Toxicity of Military Smokes and Obscurants Volume 2 (1999) / Chapter Skim
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4 Titanium Dioxide Smoke
4 Titanium Dioxide Smoke
Pages 68-96
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From page 68... ...
In using this training grenade, military personnel are likely to be exposed to airborne TiO2 particles. PHYSICAL AND CHEMICAL PROPERTIES TiO2 is a noncombustible, white crystalline solid.
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From page 69... ...
,um. Both fine and ultrafine TiO2 particles can exist as aggregates of the individual particles.
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Lung-particle clearance was also significantly slower for the ultrafine TiO2 particles than for the fine; clearance halftimes were 501 days and 174 days, respectively. Similar to observations made after inhalation exposure, intratracheal instillation of ultrafine and fine TiO2 particles was associated with greater interstitialization of the ultrafine particles (Ferin et al.
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(1992) exposed rats for 30 min to aerosols of fine TiO2 particles generated with a XMS2 grenade.
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74 Cat a)
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75 _ Go ° ~ E C,, .= rs, E C~ ' ~ - =} ~ a' Cal ._ ~ au ~ O)
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(1991) exposed rats via inhalation to fine TiO2 particles at 50 mg/m3 for 6 hr per day for 5 days and examined responses by analyses of BAL-fluid, alveolar macrophage-derived cytokine production, and histopathological changes in the lungs for up to 63 days after expo
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(1996) exposed rats to fine TiO2 particles at 5 and 250 mg/m3 for 6 hr per day, 5 days per week for 4 weeks and examined inflammatory and proliferative responses in the lungs for up to 6 months following exposure.
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Briefly, exposure of rats by intratracheal instillation of ultrafine TiO2 particles at 10 mg/kg (lung burden of I.S ma) resulted in a marked and persistent inflammatory response in the Jung.
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In this study, similar histopathological effects were reported for rats exposed at a similar concentration of ultrafine carbon-black particles and diesel soot. Mice exposed to ultrafine TiO2 particles had average Jung burdens of 5.2 mg per Jung at the end of 12 months of exposure.
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(1995) observed increases in rat lung tumors at an exposure concentration and lung mass burden of ultrafine TiO2 particles that were below the concentration and mass burden for fine TiO2 particles that produced no rat lung tumors in a study by Lee et al.
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(1995) reported on clearance of tracer particles from the lungs of rats exposed chronically to an aerosol of ultrafine TiO2 particles.
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1979~. In vitro exposure of rat lung epithelial cells to TiO2 did not increase the frequency of mutation in the hgprt locus (Driscoll et al.
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in rats do not demonstrate adverse effects at concentrations of 10 mg/m3 for chronic inhalation of fine TiO2 particles. Studies using ultrafine TiO2 particles, indicate that these particles would be expected to have an effect at a lower concentration than fine particles in the rat lung (Driscoll et al.
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In addition to TiO2, other poorly soluble, low-toxicity particles have been shown to increase the incidence of lung tumors in rats. Hamsters and mice do not have an increased incidence of lung tumors even when lung burdens of poorly soluble, low-toxicitr particles are similar to those of rats.
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. When lung burdens of poorly soluble, low-toxicity particles at > I-2 mg/g of lung tissue are obtained in the rat, considerable evidence shows that there is an overloading of alveolar-clearance mechanisms and a consequent slowing of particle clearance (Morrow et al.
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19911. Still, to address the potential for greater response to high-dose rate in acute inhalation exposures, the subcommittee reduced the 4-mg/g lung dose by a factor of 10 and estimated the maximal 15-min, I-hr, and 6-fur exposure concentrations that would result in a lung dose of <0.4 mg/g of lung.
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In considering an appropriate exposure limit for repeated exposure to TiO2, the subcommittee noted that chronic inhalation to high concentrations of fine or ultrafine TiO2 particles is shown to result in pulmonary inflammation, fibrosis, andIungtumorsin rats (Lee et al. 1985a,b; Heinrich et al.
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From page 88... ...
Thus, the data base on chronic inhalation of low-toxicity, poorly soluble particles by rats indicates that lung burdens of > 1-2 mg/g of lung carry an increased risk of adverse lung effects that might contribute to the development of lung cancer in the rat (Morrow 19921. It is further noted that the overloading of lung particle-clearance mechanisms in the rat is more closely related to the volume than the mass of particles in the lung (Morrow 19921.
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1982) for humans and accounting for the density of TiO2, the subcommittee estimated that chronic inhalation of poorly soluble particles at 2 mg/m3 for ~ hr per day, 5 days per week is the maximal exposure concentration that would result in a lung burden of <4 mg/g of lung.3 The calculation takes into account sources of uncertainty in lung dosimetry between rodents and humans and therefore, an additional uncertainty factor extrapolating from animals to humans was not applied.
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From page 90... ...
As with the EEGLs and the REGL, in the event that exposures are to ultrafine TiO2 particles, an adjustment in the SPEGLs based on particle surface-area differences can be considered. Repeated Public Exposure Guidance Level (RPEGL)
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From page 91... ...
RESEARCH NEEDS In the event that the military considers the use of ultrafine TiO2 particles in smokes and obscurants, research to clearly define the differences in the toxic potential of the ultrafine particles and fine particles should be considered. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists)
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1990. Clearance and retention of inhaled diesel exhaust particles, carbon black, and titanium dioxide in rats at lung overload conditions.
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1994. Formation of DNA adducts in rat lung following chronic inhalation of diesel emissions, carbon black and titanium dioxide particles.
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1986. Pulmonary response to impaired lung clearance in rats following excessive titanium dioxide dust deposition.
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1988. Chronic inhalation exposure of rats to titanium dioxide dust.
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1989. Pathogenic effects of titanium dioxide dust on the lung of dogs A histopathological and ultrastructural study fin Chinese]
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