Pulmonary response to toner upon chronic inhalation exposure in rats

Muhle, H.; Bellmann, B.; Creutzenberg, Otto; Dasenbrock, Clemens; Ernst, Heinrich; Kilpper, R.; MacKenzie, Jane; Morrow, Paul E.; Möhr, U.; Takenaka, Shinji; Mermelstein, Robert

doi:10.1016/0272-0590(91)90219-t

Cited by 127 publications

(57 citation statements)

References 23 publications

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“…The aerosol mass median aerodynamic diameter (MMAD) of 800 nm (geometric standard deviation, GSD 1.4) and count median diameter (CMD) of 900 nm (1.8 GSD) were very similar and together indicate that TiO 2 NPs agglomerated in air. This is consistent with reports that aerosolized TiO 2 tends to agglomerate to ~0.7-1.5 μm in air whether the material has a primary size in the micrometer range [7,14-16] or in the nanometer range [6,8,9]. The aerosol diameters were the same at concentrations of 33 ± 4 mg/m 3 or 13 ± 1 mg/m 3 and over the course of the exposures, indicating that the animals were exposed to similarly sized agglomerates.…”

Section: Resultssupporting

confidence: 92%

Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation

et al. 2014

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BackgroundThe increased production of nanomaterials has caused a corresponding increase in concern about human exposures in consumer and occupational settings. Studies in rodents have evaluated dose–response relationships following respiratory tract (RT) delivery of nanoparticles (NPs) in order to identify potential hazards. However, these studies often use bolus methods that deliver NPs at high dose rates that do not reflect real world exposures and do not measure the actual deposited dose of NPs. We hypothesize that the delivered dose rate is a key determinant of the inflammatory response in the RT when the deposited dose is constant.MethodsF-344 rats were exposed to the same deposited doses of titanium dioxide (TiO2) NPs by single or repeated high dose rate intratracheal instillation or low dose rate whole body aerosol inhalation. Controls were exposed to saline or filtered air. Bronchoalveolar lavage fluid (BALF) neutrophils, biochemical parameters and inflammatory mediator release were quantified 4, 8, and 24 hr and 7 days after exposure.ResultsAlthough the initial lung burdens of TiO2 were the same between the two methods, instillation resulted in greater short term retention than inhalation. There was a statistically significant increase in BALF neutrophils at 4, 8 and 24 hr after the single high dose TiO2 instillation compared to saline controls and to TiO2 inhalation, whereas TiO2 inhalation resulted in a modest, yet significant, increase in BALF neutrophils 24 hr after exposure. The acute inflammatory response following instillation was driven primarily by monocyte chemoattractant protein-1 and macrophage inflammatory protein-2, mainly within the lung. Increases in heme oxygenase-1 in the lung were also higher following instillation than inhalation. TiO2 inhalation resulted in few time dependent changes in the inflammatory mediator release. The single low dose and repeated exposure scenarios had similar BALF cellular and mediator response trends, although the responses for single exposures were more robust.ConclusionsHigh dose rate NP delivery elicits significantly greater inflammation compared to low dose rate delivery. Although high dose rate methods can be used for quantitative ranking of NP hazards, these data caution against their use for quantitative risk assessment.

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Section: Resultssupporting

confidence: 92%

Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation

et al. 2014

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“…Comparable inflammatory and fibrotic responses were also observed in rats exposed to toner powders (Morimoto et al, 2013). A historic rodent chronic inhalation exposure concluded that toner led to a substantial increase in lung weight, a chronic inflammatory response, pulmonary fibrosis and increased incidence of primary lung tumors in exposed rats (Muhle et al, 1991). However, as extensive as these studies were in identifying the biological response in the rodent lung following exposure to toner, they are limited by addressing only the toxicity of toner powder, which may be relevant to occupational settings and workers directly handling toner powders but is not applicable to consumers using laser printers.…”

Section: Introductionmentioning

confidence: 99%

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

Pirela

Miousse

et al. 2016

NanoImpact

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Incorporation of engineered nanomaterials (ENMs) into toners used in laser printers has led to countless quality and performance improvements. However, the release of ENMs during printing (consumer use) has raised concerns about their potential adverse health effects. The aim of this study was to use “real world” printer-emitted particles (PEPs), rather than raw toner powder, and assess the pulmonary responses following exposure by intratracheal instillation. Nine-week old male Balb/c mice were exposed to various doses of PEPs (0.5, 2.5 and 5 mg/kg body weight) by intratracheal instillation. These exposure doses are comparable to real world human inhalation exposures ranging from 13.7 to 141.9 h of printing. Toxicological parameters reflecting distinct mechanisms of action were evaluated, including lung membrane integrity, inflammation and regulation of DNA methylation patterns. Results from this in vivo toxicological analysis showed that while intratracheal instillation of PEPs caused no changes in the lung membrane integrity, there was a pulmonary immune response, indicated by an elevation in neutrophil and macrophage percentage over the vehicle control and low dose PEPs groups. Additionally, exposure to PEPs upregulated expression of the Ccl5 (Rantes), Nos1 and Ucp2 genes in the murine lung tissue and modified components of the DNA methylation machinery (Dnmt3a) and expression of transposable element (TE) LINE-1 compared to the control group. These genes are involved in both the repair process from oxidative damage and the initiation of immune responses to foreign pathogens. The results are in agreement with findings from previous in vitro cellular studies and suggest that PEPs may cause immune responses in addition to modifications in gene expression in the murine lung at doses that can be comparable to real world exposure scenarios, thereby raising concerns of deleterious health effects.

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“…The lung-associated lymph nodes were slightly enlarged and pigmented at the higher exposure concentrations. Since these findings will be supplemented by those obtained in the more extensive chronic inhalation study, their detailed interpretation will await the availability of such results (Muhle et al, 1990).…”

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confidence: 96%

Subchronic Inhalation Study of Toner in Rats

Muhle

Bellmann

Creutzenberg

et al. 1990

Inhalation Toxicology

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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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Pulmonary response to toner upon chronic inhalation exposure in rats

Cited by 127 publications

References 23 publications

Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation

Equivalent titanium dioxide nanoparticle deposition by intratracheal instillation and whole body inhalation: the effect of dose rate on acute respiratory tract inflammation

Effects of intratracheally instilled laser printer-emitted engineered nanoparticles in a mouse model: A case study of toxicological implications from nanomaterials released during consumer use

Subchronic Inhalation Study of Toner in Rats

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