Albert F. Gunnison

Personal sampler for nitrogen dioxide

A new type of personal sampler for gases in air, originally reported from this laboratory, has been adapted to measurement of NO2. The sampler depends on the transfer of NO2 by diffusion to a triethanolamine coated collector at the sealed end of a tube; the open end of the tube is exposed to the test environment. The devices are accurate, light, simple to use and have very good shelf life before and after sampling.

Personal Monitoring Device for Gaseous Contaminants

A passive sampling unit based on molecular diffusion of the gas to be measured has been designed for use as a personal monitoring device. To demonstrate the applicability of the approach, the sampler was initially used to measure water vapor concentration in the air; the results showed good accuracy and reproducibility. It was then tested with sulfur dioxide as a means of measuring time-weighted average exposure to this gas. The quantity of gas transferred by diffusion from the environment through an orifice of known dimensions into a chamber maintained at substantially zero concentration by a suitable collecting medium can be used as the basis for calculating average concentration during the time the sampler is in the environment. Calculated and observed values for chamber sulfur dioxide concentrations from 10 ppm to about 0.1 ppm agreed very well over a considerable range of orifice dimensions.

Sulfite Hypersensitivity. A Critical Review

Sulfiting agents (sulfur dioxide and the sodium and potassium salts of bisulfite, sulfite, and metabisulfite) are widely used as preservatives in foods, beverages, and pharmaceuticals. Within the past 5 years, there have been numerous reports of adverse reactions to sulfiting agents. This review presents a comprehensive compilation and discussion of reports describing reactions to ingested, inhaled, and parenterally administered sulfite. Sulfite hypersensitivity is usually, but not exclusively, found within the chronic asthmatic population. Although there is some disagreement on its prevalence, a number of studies have indicated that 5 to 10% of all chronic asthmatics are sulfite hypersensitive. This review also describes respiratory sulfur dioxide sensitivity which essentially all asthmatics experience. Possible mechanisms of sulfite hypersensitivity and sulfur dioxide sensitivity are discussed in detail. Sulfite metabolism and the role of sulfite oxidase in the detoxification of exogenous sulfite are reviewed in relationship to the etiology of sulfite hypersensitivity.

Sulphite toxicity: A critical review of in vitro and in vivo data

Abstract Data on sulphite chemistry and toxicity in in vitro systems are reviewed from the perspective of potential mammalian toxicity. The observed toxicity of ingested sulphite in mammals is also summarized and the conclusions reached are compared with the results of the in vitro experiments. Information on sulphite metabolism is included to reconcile the different conclusions that may be drawn from these two sets of data. Consideration of data from all sources facilitates the selection of the specific reactions of sulphite most likely to be of toxicological significance in mammals.

Long-term inhalation exposure to nickel nanoparticles exacerbated atherosclerosis in a susceptible mouse model.

Background Because associations have been reported between inhaled ambient ultrafine particles and increased risk of cardiopulmonary disease, it has been suggested that inhaled engineered nanoparticles (NPs) may also induce adverse effects on the cardiovascular system. Objective We examined the long-term cardiovascular effects of inhaled nickel hydroxide NPs (nano-NH) using a sensitive mouse model. Methods Hyperlipidemic, apoprotein E-deficient (ApoE−/−) mice were exposed to nano-NH at either 0 or 79 μg Ni/m3, via a whole-body inhalation system, for 5 hr/day, 5 days/week, for either 1 week or 5 months. We measured various indicators of oxidative stress and inflammation in the lung and cardiovascular tissue, and we determined plaque formation on the ascending aorta. Results Inhaled nano-NH induced significant oxidative stress and inflammation in the pulmonary and extrapulmonary organs, indicated by up-regulated mRNA levels of certain antioxidant enzyme and inflammatory cytokine genes; increased mitochondrial DNA damage in the aorta; significant signs of inflammation in bronchoalveolar lavage fluid; changes in lung histopathology; and induction of acute-phase response. In addition, after 5-month exposures, nano-NH exacerbated the progression of atherosclerosis in ApoE−/− mice. Conclusions This is the first study to report long-term cardiovascular toxicity of an inhaled nanomaterial. Our results clearly demonstrate that long-term exposure to inhaled nano-NH can induce oxidative stress and inflammation, not only in the lung but also in the cardiovascular system, and that this stress and inflammation can ultimately contribute to progression of atherosclerosis in ApoE−/− mice.

Sulfur dioxide: Sulfite. Interaction with mammalian serum and plasma.

The chemistry of sulfite-bisulfite (the hydrate of sulfur dioxide in mammalian plasma and serum was investigated in vitro and in vivo. The longevity of sulfite in contact with mammalian plasma and known components of blood was determined by adaptation of a colorimetric method for sulfite analysis. Evidence from all experiments indicated that, under physiological conditions, sulfite reacts reversibly with disulfide bonds present in the plasma resulting in formation of S-sulfonates (sulfitolysis). Free sulfite was not detected in plasma of rabbits immediately following exposure to approximately 25 ppm SO2, but there was good evidence for substantial elevation of plasma and serum S-sulfonate content. Reactivity of sulfite with plasma constituents may protect many body tissues from the insult of relatively high concentrations of sulfite and may facilitate prolonged exposure to very low levels of sulfite.

