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By Marlin D. Schutte, Graham M. Fraser, Paul M. Kubera, Ronald J. Weetman

Mixers play an important function in the operation of multi-phase reactors in the minerals processing industry. They must suspend solids, transfer oxygen, maintain pH and temperature uniformity, assist in heat transfer, and, in biological processes, avoid the development of excessive shear rates. The LIGHTNIN A315 impeller (Figure 1) effectively supersedes the older Rushton turbine (Figure 2) which has been classically employed in gas­Iiquid-solids applications such as bacterial oxidation, cyanide destruction, etc. Since a stirred tank reactor can be such a key part of the overall process, it is essential that the mixers be designed for long term reliable operation, both process and mechanical, to insure a high percentage of on-line availability. Mixers in gas-liquid-solids processes may experience extraordinary loading conditions which must be taken into account to guarantee a robust mechanical design. Given the recent trend towards the design of world-class process units with maximum capacity equipment, there is increased importance and emphasis on the integrated design of the complete agitation system -mixer, vessel, and structure -to insure trouble free, post­commissioning performance. This paper presents some of the considerations necessary to specify the process functions of the mixer in multiphase applications, as well as special considerations for the mechanical design of the integrated reactor system.

Jan 1, 1993

By C. J. Ferron

Gold occurrence in operating plant tailings ranges from gold in solution, fine free gold, gold associated with sulphides/arsenides/tellurides and gold occluded within iron oxides or arsenates and silica gangue. This paper briefly presents various alternatives to reprocess gold tailings, with examples. These include the use of centrifugal gravity separators, CIL, magnetic separation, flotation and pressure oxidation.

Jan 1, 1993

By Gary Krix

The Amdel Thickener Interface Gauge (TIG) provides continuous on-line measurement of the level of the liquid/solid interface in thickeners and Counter Current Decantation (CCD) washers. Unlike other interface level measurement systems, the TIG also determines the span of the transition zone. The transition zone is the region between the clear liquid overflow zone and the compressed solids zone. The Thickener Interface Gauge determines the level of the interface by measuring the natural radioactivity of the solids in the thickener tank using an array of up to twelve detectors mounted vertically in a stainless steel probe. All solids contain low levels of natural radioactivity while the liquid phase generally does not. The concentration of natural radioactivity at each level in the thickener therefore depends on the concentration of solids. The radiation emitted by the solids is converted to electrical pulses by the detectors in the probe and the pulse-rate provides an accurate measurement of the density. A typical count-rate profile is presented in Figure 1. The vertical axis indicates the depth in the tank referenced to the surface of the liquid. The horizontal axis indicates the count-rate measured by the TIG probe, this count-rate is proportional to the density and can be used to determine the settling rate. The count-rate at the top of the graph is relatively low, this region corresponds to the clear overflow zone which contains virtually no solids. Moving down the vertical axis the count-rate increases dramatically at the level of the transition zone where the solids content increases with the depth in the tank. In this region the settling conditions of the solid particles change from free settling to compression. Moving further down the vertical axis the count-rate reaches a plateau where the count-rate remains relatively constant although there are often small fluctuations, this region corresponds to the solids compression zone. The liquid/solid interface as measured by the TIG corresponds to the depth at which the count-rate crosses the target count-rate which is generally selected to be midway between the liquid count-rate and the compressed solids count-rate. The length of the TIG probe is selected to cover the typical operating range of the liquid/solid interface in the thickener or washer. If, for example, the minimum bed level is 3.0 metres below the surface of the liquid then the probe length is selected to extend 30 metres below the surface. The TIG probe can include up to twelve detectors and the se are spaced over the measurement range. For small measurement ranges of around one metre 4 to 6 detectors would normally be used while for larger measurement ranges of three metres or more twelve detectors would be supplied.

Jan 1, 1993

By Q. Yuan, B. Yarar

Steric stabilization is a phenomenon observed when relatively high doses of flocculants are added to fine particle suspensions. Experiments were conducted to establish conditions under which medium viscosity and the sedimentation properties of black sand components in a slurry could be controlled so as to enhance the selective sedimentation of gold grains. It was shown that black sand concentrates containing as low as 2.65 g/mt gold could be upgraded by selectively hindering the sedimentation of non-gold components in an aqueous slurry. This paper presents data describing the theory and practical implementation of this cyanide or mercury-free novel approach where gold could be concentrated by as much as 15 times with relatively high recoveries. The relationships of solids content of slurries, type and dose of polymers with the recovery process are documented. Key words: Gold, black sand, selective flocculation, steric stabilization.

