David M. Bernstein

Testing of Fibrous Particles: Short-Term Assays and Strategies

WORKING GROUP David Bernstein (Consultant, Geneva, Switzerland) Vince Castranova (National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA) Ken Donaldson (University of Edinburgh Medical School, Edinburgh, UK) Bice Fubini (Interdepartmental Center “G. Scansetti” for Studies on Asbestos and other Toxic Particulates, University of Torino, Italy) John Hadley (Owens Corning Science and Technology Center, Granville, OH, USA) Tom Hesterberg (International Truck and Engine Corp., Warrenville, IL, USA) Agnes Kane (Brown University School of Medicine, Providence, RI, USA) David Lai (U.S. Environmental Protection Agency, Washington, DC, USA) Ernest E. McConnell (ToxPath, Inc., Raleigh, NC, USA) Hartwig Muhle (Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany) Gunter Oberdorster (University of Rochester School of Environmental Medicine, Rochester, NY, USA) Stephen Olin (ILSI Risk Science Institute, Washington, DC, USA) David B. Warheit (DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, DE, USA)

Chronic Inhalation Toxicity of a Kaolin-Based Refractory Ceramic Fiber in Syrian Golden Hamsters

AbstractKaolin-based refractory ceramic fiber (RCF) is a man-made vitreous fiber used primarily in industrial high-temperature applications, especially for insulation of furnaces and kilns. Because of its increasing use and potential for human exposure, a chronic toxicity/ carcinogenicity inhalation study was conducted in Syrian golden hamsters. Two groups of 140 weanling male hamsters were exposed via nose-only inhalation to either HEPA-filtered air (chamber controls) or 30 mg/m3 (-220 fibers/cm3) of “size-selected” RCF fibers (1 µm in diameter and -25 /jm in length) for 6 h/day, 5 dayslwk for 18 mo. They were then held unexposed until -20% survival (20 mo). A positive control group of 80 hamsters was exposed to 10 mg/m3 chrysotile asbestos (0.09 µm average diameter and 2.2 µm average length). Groups of 3 hamsters were sacrificed at 3, 6, 9, 12, 15, and 18 mo to follow the progression of lesions. Additional groups of 3 hamsters were removed from exposure at 3, 6, 9, and 12 mo and were held until 18 mo (r...

The Laskin aerosol generator

This paper describes construction details and operating characteristics of a nebulizer developed by Sidney Laskin and used over a period of 30 yr in various laboratories to generate respirable aerosols for whole-animal inhalation exposure studies. Under the proper operating conditions, the device is capable of producing nearly monodisperse aerosols in the respirable size range (1.5 micron volume median diameter with a geometric standard deviation of 1.1) for long periods of time

The Toxicological Response of Brazilian Chrysotile Asbestos: A Multidose Subchronic 90-Day Inhalation Toxicology Study with 92-Day Recovery to Assess Cellular and Pathological Response

Inhalation toxicology studies with chrysotile asbestos have in the past been performed at exceedingly high doses without consideration of fiber number or dimensions. As such, the exposures have exceeded lung overload levels, making quantitative assessment of these studies difficult if not impossible. To assess the cellular and pathological response in the rat lung to a well-characterized aerosol of chrysotile asbestos, a 90-day subchronic inhalation toxicology study was performed using a commercial Brazilian chrysotile (CA 300). The protocol was based on that established by the European Commission for the evaluation of synthetic vitreous fibers. The study was also designed to assess the potential for reversibility of any such changes and to permit association of responses with fiber dose in the lung and the influence of fiber length. Wistar male rats were randomly assigned to an air control group and to 2 CA 300 exposure groups at mean fiber aerosol concentrations of 76 fibers L > 20 μm/cm3 (3413 total fibers/cm3; 536 WHO fibers/cm3) or 207 fibers L > 20 μm/cm3 (8941 total fibers/cm3; 1429 WHO fibers/cm3). The animals were exposed using a flow-past, nose-only exposure system for 5 days/wk, 6 h/day, during 13 consecutive weeks (65 exposures), followed by a subsequent nonexposure period lasting for 92 days. Animals were sacrificed after cessation of exposure and after 50 and 92 days of nonexposure recovery. At each sacrifice, subgroups of rats were assessed for the determination of the lung burden; histopathological examination; cell proliferation response; bronchoalveolar lavage with the determination of inflammatory cells; clinical biochemistry; and for analysis by confocal microscopy. Through 90 days of exposure and 92 days of recovery, chrysotile at a mean exposure of 76 fibers L > 20 μm/cm3 (3413 total fibers/cm3) resulted in no fibrosis (Wagner score 1.8 to 2.6) at any time point. The long chrysotile fibers were observed to break apart into small particles and smaller fibers. In vitro modeling has indicated that these particles are essentially amorphous silica. At an exposure concentration of 207 fibers L > 20 μm/cm3 (8941 total fibers/cm3) slight fibrosis was observed. In comparison with other studies, chrysotile produced less inflammatory response than the biosoluble synthetic vitreous fiber CMS. As predicted by the recent biopersistence studies on chrysotile, this study clearly shows that at that at an exposure concentration 5000 times greater than the U.S. threshold limit value of 0.1 f(WHO)/cm3, chrysotile produces no significant pathological response.

The major parameters affecting temperature inside inhalation chambers

Variations in inhalation chamber temperature can produce alterations in animal physiology, metabolism of foreign compounds as well as the chemical interaction of pollutant aerosols. This report presents the results of an investigation of the different mechanisms of heat transfer in a 380 L inhalation chamber and discusses the relative effectiveness of various methods that may be used to maintain a uniform chamber temperature during animal exposures. The thermal characteristics of the inhalation chamber were studied using an array of 40 thermocouples, with and without rats in the chamber and with and without 5 cm fiber glass insulation surrounding the chamber. Temperature profiles were measured with different animal loadings and intake air temperatures. An effective heat transfer coefficient of 6.6 +/- 1.8 W/m2 degrees C was determined for the stainless steel walls of the chamber. Heat balance studies with rats in this chamber have shown that with room air intake at a flow rate of 100 L/min, the stainless steel chamber walls were effective at removing approximately ninety percent of the animal heat as compared to the airstream.