A rationale for assessing exposure-dose-response relationships for occupational dust-related lung disease.
Vincent JH; Mark D; Jones AD; Donaldson K
Proceedings of the VIIth International Pneumoconioses Conference, August 23-26, 1988, Pittsburgh, Pennsylvania, USA. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 90-108, 1990 Sep; (Part I):151-157
A dosimetric approach for assessing dose response relationships for dust related occupational lung diseases was described. A quantitative dosimetric model was derived based on considerations of exposure intensity, rate of deposition in the lungs, time dependent history of exposure, chemical composition of the agent, and indices of the biological response. The model consisted of an equation that expressed cumulative dose as the sum of the mass of material deposited in the lung for a specified time after exposure times the product of a retention function and damage function summed over the elapsed time since the agent was deposited in the lung. The model was illustrated by applying it to a cell lavage study of rats that had been exposed by inhalation to 50mg/m3 quartz (14808607) and titanium-dioxide (13463677). Influx of neutrophils into the lavage fluid represented the damage function. Inhalation of titanium- dioxide provoked an increased neutrophil influx that decreased sharply after exposure stopped. This suggested that the intrinsic harmfulness of titanium-dioxide was not persistent but that the damage function decayed with time. The neutrophil influx induced by quartz was much larger and persisted after exposure ended. This indicated that the damage function for quartz was much larger than that of titanium-dioxide and did not decline after exposure ended. The authors conclude that the dosimetric approach should be useful for assessing risks associated with inhaling airborne particles. If it can be validated it should be useful in epidemiological studies.
Mathematical models; Occupational diseases; Respiratory system disorders; Mineral dusts; Dose response; Lung cells; Simulation methods; In vivo studies; Laboratory animals
DHHS (NIOSH) Publication No. 90-108
Proceedings of the VIIth International Pneumoconioses Conference, August 23-26, 1988, Pittsburgh, Pennsylvania, USA