Pulmonary Effects of Inhaled Zinc Oxide in Human Subjects, Guinea Pigs, Rats, and Rabbits

Gordon, Terry; Chen, Lung Chi; Fine, Jonathan; Schlesinger, Richard B.; Su, Wei; Kimmel, Tracy A.; Amdur, Mary O.

doi:10.1202/0002-8894(1992)053<0503:peoizo>2.0.co;2

Cited by 15 publications

(25 citation statements)

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“…The analysis focused on the time course of endpoints in bronchoalveolar lavage, a technique previously used for the quantitative evaluation of pulmonary damage caused by inhalation/instillation of ZnO (Conner et al, 1988;Gordon et al, 1992;Hirano et al, 1989). Cellular responses to inhaled Zn-organic substances include the induction of proteins that function to prevent adverse effects, for example, metallothionein (MT).…”

mentioning

confidence: 99%

Inhalation Toxicity of Propineb. Part II: Results of Mechanistic Studies in Rats

Pauluhn

Emura²,

Möhr³

et al. 2003

Inhalation Toxicology

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Previous repeated inhalation exposure studies revealed two independent organotropic effects of inhaled propineb dust: One was restricted to the lung, the other to muscle weakness of hindlimbs. These effects were believed to be causally related to the principle decomposition products of this type of dithiocarbamate in the biological milieu and related to zinc and carbon disulfide. Two mechanistic 1-wk inhalation studies were performed, each focusing on one of these findings. The 7 x 6-h/day repeated-exposure inhalation study analyzed whether the nature of the response occurring at the alveolar level is "adaptive" or "early adverse" and whether soluble zinc is the causative agent. Groups of 18 female rats were exposed nose-only to mean concentrations of 0, 1.1, 5.5, and 25.8 mg propineb/m(3) and 6.9 mg ZnO/m(3). On postexposure days 1, 3, and 15 the time course of responses was analyzed by bronchoalveolar lavage (BAL), including quantification of Zn and metallothionein (MT) in BAL cells. Clinical evidence of muscular weakness was investigated separately in 20 female Wistar rats exposed to 70 mg propineb/m(3) on 5 consecutive days (6 h/day), followed by a 2-wk postexposure period. Clinical signs, body weights, and feed and water consumption were recorded as frequently as technically feasible. Fifty percent of rats received an oral cysteine supplementation to verify/refute the hypothesis that the incapacitation observed in previous studies is the cause of emaciation and associated impairment of CS(2) detoxification. The findings of the first study are consistent with this hypothesis, namely, that soluble Zn triggers a series of pulmonary events that is consistent with the homeostasis of this essential metal. It is concluded, accordingly, that the adjusted maximal workplace level for ZnO is also valid for propineb to preclude Zn-mediated responses to occur in the lung. With respect to muscular effects, this mechanistic study demonstrates further that the increased detoxification capacity afforded by oral supplementation of cysteine mitigates markedly the toxic potency of propineb. Procedural variables specific to the inhalation bioassay appear to be decisive for the elicitation of muscular effects. The major variable is considered to be the large drop in body weights associated with each exposure session and the concomitantly decreased uptake of essential nutritional factors (e.g., cysteine) involved in the detoxification of this compound. Accordingly, the muscular deficits elicited by high concentrations of propineb are viewed to be secondary effects in an animal species likely to be more susceptible to this type of change than humans (Pauluhn & Rosenbruch, 2003).

