Route of exposure alters inflammation and lung function responses to diesel exhaust
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Context: Mice are commonly used in studies investigating the effects of diesel exhaust exposure on respiratory health. A plethora of studies in this field has resulted in a range of exposure protocols, from inhalation of diesel exhaust, to the administration (via various routes) of diesel exhaust particles in solution.Objective: In this study, we compared the physiological consequences of short-term exposure to diesel exhaust via inhalation to those due to exposure to the same diesel exhaust particles suspended in solution and delivered intranasally.Materials and methods: Adult BALB/c mice were exposed to diesel exhaust via inhalation for 2 hours per day for 8 days. A representative, simultaneous sample of particles was collected and a second group of mice then exposed to them suspended in saline. A low and a high-dose were studied, with these matched based on respiratory parameters. Six and twenty-four hours after the last exposure we measured bronchoalveolar inflammation, lung volume, lung function and the amount of elemental carbon in alveolar macrophages.Results: Exposure via either route elicited pulmonary inflammation and changes in lung function. We identified significant differences in response between the two routes of exposure, with mice exposed via inhalation generally displaying more realistic dose-response relationships. Mice exposed via intranasal instillation responded more variably, with little influence of dose.Conclusions: Our results suggest that selection of the route of exposure is of critical importance in studies such as this. Further, inhalation exposure, while more methodologically difficult, resulted in responses more akin to those seen in humans.Keywords:
Inhalation exposure
Lung cancer following inhalation in rodents is a major concern regarding exposure to cobalt substances. However, little information is available on adverse effects and toxicity following long-term inhalation exposure to poorly soluble cobalt substances with low bioavailability. Thus, the present study focused on pulmonary effects of the poorly soluble tricobalt tetraoxide (5, 20, 80 mg/m³) in a 28-day inhalation exposure study. Lung weights increased with increasing exposures. Bronchoalveolar lavage fluid analysis and histopathology revealed lung tissue inflammation at the mid-dose with increasing severity in the high-dose group and post-exposure persistency. Markers for cellular damage and cell proliferation were statistically significantly increased. No increase in 8-OH-dG lesions was observed, indicating an absence of oxidative DNA lesions. The primary effect of inhaled Co3O4 particles is inflammation of the respiratory tract strongly resembling responses of inhaled "inert dust" substances, with a NOAEC of 5 mg/m³ under the conditions of this test.
Inhalation exposure
Pulmonary toxicity
Respiratory tract
No-observed-adverse-effect level
Histopathology
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Abstract Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m 3 . Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m 3 ) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.
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The automobile industry plans to increase production of diesel-powered passenger cars because diesel engines provide better fuel economy than conventional gasoline engines. Diesel engines, however, produce more soot, and increased use of diesel cars will result in more discharge of diesel soot into the atmosphere. Recently, a new class of chemicals, called nitroaromatic compounds, have been identified in chemical extracts of diesel soot. Some of these nitroaromatic compounds produce mutations when tested in in vitro bacterial and mammalian cell assays, and cancer when tested in animals. Here, we review the relevance of these new laboratory findings to current deliberations over emission standards for particles from diesel cars.
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The objective of this study was to determine the average reduction in inhalation exposures produced by intermittent use of filter cartridge respirators by cadmium workers. Inhalation exposure was estimated by measuring the cadmium concentration inside the respirator while it was worn or hanging around the worker's neck. Air concentrations of cadmium were measured simultaneously inside the respirator and at the worker's lapel with a dual sampling system. Each of nine workers were measured on three consecutive days for a full work shift. The average inhalation exposures ranged from 3 to 67 micrograms/m3 while the TWA lapel concentrations ranged from 19 to 3600 micrograms/m3; respirator use produced a substantial reduction in inhalation exposures when lapel concentrations were above 100 micrograms/m3. On the average, the inhalation exposure was 26% of the lapel concentration, but the effective protection varied widely between individuals and from day to day. If used cautiously, this relationship may be useful for estimating the approximate average inhalation exposure of a group of workers routinely using half mask respirators.
