Ray L. Hanson

Comparative inhalation toxicity of nickel subsulfide to F344/N rats and B6C3F1 mice exposed for 12 days.

Groups of F344/N rats and B6C3F1 mice were exposed to aerosols of nickel subsulfide (Ni3S2) 6 hr/day for 12 days not including weekends. Actual exposure concentrations were within 3% of target (target = 10.0, 5.0, 2.5, 1.2, 0.6, and 0.0 mg Ni3S2/m3). Nickel lung burdens of exposed rats and mice increased linearly with exposure concentration. Two male rats and all mice exposed to 10.0 mg Ni3S2/m3 died before the end of the exposures. Exposure to Ni3S2 had no effect on the natural killer cell activity of mouse spleen cells. Lesions in rats and mice related to inhalation of Ni3S2 were found in the nasal epithelium, lung, and bronchial lymph nodes. The most extensive lesions were found in the lung and included necrotizing pneumonia. Emphysema developed in rats exposed to 5.0 or 10.0 mg Ni3S2/m3, while fibrosis developed in mice exposed to 5.0 mg Ni3S2/m3. Degeneration of the respiratory epithelium and atrophy of the olfactory epithelium of the nose occurred in rats exposed to as low as 0.6 mg Ni3S2/m3 and mice exposed to 1.2 mg/m3. Results indicate that inhalation exposure of rats and mice to Ni3S2 aerosol concentrations near the current threshold limit value (TLV) for nickel compounds (1 mg/m3 for Ni metal and roasting fume and dust and 0.1 mg/m3 as Ni for soluble compounds) can produce lesions in the respiratory tract. Atrophy of lymphoid tissues (spleen, thymus, and bronchial lymph nodes) was found in animals of the highest exposure concentration. Degeneration of the testicular germinal epithelium was also observed in mice and rats that survived 5.0 or 10.0 mg/m3 exposure concentrations.

Comparative inhalation toxicity of nickel sulfate to F344/N rats and B6C3F1 mice exposed for twelve days.

Groups of F344/N rats and B6C3F1 mice were exposed to aerosols of nickel sulfate hexahydrate (NiSO4.6H2O) 6 hr/day for 12 days to determine the short-term inhalation toxicity of this compound. Target exposure concentrations were 60, 30, 15, 7, 3.5, and 0 mg NiSO4.6H2O/m3. Endpoints evaluated included clinical signs, mortality, quantities of Ni in selected tissues, effect on mouse resistance to tumor cells, and pathological changes in tissues of both rats and mice. All mice exposed to 7 mg NiSO4.6H2O/m3 or greater and 10 rats exposed to 15 mg NiSO4.6H2O/m3 or greater died before the termination of exposures. Quantities of Ni remaining in lungs of rats at the end of the exposure were independent of exposure concentration. Lung burdens of Ni in mice were approximately one-half that in lungs of rats. Exposure of female mice to 3.5 mg NiSO4.6H2O/m3 had no effect on resistance to tumor cells as determined by spleen natural killer cell activity. Histopathological changes were seen in tissues of rats and mice exposed to as low as 3.5 mg NiSO4.6H2O/m3. Lesions related to NiSO4.6H2O exposure occurred in lung, nose, and bronchial and mediastinal lymph nodes. Results indicated that exposure of rats and mice to amounts of NiSO4.6H2O aerosols resulting in Ni exposure concentrations only eight times greater than the current threshold limit value for soluble Ni (0.1 mg/m3) for as little as 12 days can cause significant lesions of the respiratory tract.

Evaluation of Tenax-GC and XAD-2 as polymer adsorbents for sampling fossil fuel combustion products containing nitrogen oxides.

Tenax-GC and Amberlite XAD-2 are porous polymer adsorbents used to sample organic vapors in effluents from fossil fuel combustion technologies. Experiments determining the efficacy of the two adsorbents are summarized. Gas chromatography-mass spectrometry analysis indicates that Tenax-GC would be more suitable than XAD-2 for the sampling of stack effluents from fossil fuel combustion.

