Lung particle overload: old school –new insights?

Borm, Paul; Cassee, Flemming R.; Oberdörster, Günter

doi:10.1186/s12989-015-0086-4

Cited by 60 publications

(39 citation statements)

References 29 publications

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“…a concentration where cell lethality begins to appear while the number of dead cells will not hamper the subsequent proteomic analysis. Another toxic mechanism in lungs lies in the lung overload phenomenon (recently reviewed in [60]), occurring when a sufficient amount of inert, particulate material has been ingested by the alveolar macrophages. Transposed to in vitro systems [61], this impairment phenomenon begins to appear at 0.4 μg/mm 2 , while 0.2 μg/mm 2 shows no effect.…”

Section: Discussionmentioning

confidence: 99%

A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

Aude-Garcia

Dalzon

Ravanat

et al. 2016

Journal of Proteomics

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The responses of the murine J774 macrophage cell lines to two types of metallic oxide nanoparticles (zinc oxide and zirconium dioxide) were studied by a comparative 2D gel based approach. This allows sorting of shared responses from nanoparticle-specific responses. Zinc oxide nanoparticles induced specifically a strong decrease in the mitochondrial function, in phagocytosis and also an increase in the methylglyoxal-associated DNA damage, which may explain the well known genotoxicity of zinc. In conclusion, this study allows highlighting of pathways that may play an important role in the toxicity of the zinc oxide nanoparticles.

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Section: Discussionmentioning

confidence: 99%

A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

Aude-Garcia

Dalzon

Ravanat

et al. 2016

Journal of Proteomics

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“…The rodent lung overloading mechanism has been well-studied for many types of poorly-soluble particles (recently reviewed in Pauluhn 2014a; Morfeld et al 2015; Borm et al 2015). At sufficiently high doses, the rodent (rat and mouse) alveolar macrophages become overloaded with engulfed particles, resulting in impaired pulmonary clearance and increased particle build-up and retention in the lungs (Bolton et al 1983; Morrow 1988; Elder et al 2005).…”

Section: Deposition Clearance and Retention Kinetics Relevant To Pomentioning

confidence: 99%

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

Kuempel

Jaurand

Møller

et al. 2016

Critical Reviews in Toxicology

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In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between in vitro and early-stage in vivo events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose–response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.

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“…Moreover, epidemiology or studies of chronic effects of engineered nanomaterials are scarce. GBP materials are also referred to as poorly soluble particles (PSPs) (Borm et al 2015) or poorly soluble low toxicity dusts (Dankovic et al 2007). In the following, recent studies on NM biokinetics and biopersistence are discussed in relation to potential toxicity.…”

Section: Introductionmentioning

confidence: 99%

Biokinetics of nanomaterials: The role of biopersistence

et al. 2017

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Nanotechnology risk management strategies and environmental regulations continue to rely on hazard and exposure assessment protocols developed for bulk materials, including larger size particles, while commercial application of nanomaterials (NMs) increases. In order to support and corroborate risk assessment of NMs for workers, consumers, and the environment it is crucial to establish the impact of biopersistence of NMs at realistic doses. In the future, such data will allow a more refined future categorization of NMs. Despite many experiments on NM characterization and numerous in vitro and in vivo studies, several questions remain unanswered including the influence of biopersistence on the toxicity of NMs. It is unclear which criteria to apply to characterize a NM as biopersistent. Detection and quantification of NMs, especially determination of their state, i.e., dissolution, aggregation, and agglomeration within biological matrices and other environments are still challenging tasks; moreover mechanisms of nanoparticle (NP) translocation and persistence remain critical gaps. This review summarizes the current understanding of NM biokinetics focusing on determinants of biopersistence. Thorough particle characterization in different exposure scenarios and biological matrices requires use of suitable analytical methods and is a prerequisite to understand biopersistence and for the development of appropriate dosimetry. Analytical tools that potentially can facilitate elucidation of key NM characteristics, such as ion beam microscopy (IBM) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), are discussed in relation to their potential to advance the understanding of biopersistent NM kinetics. We conclude that a major requirement for future nanosafety research is the development and application of analytical tools to characterize NPs in different exposure scenarios and biological matrices.

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Lung particle overload: old school –new insights?

Cited by 60 publications

References 29 publications

A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

A combined proteomic and targeted analysis unravels new toxic mechanisms for zinc oxide nanoparticles in macrophages

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

Biokinetics of nanomaterials: The role of biopersistence

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