This article briefly reviews the history of the current threshold limit value and the permissible exposure limit for occupational dusts derived originally from the Nuisance Dust standard. Chronic inhalation studies of appropriate design are described in terms of their key findings and potential impact on the dust standards, especially modern, experimental studies which have been affected by the problem of dust overloading. Many studies show that dust overloading produces a significant and progressive retardation of macrophage-mediated dust removal leading to various dysfunctional and pathologic changes which confound the interpretation of chronic toxicity study findings. Assuming that there may be a human counterpart to this condition at the same milligram dust per gram lung concentration, extrapolation modeling can be used to show that the current occupational dust limits do not protect worker lungs from this eventuality. Several bases for substantially reducing the current occupational standards are discussed.

This paper briefly reviews the development of regulatory agency guidelines for toxicity testing and the impact of the maximum tolerated dose (MTD) concept on chronic study designs within and outside of the regulatory arena. From the orientation of an inhalation toxicologist, the MTD is viewed as a difficult and costly concept to implement and one that is generally inappropriate as a general basis for setting dust exposure levels in sub-chronic and chronic inhalation toxicity studies. Two possible alternatives are discussed, especially in the context of accumulating evidence that most dusts, even the most innocuous, when presented in excessive amounts produce a spectrum of pulmonary responses that cannot be dissociated from injury.

Several investigators have described an initial “lag” in the phagocytic rates of macrophages in assay systems involving these phagocytes in monolayer. In the present study, we determined whether this apparent lag in phagocytic activity is due to a delay in the onset of macrophage phagocytic function perse, or if the lag phase can be explained by a relative lack of particle availability in terms of particle encounters and binding during the early phases of a phagocytic assay. Studies involving the pre-binding of opsonized erythrocytes to macrophages revealed that the lag in phagocytosis usually seen in assay systems involving macrophages in monolayer is related to particle availability.

Coal dust aerosols with cesium-134 and scandium-46 labels were studied in dogs and rats following brief inhalation exposures by external measurement of gamma photons in the 0.6 to 0.8 and 0.9 to 1.1 MeV regions, respectively. Ancillary in vitro studies of the leaching characteristics of the two radionuclides from coal were made and control studies utilizing the "free" radionuclides were undertaken for each of the investigations with radioactive coal dust. The biological data strongly infer that coal dust retention in canine lungs is extremely protracted with a biological half-life no shorter than approximately 4.3 yr and probably much longer. The biological model which was formulated and analyzed to obtain this finding is discussed along with its limitations.

Studies of tantalum dust labelled with 182Ta in dogs following either inhalation or insufflation exposures demonstrated that (a) the “alveolarization” of tantalum dust leads to prolonged retention, viz., a mean biological removal half-time greater than two years; (b) mucociliary transport, the dominant clearance mechanism, was somewhat longer than that reported for other "insoluble" dusts and apparently independent of the absolute amount of tantalum present; (c) the minimal surface density suitable for clinical bronchography is of the order of 10 mg tantalum/cm2 of bronchial surface; and (d) radiographic assessments of either airways or alveolar areas cannot utilize a surface deposition of ≤mg/cm2 tantalum and therefore are of limited value in quantitative applications, e.g., absolute tantalum retention.

Pulmonary and lymph node lesions and leukopenia which developed in dogs after plutonium-239 and -238 dioxide inhalation have been related to various radiation dose parameters, over a wide range of postexposure time intervals (16-468 days). The degree of radiation pathology in lungs was found to increase with increasing accumulated alpha doses above 1500-2000 rads and up to about 15,000 rads. In general no damage to tracheobronchial lymph nodes was evident unless radiation changes were also present in the lungs. The degree and extent of the lymph node changes did not correlate well with estimates of total lymph node dose, but there was a relatively good relationship with dose rate (rads per day) to the lymph nodes adjacent to trachea and main bronchi. Radiation changes in both types of tissue, and due to both plutonium isotopes, were unrelated to length of postexposure period except for increasing fibrosis with time. In contrast, the leukopenia which developed was related to mean, post-exposure, fixed tiss...

Recent technological advancements and newly available radioactive, isotopic aerosols have accelerated and broadened experimental investigations of dust deposition and retention in the human respiratory system. Collectively, these studies have provided a much improved basis for designing respiratory models of interest and value to biomedical research, and particularly to environmental scientists, occupational hygienists, and health physicists. This communication reviews these models chronologically and includes some recent information which appears to correlate deposition and clearance to measurements of the inhaled aerosol. It concludes with a brief critique.