Wistar rats were exposed for 2 y r to diesel engine exhaust, carbon black (Printex 90, Degussa, FRC), and ultrafine TiO, (P25, Degussa, FRC) and were subsequently kept in clean air for 6 mo. Particle exposure concentration was increased during the course of the experiment for carbon black and TiO, to reach particle lung loads similar to those found in the diesel soot-exposed rats. The average particle exposure concentrations for diesel soot, carbon black, and JiO, were 7, 11.6, and 70 mg/m', respectively. Lung tumor rates in these rats increased with increasing cumulative particle exposure (mg/m3 x h) independent of the type of particle employed. The exposure to 2.5 mg/m3 diesel soot also induced a significantly increased lung tumor rate, but 0.8 mg/m' diesel soot did not. With this study, it could be demonstrated that the carbon core of diesel soot is mainly responsible for the occurrence of diesel engine exhaust-related lung tumors; the role of diesel soot-attached polycyclic aromatic hydrocarbons (PAH) and NO,-PAH is probably of minor importance in the rat lung. Agglomerates of ultrafine carbon and TiO, particles seem particularly suited to exert toxic effects primarily on alveolar macrophages and alveolar lung particle clearance. Although such lung toxic effects were also seen with the lowest diesel soot exposure concentration (0.8 mg/m3) used, no increased lung tumor rate was detected in this group of rats. Whether this result implies a threshold for the particle-related lung tumor induction mechanism as already discussed by Vostal (7986) or whether the tumor effect was simply not observed because of statistical reasons needs further research on the possible mode of action of ultrafine insoluble particles in the lung. NMRl mice that were kept in the same exposure atmospheres (high diesel soot, car6on black, TiOJ as the rats did not show an increased lung tumor rate. furthermore, there was no treatment-related tumor response in NMRl nor in C57BL/6N mice exposed to diesel exhaust containing 4.5 mg/m3 diesel soot or to the same exhaust dilution but devoid of soot particles. C57BU6N mice were exposed for 24 mo and were subsequently kept in clean air for another 6 mo. Not only the average survival time but also the particle load per gram lung wet weight of the C57BL/6N mice was very similar to rats exposed to 7 mg/m' diesel soot.In 1986, the lung tumor-inducing activity of diesel engine exhaust in rats exposed to diesel soot concentrations of at least 2.2 mg/m3 was observed by various laboratories (Brightwell et al., 1986;Heinrich et al., 1986a;Mauderly et al., 1986). In 1987, based o n these results, diesel exhaust was classified in Germany as a carcinogenic working material. In

A long-term exposure study with hamsters, mice and rats inhaling filtered and unfiltered diesel engine exhaust was carried out to investigate effects of chronic toxicity and, predominantly, carcinogenicity in the respiratory tract. The level of diesel exhaust in the exposure chambers corresponded to a concentration close to 4 mg m-3 in the unfiltered diesel exhaust. Satellite groups of animals were additionally treated with BaP, DBahA or nitrosamines in order to check for syncarcinogenic effects. In hamsters and rats, alveolar lung clearance and mechanical lung function tests as well as biochemical and cytological measurements in lung lavage fluids showed significant changes only after exposure to unfiltered diesel exhaust and, predominantly, in rats. No lung tumors were found in hamsters. Spontaneous tumor rates occurred in mice and both types of diesel exhaust increased the incidence of adenocarcinomas in the lungs. In rats, only the unfiltered diesel exhaust caused a lung tumor incidence. It amounted to 16% with no tumors in the controls. The heavy load of particulate matter in the lungs of rats was caused by an exposure-related impairment of the alveolar lung clearance and may have been instrumental in the induction of squamous cell tumors. However, an effect of particle-associated PAH cannot be excluded. Syncarcinogenic effects of diesel exhaust after initial carcinogen treatment were found only in the respiratory tract of rats.

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Frau n hofer-l nstitut fur Toxi kologie u nd Aerosolforschung, Hannover, Federal Republic of Germany I A subchronic inhalation study of a special test toner was conducted by exposure of groups of F-344 SPF (specific pathogen free) rats for 6 hlday, 5 dayslwk for 73 wk. The test material was a special 9OOO type xerographic toner, enriched in respirable size particles compared to commercial toner, such that it was about 35% respirable according to the ACGIH criteria. The nominal aerosol exposure concentrations were 0, 7.0, 4.0, 76.0, and 64.0 mglm? Body weight, clinical chemistry values, food consumption, and organ weights were normal except for a 40% increase in lung weight for the highest exposure group. Histopathological examination of the lungs indicated an exposure-related accumulation of particle-laden alveolar macrophages. A very slight degree of septa1 thickening of the alveolar structure was noted in the highest exposure group. Clearance results for the test material and a superimposed spike of 59Fe203 were essentially unchanged at exposure concentrations of 0, 1, and 4 mg/m3. , At 76 mg/m3, some indications of retarded clearance were noted and at 64 mg/m3, no appreciable toner clearance was observed. The pulmonary changes observed at the two highest exposure levels are interpreted on the basis of the "lung overloading" concept. Based upon the above observations, as well as the increase in lung weight, both the maximum tolerated dose (MTD) and the maximum functionally tolerated dose of test toner (MFTD) in this subchronic study were exceeded at the 64 mg/m3 exposure level.Inhalation Toxicology Downloaded from informahealthcare.com by University of Auckland on 11/18/14For personal use only.

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