Fate and Toxic Effects of Inhaled Ultrafine Cadmium Oxide Particles in the Rat Lung

Female Fischer 344 rats were exposed to ultrafine cadmium oxide particles, generated by spark discharging, for 6 h at a concentration of 70 μg Cd/m3 (1× 106/cm3) (40 nm modal diameter). Lung morphology and quantification of Cd content/concentration by inductively coupled plasma (ICP)–mass spectrometry were performed on days 0, 1, 4, and 7 after exposure. Cd content in the lung on day 0 was 0.53± 0.12 μg/lung, corresponding to 19% of the estimated total inhaled cumulative dose, and the amount remained constant throughout the study. In the liver no significant increase of Cd content was found up to 4 days. A slight but statistically significant increase was observed in the liver on day 7. We found neither exposure-related morphological changes of lungs nor inflammatory responses in lavaged cells. Another group of rats were exposed to a higher concentration of ultrafine CdO particles (550 μg Cd/m3 for 6 h, 51 nm modal diameter). The rats were sacrificed immediately and 1 day after exposure. The lavage study performed on day 0 showed an increase in the percentage of neutrophils. Multifocal alveolar inflammation was seen histologically on day 0 and day 1. Although the Cd content in the lung was comparable between day 0 and day 1 (3.9 μg/lung), significant elevation of Cd levels in the liver and kidneys was observed on both days. Two of 4 rats examined on day 0 showed elevation of blood cadmium, indicating systemic translocation of a fraction of deposited Cd from the lung in this group. These results and comparison with reported data using fine CdO particles indicate that inhalation of ultrafine CdO particles results in efficient deposition in the rat lung. With regard to the deposition dose, adverse health effects of ultrafine CdO and fine CdO appear to be comparable. Apparent systemic translocation of Cd took place only in animals exposed to a high concentration that induced lung injury.

[1]  C. L. Sanders,et al.  Rapid solubilization and translocation of 109CdO following pulmonary deposition. , 1980, Toxicology and applied pharmacology.

[2]  U. Heinzmann,et al.  Pulmonary and systemic distribution of inhaled ultrafine silver particles in rats. , 2001, Environmental health perspectives.

[3]  B. Asgharian,et al.  A multiple-path model of particle deposition in the rat lung. , 1995, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[4]  J. Angerer,et al.  The determination of metals (antimony, bismuth, lead, cadmium, mercury, palladium, platinum, tellurium, thallium, tin and tungsten) in urine samples by inductively coupled plasma-mass spectrometry , 1997, International archives of occupational and environmental health.

[5]  P. Hainaut,et al.  Cadmium Induces Conformational Modifications of Wild-type p53 and Suppresses p53 Response to DNA Damage in Cultured Cells* , 1999, The Journal of Biological Chemistry.

[6]  J. Escolar,et al.  Emphysema as a result of involuntary exposure to tobacco smoke: morphometrical study of the rat. , 1995, Experimental lung research.

[7]  S. Takenaka,et al.  Carcinogenicity of cadmium chloride aerosols in W rats. , 1983, Journal of the National Cancer Institute.

[8]  G. Snider,et al.  Cadmium-chloride-induced air-space enlargement with interstitial pulmonary fibrosis is not associated with destruction of lung elastin. Implications for the pathogenesis of human emphysema. , 1988, The American review of respiratory disease.

[9]  C. Kim,et al.  Measurement of total lung deposition of inhaled ultrafine particles in healthy men and women. , 2000, Inhalation toxicology.

[10]  J. Ring,et al.  Effects of Inhaled CdO Particles on the Sphingolipid Synthesis of Rat Lungs , 2003, Inhalation toxicology.

[11]  R. Vincent,et al.  Toxicity of inhaled cadmium chloride: early responses of the antioxidant and surfactant systems in rat lungs. , 1988, Journal of toxicology and environmental health.

[12]  L. Morawska,et al.  Size characteristics and ageing of the environmental tobacco smoke , 1997 .

[13]  Güunter Oberdürster.  Toxicology of ultrafine particles: in vivo studies , 2000, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[14]  K. Kalcher,et al.  Cadmium and lead in the smoke of a filter cigarette. , 1993, The Science of the total environment.

[15]  M. Waalkes.  Cadmium carcinogenesis in review. , 2000, Journal of inorganic biochemistry.

[16]  W. MacNee,et al.  Ultrafine (nanometre) particle mediated lung injury , 1998 .

[17]  J. Heyder,et al.  A Morphologic Study on the Fate of Ultrafine Silver Particles: Distribution Pattern of Phagocytized Metallic Silver in Vitro and in Vivo , 2000, Inhalation toxicology.