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ABSTRACT Diesel exhaust (DE) characteristic of pre-1988 engines is classified as a "probable" human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC), and the U.S. Environmental Protection Agency has classified DE as "likely to be carcinogenic to humans." These classifications were based on the large body of health effect studies conducted on DE over the past 30 or so years. However, increasingly stringent U.S. emissions standards (1988–2010) for particulate matter (PM) and nitrogen oxides (NOx) in diesel exhaust have helped stimulate major technological advances in diesel engine technology and diesel fuel/lubricant composition, resulting in the emergence of what has been termed New Technology Diesel Exhaust, or NTDE. NTDE is defined as DE from post-2006 and older retrofit diesel engines that incorporate a variety of technological advancements, including electronic controls, ultra-low-sulfur diesel fuel, oxidation catalysts, and wall-flow diesel particulate filters (DPFs). As discussed in a prior review (T. W. Hesterberg et al.; Environ. Sci. Technol. 2008, 42, 6437-6445), numerous emissions characterization studies have demonstrated marked differences in regulated and unregulated emissions between NTDE and "traditional diesel exhaust" (TDE) from pre-1988 diesel engines. Now there exist even more data demonstrating significant chemical and physical distinctions between the diesel exhaust particulate (DEP) in NTDE versus DEP from pre-2007 diesel technology, and its greater resemblance to particulate emissions from compressed natural gas (CNG) or gasoline engines. Furthermore, preliminary toxicological data suggest that the changes to the physical and chemical composition of NTDE lead to differences in biological responses between NTDE versus TDE exposure. Ongoing studies are expected to address some of the remaining data gaps in the understanding of possible NTDE health effects, but there is now sufficient evidence to conclude that health effects studies of pre-2007 DE likely have little relevance in assessing the potential health risks of NTDE exposures. IMPLICATIONS Based on the distinct physical and chemical properties of New Technology Diesel Exhaust (NTDE), it has become clear that findings from the health effects studies conducted on traditional DE (TDE) over the last 30 years have little relevance to NTDE, which is more similar to the exhaust from compressed natural gas (CNG) or gasoline engine emissions than to traditional TDE. Once sufficient health effects data are available for NTDE, it will thus be necessary to conduct new hazard and risk assessments for NTDE that are independent of the DE toxicological database acquired on emissions from pre–2007 diesel technology.
Diesel exhaust fluid
Ultra-low-sulfur diesel
Vegetable oil refining
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We evaluated the pulmonary pathological features of rats that received a single intratracheal instillation and a 4-week inhalation of a fullerene. We used fullerene C60 (nanom purple; Frontier Carbon Co. Ltd, Japan) in this study. Male Wistar rats received intratracheal dose of 0.1, 0.2, or 1 mg of C60, and were sacrificed at 3 days, 1 week, 1 month, 3 months, 6 months, and 12 months. In the inhalation study, Wistar rats received C60 or nickel oxide by whole-body inhalation for 6 h/day, 5 days/week, 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. During the observation period, no tumors or granulomas were observed in either study. Histopathological evaluation by the point counting method (PCM) showed that a high dose of C60 (1 mg) instillation led to a significant increase of areas of inflammation in the early phase (until 1 week). In the inhalation study of the C60-exposed group, PCM evaluation showed significant changes in the C60-exposed group only at 3 days after exposure; after 1 month, no significant changes were observed. The present study demonstrated that the pulmonary inflammation pattern after exposure to well-characterized C60 via both intratracheal and inhalation instillation was slight and transient. These results support our previous studies that showed C60 has no significant adverse effects in intratracheal and inhalation instillation studies.
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The inhalation toxicity of carbon nanofibers (CNFs) is not clearly known due to relatively few related studies reported. An acute inhalation study and short-term inhalation study (5 days) were therefore conducted using Sprague-Dawley rats. In the acute inhalation study, the rats were grouped and exposed to a fresh air control or to low (0.238 ± 0.197), moderate (1.935 ± 0.159), or high (24.696 ± 6.336 mg/m3) CNF concentrations for 6 h and thereafter sacrificed at 14 days. For the short-term inhalation study, the rats were grouped and exposed to a fresh air control or low (0.593 ± 0.019), moderate (2.487 ± 0.213), or high (10.345 ± 0.541 mg/m3) CNF concentrations for 6 h/day for 5 days and sacrificed at 1, 3, and 21 days post-exposure. No mortality was observed in the acute inhalation study. Thus, the CNF LC50 was higher than 25 mg/m3. No significant body or organ weight changes were noted during the 5 days short-term inhalation study or during the post-exposure period. No significant effects of toxicological importance were observed in the hematological, blood biochemical, and coagulation tests. In addition, the bronchoalveolar lavage (BAL) fluid cell differential counts and BAL inflammatory markers showed no CNF-exposure-relevant changes. The histopathological examination also found no CNF-exposure-relevant histopathological lesions. Thus, neither acute nor 5 days inhalation exposure to CNFs induced any noticeable toxicological responses.
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We performed the two inhalation exposures, whole-body inhalation and nose-only inhalation, to investigate the pulmonary deposition and health effects of the two inhalation methods. In both methods, we exposed rats to the same TiO2 nanoparticles at almost the same exposure concentration for 6 h and compared the deposited amounts of nanoparticles and histopathological changes in the lungs. Rats were exposed to rutile-type TiO2 nanoparticles generated by the spray-dry method for 6 h. The exposure concentration in the whole-body chamber was 4.10 ± 1.07 mg/m3, and that in nose-only chamber was 4.01 ± 1.11 mg/m3. The particle sizes were 230 and 180 nm, respectively. A control group was exposed to fresh air. The amounts of TiO2 deposited in the lungs as measured by ICP-AES after acid digestion just after the exposure were: 42.6 ± 3.5 μg in the whole-body exposure and 46.0 ± 7.7 μg in the nose-only exposure groups. The histopathological evaluation was the same in both exposure groups: no infiltration of inflammatory cells in the alveolar space and interstitium, and no fibrosis. The two inhalation methods using the same material under the same exposure conditions resulted in the same particle deposition and histopathology in the lung.
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Intratracheal instillation
Histopathology
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