Recent Chronic Inhalation Study Results And Their Implications On The Respirable Dust Standard

In a long term toxicology study SPF, F-344 rats were exposed 6 hours/day, 5 days/week for up to 24-months to a special test toner at 0, 1 (low), 4 (medium), and 16 (high) mg/m3, or Ti02 at 5 mg/m3, or Si02 at 1 mg/m3 by the inhalation route. The test toner was composed of about 90% random, high molecular weight acrylic copolymer and 10% high purity, medium color, furnace type, carbon black. It was enriched in fine particles such that the respirable aerosol concentrations (ACGIH) were to 0, 0.35, 1.4 and 5.6 mg/m3. There were no effects of exposure on survival, causes of death, body weight, food consumption or clinical chemistry and hematology parameters. There was no evidence for systemic or upper respiratory system toxicity as all of the changes were restricted to the lungs and associated lymph nodes. The lung tumor frequencies in the control (air and Ti02) and toner exposed groups were comparable. There were no changes at the low exposure level, which is the most relevant in regard to potential human exposures. The lung changes at the high exposure level consisted of decreased alveolar clearance, increased toner retention, increased lung weight, chronic inflammation, decreased pulmonary function and a moderate degree of focal fibrosis in all animals. The changes in the middle exposure level were smaller in magnitude than at the high level, and a very slight degree of fibrosis was found in 20% of the animals. In a follow-up investigation, female F-344 rats were exposed to one of three toner concentrations; control, low (10 mg/m3) or high (40 mg/m3) for 13 weeks followed by five, 13 week observation intervals. At the low exposure level, slight clearance retardation and modest inflammatory changes were observed at the end of exposure. They returned to normal values within six months post-exposure. In contrast, at the high exposure level, increased lung weight, decreased alveolar clearance and a disproportionate increase in toner retention, as well as an inflammatory response, were noted, which persisted throughout the post-exposure interval. While no significant histopathological changes were noted at the end of exposure, a very slight degree of fibrosis was observed in all of the animals in the high exposure group, after 65 weeks of observation. All of the above alterations are ascribable to "lung overloading", a generic response to excessive amounts of any dust retained in the lungs for a prolonged time interval. Published accounts in the toxicology literature document that long-term inhalation of large quantities of even innocuous particles such as Ti02, carbon black, petroleum coke, toner, and other polymeric and insoluble materials has resulted in a spectrum of generically similar pulmonary changes. Scaling of the rat-data, using 1 mg dust/g of lung as a threshold for "lung overloading", normal ventilatory parameters and 300-500 day human retention halftimes project "lung overloading" upon long-term exposure to insoluble respirable dust above 0.2-0.33 mg/m3. Other types of information are consistent with an exposure limit in the range of 0.4-1.0 mg/m3 for respirable dust. The absence of definitive toxicology data in support of the current OSHA respirable nuisance dust limit, coupled with the lack of sound epidemiology data, indicate the need to reexamine the validity of the current nuisance dust health standard.