[18]  I. Hertz-Picciotto,et al.  Contribution of cadmium in cigarettes to lung cancer: an evaluation of risk assessment methodologies. , 1994, Archives of environmental health.

[19]  M. Waalkes,et al.  Comparison of inflammatory lung responses in Wistar rats and C57 and DBA mice following acute exposure to cadmium oxide fumes. , 1997, Toxicology and applied pharmacology.

[20]  G. Snider,et al.  Centrilobular emphysema experimentally induced by cadmium chloride aerosol. , 2015, The American review of respiratory disease.

[21]  D. Helm,et al.  The German Environmental Survey 1990/1992 (GerES II): cadmium in blood, urine and hair of adults and children , 2000, Journal of Exposure Analysis and Environmental Epidemiology.

[22]  S. Shapiro,et al.  Cadmium content of cigarettes. , 1969, Lancet.

[23]  S. Landsberger,et al.  The impact of heavy metals from environmental tobacco smoke on indoor air quality as determined by Compton suppression neutron activation analysis. , 1995, The Science of the total environment.

[24]  K. Driscoll,et al.  Stimulation of rat alveolar macrophage fibronectin release in a cadmium chloride model of lung injury and fibrosis. , 1992, Toxicology and applied pharmacology.

[25]  Carr J. Smith,et al.  An international literature survey of "IARC Group I carcinogens" reported in mainstream cigarette smoke. , 1997, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[26]  W. Bergmann.  PREDICTIONS OF PARTICLE DEPOSITION PATTERNS IN HUMAN AND RAT AIRWAYS , 1998 .

[27]  P. Jaques,et al.  Respiratory dose of inhaled ultrafine particles in healthy adults , 2000, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[28]  D. Hochrainer,et al.  The clearance of cadmium aerosols after inhalation exposure. , 1979, American Industrial Hygiene Association journal.

[29]  R. Świergosz-Kowalewska.  Cadmium distribution and toxicity in tissues of small rodents , 2001, Microscopy research and technique.

[30]  S. Larson,et al.  Evaluation of elemental cadmium as a marker for environmental tobacco smoke. , 1995, Environmental science & technology.

[31]  F. Hahn,et al.  Cigarette smoke exposure produces more evidence of emphysema in B6C3F1 mice than in F344 rats. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[32]  A. Churg,et al.  Cigarette smoke causes physiologic and morphologic changes of emphysema in the guinea pig. , 1990, The American review of respiratory disease.

[33]  S. Hirano,et al.  Toxicity of cadmium oxide instilled into the rat lung. II. Inflammatory responses in broncho-alveolar lavage fluid. , 1989, Toxicology.

[34]  J. Heyder,et al.  Do inhaled ultrafine particles cause acute health effects in rats? I: particle production , 1998 .

[35]  G. Oberdörster,et al.  Pulmonary deposition, clearance and effects of inhaled soluble and insoluble cadmium compounds. , 1992, IARC scientific publications.

[36]  U. Glaser,et al.  Carcinogenicity and toxicity of four cadmium compounds inhaled by rats , 1990 .

[37]  M. Brauer,et al.  Restaurant smoking restrictions and environmental tobacco smoke exposure. , 1998, American journal of public health.

[38]  G. Scherer,et al.  Cadmium concentrations in tobacco and tobacco smoke. , 1983, Ecotoxicology and environmental safety.

[39]  C. P. Yu,et al.  A dosimetry model of nickel compounds in the rat lung. , 1999, Inhalation toxicology.

[40]  Günter Oberdörster,et al.  Toxicology of ultrafine particles: in vivo studies , 2000 .

[41]  D. Bassett,et al.  Pulmonary cadmium oxide toxicity in the rat. , 1987, Journal of toxicology and environmental health.

[42]  S. Anttila,et al.  Cadmium and chromium as markers of smoking in human lung tissue. , 1989, Environmental research.

[43]  G. Schwartz,et al.  Is cadmium a cause of human pancreatic cancer? , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[44]  S. Hirano,et al.  Toxicity of cadmium oxide instilled into the rat lung. I. Metabolism of cadmium oxide in the lung and its effects on essential elements. , 1989, Toxicology.

[45]  A. Boudou,et al.  113Cd-, 31P-NMR and fluorescence polarization studies of cadmium(II) interactions with phospholipids in model membranes. , 1998, Biochimica et biophysica acta.

[46]  Flemming R. Cassee,et al.  Particle size-dependent total mass deposition in lungs determines inhalation toxicity of cadmium chloride aerosols in rats. Application of a multiple path dosimetry model , 2002, Archives of Toxicology.

[47]  M. Ménache,et al.  A comparative study of the effects of inhaled cadmium chloride and cadmium oxide: pulmonary response. , 1987, Journal of toxicology and environmental health.