This review considers the molecular toxicology of combustion-derived nanoparticles (CDNP) following inhalation exposure. CDNP originate from a number of sources and in this review we consider diesel soot, welding fume, carbon black and coal fly ash. A substantial literature demonstrates that these pose a hazard to the lungs through their potential to cause oxidative stress, inflammation and cancer; they also have the potential to redistribute to other organs following pulmonary deposition. These different CDNP show considerable heterogeneity in composition and solubility, meaning that oxidative stress may originate from different components depending on the particle under consideration. Key CDNP-associated properties of large surface area and the presence of metals and organics all have the potential to produce oxidative stress. CDNP may also exert genotoxic effects, depending on their composition. CDNP and their components also have the potential to translocate to the brain and also the blood, and thereby reach other targets such as the cardiovascular system, spleen and liver. CDNP therefore can be seen as a group of particulate toxins unified by a common mechanism of injury and properties of translocation which have the potential to mediate a range of adverse effects in the lungs and other organs and warrant further research.

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Combustion-derived nanoparticles: A review of their toxicology following inhalation exposure

Many of the epidemiology studies performed are difficult to compare because of differences in worker populations, industrial settings, welding techniques, duration of exposure, and other occupation...

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Health effects of welding.

The antimicrobial activity of silver nanoparticles has resulted in their widespread use in many consumer products. However, despite the continuing increase in the population exposed to silver nanoparticles, the effects of prolonged exposure to silver nanoparticles have not been thoroughly determined. Accordingly, this study attempted to investigate the inflammatory responses and pulmonary function changes in rats during 90 days of inhalation exposure to silver nanoparticles. The rats were exposed to silver nanoparticles (18 nm diameter) at concentrations of 0.7 x 10(6) particles/cm(3) (low dose), 1.4 x 10(6) particles /cm(3) (middle dose), and 2.9 x 10(6) particles /cm(3) (high dose) for 6 h/day in an inhalation chamber for 90 days. The lung function was measured every week after the daily exposure, and the animals sacrificed after the 90-day exposure period. Cellular differential counts and inflammatory measurements, such as albumin, lactate dehydrogenase (LDH), and total protein, were also monitored in the acellular bronchoalveolar lavage (BAL) fluid of the rats exposed to the silver nanoparticles for 90 days. Among the lung function test measurements, the tidal volume and minute volume showed a statistically significant decrease during the 90 days of silver nanoparticle exposure. Although no statistically significant differences were found in the cellular differential counts, the inflammation measurements increased in the high-dose female rats. Meanwhile, histopathological examinations indicated dose-dependent increases in lesions related to silver nanoparticle exposure, such as infiltrate mixed cell and chronic alveolar inflammation, including thickened alveolar walls and small granulomatous lesions. Therefore, when taken together, the decreases in the tidal volume and minute volume and other inflammatory responses after prolonged exposure to silver nanoparticles would seem to indicate that nanosized particle inhalation exposure can induce lung function changes, along with inflammation, at much lower mass dose concentrations when compared to submicrometer particles.

Lung Function Changes in Sprague-Dawley Rats After Prolonged Inhalation Exposure to Silver Nanoparticles

With the development of nanotechnology, there is a tremendous growth of the application of nanomaterials, which increases the risk of human exposure to these nanomaterials through inhalation, ingestion, and dermal penetration. Among different types of nanoparticles, single-walled carbon nanotubes (SWCNT) with extremely small size (1 nm in diameter) exhibit extraordinary properties and offer possibilities to create materials with astounding features. Since the release of nanoparticles in an enclosed environment is of great concern, a study of possible genotoxic effects is important. Our previous data showed that pharyngeal aspiration of SWCNT elicited pulmonary effects in C57BL/6 mice that was promoted by a robust, acute inflammatory reaction with early onset resulting in progressive interstitial fibrogenic response and the formation of granulomas. In the present study, the genotoxic potential of SWCNT was evaluated in vitro. The genotoxic effects of nanoparticles were examined using three different test systems: the comet assay and micronucleus (MN) test in a lung fibroblast (V79) cell line, and the Salmonella gene mutation assay in strains YG1024/YG1029. Cytotoxicity tests showed loss of viability in a concentration- and time-dependent manner after exposure of cells to SWCNT. Results from the comet assay demonstrated the induction of DNA damage after only 3 h of incubation with 96 microg/cm2 of SWCNT. The MN test indicated some but not significant micronucleus induction by SWCNT in the V79 cell line at the highest concentrations tested. With two different strains of Salmonella typhimurium, no mutations were found following SWCNT exposure.

Single-walled carbon nanotubes: geno- and cytotoxic effects in lung fibroblast V79 cells.

