Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test.

Szyba, K.; Lange, Andrzej

doi:10.1289/ehp.8351337

Cited by 3 publications

(1 citation statement)

References 15 publications

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“…The decade between 1980 and 1990 produced an impressive number of investigations on the importance of the physicochemical properties of particles and fibres in producing toxicity and pathogenicity. These have included once again size [315, 316] and also crystalline nature [317], adsorptive ability of alveolar and serum components as well benzo(a) pyrene [318–321], and dissolution and biodegradation of mineral fibres [322, 323]. Moreover, surface reactivity with the generation of free radicals [324–328], and their ability to induce the peroxidation of cellular lipids were also studied [329–334].…”

Section: Main Textmentioning

confidence: 99%

Particle toxicology and health - where are we?

Riediker¹,

et al. 2019

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Background Particles and fibres affect human health as a function of their properties such as chemical composition, size and shape but also depending on complex interactions in an organism that occur at various levels between particle uptake and target organ responses. While particulate pollution is one of the leading contributors to the global burden of disease, particles are also increasingly used for medical purposes. Over the past decades we have gained considerable experience in how particle properties and particle-bio interactions are linked to human health. This insight is useful for improved risk management in the case of unwanted health effects but also for developing novel medical therapies. The concepts that help us better understand particles’ and fibres’ risks include the fate of particles in the body; exposure, dosimetry and dose-metrics and the 5 Bs: bioavailability, biopersistence, bioprocessing, biomodification and bioclearance of (nano)particles. This includes the role of the biomolecule corona, immunity and systemic responses, non-specific effects in the lungs and other body parts, particle effects and the developing body, and the link from the natural environment to human health. The importance of these different concepts for the human health risk depends not only on the properties of the particles and fibres, but is also strongly influenced by production, use and disposal scenarios. Conclusions Lessons learned from the past can prove helpful for the future of the field, notably for understanding novel particles and fibres and for defining appropriate risk management and governance approaches.

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Section: Main Textmentioning

confidence: 99%

Particle toxicology and health - where are we?

Riediker¹,

et al. 2019

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On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats

et al. 1998

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Mechanisms of Genotoxicity of Particles and Fibers

Schins

2002

Inhalation Toxicology

228

108

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With regard to genotoxicity testing and cancer risk assessment, particles and fibers form a rather specific group among all toxicants. First, the physicochemical behavior of fibrous and nonfibrous particles is usually very different from that of nonparticulate, chemical carcinogens. Reactive oxygen species (ROS) are believed to play a major role in primary genotoxicity of particles, which may derive from their surface properties, the presence of transition metals, intracellular iron mobilization, and lipid peroxidation. Other aspects relevant to primary genotoxicity are particle size, shape, crystallinity (e.g., silica), and solubility, and may also include particle uptake, interaction with cell division machinery (e.g., asbestos), and the presence of mutagens carried with the particle (e.g., diesel exhaust particles, DEP). Excessive and persistent formation of ROS from inflammatory cells is considered as the hallmark of the secondary genotoxicity of nonfibrous and fibrous particles. Since lung inflammation is known to occur and persist only at sufficient particle dose, this secondary pathway is considered to contain a threshold (Greim et al., 2001). Identification of (mechanisms of) particle genotoxicity has been/can be achieved via (1) acellular assays, (2) in vitro tests, (3) in vivo studies, usually in mice or rats, and finally (4) biomarker studies in humans with (occupational) exposure. The significance of acellular assays and biomarker studies for risk assessment is limited, but has provided some mechanistic insights (e.g., in oxidant generating properties of quartz and asbestos) and may also contribute to hazard identification. In vitro studies have lead to identification of primary genotoxic properties of particles, whereas recent in vivo studies provide further support for the correlation between particle-induced lung inflammation and secondary genotoxicity. Proper risk assessment of particles necessitates identification of the relative impact of primary versus secondary genotoxicity in realistic exposure conditions. However, since it is impossible to discern between primary and secondary genotoxicity with current in vivo tests, concomitant in vitro assays are required to determine primary genotoxicity. In vivo tests should ideally be designed using different doses to allow dose-effect analysis for both inflammation and genotoxicity.

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Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test.

Cited by 3 publications

References 15 publications

Particle toxicology and health - where are we?

Particle toxicology and health - where are we?

On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats

Mechanisms of Genotoxicity of Particles and Fibers

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