Dorato M A, Wolff R K
Toxicology Division, Lilly Research Laboratories, Eli Lilly and Company, Greenfield, Indiana 46140.
Toxicol Pathol. 1991;19(4 Pt 1):373-83. doi: 10.1177/0192623391019004-106.
Inhalation toxicology technology has provided the scientific community with important advances in studies of inhaled toxicants. These advances include new and more efficient exposure systems (e.g., flow-past nose-only exposure systems), and improved approaches to inhalation chamber environmental control (e.g., temperature, humidity, air quality). Practical problems and approaches to testing and operating inhalation exposure systems and the advantages and disadvantages of the major inhalation exposure types (e.g., whole-body, nose-only) are discussed. Important aspects of study design, such as high level particulate exposures resulting in large lung burdens (e.g., greater than or equal to 2 mg/g of lung), slowed pulmonary clearance rates, and nonspecific toxicity are considered, along with practical issues of comparative dosimetry. Regulatory guidelines have continued to present challenges in designing and conducting acute, subchronic, and chronic inhalation studies. The important regulatory issue of performing acute inhalation toxicity studies at high aerosol concentrations and "respirable" particle size distribution is discussed.
吸入毒理学技术为科学界在吸入性毒物研究方面带来了重要进展。这些进展包括新型且更高效的暴露系统（例如，流经式仅鼻暴露系统），以及吸入舱环境控制的改进方法（例如，温度、湿度、空气质量）。讨论了测试和操作吸入暴露系统的实际问题与方法，以及主要吸入暴露类型（例如，全身暴露、仅鼻暴露）的优缺点。研究设计的重要方面，如导致肺部负荷较大（例如，大于或等于2毫克/克肺组织）的高浓度颗粒物暴露、肺部清除率减慢和非特异性毒性，以及比较剂量学的实际问题都被纳入了考量。监管指南在设计和开展急性、亚慢性和慢性吸入研究方面持续带来挑战。文中讨论了在高气溶胶浓度和“可吸入”粒径分布条件下进行急性吸入毒性研究这一重要监管问题。
