asbestos--amosite and ferroactinolite

Studies recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute-phase proteins (APP; α-2 macroglobulin, A2M; and α-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and lipocalin) in rats. In this study, objectives were to (1) compare changes in biomarkers of rats after instillation of different naturally occurring asbestos (NOA) minerals including LA, Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON), and (2) examine biomarkers after subchronic LA or amosite inhalation exposure. Rat-respirable fractions (aerodynamic diameter approximately 2.5 μm) prepared by water elutriation were delivered via a single IT instillation at doses of 0, 0.5, and 1.5 mg/rat in male F344 rats. Nose-only inhalation exposures were performed at 0, 1, 3.3, and 10 mg/m(3) for LA and at 3.3 mg /m(3) for amosite, 6h/d, 5 d/wk for 13 wk. Inflammation, metabolic syndrome, and cancer biomarkers were analyzed in the serum for up to 18 mo. IT instillation of some asbestos materials significantly increased serum AGP and A2M but to a varying degree (SM = LA > ON = ED). Numerical increases in interleukin (IL)-6 and osteopontin occurred in rats instilled with SM. SM and ED also elevated leptin and insulin at 15 mo, suggesting potential metabolic effects. LA inhalation tended to raise A2M at d 1 but not cytokines. Serum mesothelin appeared to elevate after 18 mo of LA inhalation. These results suggest that the lung injury induced by high levels of asbestos materials may be associated with systemic inflammatory changes and predisposition to insulin resistance.

Topics: alpha-Macroglobulins; Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Asbestos, Serpentine; Biomarkers; Dose-Response Relationship, Drug; Immune System Diseases; Inflammation; Inhalation Exposure; Lung; Male; Metabolic Diseases; Neoplasms; Orosomucoid; Particle Size; Rats; Rats, Inbred F344

Topics: Asbestos, Amosite; Asbestos, Amphibole; Carcinogens, Environmental; Female; Humans; Male; Mediterranean Region; Mesothelioma; Mineral Fibers; Minnesota; South Africa

In vivo tests available to determine the toxicity of mineral fibers are too expensive and time-consuming to be regularly employed in the evaluation of the potential health hazard posed by natural and man-made fibers. In vitro procedures, while economical, convenient and capable of ranking "relative toxicity," are uncertain predictors of specific lesions. Thus, it is of interest to compare the results of various standard in vitro tests with the results of in vivo tests. Data are available for intratracheal and intrapleural exposures of animals to amphibole mineral fibers from UICC amosite and a fibrous form of ferroactinolite. This paper presents data from parallel in vitro studies employing these minerals. The methods used were mammalian erythrocyte lysis, Chinese hamster ovary cell clonal cytotoxicity assay, and rabbit alveolar macrophage cytotoxicity assay. The experiments were conducted in triplicate to determine dose effect by mass and by number of fibers with aspect ratios greater than 3. A comparison of relative toxicity was made between the ferroactinolite and amosite. In the erythrocyte system, there was a greater lytic effect per unit of fibers for ferroactinolite than for the UICC amosite.

Topics: Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Cell Survival; Clone Cells; Cricetinae; Cricetulus; Female; Hemolysis; In Vitro Techniques; Macrophages; Minerals; Ovary; Pulmonary Alveoli; Sheep

Oncogenesis and in vitro data (reported elsewhere in detail) are compared on the basis of relative activity by mass and by dimensional fiber parameters. When tumor induction is compared to the number of fibers of various lengths and aspect ratios in the dose in rats to the degree of tumor induction, a degree of difference with the long thin fiber concept of tumorigenesis by mineral fibers is noted. Consistency is re-established, however, when cognizance is taken of the change in the length and aspect ratio that took place during residence in the lung. This change resulted in a severalfold excess for ferroactinolite of all fiber lengths with high aspect ratios, produced as a result of longitudinal splitting of the introduced fibers. The response by mass in the in vitro procedures did not mimic oncogenesis. When mass was so adjusted that there were an equal number of mineral fibers, aspect ratio greater than 3, for dose for the two minerals, agreement was closer in both the rabbit alveolar macrophage toxicity test and the clonal cytotoxicity assay in Chinese hamster ovary cells. When activity was related to the number of mineral fibers, the same aspect ratio computed to have been contained in the mass dose, agreement with the relative induction of lung tumors was closer. In all cases, erythrocyte lysis was more active in reflecting the number of mineral fibers.

Topics: Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Lung; Lung Neoplasms; Minerals; Pleura; Pleural Neoplasms; Rats; Rats, Inbred F344

In lifetime exposure of male Fischer-344 rats to ferroactinolite fibers and to UICC amosite asbestos fibers by means of intratracheal and intrapleural treatments, oncogenesis was greater in the lung for the ferroactinolite and in the pleura for the amosite. The lack of correlation between the effects of the two methods of exposure suggests that in this instance intrapleural inoculation was not a good predictor of pulmonary response on the basis of mass dose. Another feature of the ferroactinolite was that pleural tumors resulted from intratracheal instillations. Conversely, lung tumors or tumorlike lesions were also induced by intrapleural inoculations of ferroactinolite. These facts suggest a greater in vivo transport for the ferroactinolite than for the amosite. Since there are far fewer mineral fibers per mass unit in the ferroactinolite the tumor yield per unit of mineral fibers was strikingly greater by both routes of administration for ferroactinolite than for amosite.

Topics: Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Carcinogens; Injections; Intubation, Intratracheal; Male; Minerals; Pleura; Rats; Rats, Inbred F344

Rats were exposed to amosite asbestos and ferroactinolite fibers by intrapleural inoculation and intratracheal instillation. The ferroactinolite sample was found to be more carcinogenic in both exposures than the amosite sample on the basis of total fiber dose or fiber dose expressed for any size category of hypothetical greatest carcinogenic potency. Quantitative transmission electron microscope analysis of low-temperature ashed whole lung samples collected at different times following intratracheal instillation of fibers demonstrated that concentrations and sizes of fibers retained in rat lungs were greatly influenced by the relative ability of each mineral to undergo longitudinal splitting as a consequence of dissolution in vivo. Ferroactinolite fibers rapidly split to produce many thin fibers so that the number of ferroactinolite fibers retained in the lung 2 years after intratracheal instillation was four times greater than the number of fibers originally instilled. The number of short, thin ferroactinolite fibers retained (10-fold more than amosite) after in vivo splitting best explains the greater lung carcinogenicity of ferroactinolite compared to amosite.

Topics: Animals; Asbestos; Asbestos, Amosite; Asbestos, Amphibole; Carcinogens; Intubation, Intratracheal; Lung; Male; Minerals; Rats; Rats, Inbred F344; Time Factors