Relationship of pulmonary toxicity and carcinogenicity of fine and ultrafine granular dusts in a rat bioassay. 2011

Angelika Kolling, and Heinrich Ernst, and Susanne Rittinghausen, and Uwe Heinrich
Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), Hannover, Germany. angelika.kolling@item.fraunhofer.de

The current carcinogenicity study with female rats focused on the toxicity and carcinogenicity of intratracheally instilled fine and ultrafine granular dusts. The positive control, crystalline silica, elicited the greatest magnitude and progression of pulmonary inflammatory reactions, fibrosis and the highest incidence of primary lung tumors (39.6%). Addition of poly-2-vinylpyridine-N-oxide decreased inflammatory responses, fibrosis, and the incidence of pulmonary tumors induced by crystalline quartz to 21.4%. After repeated instillation of soluble, ultrafine amorphous silica (15 mg) a statistically significant tumor response (9.4%) was observed, although, the inflammatory response in the lung was not as persistently severe as in rats treated with carbon black. Instillation of ultrafine carbon black (5 mg) caused a lung tumor incidence of 15%. In contrast to a preceding study using a dose of 66 mg coal dust, lung tumors were not detected after exposure to the same coal dust at a dose of 10 mg in this study. Pulmonary inflammatory responses to coal dust were very low indicating a mechanistic threshold for the development of lung tumors connected with particle related chronic inflammation. The animals treated with ultrafine carbon black and ultrafine amorphous silica showed significantly more severe lesions in non-cancerous endpoints when compared to animals treated with fine coal dust. Furthermore, carbon black treated rats showed more severe non-cancerous lung lesions than amorphous silica treated rats. Our data show a relationship between tumor frequencies and increasing scores when using a qualitative scoring system for specific non-cancerous endpoints such as inflammation, fibrosis, epithelial hyperplasia, and squamous metaplasia.

UI MeSH Term Description Entries
D007322 Instillation, Drug The administration of therapeutic agents drop by drop, as eye drops, ear drops, or nose drops. It is also administered into a body space or cavity through a catheter. It differs from THERAPEUTIC IRRIGATION in that the irrigate is removed within minutes, but the instillate is left in place. Drug Instillation,Drug Instillations,Instillations, Drug
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D010316 Particle Size Relating to the size of solids. Particle Sizes,Size, Particle,Sizes, Particle
D011791 Quartz Quartz (SiO2). A glassy or crystalline form of silicon dioxide. Many colored varieties are semiprecious stones. (From Grant & Hackh's Chemical Dictionary, 5th ed)
D003031 Coal A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. Anthracite,Bituminous Coal,Brown Coal,Lignite,Lignitious Coal,Peat Coal,Soft Coal,Anthracites,Bituminous Coals,Brown Coals,Coal, Bituminous,Coal, Brown,Coal, Lignitious,Coal, Peat,Coal, Soft,Coals,Coals, Bituminous,Coals, Brown,Coals, Lignitious,Coals, Peat,Coals, Soft,Lignites,Lignitious Coals,Peat Coals,Soft Coals
D003460 Crystallization The formation of crystalline substances from solutions or melts. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Crystalline Polymorphs,Polymorphism, Crystallization,Crystal Growth,Polymorphic Crystals,Crystal, Polymorphic,Crystalline Polymorph,Crystallization Polymorphism,Crystallization Polymorphisms,Crystals, Polymorphic,Growth, Crystal,Polymorph, Crystalline,Polymorphic Crystal,Polymorphisms, Crystallization,Polymorphs, Crystalline
D004391 Dust Earth or other matter in fine, dry particles. (Random House Unabridged Dictionary, 2d ed) House Dust,Housedust,Dust, House
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012822 Silicon Dioxide Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, QUARTZ, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. Silica,Aerosil,Aerosil 380,Cristobalite,Quso G-32,Quso G32,Tridymite,380, Aerosil,Dioxide, Silicon,G32, Quso,Quso G 32

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