Jan 1, 1993

By Satid Therdkiattikul, Donald A. Dahlstrom

Many gold ores are known to be refractory so that conventional cyanide processing will result in serious losses of gold and silver values. A significant percentage of these refractory ores contain aresenopyrite and the gold and silver is usually encapsulated within this matrix as well as the pyrite matrix. Normally the values can be recovered as flotation concentrates because of the sulfide compounds with recoveries of over 90% and at very good grades. In order to free the gold and silver, the sulfide matrix must be destroyed. This can presently be achieved by (1) pressure­temperature leaching (2) roasting and (3) bacterial leaching. All of them have advantages and disadvantages as well as an obviously increased cost for the each processing method. However, the increased gold and silver recovery should and must more than offset this cost. It is believed that gold recovery should be well over 90% from the concentrate so that overall recovery from the ore should be in the 90-95% region. All three processes must consider pollution control of both sulfur and arsenic to prevent contamination of air, water or land through improper waste disposal. This paper will concern only bacterial leaching and its necessary control of effluents and solids. Sulfur does not appear to be a problem as the element is oxidized to sulfate and is precipitated with an acceptable solubility. Other important improvements that must be controlled are arsenic and iron which are present as significant values (1-12 g/1 of arsenic, 20-40 g/1 of iron). In addition much smaller values of base metals, aluminum and magnesium can be present as well as other elements depending on the ore and these must be low enough after treatment to meet EPA regulations.

Jan 1, 1993

By Hans von Michaelis

This paper examines the process options available for treatment of "refractory" gold ores. As more and more of the easily leached oxidized gold ore zones are exhausted, the pressure is on to find more economical ways of treating refractory gold ore deposits. Historically, refractory ores were generally concentrated, e.g. to make a flotation concentrate that could be roasted. A major development is taking place in the USA in which ores from which gold cannot be concentrated well by flotation are being treated using whole ore oxidation processes prior to cyanidation. Refractory gold ore treatment processes are generally expensive to install and operate. Thus, for a refractory gold ore project to be economically viable, the grade must generally be higher than for free milling gold ores.

Jan 1, 1993

By Stephen LaBrooy, David Muir

Gold ores in the geologically more recent rocks are often associated with copper minerals which pose problems of high reagent consumption with conventional cyanidation practice. Many examples exist in northern Australia, Indonesia, Papua­New Guinea, Chile, and Brazil where, despite various treatment options (LaBrooy, 1992), the processing of oxide and transition ores is uneconomic either for copper or gold recovery. Hence, there is a need for a reagent which is selective for gold without leaching copper minerals. The ammonia-cyanide system appears to meet this criterion (Muir et al, 1989; LaBrooy et al, 1991; Costello et al, 1992; Hayes and Corrans, 1992) but it has proven difficult to optimise and apply to a variety of ores due to differences in the mineralogy and reactivity of ores and a lack of understanding of how the system works. Recent work on the mechanism, however, (Muir et al, 1993) has thrown a new light on the problem which should allow better process control. Ammonia­cyanide mixtures behave neither like free cyanide nor free ammonia and too much of either reagent in the mixture is detrimental. The key to the process is understanding how ammonia enhances gold extraction yet inhibits copper extraction in an essentially cyanide environment.

Jan 1, 1993

By A. R. Laplante

In this paper, the performance of the Knelson Concentrator and of the batch and continuous Falcon Concentrators are compared. The units are based on different operating principles, and perform quite differently. The Knelson yields very high free gold recoveries over a wide size range of both the recovered and rejected species. It is less effective in recovering very fine (<15 μm) or very flaky gold, as encountered in flotation feeds, concentrates or tails. It is the preferred unit for gold recovery from grinding circuits. The batch Falcon is effective in the fine range, typically less than 37 μm for gold. Its recovery zone is quickly saturated when there is significant heavies in the feed. It works best as a pre-concentration unit, or when sulphide content is low. The continuous Falcon is a versatile unit which is capable of recovering fine heavies (density down to 5 g/cm 3), especially from coarser gangue.

