行的各种病理学任务来完成的，作为病理学质量评估、病理学工作组（PWG）协调员和PWG小组研究审查的一部分，或在PWG审查之后的审查中。此外，随着研究结果的出现，往往需要进行更多的研究，以进一步确定所研究化学品的毒性和/或致癌性，以及可能涉及的机制。这些研究可能包括额外的常规大体和/或组织病理学评价，应用专门程序，如免疫组织化学，电子显微镜，形态测量学或细胞复制和凋亡的测量。 此外，由内部NIEHS研究人员进行的研究通常需要常规和/或专门的病理学支持和评估，然后才能完成研究并报告结果。这些活动还需要大量的专业和技术病理学支持，以及用于生成数据的诊断标准和病理学程序的统一性、一致性和准确性的相同高标准。