Patterns of Histopathological Change Determined by the Point Counting Method and Its Application for the Hazard Assessment of Respirable Dust

Abstract

We evaluate the morphometric point counting method (PCM) for qualitatively analyzing pulmonary inflammation and collagen deposits (i.e., fibrosis) in the assessment of the biological hazards of inhaled respirable particles at a realistic dose comparable to that of exposure in the work environment. Rats were exposed by intratracheal instillation to a 2-mg dose, which is close to the estimated overdose at which macrophage clearance is impared, of each of 3 kinds of particulate matter: crystalline silica, crocidolite asbestos, and titanium dioxide. The lung tissue was evaluated at 3 days, 1 wk, and 1, 3, and 6 mo after exposure. Digital images taken of the lung tissue after processing and staining of the lung sections were examined by the PCM under light microscopy. Evidence of inflammation along with progressive inflammatory changes occurred with crystalline silica and crocidolite, which are well-known hazardous particle types. In contrast, lung tissue from rats exposed to titanium dioxide particles demonstrated a decreasing pattern of histopathological change with increasing retention time. Differences in repair patterns of TiO(2) versus crocidolite and silica following the 2-mg dose exposure suggest that the PCM scoring system may be a useful and sensitive tool for qualitatively evaluating the biological hazards of new particle types, for which no toxicological information exists for low-dose exposure, by using the results from assessment of fibrogenic particle types (such as crocidolite and crystalline silica) as well as particle types with low toxicity (such as TiO(2)) as reference points.

Differential Expression of EC‐SOD, Mn‐SOD and CuZn‐SOD in Rat Lung Exposed to Crystalline Silica

“…Potter et al 11) reported that lung burden increased progressively in rat lungs exposed to crystalline silica (15 mg/m 3 , 6 h/d, 5 d/wk) from the start of exposure and that a lung burden of 2 mg of silica was equivalent to the dose of silica that would result from approximately 30 d of inhalation. In this experiment, granulomatous formations including silica were not observed 12) . The expression of EC-SOD was increased not only at the mRNA level but also at the protein level.…”

Effect of Particle Size of Intratracheally Instilled Crystalline Silica on Pulmonary Inflammation

“…Sections were stained with hematoxylin-eosin (HE). The procedure for evaluation of inflammatory areas has been described elsewhere 14) . Six images per HE-stained section were digitally captured at random.…”

Simple Flow‐through Solubility Measurement Apparatus and its Effectiveness for Hazard Assessment of Particles/Fibers

“…Histopathological changes of the lung after exposure to PT1 and CS, which show high biopersistence in the lung, were observed in our previous experiment. For CS, expanding alveolitis, type II epitheliall-cell hypertrophy and hyperplasia, and alveolar lipoproteinosis were observed 15) , and for PT1, mild fibrotic changes around macrophages that had engulfed the fibers were observed 16) . Based on these results and the results of the present study, we consider that highly soluble particles and fibers are rapidly cleared from the lung while having only minor effects on the lung.…”