Jan 1, 1993

By Dennis J. Appelhans

Lac Minerals Bullfrog conducted research and testwork to find an environmentally acceptable alternative to lead for fire assaying. The result of this work was the substitution of bismuth for lead in all fire assaying performed at the Bullfrog Mine. The environmental and economic ramifications of this discovery are highlighted.

Jan 1, 1993

By Yeonuk Choi, Gus Van Weert

cyanide control in effluents is becoming a critical environmental issue for the gold extraction industry. Silver impregnated carbon removes free cyanide effectively to the ppb level from solution in high throughput columns. By re-calcining the cyanide saturated carbon, the impregnated silver is restored to activity and the cyanide destroyed outside the effluent stream. Many gold mills already have an activation kiln on site, which could make retrofit relatively easy.

Jan 1, 1993

By Diane Schwegler-Berry, Vincent Castranova, Chang-geng Moe, Jane Y. C. Ma, Mark D. Moore, Joseph K. H. Ma, Carl J. Malanga, Ji-Hee Kane

"Effects of Bisbenzylisoquinoline Alkaloids on Alveolar Macrophages: Correlation between Binding Affinity. Inhibitory Potency and Antifibrotic Potential. CASTRANOVA, V., KANG, J-H., MA. J. K. H., Mo, C-H., MALANGA, L. J., MOORE M. D., SCHWEGLER-BERRY, D.. AND MA. J. Y. C. (1991). Toxicol. Appl. Pharmacol 108, 242-252. The Chinese have conducted extensive studies concerning the medicinal properties of plant products. In this investigation the ability of three bisbenzylisoquinoline alkaloids to inhibit particle-induced activation of alveolar macrophages was evaluated and this inhibitory potential was correlated with the ability of those drugs to bind to membrane components. Tetrandrine. i.e.. an herbal medicine used as an antifibrotic agent in China, was a potent inhibitor of particle-stimulated oxygen consumption, superoxide release, and hydrogen peroxide secretion by alveolar macrophages. Tetrandrine also exhibited substantial binding affinity for membrane lipids and alveolar macrophages. In contrast, tubocurine, an analogue with little antifibrotic potential, exhibited low binding affinity and had little effect on macrophage activation. Methoxyadiantifoline, an alkaloid of unknown antifibrotic potential, exhibited inhibitory and binding properties similar to those of tetrandrine. The data indicate that a strong relationship exists between the antifibrotic potential of these alkaloids and their ability to bind to alveolar macrophages and inhibit particle-induced activation of these phagocytes. These drugs should serve as useful probes to evaluate the role of alveolar macrophages in pulmonary fibrosis. © 1991 Academic Press, Inc.Chronic silicosis is a fibrotic disease resulting from occupational exposure to silica dust. It is manifested initially by an increase in the quantity of pulmonary surfactant (Dethloff et al., 1986). However, in later stages it is characterized by an increase in collagen formation and the development of concentric hyalinized nodular lesions in the lung (Ziskind et al., 1976). Although mechanisms for the progression of silicosis have not yet been completely defined, activation of alveolar macrophages by respirable silica particles is believed to play an important role in the etiology of this disease. Studies from our laboratory have shown that both in vitro and in vivo silica exposures result in a stimulation of macrophage release of reactive products capable of damaging the lung parenchyma (Castranova et al., 1990; Goodman et al., 1990). In addition, exposure of al¬veolar macrophages to silica results in the release of fibrogenic factors which enhance the proliferation of fibroblasts and the synthesis of collagen by these pneumocytes (Leibovich and Ross, 1976; Bitterman et al., 1982, 1983).The bisbenzylisoquinoline alkaloids, which represent the largest group among the iso-quinoline compounds isolated from the plant kingdom, are known to exhibit a broad rangeof pharmacological activities. Tetrandrine, for example, an alkaloid isolated from the root of Stephania tetrandra, has been tested for its antitumor, antihypertensive, and antisilicotic effects (Kupchan and Atland, 1973; Zeng et al., 1985; Yu et al., 1983). It is currently used in China as a treatment for angina, hypertension, and silica-induced pulmonary fibrosis (Li et al., 1981). Several related bisbenzylisoquinoline alkaloids such as methoxyadiantifoline and tubocurine have also been evaluated for medicinal effects. Methoxyadiantifoline has been shown to exhibit effects on the cardiovascular system similar to those reported for tetrandrine (Jia et al., 1988). However, to date, the antifibrotic activity of methoxyadiantifoline has not been evaluated. In contrast to tetrandrine, tubocurine, a structural analogue of this drug, has been reported to be relatively ineffective against fibrosis (Mo et al., 1982)."

