Pulmonary clearance of UICC amosite fibres inhaled by rats during chronic exposure at low concentration.

Abstract

Clearance of UICC amosite asbestos from the lungs during chronic-that is, repeatedexposure was investigated by using the scanning electron microscope to measure lung burdens from rats which had inhaled amosite asbestos at an approximately constant concentration of0-1 mg/m3 or, equivalently, 20 fibres/ml for seven hours a day, five days a week for up to 18 months. The lung burdens were compared with previous results for higher exposure concentrations of 1 and 10 mg/m3. Those previous lung burdens had been measured using other analytical methods (infrared spectrophotometry) that were not suitable for the new lower lung burdens. Taken together, these results showed lung burdens rising pro rata with exposure concentration and exposure time. This accumulation of lung burden has been described by a kinetic model that takes account of the sequestration ofmaterial at locations in the lung from where it cannot be cleared. Unlike some earlier models in which lung burdens eventually reach a plateau with equilibrium between deposition and clearance during chronic exposure, this sequestration model shows lung burdens continuing to rise with exposure time. The latest results reported here support the application of such a model to lower exposure concentrations closer to those of asbestos in workplaces.The amount of material retained by the lung during and after exposure to airborne dusts is determined by the physical processes governing inhalation and deposition and the biological processes governing clearance. In some circumstances the dust may be inhaled on a single occasion (which is often the concern with, for example, radioactive aerosols) and the amount of material retained (at any subsequent time) may be estimated from mathematical models describing the clearance of particles from the lung. More In a previous paper we reported the results of an experiment in which two groups of rats were exposed to amosite asbestos at two respirable concentrations (1 and 10 mg/m3) for periods up to one year.7 Under the overload hypothesis it was expected that, for the lower concentration, the lung burden would not reach the critical level at which clearance mechanisms were expected to be overloaded. Moreover, for the lower concentration, it was expected that the rates of deposition DL into, and clearance from, the lung would eventually reach equilibrium and the lung burden BL would reach a plateau during continued chronic exposure at constant concentration. When this occurs, 300 Pulmonary clearance of UICC amositefibres inhaled by rats during chronic exposure at low concentration 301 fibres/ml for fibres longer than 5 gm). The aim is to examine the extent to which ideas developed at higher concentrations may be applied at much lower ones that are more akin to exposure to asbestos at the workplace. MethodsThe experiment was conducted using outbred male SPF Wistar rats of the AF/HAN strain, exposed to airborne dust of UICC amosite in a 1 m3 inhalation chamber in separate groups of 12 animals (with up to 48 in the chamber ...

Pulmonary Endpoints (Lung Carcinomas and Asbestosis) Following Inhalation Exposure to Asbestos

“… Jones et al (1988) extended the inhalation studies to lower concentrations; rats inhaled UICC amosite asbestos at approximately 0.1 mg/m 3 (equivalent to 20 fibers/ml) for 7 h/d, 5 d/wk, for up to 18 mo. The lung burdens were compared with the previous results for concentrations of 1 and 10 mg/m 3 .…”

Inferences on the kinetics of asbestos deposition and clearance among chrysotile miners and millers

“…The ''overload'' hypothesis [Bolton et al, 1983] suggests that at high dust burdens clearance mechanisms will fail, and dust will continue to accumulate beyond the plateau level. On the other hand, the ''sequestration'' model [Jones et al, 1988] suggests that lung burdens will continue to increase with exposure because of the ongoing sequestration of fibers in a compartment with very slow or absent clearance. Clearance kinetics may differ in humans and rodents.…”

A Biomathematical Model of Particle Clearance and Retention in the Lungs of Coal Miners

“…Another process that can result in higher lung dust burdens than expected from first-order clearance is sequestration, the retention of some portion of dust that is unavailable for clearance (Soderholm, 1981). Sequestration may occur as a first-order process at any exposure (Vincent et al, 1987;Jones et al, 1988b) or as a consequence of the overloading of alveolar-macrophagemediated clearance (Tran et al, 1997;Stöber et al, 1989). Thus, lung dust burdens that exceed the steadystate burden expected with simple first-order clearance could be due to sequestration, overloading, or a combination of both processes.…”