Comparative Acute Toxicity of Four Nickel Compounds to F344 Rat Lung

Nickel subsulfide (Ni3S2), nickel chloride (NiCl2), nickel sulfate (NiSO4), and nickel oxide (NiO) are compounds of widely differing solubility encountered in the nickel-refining and electroplating industries. Inhalation is a common route of exposure and toxicity to the respiratory tract is possible. The purpose of this study was to evaluate the biochemical, cytological, and morphological changes in lung following administration of these compounds by intratracheal instillation. F344/Crl rats were administered a single dose of nickel compound containing 0.0, 0.01, 0.10, or 1.0 mumol Ni by intratracheal instillation. Rats were sacrificed at 1 or 7 days after compound administration, with half the animals in each exposure group taken for determination of nickel lung burden and the remaining half used for evaluation of biochemical, cytological, and histological changes. In the latter group, the right lung was lavaged and the fluid obtained was analyzed for indicators of pulmonary inflammation: lactate dehydrogenase (LDH), beta-glucuronidase (BG), total protein (TP), glutathione reductase (GR), glutathione peroxidase (GP), and sialic acid (SA). Total and differential cell counts on cells recovered in lavage fluid were also determined. The left lobe was examined for morphological changes. Clearance of nickel from the lung was most rapid for NiCl2 and NiSO4, followed by Ni3S2 and NiO. Minimal changes in all parameters were observed at 1 day after exposure. No significant changes in any parameter occurred in rats exposed to NiO, while Ni3S2, NiSO4, and NiCl2 caused increased in LDH, BG, TP, GR, SA, and total nucleated cells at 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

A Method for the Continuous Measurement of Respiration and Vapor Uptake in Rats

A method for determining the uptake of inhaled vapors in rats is described. The method uses gas chromatographic data to enable calculations of vapor concentration differences upstream and downstream from a rat exposed to the vapor by the nose-only route. Respiratory data are recorded simultaneously. The data can be used to determine the rate of uptake, uptake as a fraction of vapor inhaled and the effects of vapor inhalation on respiration.

Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc

The relationship between the inhalation exposure concentration of talc and the resulting lung burdens and histologic lesions was studied using groups of 20 F344/Crl rats and 20 B6C3F mice (10 male and 10 female) exposed to one of three concentrations of asbestos-free talc for 6 hr/day, 5 days/week for 4 weeks. Controls were exposed to filtered air using the same schedule. The pulmonary retention of talc and the development of pulmonary pathology were evaluated. The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 microns with a geometric standard deviation (sigma g) of 1.9. The mean exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus, the amount retained in the lung per unit of exposure concentration increased with increasing concentration. Mean exposure concentrations for the mice were 0, 2.2, 5.7, and 20.4 mg of talc/m3, which resulted in lung burdens of 0, 0.10, 0.29, and 1.0 mg talc/g lung; thus, the relationship between exposure concentration and the amount retained in the lung was approximately constant. Lung burdens from this study were used to project lung burdens that would result from longer exposures of rodents and man. No clinical signs were observed in the rats or mice prior to sacrifice 24 hr after the last exposure day. Histologic alterations in lung tissue consisted of only a modest, diffuse increase of talc-containing, free macrophages within alveolar spaces in both rat and mouse groups exposed to the highest level of talc for 20 days. A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens of 2-3 mg talc/g lung (wet wt) if animals were exposed to 17 mg talc/m3 for 2 years, and deposition and clearance of talc were unchanged by continued exposure. A potential limitation in this modeling is that if clearance of talc is delayed by continued exposure, the accumulated talc lung burdens would be higher than those projected by the simulation model. Humans exposed to aerosols of respirable talc are projected to accumulate much higher lung burdens than would occur in rodents exposed to the same aerosol, because humans have a higher estimated deposition fraction and slower estimated clearance of the deposited talc dust. Equilibrium lung burdens of greater than or equal to 2 mg talc/g lung were predicted for human exposures at or near the TLV for talc.

Toxicological and chemical characterization of the process stream materials and gas combustion products of an experimental low-Btu coal gasifier