Mar 1, 1992

By R. L. Grayson

"Compliance standards for respirable dust, which are reduced because of high quart: concentrations, have become an industry-wide problem. Research on the physical and chemical character of quart-classified particles in respirable coal mine dusts indicates that they may exist in intermixed layers or may be coated by clay or coal material. The relative amount of intermixing varies with the coal seam being mined. If most of the quart: particles of a mine dust are ""pure,"" then the dust may have a high fibrogenic risk potential because of truly free silica and the compliance standard should be lowered. lf, however, quart: is locked inside another material matrix, or coated, a reduced compliance standard may not be appropriate.Although much research has been done on coal workers' pneumoconiosis (CWP) over the past decades, the etiologic agents of the disease still have not been pinpointed. The predominant methods of characterizing respirable coal mine dusts were bulk analysis techniques for determination of elemental and mineralogical concentrations, the results of which were used in statistical analyses to determine relationships between dust composition and the occurrence of CWP. These methods are incapable of finding the etiologic agents in the dust primarily because of complicated and confounding physiochemical factors, which may be discovered if the focus of characterization was done on a dust particle level.The SEM/EDXA-based research discussed here shows a significant difference in the number of ""pure"" quartz particles in respirable dusts collected from different mines. Some of the results have been reported previously (Grayson, Andre, and Simonyi, 1988). Concurrent research by other investigators (Wallace et al., 1989) demonstrates an SEM/EDXA-based methodology to pinpoint the location of the ""contaminating"" substance(s ) in a quartz-classified particle. The research of the European Economic Community has also begun analyses on the respirable-dust-particle level (Robock and Bauer, 1988).Since the compensatory and intangible costs of CWP are substantial in the United States, it is important that the etiologic agents be determined and then either controlled or neutralized in a cost-effective way. This line of research is especially important consid-ering the forecasted. near-term growth of coal production and the evolution of high productivity longwall panels (an immediate problem in compliance) and continuous mining sections ( a probable future problem).This need has been accentuated now that nearly all respirable dust samples submitted to MSHA are analyzed for free silica (Tomb, Parobeck, and Gem, 1986). Today a real problem exists in the coal industry, both underground and surface, because of high quartz levels in respirable dusts causing substantially reduced compliance standards (Murphy, 1989).The combined results of the respirable dust particle investigators indicate that conventional bulk sample analyses may not faithfully represent the amount of biologically available or active quartz in all mines with a high level (greater than 5% ) of quartz in the dust For example, some mine dusts might contain predominantly occluded (or coated) quartz particles where bulk analysis would result in anomalously high ""free silica"" measurements. The same result would occur when quartz particles are intermixed substantially with other minerals that can alter the surface of the composite particle away from a quartz-behaving character."

Mar 1, 1992

By Vincent Castranova, Jane Y. C. Ma, Joseph K. H. Ma, Chang-geng Mo, Carl J. Malanga

"A group of bisbenzylisoouinoline alkaloids has been shown to exhibit various degrees of effectiveness in preventing silica-induced fibrosis in animal models [1, 2]. The objective the present study was to characterize the binding of several of these alkaloids to phosphatidylcholine vesicles and rat alveolar macrophages using fluorometric and equilibrium dialysis methods, respectively. The lipid binding affinity of these alkaloids was found to depend upon several structural factors including hydrophobic substitutions, chiral configurations, and double oxygen bridge-restricted conformation of the benzylisoquinoline moieties. Tetrandrine, which is a highly effective agent in preventing fibrosis, showed strong binding to both lipid vesicles and alveolar macrophages. In contrast, certain analogues of tetrandrine such as curine and tubocurine, which have little or no effect on silicosis, exhibited only weak binding to lipid vesicles and almost no binding to cells. The moderate binding affinity of fangchinoline to vesicles and cells corresponded to a moderate effectiveness of the compound as an antifibrogenic agent. Methoxyadiantifoline, an alkaloid of unknown antifibrogenic potential, also exhibited high binding affinities for lipid and cells. In conclusion, the results of these studies indicate that alveolar macrophages exhibit large binding capacities for certain members of this class of bisbenzylisoquinoline alkaloids. A positive correlation was observed between binding affinity to alveolar macrophages and the reported antifibrotic potency of these compounds. These data also suggest that the ability of these drugs to interact with alveolar macrophages may be a key step in inhibition of the progression of silica-induced pulmonary disease.INTRODUCTIONInhalation of crystalline silica is associated with the development of silicosis. This fibrotic disease is characterized by the appearance of concentric hyalinized nodular lesions in the lungs with the progressive development of pulmonary dysfunction [3, 4]. Many theories concerning the etiology of silicosis involve silica-induced activation of alveolar macrophages. Evidence indicates that in vitro silica exposures result in the generation of chemiluminescence, and the release of superoxide and hydrogen peroxide from alveolar macrophages [5]. Activation of alveolar macrophages has also been demonstrated after intratracheal instillation or inhalation of silica [5, 6]. Such excess release of reactive products from pulmonary phagocytes has been associated with damage to the lung parenchyma [7, 8]. In addition, silica exposure results in the release of mediators from alveolar macrophages, which enhance proliferation of fibroblasts and collagen synthesis by these pneumocytes [9-12]."