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confidence: 99%

Inhalation Toxicity of Propineb. Part II: Results of Mechanistic Studies in Rats

Pauluhn

Emura²,

Möhr³

et al. 2003

Inhalation Toxicology

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“…The effects of ingestion of large amounts of ZnO have been investigated in humans, and ultrafine nanoparticle metal oxides have been shown to cause corrosive gastroduodenal injury without systemic toxicity. Inhaled ZnO can cause pulmonary toxicity but minimal toxicity to other organs [39][40][41][42][43][44][45]. Increased consumption of fine and ultrafine particulate matter has been hypothesized to exacerbate inflammatory bowel disease [46][47][48][49].…”

Section: Resultsmentioning

confidence: 99%

Sensitivity of A-549 human lung cancer cells to nanoporous zinc oxide conjugated with Photofrin

et al. 2011

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In the present study, we demonstrated the use of nanoporous zinc oxide (ZnO NPs) in photodynamic therapy. The ZnO NPs structure possesses a high surface to volume ratio due to its porosity and ZnO NPs can be used as an efficient photosensitizer carrier system. We were able to grow ZnO NPs on the tip of borosilicate glass capillaries (0.5 μm diameter) and conjugated this with Photofrin for efficient intracellular drug delivery. The ZnO NPs on the capillary tip could be excited intracellularly with 240 nm UV light, and the resultant 625 nm red light emitted in the presence of Photofrin activated a chemical reaction that produced reactive oxygen species (ROS). The procedure was tested in A-549 cells and led to cell death within a few minutes. The morphological changes in necrosed cells were examined by microscopy. The viability of control and treated A-549 cells with the optimum dose of UV/visible light was assessed using the MTT assay, and ROS were detected using a fluorescence microscopy procedure.

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“…Inhaled ultrafine particles deposit in the respiratory tract almost exclusively by diffusional mechanisms (ICRP 1994). Inhalation of fumes, consisting mainly of ultrafine particles, lead to the well-known effects of metal or polymer fume fever (Drinker et al 1927;Gordon et al 1992). Scientists have attributed the greater pulmonary effects of ultrafine particles, compared to larger submicrometer particles, to their larger specific surface area, the greater interstitial access, and their altered biopersistence (Oberdorster et al 1994;Johnston et al 2000).…”

Section: Introductionmentioning

confidence: 97%

Effects of Physicochemical Properties of Ultrafine Particles on the Performance of an Ultrafine Particle Concentrator

Gupta¹,

Demokritou²,

Koutrakis³

2004

Aerosol Science and Technology

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Condensational growth of ultrafine particles under saturation conditions in conjunction with virtual impaction technology hasbeen used recently as a method to concentrate ultrafine particles for conducting inhalation toxicological studies. The Harvard Ultrafine Concentrated Ambient Particle System (HUCAPS) was challenged with a variety of artificially generated aerosols of different chemistry, solubility, and hygroscopicity as well as by ambientorigin ultrafine particles. The system's ability to concentrate these different particles was evaluated for a wide range of saturation ratios. It was found that hygroscopic particles grow and are concentrated more efficiently than hydrophobic ones. The effect of aerosol-hygroscopicity and water solubility on the overall aerosol concentration enrichment factor diminishes with increasing saturation ratios. Results indicated that a saturation ratio higher than that predicted by theory, with a value of about 3, is needed to assure that all particles grow and are efficiently concentrated by the same enrichment factor, regardless of particle hygroscopicity and solubility. Under such an optimum saturation ratio, the performance of the HUCAPS was evaluated using ambient-origin ultrafine particles. The results show that the HUCAPS concentrates ambient ultrafine particles by a factor of 40-50 with a little size distortion. Its overall low-pressure drop (2.2 kPa) and its high concentration enrichment factor make the HUCAPS a versatile device suitable for in vitro and in vivo inhalation toxicological studies.

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Pulmonary Effects of Inhaled Zinc Oxide in Human Subjects, Guinea Pigs, Rats, and Rabbits

Cited by 15 publications

References 0 publications

Inhalation Toxicity of Propineb. Part II: Results of Mechanistic Studies in Rats

Inhalation Toxicity of Propineb. Part II: Results of Mechanistic Studies in Rats

Sensitivity of A-549 human lung cancer cells to nanoporous zinc oxide conjugated with Photofrin

Effects of Physicochemical Properties of Ultrafine Particles on the Performance of an Ultrafine Particle Concentrator

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