The process gas stream of an experimental pressurized McDowell-Wellman stirred-bed low-Btu coal gasifier, and combustion products of the clean gas were characterized as to their mutagenic properties and chemical composition. Samples of aerosol droplets condensed from the gas were obtained at selected positions along the process stream using a condenser train. Mutagenicity was assessed using the Ames Salmonella mammalian microsome mutagenicity assay (TA98, with and without rat liver S9). All materials required metabolic activation to be mutagenic. Droplets condensed from gas had a specific mutagenicity of 6.7 revertants/microgram (50,000 revertants/liter of raw gas). Methylnaphthalene, phenanthrene, chrysene, and nitrogen-containing compounds were positively identified in a highly mutagenic fraction of raw gas condensate. While gas cleanup by the humidifier-tar trap system and Venturi scrubber led to only a small reduction in specific mutagenicity of the cooled process stream material (4.1 revertants/microgram), a significant overall reduction in mutagenicity was achieved (to 2200 revertants/liter) due to a substantial reduction in the concentration of material in the gas. By the end of gas cleanup, gas condensates had no detectable mutagenic activity. Condensates of combustion product gas, which contained several polycyclic aromatic compounds, had a specific mutagenicity of 1.1 revertants/microgram (4.0 revertants/liter). Results indicate that the process stream material is potentially toxic and that care should be taken to limit exposure of workers to the condensed tars during gasifier maintenance and repair and to the aerosolized tars emitted in fugitive emissions. Health risks to the general population resulting from exposure to gas combustion products are expected to be minimal.

Chemical and biological characterization of volatile components of environmental samples after fractionation by vacuum line cryogenic distillation

Volatile components from diesel exhaust particles and coal gasifier process gas condensate were vacuum fractionated by cryogenic distillation and identified by infrared spectroscopy and gas chromatography/mass spectrometry. The vacuum distillation line consisted of a sample flask and nine traps cooled from 0°C to −196°C in approximately 20°C steps. The pressure in the vacuum line of about 10−2 Torr was maintained with a vacuum pump. Separated compounds were identified by comparison to reference infrared spectra and confirmed by comparison with standards when practical. Volatile compounds identified from the diesel exhaust particle sample included NOx, carbon dioxide, sulfur dioxide, alkanes, aldehydes, and one and two ring aromatic hydrocarbons. Volatile compounds identified in process gas condensate from a coal gasifier were ammonia, carbonyl sulfide, carbon dioxide, C3-C7 hydrocarbons, one and two ring aromatic hydrocarbons, and phenols. Volatile components collected at either 0° or −24°C were evaluated to determine their genotoxicity using the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyltransferase (CHO/HGPRT) assay. Neither the gasifier condensate nor diesel particle samples produced mutations at the HGPRT locus. The diesel samples were not cytotoxic at the concentrations tested (100 μg/ml) but the gasifier samples resulted in 50% cell killing at concentrations between 25 and 100 μg/ml depending on the temperature of collection and the test conditions. Vacuum desorption with cryogenic distillation has provided a means to separate the volatile components in complex environmental samples to allow chemical and biological characterization of these components.

A Simple Dynamic Flow-through Exposure System for Assessment of Biological Activity of Complex Organic Mixtures to Mammalian Cells In Vitro

A system for in vitro exposure of lung epithelial cells and Chinese hamster ovary cells maintained at an air-medium interface to volatile organic compounds has been developed. The system has been used for exposure of cells to phenol (vapor pressure at 40 degrees C = 1.6 mm Hg) and to a complex mixture of organic compounds (vapor pressure range at 32 degrees C = 0.17 to 269 mm Hg). A linear relationship was found between vapor generator air flow rate (0.25 to 1.0 L/min at 39 degrees C) and exposure chamber phenol concentration. The relationship between generator air flow rate (0.5 to 1.0 L/min at 39 degrees C) and concentration of the complex mixture in the exposure chamber was also linear. Gas chromatographic analyses of chamber exhaust indicated that a majority of the compounds present in the crude mixture had been volatilized and made available to the cells in the chamber. This exposure system appears suitable for screening of complex mixtures of volatile organic pollutants for biological activity in mammalian cells in culture.

Low Btu Coal Gas Combustion Emission Characteristics

Information presented in this paper is directed to individuals concerned with the emission characterization and control of process streams. Emissions from burning low Btu gas from an experimental gasifier were sampled and characterized. Both particulate and vapor samples were collected. Transmission electron micrographs showed that the particles were single droplets less than 1 μm in diameter. Size distributions of aerosols as measured by the electrical aerosol analyzer showed a bimodal distribution. Energy dispersive X-ray analysis and ion chromatography analyses indicated that SO4 -2 was the major component of the aerosol. This suggested that the combustion aerosol from low Btu gas may be sulfuric acid droplets or other sulfates produced from oxidation of H2S in the combustion process. Particulate mass loadings were estimated to be 0.1 and 0.0024 lb/106 Btu for H2S levels of 3600 and 500 ppm respectively. Some reduction of organic vapors in the combustion products was observed when the H2S level was red...