Mar 1, 1992

By C. P. Fang, V. A. Marple, K. L. Rubow, P. H. McMurry

"It has been known for some time that sizes of aqueous particles may be affected by flow-induced relative humidity (RH) changes. The RH of air flowing through an impactor decreases as a result of pressure drop through the impactor and increases because of aerodynamic cooling within the high-speed jets, as illustrated in Figure 1. Because the sizes of aqueous particles depend on RH, the impaction stage on which such particles are collected may be different from the stage where they ought to be col¬lected, based on the particle size at the sampler inlet.Fuchs (1980) reviewed literature on water vapor condensation in impactors. The reviewed impactors operated at jet velocities of 100-250 m/s. Particle size increases ow¬ing to water vapor condensation were found in all cases. In one case (Khorguani et al., 1970), it was found that very small droplets (Dp <_ 0.02 um) containing sodium chloride and silver iodide were collected in an impactor with a cut point of 0.32 µm and a jet velocity of 100 m/s. Fuchs believed that such particles could not be captured in an impactor without having been enlarged by condensation. Winkler (1974) sampled at¬mospheric dust with a rectangular nozzle impactor that had a nozzle cross section of 0.3 x 15 mm, a cut size of 0.4 um, and an average jet velocity of 100 m/s. No adhesive was used on the impaction plate. The collection efficiency increased as air humidity was increased from 20% to 100%. The effect was especially noticeable in the increased collection efficiency for hygroscopic particles, and was attributed to condensation.Extensive theoretical and experimental research work on the distortion of the particle size distributions in impactors was done by Biswas and coworkers (1985, 1987). The impactors employed in the study were a low-pressure impactor with high jet velocity stages (Hering et al., 1978, 1979) and a conventional six-stage impactor, Sierra's model 226, operated in the incompressible regime. Ammonium sulfate aerosols were chosen for the study. In the low-pressure impactor, an orifice operating at a Mach number of 1 causes a sudden pressure drop, significantly reducing the RH in the next two stages (stages 5 and 6). This results in a 0.15-um diameter ammonium sulfate droplet shrinking to about 0.07 um at stage 5 when the inlet RH is 95%. In stage 7, the tempera¬ture drop is considerable because the jet speed is sonic. For an inlet RH of 95%, a 0.03 um droplet grows to about 0.06 um. However, the same size droplet at an inlet RH of 25% grows to only 0.04 um. For the Sierra model 226 cascade impactor that is operated with a Mach number of 0.27 at the last stage (stage VI), it was found that for an inlet RH of about 67%, particle growth would occur in stage VI. At 80% RH, both stages V and VI were affected. Biswas et al. (1987) stated that Mach number alone does not determine the size biasing; the type of aerosol, the inlet conditions, the temperature and pressure ratio, and the impactor geometry (throat length, jet-to-plate distance, etc.) must be considered for each stage in evaluating the distortion of the particle size distribution."

