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2744 
Journal Article 
A comparison of the inflammatory response of the lung to inhaled versus instilled particles in F344 rats 
Henderson, RF; Driscoll, KE; Harkema, JR; Lindenschmidt, RC; Chang, IY; Maples, KR; Barr, EB 
1995 
1 
Toxicological Sciences
ISSN: 1096-6080
EISSN: 1096-0929 
NIOSH/00225019 
24 
2 
183-197 
English 
7737430 
WOS:A1995QH46600005 
U.S. Department of Energy; Proctor & Gamble Company. The potential pulmonary toxicity of poorly soluble airborne dusts generated in industrial and environmental settings is often evaluated by inhalation studies in rodents. Studies using intra-tracheal instillation of particles have been suggested as a less expensive alternative. We conducted a study to compare the inflammatory response of the lung to instilled versus inhaled particles. In one study, female F344/N rats, 11-13 weeks of age, were exposed for 6 hr/day, 5 days/week for 4 weeks by inhalation to 0, 0.1, 1.0, or 10 mg/m3 of either a-quartz (toxic particle) or TiO2 (relatively low toxicity particle) and the lung burdens were determined at 1 week after the end of the exposure. The lungs were evaluated by analysis of bronchoalveolar lavage fluid (BALF) at 1, 8, and 24 weeks after the end of the exposure and by histopathology at 24 weeks. In a second study, rats were exposed by instillation to the lung burdens present in the preceding study at 1 week after the inhalation exposure, and the rats were evaluated in the same manner as in the inhalation study. In general, the degree of alveolitis, as evaluated by histopathology and BALF analysis, was similar by the two methods of exposure. With lung burdens up to 750 Ág/g lung, the TiO2 elicited no changes in BALF parameters at any time by either method of exposure, nor was any histopathology observed. The BALF changes elicited by a-quartz were of approximately the same magnitude and followed the same time course by either exposure method with the lowest dose delivered to the lung by either method being a "no-effect" dose. At the highest dose, microgranulomas were observed in bronchial-associated lymphoid tissue (BALT) in both sets of rats. However, the highest inhalation exposure induced pleural granulomatous lesions that were not observed in the animals instilled with "alpha"-quartz. The results indicate that the relative potentials of the two materials to produce bronchoalveolitis and granulomatous lesions in BALT could be appropriately evaluated using either intratracheal or inhalation exposures. 
DCN-225757; Mineral dusts; Quartz dust; In vivo studies; Lung burden; Laboratory animals; Inhalation studies; Laboratory techniques; Lung tissue; Histopathology; Chronic inflammation