Persistence of plasma S-sulfonates following exposure of rabbits to sulfite and sulfur dioxide

The kinetics of the formation and clearance of plasma S-sulfonate is presented for rabbits exposed to oral and intravenous sulfite and to inhaled SO2. Rabbits injected with sulfite at 0.9 mmol/kg, iv, showed rapid formation of plasma exogenous S-sulfonate, half of which was cleared in approximately 1 hr. Sulfite in drinking water (8.9 or 26 μmol/ml) and atmospheric SO2 (10 ppm) were administered to rabbits over a period of days. Plasma S-sulfonate increased progressively during exposure and then leveled off, indicating that equilibrium had been established. The rabbits were then removed from exposure and the clearance of plasma exogenous S-sulfonate measured. The pattern agreed quite closely to a single exponential rate with a half-life on the order of days. The clearance following SO2 inhalation, however, was significantly slower (p < 0.01) than that following sulfite ingestion. The diffusibility of plasma S-sulfonate was investigated by using dialysis procedures. The results showed that the diffusibility of exogenous S-sulfonate varied depending upon its mode of formation, i.e., in vitro, in vivo via ingestion of sulfite, or in vivo via iv injection. Data gathered from both dialysis and in vivo experiments support the conclusion that plasma protein S-sulfonate is cleared rather slowly in vivo and that there is a fraction of plasma exogenous S-sulfonate (probably cysteine S-sulfonate) which is cleared much more rapidly. The presence of previously reported plasma endogenous S-sulfonate in rabbits was confirmed.

Distribution, metabolism and toxicity of inhaled sulfur dioxide and endogenously generated sulfite in the respiratory tract of normal and sulfite oxidase-deficient rats.

We report on the distribution, metabolism, and toxicity of sulfite in the respiratory tract and other tissues of rats exposed to endogenously generated sulfite or to inhaled sulfur dioxide (SO2). Graded sulfite oxidase deficiency was induced in several groups of rats by manipulating their tungsten to molybdenum intake ratio. Endogenously generated sulfite and S-sulfonate compounds (a class of sulfite metabolite) accumulated in the respiratory tract tissues and in the plasma of these rats in inverse proportion to hepatic sulfite oxidase activity. In contrast to this systemic mode of exposure, sulfite exposure of normal, sulfite oxidase-competent rats via inhaled SO2 (10 and 30 ppm) was restricted to the airways. Minor pathological changes consisting of epithelial hyperplasia, mucoid degeneration, and desquamation of epithelium were observed only in the tracheas and bronchi of the rats inhaling SO2, even though the concentration of sulfite plus S-sulfonates in the tracheas and bronchi of these rats was considerably lower than that in the endogenously exposed rats. We attribute this histological damage to hydrogen ions stemming from inhaled SO2, not to the sulfite/bisulfite ions that are also a product of inhaled SO2. In addition to the lungs and trachea, all other tissues examined, except the testes, appeared to be refractory to high concentrations of endogenously generated sulfite. The testes of grossly sulfite oxidase-deficient rats were severely atrophied and devoid of spermatogenic cells.

A model for the metabolism of sulfite in mammals.

Abstract The distribution of sulfite in the rabbit fits a two-compartmental open-system model ( Riegelman et al., 1968 ) characterized by rapid distribution and elimination with the rate constants of the order 0.1 to 1.0 min−1. Sulfite clearance can be calculated from this model using plasma decay data obtained after a single iv injection of sulfite, and the theoretical rate thus calculated is in satisfactory agreement with clearance determined at steady state conditions. Measurement of urinary sulfite following iv sulfite administration and demonstration of mass balance in the conversion of the remaining sulfite to sulfate using a mathematical model show that sulfite clearance occurs predominantly by metabolism to sulfate. It is concluded that sulfite clearance is primarily dependent upon the efficiency of sulfite oxidase, the enzyme catalyzing the oxidation of sulfite to sulfate. The results indicate that the efficiency of this enzyme decreases as sulfite dose increases. Preliminary experiments with one rhesus monkey suggest that the pattern of sulfite distribution and elimination is similar to that in rabbits but that the kinetics of the removal mechanisms are different. It is felt that meaningful inter- and intraspecific comparisons can be made using the technique presented, and that these comparisons would provide a quantitative basis for predictions of risks of systemic sulfite toxicity.

Comparative pulmonary toxicity of inhaled nickel nanoparticles; role of deposited dose and solubility

In this pilot study, we investigated which physicochemical properties of nickel hydroxide nanoparticles (nano-NH) were mainly responsible in inducing pulmonary toxicity. First, we studied the role of nickel ions solubilized from nano-NH by comparing the toxic effects of nano-NH to those of readily soluble nickel sulfate nanoparticles (nano-NS). Additionally, to test whether there was a non-specific stress response due to particle morphology, we compared the toxicity of nano-NH with that of carbon nanoparticles (nano-C) and titanium dioxide nanoparticles (nano-Ti), both of which had similar physical properties such as particle size and shape, to nano-NH. We exposed mice to each type of nanoparticles for 4 h via a whole-body inhalation system and examined oxidative stress and inflammatory responses in the lung. We also determined the lung burden and clearance of Ni following nano-NH and nano-NS exposures. The results showed that lung deposition of nano-NH was significantly greater than that of nano-NS and nano-NH appeared to have stronger inflammogenic potential than nano-NS even when lung Ni burden taken into consideration. This suggests that the toxicity of nano-NH is not driven solely by released Ni ions from deposited nano-NH particles. However, it is unlikely that the greater toxic potential of nano-NH is attributable to a generic stress response from any nanoparticle exposure, since nano-C and nano-Ti did not elicit toxic responses similar to those of nano-NH. These results indicate that the observed pulmonary toxicity by inhaled nano-NH were chemical-specific and deposited dose and solubility are key factors to understand toxicity induced by nano-NH.