Mar 1, 1992

"The following articles were produced through funding under Generic Mineral Technology Center for Respirable Dust research. Full articles appear in the proceedings, 3rd Symposium in the Mineral Industries, published in 1991 by the Society for Mining, Metallurgy and Exploration, Inc.Personal Diesel Exhaust Aerosol SamplerV.A. Marple, K.L. Rubow, and Y. TaoParticle Technology, Mechanical Engineering Department, University of Minnesota, Minneapolis, Minnesota(Section ill. Diesel I: Diesel Particulate Measurement, pp. 73-81)Abstract. Techniques are being developed for measuring the mass concentration of respirable diesel exhaust particles found in underground coal mines. Studies have been conducted over the past five years to investigate size selective 18Dlpling techniques to measure the respirable mass concentrations of diesel exhaust and mine dust aerosol particles in underground coal mines. Results from these studies have been used to develop design and performance criteria for a personal diesel exhaust aerosol sampler.Three personal diesel exhaust aerosol samplers have subsequently been designed and evaluated in both laboratory and field settings. These samplers use size selective classifiers for the determination of respirable mass concentrations of mineral dust and diesel exhaust particles. Their designs are based on the premise that diesel exhaust particles are predominantly less than 0.8 µm while mineral dust is greater than 0.8 µm.One design, selected for field evaluation, consists of a 10 mm nylon respirable dust cyclone followed by a 0.8 µm cutpoint impactor and afterfilter. The cyclone removes the nonrespirable particles while the inertial impactor state, collects the mineral dust on an impaction plate and allows the diesel particles to penetrate to an afterfilter. The two sample fractions of the respirable particles ( <0.8 µ.m and >0.8 µm) are gravimetrically analyzed to determine the concentrations of the diesel and mineral dust portions in the respirable coal mine aerosol."

Mar 1, 1992

By N. S. Dalal, J. F. Mega, X. Shi, V. Vallyathan

Several studies have suggested that pulmonary toxicity to asbestos and silica may be mediated through oxidant-induced cell injury. We have reported recently that surface radicals associated with freshly fractured silica may be an imponant factor in cell injury and induction of pulmonary disease. Although the generation of oxygenated radicals in dust-cell interactions has been demonstrated, there are no data correlating the toxicity of a dust with the level of oxygen radical generation by the dust during its interaction with phagocytic cells. In the present study, we have investigated the in vitro generation of oxygen free radicals from human neutrophils and rat alveolar macrophages stimulated with freshly fractured silica, aged silica, amosite, crocidolite, chrysotilc, and a nontoxic dust, barite. Electron spin resonance (ESR) with the aid of a spin trap phenyl-N-ten-butyl nitronc (PBN) was used to measure the oxygen radicals generated during phagocytosis of the dusts. The relative toxicity index and ESR peak heights, on an equal surface area basis and normalized to barite as one, showed a direct relationship. The normalized toxicity indices and peak heights were: silica, 3.5 versus 2; chrysotile, 4 versus 2; crocidolite, 11 versus 8; and amosite, 26 versus 13. Addition of hydroxyl radical scavengers such as catalase, dimethyl sulfoxide, 1,3 dimethyl-2-thiourea (DMTU), sodium benzoate, and mannitol prevented the radical generation. Carmustine, a glutathione reductase- glutathione peroxidase inhibitor, caused a 5-fold increase in the radical generation. These results indicate that a nontoxic dust such as barite generates toxic oxygen radicals at a minimal level that can be quenched by the normal cellular defense system. For toxic dusts such as silica, amositc, chrysotile, and crocidolite, the potential for oxygen radical generation is enhanced by their surface propenies, physical dimensions, and the surface-based radical-generating redox sites. The enhanced radical generation may impair the cellular defense system, resulting in cell injury. Use of scavengers, chelators, and potentiating agents suggests the membrane-based oxidase system as the probable primary source of the radical-generating system. The data presented herein suggest the generation of oxygen free radicals as an important primary event in silica- as well as asbestos-induced cell injury.

