Intratracheal instillation of zinc-cadmium sulfide (ZnCdS) in Fischer 344 rats.

The purpose of this study was to assess the bioavailability and pulmonary toxicity of ZnCdS in rats. Groups of 30 male Fischer 344 rats each were anesthetized and dosed via intratracheal instillation with 5 mg of either ZnCdS, quartz (positive control), or titanium dioxide (TiO(2), negative control) suspended in 0.5 ml saline. A vehicle control group received 0.5 ml saline. Ten animals from each test group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for bronchoalveolar lavage fluid (BALF) analysis and histopathology. The BALF was analyzed for alkaline phosphatase, acid phosphatase, lactate dehydrogenase (LDH), beta-glucuronidase (beta-glu), total protein, and cell counts. Two separate groups of 24 rats each were dosed as already described with either ZnCdS or saline. Eight rats from each group were sacrificed at 1 day, 1 wk, and 14 wk after dosing for determination of cadmium (Cd) and zinc (Zn) concentrations in the lung, liver, kidney, and blood. Results indicate that at 1 day after dosing, all enzyme activities (except acid phosphatase) and cell counts in BALF from the quartz and ZnCdS groups were significantly higher than in the TiO(2) and saline groups. At 7 days after dosing, high enzyme activity persisted in the quartz group, while the ZnCdS group showed only LDH and total protein levels significantly higher than the saline group. At 14 wk after dosing, LDH, total protein, beta-glu, and cell counts in the quartz group were significantly higher than all other groups. Histologic examination revealed interstitial inflammation and accumulation of foreign material in the lungs and mediastinal lymph nodes of quartz-, TiO(2)-, and ZnCdS-treated rats. Metal analyses in tissues showed profuse Cd and Zn concentrations in the lung 1 day after dosing, followed by a successive decline at 7 days and 14 wk after dosing. A very small, but statistically significant, amount of Cd and Zn was found in the kidneys at 14 wk after dosing. In conclusion, ZnCdS appears to cause temporary lung inflammation, is cleared slowly, and is poorly bioavailable.

Chemical and toxicological evaluation of pyrotechnically disseminated terephthalic acid smoke.

The terephthalic acid (TPA) smoke obscurants (M-83 grenade and M-8 smoke pot) were developed by the U.S. Army for training purposes to replace the more toxic hexachloroethane (HC) smoke. Inhalation toxicity testing and chemical characterization of pyrotechnically generated TPA was conducted to assess the health hazard potential of TPA and its combustion products. Fisher 344 rats were subjected to acute and repeated exposures to TPA smoke generated from the M-83 grenade. Acute exposure levels ranged from 150-1,900 mg/m3 for 30 minutes and repeated dose exposures ranged from 128-1,965 mg/m3 for 30 min/day for 5 days. Exposed and control rats were evaluated for toxic signs, and histopathologic changes. During exposure, the rats exhibited slight to moderate lacrimation, rhinorrhea, lethargy and dyspnea, which reversed within 1-hr post-exposure. No deaths occurred, even at the highest smoke concentrations. Histopathological changes were confined to exposure related nasal necrosis and inflammation in both the acute and repeated dose exposures at levels above 900 mg/m3. Chemical characterization of the M-83 grenade and the M-8 smoke pot showed that formaldehyde, benzene and carbon monoxide were the major organic vapor by-products formed. These by-products were above their respective ACGIH threshold limit values at various concentrations, but should not pose a hazard if the smoke is deployed in an open area. Overall, TPA is a safer training smoke to replace the HC smoke.

Comparative inhalation hazards of aluminum and brass powders using bronchopulmonary lavage as an indicator of lung damage.

Bronchopulmonary lavage has been used as a rapid screening test for acute lung injury from many pneumotoxic chemicals. We demonstrated the efficacy of lavage fluid analysis for detection of acute pulmonary damage from inhaled metal dusts. Groups of male, Fischer 344 rats were exposed 4 h to one of five dosage levels of either brass (200, 100, 50, 10, 1 mg m-3) or aluminum (1000, 200, 100, 50, 10 mg m-3). At 24 h, 14 days and 3 months post-exposure (PE), rats were evaluated for physiological and histological alterations to correlate with enzymatic and cytological profiles of lavage fluid. At 24 h PE, there were dose-related increases in lactate dehydrogenase and protein in lavage fluid of the brass exposed rats, acute inflammatory response in terminal airways, increases in macrophages and neutrophils, and increased pulmonary resistance. All reactions were resolved by 14 days PE. In contrast, aluminum powder produced no alteration in pulmonary function, but elicited persistent changes in enzymatic and cytological lavage fluid parameters with multifocal microgranulomas in lungs and hilar lymph nodes. Bronchopulmonary lavage analysis was useful as an indicator of inhalation hazards of brass and aluminum powders.