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Inflammatory effects of two quartz samples after intratracheal instillation in a 90-day study with rats

 
: Creutzenberg, O.; Oberdörster, G.; Coogan, L.; Moll, W.F.; Hamilton, R.; Ziemann, C.; Muhle, H.

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Toxicology letters 164 (2006), Suppl.1, pp.86-87
ISSN: 0378-4274
ISSN: 1879-3169
English
Journal Article
Fraunhofer ITEM ()

Abstract
Respirable crystalline silica was classified by IARC (1997) as human carcinogen. However, as different polymorphs react differently in lungs, assays are needed for differentiation. The objective of this 90-day study was to characterize differences in biological activity between two quartz species, ground quartz particles (well-characterized Positive Control DQ12) versus a quartz-containing material (geologically ancient Quartz Isolate from bentonite). Total doses of 15.2 mg/kg body weight of the Positive Control and Quartz Isolate were administered to rats by intratracheal instillation. Controls received saline only. Bronchoalveolar lavagate analysis showed that, relative to the controls, the total leukocyte counts at 3 days were significantly elevated in both the Quartz Isolate and Positive Control groups. At 28 and 90 days, the Quartz Isolate values were no longer statistically different from the control values whereas the corresponding Positive Control values were about 12 and 65 times greater than control values. At 3, 28 and 90 days, the percentages of polymorphonuclear neutrophils (PMNs) were 18%, 25% and 32% for the Quartz Isolate group and 39%, 45% and 46% for the Positive Control group, respectively. Histopathologically, the Quartz Isolate group showed moderate effects compared to controls after 28 days with no progression of severity at 90 days. In contrast, the Positive Control group exhibited more severe effects at 28 days and a progression in intensity at 90 days. In conclusion, in the Positive Control group, a persistent inflammation (interstitial fibrosis, alveolar lipoproteinosis) was observed. Conclusions: i) Controls did not induce lung inflammation ii) The Positive Control produced significant and progressive lung inflammation. iii) The Quartz Isolate induced a significantly weaker inflammatory response than the Positive Control (not progressive). From a regulatory point of view, these substance-specific toxicological effects of Quartz Isolate may need to be considered for its classification.

: http://publica.fraunhofer.de/documents/N-47022.html