This review attempts to summarize and clarify our basic knowledge as to the various factors that potentially influence the risks imposed from chronic exposure to high atmospheric levels of manganese (Mn). The studies describe the interrelationship of the different systems in the body that regulate Mn homeostasis by characterizing specific, biological components involved in its systemic and cellular uptake and its elimination from the body. A syndrome known as manganism occurs when individuals are exposed chronically to high levels of Mn, consisting of reduced response speed, intellectual deficits, mood changes, and compulsive behaviors in the initial stages of the disorder to more prominent and irreversible extrapyramidal dysfunction resembling Parkinson’s disease upon protracted exposure. Mn intoxication is most often associated with occupations in which abnormally high atmospheric concentrations prevail, such as in welding and mining. There are three potentially important routes by which Mn in inspired air can gain access the body to: 1) direct uptake into the CNS via uptake into the olfactory or trigeminal presynaptic nerve endings located in the nasal mucosa and the subsequent retrograde axonal transport directly into the CNS; 2) transport across the pulmonary epithelial lining and its subsequent deposition into lymph or blood; and/or 3) mucocilliary elevator clearance from the lung and the subsequent ingestion of the metal in the gastrointestinal tract. Each of these processes and their overall contribution to the uptake of Mn in the body is discussed in this review as well as a description of the various mechanisms that have been proposed for the transport of Mn across the bloodbrain barrier which include both a transferrin-dependent and a transferrin-independent process that may involve store-operated Ca channels. Key terms: manganese, iron, lung, Parkinson’s disease, divalent metal transporter (DMT1), transferrin, transferrin receptor

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Homeostatic and toxic mechanisms regulating manganese uptake, retention, and elimination

Pattern of deposition of stainless steel welding fume particles inhaled into the respiratory systems of Sprague–Dawley rats exposed to a novel welding fume generating system

Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc-stainless steel welding fumes.

Inflammatory and genotoxic responses during 30-day welding-fume exposure period

2-Bromopropane (2BP) has been implicated to be the reason for the mass intoxication of workers at an electronic company in Korea. A case series study indicated that 2BP was the possible causative chemical for reproductive toxicity, causing severe anemia accompanied by amenorrhea among female workers, and azoospermia or oligospermia among male workers. To clarify the effect of 2BP on the female reproductive function, repeated doses of 2BP were tested on female Sprague-Dawley rats for 21 days. Ten rats were assigned to each treatment group. The rats were maintained in a 12hr:12hr light-dark cycle and vaginal smears were monitored daily for 3 cycles. After the rats had completed 3 estrous cycles, vehicle control olive oil, 300mg, 600mg, and 900mg/kg of 2BP were injected into intraperitoneum for 14 days. The female rats were then mated with male rats on a 1:1 ratio basis. The treatment continued for an additional 7 days. Rats treated with 2BP experienced a significant decrease in body weight gain depending on the dose of 2BP. The estrous cycles of the rats continued at a normal duration of time before the initiation of treatment, showing 4.32 days for the control group, 4.79 days for the low dose, 4.63 days for the middle dose, and 4.75 days of estrous cycle for the high dose group. 2BP treatment, however, induced a significant delay of the estrous cycle in the high dose treated group, showing 11.1±3.82 days of the estrous cycle. 2BP decreased the fertility and tended to decrease in the number of pups born, depending on the dose. A 900mg/kg treatment of 2BP decreased ovarian weight, but 2BP did not affect the length of gestation. Our results indicated that 2BP seemed to be the causative agent for amenorrhea observed in female workers.

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Effects of 2-Bromopropane on the Female Reproductive Function in Sprague-Dawley Rats.

2-Bromopropane (2BP, isopropyl bromide), a substitute for freon, has recently been suspected to be the causative chemical for the outbreak of some reproductive dysfunctions such as amenorrhea and oligospermia in workers who has been exposed to this solvent in an electronic factory. Bacterial mutation assays, chromosome aberration analysis in vitro, and micronucleus tests in vivo, were carried out to clarify the mutagenicity of 2BP. 2BP induced mutagenicity in Salmonella typhimurium TA100 with metabolic activation in a dose-dependant manner. 2BP induced mutagenicity in TA1535 as well, with or without metabolic activation. These observations indicated that 2BP induced the base-pair substitution type mutations in Salmonella strains. The chromosome aberration analysis showed negative results in Chinese hamster lung cells treated with different concentrations, ranging from 0.077 to 2.46 mg/ml for 6 h with metabolic activation and for 24 h without metabolic activation. The micronucleus frequencies were recorded by examining polychromatic erythrocytes in the bone marrows of rats which were intraperitoneally injected with 2BP for 28 days. There was no significant increase in the micronucleus frequencies at any of the different doses of 2BP (125 mg/ kg b.w./day, 250 mg/kg b.w./day, and 500 mg/kg b.w./day). However, in comparison to controls, there was a significant decrease in the percentage of polychromatic erythrocytes in the total number of erythrocytes. This suggests that there may be bone marrow depression in hematopoiesis at these dose levels of 2BP. Despite the dose levels which showed hematopoietic inhibition in the bone marrow, no micronucleus formation was induced.

Seung Hee Maeng

Papers

Pattern of deposition of stainless steel welding fume particles inhaled into the respiratory systems of Sprague–Dawley rats exposed to a novel welding fume generating system

Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc-stainless steel welding fumes.

Inflammatory and genotoxic responses during 30-day welding-fume exposure period

Effects of 2-Bromopropane on the Female Reproductive Function in Sprague-Dawley Rats.

Mutagenicity of 2-bromopropane.