LUNG-CANCER IN RATS FROM PROLONGED EXPOSURE TO HIGH-CONCENTRATIONS OFCARBONACEOUS PARTICLES - IMPLICATIONS FOR HUMAN RISK ASSESSMENT

High incidences of lung cancers have been observed in a number of stud ies in which rats were chronically exposed by inhalation to high conce ntrations of diesel engine exhaust and carbon black particles. These p articles have previously been viewed as being relatively innocuous com pared with other particles such as benzo[a]pyrene that are carcinogeni c because of specific chemical properties. Studies with mice and Syria n hamsters exposed to similar concentrations of diesel exhaust did not produce an excess of lung cancer or yielded equivocal outcomes. Diese l exhaust soot and carbon black particles are readily inhaled and depo sited in the pulmonary region, where they are retained with a long hal f-life because of their low solubility. Substantial evidence indicates that the increased incidence of at lung cancers results from the accu mulation of large burdens of particles in the lungs, altered clearance of particles from the lungs, persistent inflammation, increased cell turnover, and induction of mutations in lung epithelial cells. The mut ations and subsequent rumors are hypothesized to occur as a result of persistent inflammation and increased cell turnover rather than as a r esult of direct interaction of chemical constituents of the particles with DNA of lung cells. The observed effects in rats appear to be thre shold phenomena that occur only with prolonged exposure to high concen trations of particles. Thus the rat lung cancer findings at high conce ntrations should not be extrapolated to low concentrations using the l inearized multistage model typically used as a default assumption for assessing the cancer risk of chemicals. This article reviews past appr oaches to evaluating the carcinogenic risk of diesel exhaust and carbo n black and suggests alternative approaches to characterizing their hu man cancer risk.