You are here:
Responses of Fischer Rats to Intratracheal Instillations of PM2.5 Samples of Libby Amphibole (LA), Sumas Mountain Chrysotile, EI Dorado Tremolite, and Ontario Actinolite.
Citation:
Cyphert, J. M., D. J. Padilla-Carlin, M. SCHLADWEILER, A. Nyska, J. H. Shannahan, U. P. KODAVANTI, AND S. H. GAVETT. Responses of Fischer Rats to Intratracheal Instillations of PM2.5 Samples of Libby Amphibole (LA), Sumas Mountain Chrysotile, EI Dorado Tremolite, and Ontario Actinolite. Presented at 2011 ASTM Johnson Conference, Burlington, VT, July 25 - 29, 2011.
Impact/Purpose:
Animal models of asbestos exposure provide valuable insight into the health effects of these exposures in the human population. Respirable fractions of several environmental asbestos samples were intratracheally instilled in rats and comparative acute toxicological effects were assessed.
Description:
To support risk assessment efforts, a comparative intratracheal instillation (IT) study is being conducted to provide mechanistic understanding of the toxicity of different types of fibers encountered in EPA clean-up efforts. While other types of asbestos have been shown to cause differential toxicity and carcinogenicity, the relative toxicity of Libby Amphibole (LA) compared to other site-specific samples is unknown. Physico-chemical properties, and consequentially toxicity and carcinogenicity, are likely to be different among various fiber types. Several naturally occurring "environmental asbestos" samples were obtained, and respirable fractions (aerodynamic diameter < 2.5 um) were prepared by water elutriation. The current study was designed to compare the acute toxicity of LA with Sumas Mountain chrysotile (SM), EI Dorado tremolite (ED), and Ontario actinolite/ferroactinolite "cleavage fragments" (ON) on a mass basis (0.5 and 1.5 mg/rat). BALF endpoints were analyzed to assess lung inflammation and injury. At 1 d post-instillation, BALF cellularity was significantly increased in all asbestos-exposed groups. Specifically, low-dose (0.5 mg/rat) exposure to all samples resulted in a 3-4 fold increase in total cells compared to controls. High-dose (1.5 mg/rat) exposure had a more variable effect on lung inflammation. Exposure to high-dose LA resulted in a 4 fold increase in total cells, SM a 7 fold increase and both ON and ED exposure resulted in a 9 fold increase compared to controls. Although inducing less acute inflammation, exposure to either LA or SM resulted in a greater degree of acute lung injury. This trend in lung injury was reflected in baseline lung function. One week after instillation, an increase in Penh, a parameter correlated with airway resistance, was only noted in rats exposed to high-dose LA or SM. Three months after exposure, BALF total cells were still 1.5 fold higher in high-dose LA, ON, and ED-exposed rats. Inflammation in all other groups had returned to control levels. Additionally, increases in several lung injury markers were still elevated in LA-exposed rats 3 mo post-instillation, whereas most other groups had returned to baseline levels by this time. Despite a relative return to baseline of lung inflammatory and injury markers, only SM-treated rats exhibited elevated resting Penh 3 mo after exposure. These data show that by mass dose, SM chrysotile may have more potent acute effects, whereas LA amphibole exhibits more prolonged toxicological effects compared to other samples in terms of biological markers. However, SM chrysotile appears to have longer lasting effects on lung function. (This abstract does not represent U.S. EPA policy).