Mar 1, 1992

By M. W. Barger, J. K. H. Ma, J. Y. C. Ma, V. Castronova

The objective of this study was to investigate the effects of various bisbenzylisoquinoline (BBIQ) alkaloids on respiratory burst activity of alveolar macrophages and to characterize the interaction of these drugs with alveolar phagocytes. BBIQ alkaloids were chosen for study because they exhibit a wide range of antifibrotic potencies in a rat model, with tetrandrine being very effective and tubocurarine being ineffective. These drugs inhibited zymosan-stimulated oxygen consumption with a potency sequence of tetrandrine (IT) = fangchinoline (FA) > berbamine (BE) ., cepharanthine (CE) "" cycleanine (CY} ~ tubocurarine (TU). This inhibition of respiratory burst activity could not be attributed to a drug-induced decline in the ATP content of these pneumocytes. Drug binding to alveolar macrophages was directly dependent on temperature and drug concentration. The sequence for binding capacity was FA > TT = BE = CY > CE ~ TU. Therefore, there was no simple relationship between binding capacity and inhibitory potency. Binding capacity was not related to lipophilicity of these alkaloids. In addition, tetrandrine failed to bind to metabolically dead cells or sonicated macrophage preparations. These data suggest that the interaction of BBIQ alkaloids with phagocytes is not simply nonspecific binding to membrane lipids. Alteration of the cytoskeletal system with vinblastine, taxol, or cytochalasin B decreased tetrandrine binding by approximately 33% when adtkd separately and by 93% when added jointly. Pre-exposure of alveolar macrophages to stimulants increased the ability of BBIQ alkaloids to inhibit both oxygen consumption and superoxide release. These data suggest that the mechanism by which BBIQ alkaloids inhibit activation of phagocytes involves microtubules and bules and microfilaments. Pre-exposure of macrophages to stimulants would change the conformation of cytoskeletal components and may make these structures more susceptible to drug interaction.

Mar 1, 1992

By N. S. Dalal, X. Shi, P. M. Gannett

"Chromates are known to induce tumors (1, 2), mutations (3), and DNA damage (4-6). However, the underlying biochemical mechanism(s) is (are) not fully understood (6). Recent studies have indicated that hydroxyl (·OH) radical may play an important role (7-11). The mechanistic studies of Cr(Vl)-related ·OH radical generation in biochemical systems have shown the reaction of a Cr(V) species with hydrogen peroxide (H20 2 } through a Fenton-like mechanism to be one of the important steps (9-11): Cr(V) + H20 2 - Cr(VI) + ·OH + OH-. (1)In biological systems the Cr(V) species are generated via the reduction of Cr(VI) by a variety of components, such as microsomes (12), mitochondria (13), mitochondrial electron transfer complexes (14), and at least three flavoenzymes (glutathione reductase (GSSG-R),3 lipoyl dehydrogenase, and ferredoxin-NADP+ oxidoreductase) (9, 15, 16). In the case of flavoenzymes, Cr(V) formation is accompanied by the reduction of molecular oxygen ( 0 2 ) to H20 2 • The Cr(V) species then reduces H20 2 to generate •OH radicals and Cr(VI) (16).To understarid the mechanism by which Cr(V}-generated ·OH radicals cause cytotoxicity, Aiyar et al. (8) investigated the reaction of Cr(VI) and H20 2 to generate ·OH radical and its reaction with 2'-deoxyguanine (dG) to form 8-hydroxy-2'-deoxyguanine (8-0HdG}:"

Mar 1, 1992

By V. Vallyathan, Xianglin Shi, N. S. Dalai

While Cr(VI) is a known carcinogen, the underlying biochemical mechanism is still not fully understood (1). In a pioneering study Jennette (2) utilized electron spin resonance (ESR) spectroscopy to demonstrate that a long-lived Cr(V) species is generated during the reduction of Cr(VI) by microsomes in the presence of NADPH. Later Wetterhahn and co-workers (3, 4) showed that incubation of chromate with isolated rat liver mitochondria causes the reduction of Cr(VI), as well as the formation of a Cr(V) species. Analogous Cr(V) species have also been detected in the reduction of Cr(VI) by other cellular systems such as Hanserulla polymorphared (5) and blood cells (6, 7). All these as well as other studies (8-12) have suggested that this Cr(V) species plays a significant role in the mechanism of Cr(VI) toxicity. Thus far, however, the chemical structure of this dominant Cr(V) species formed in cellular systems has not been identified, and this observation provided an impetus for the present investigation. Another reason for undertaking this study was that some recent reports (10-16) suggest that hydroxyl ('OH) radicals may also play an important role in the mechanism of Cr(VI) toxicity. In particular, it has been shown that OH radicals are formed in reactions between Cr(V) species and H2O2 (13-16), and that the radical yield depends on the chemical structure of the Cr(V) species (15). For example, while Cr(V)-diol complexes efficiently generate OH radicals, another Cr(V) species, the tetraperoxochromate (CrO3/8) ion, does not (15). Thus in the present study, we focused our attention on the following: (a) structural identification of the Cr(V) species generated in the reduction of Cr(VI) by subcellular as well as cellular systems, using microsomes, mitochondria, and Escherichia coli; (b) possible detection of OH radical in the same systems since there is no earlier report of chromium-mediated generation of 'OH radicals in a cellular system; (c) possible involvement of molecular oxygen in chromium-related OH radical generation since a recent report (17) indicated that Cr(VI) mutagenesis is strongly oxygen dependent; and (d) elucidation of the mechanism of OH radical formation in these systems.

Mar 1, 1992

By M. S. Seehra, R. S. Pandurangi

"The interaction of amorphous silica particles with several hydrogen bonding agents (H2O,, C2H,OH, C,H,NO) was investigated by monitoring the changes in the bulk and surface IR vibrational modes of silica using photoacoustic spectroscopy, It is argued that the intensity of the silanol band at 3747 cm-1 provides (an inverse) quantitative measure of the interaction of surface groups, along with the shift in the broad hydroxyl band, the interaction following the order C,H,NO > C2H2OH > H2O.The use of IR spectroscopy to study the adsorption on solid surfaces is well documented in the literature,"" For example, hydroxylation of a clean silica surface results in the formation of the free silanol group Si-OH, with a sharp IR band near 3747 cm-1. Further hydroxylation produces a broad band near 3500 cm-1, which is believed to result from various hydrogen-bonded silanol bands leading to a multilayered surface structure of few nm.3-6 Earlier studies had indicated a relationship between the surface silanol band and various chemical activities of silica such as cytotoxicity,7-9 catalysis,10-12 and others.13 Recent studies from our group14-in which the intensity of the silanol band and cytotoxicity of silica, heat-treated at various temperatures up to 1095°C, were investigated-have provided a strong correlation between cytotoxicity and intensity of the silanol band.Coating of silica by PVPNO (polyvinyl-2-pyridine N-oxide with the empirical formula C7H8N0), a strong hydrogen bonding agent, is known to reduce the cytotoxicity of silica, presumably by chemically blocking the silanol groups from phospholipids.15 This interaction of the hydrogen bonding agents with the silica can be studied by IR spectroscopy, and Knozinger16 and Rouxlet and Semples17 have used transmission IR spectroscopy to study the effect of various chemicals on the surface IR modes of silica. However, one of the major disadvantages of transmission IR spectroscopy is that the sample preparation (grinding and mixing with KBr and pelletizing) usually distorts the surface modes (see, e.g., Ref. 14) and there is always a doubt about the effect of the sample preparation on the measured properties, In recent years, photoacoustic (PA) spectroscopy has become the technique of choice for studying the IR spectra of samples in their natural state, since no sample preparation is necessary.18,19 Moreover, according to a recent paper,20 the relative intensity of the surface modes in PA spectroscopy of silica particles is much higher than that in transmission FT-IR spectroscopy. Consequently PA spectroscopy is ideal for studying the surface chemistry, In this work, we have used PA spectroscopy to investigate the interaction of three hydrogen bonding agents (C7H8NO, C2H5OH, and H20) with the silica surface by monitoring changes in the surface IR modes, Our results show that the surface IR modes get perturbed to a larger extent than the bulk IR modes in interaction with the hydrogen bonding agents, Moreover, whereas in the earlier studies, the shift of the broad silanol band near 3500 cm-1 was used as a measure of the interaction with hydrogen bonding agents,16,17 here we show that the relative decrease in the intensity of the sharp silanol band near 3747 cm-1 also serves as a quantitative parameter for the relative surface coverage and surface modification, Details of this work are given below,The Cab-O-Sil samples of silica used here were obtained from the Cabot Corporation of Tuscola, IL, In our earlier studies,14,20 we have shown these particles to be amorphous and about 0.05 am in size, For coverage of these particles with H20 and C2H50H, the following procedure was employed. About 5 mg of silica was mixed with 50 mL of the liquid (H2O or C2H5OH) and refluxed for one hour, The remaining liquid was allowed to evap¬orate to dryness and 1 mg of the treated sample was used to collect the PA spectra. In the case of PVPNO, the amount that binds to Cab-O-Sil is taken from the data on quar"

Mar 1, 1992