Carbon disulphide absorption during xanthate reagent mixing in a gold mine concentrator.
A xanthate reagent mixer at a gold mine concentrator was exposed to carbon disulphide by extensive skin contamination with xanthate powder and solution during the reagent mixing process. Absorption of carbon disulphide was confirmed by the detection of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA). Drager colorimetric tube testing during subsequent mixing recorded a maximum concentration of at least 60 ppm carbon disulphide. An illness consisting of predominantly gastrointestinal symptoms began 20 h after the exposure. Although this may have been due to carbon disulphide toxicity this is by no means certain. The need for engineering controls, impervious protective clothing and full-face respirators with particulate and organic vapour cartridges is discussed. This episode occurred at another mine site, unrelated to Mount Isa Mines Limited. (+info
Preliminary external quality assessment for the biological monitoring of carbon disulfide with urinary 2-thiothiazolidine-4-carboxylic acid.
Four laboratories have participated in an external quality control assessment for the determination of 2-thiothiazolidine-4-carboxylic acid (TTCA). TTCA is used as a biomarker for exposure to CS2. Thirteen different urine samples were analyzed by each laboratory. Ten of these were spiked with known amounts of TTCA, and had either a high or intermediate creatinine content. Two samples without any TTCA were used as controls and one sample was a pool of samples of urine from five employees occupationally exposed to CS2. The latter had unknown TTCA content. For each sample, TTCA and creatinine concentration were determined. The samples were supplied in three consecutive deliveries. Several samples were offered more than once. Thus, within-laboratory variability could be established for creatinine and TTCA determination and accuracy could be determined for TTCA analysis. Within-laboratory variability was low for all laboratories for creatinine, although laboratory D seemed to have a slight downward bias. Accuracy for TTCA was good for all laboratories. No significant mean deviation from the expected TTCA value was encountered. There does not seem to be any clear influence of the TTCA concentration level of the samples on the accuracy and within-laboratory variability. Two of the four laboratories (A and C) showed lower within-laboratory variability than the other two for TTCA, although coefficients of variation between replicated samples are high for these two laboratories as well. The laboratory giving the best accuracy, gave the highest within-laboratory variability. A non-systematic, random error is probably the source of this. The results of this preliminary study indicate that analysis of TTCA, although regarded as an established biomarker, can give biases and thus negatively interfere with inferred dose-effect or dose-response relationships in occupational epidemiology. (+info
Exposure of C57BL/6 mice to carbon disulfide induces early lesions of atherosclerosis and enhances arterial fatty deposits induced by a high fat diet.
Even though atherosclerotic cardiovascular disease (ACVD) is the number one cause of death in the United States, the effects of environmental toxicants on this process are less well studied than the effects of chemicals on the second leading cause of death, cancer. There is considerable epidemiological evidence that workers exposed to carbon disulfide (CS2) have increased rates of ACVD, and there is conflicting evidence of the atherogenic potential of CS2 from animal studies. Chemical modification, such as oxidation of low-density lipoproteins (LDL), is tightly associated with increased LDL uptake by macrophages and the development of arterial fatty streaks. CS2 has been previously demonstrated to modify several proteins in vitro including LDL, and others in vivo through derivatization and covalent cross-linking. To investigate both the capacity of CS2 to induce arterial fatty deposits by itself, and its ability to enhance the rate of fatty deposit formation induced by a western style, high fat diet, groups of 20 female C57BL/6 mice were exposed to 0, 50, 500, or 800 ppm CS2 by inhalation. Half the animals in each group were placed on an atherogenic high fat diet and half on a control diet (NIH-07). Animals were sacrificed after 1, 4, 8, 12, 16, or 20 weeks of exposure, and the rates of fatty deposit formation under the aortic valve leaflets were evaluated. Exposure of mice on the control diet to 500 and 800 ppm CS2 induced a small but significant increase in the rate of fatty deposit formation over non-exposed controls. A more striking result was observed in the animals on the high fat diet. There was marked enhancement of the rate of fatty deposit formation in mice exposed to 500 and 800 ppm over the animals on the high fat diet alone. In addition, there was a small but significant enhancement in mice exposed to 50 ppm over the rate of fatty deposit formation induced by the high fat diet alone. Analysis of erythrocyte spectrin for protein cross-linking revealed a dose-dependent formation of alpha- and beta-heterodimers in animals on both diets. These data demonstrate that CS2 is atherogenic at high concentrations, but more importantly, suggest that, in conjunction with other risk factors, CS2 at relatively low concentrations can enhance atherogenesis. (+info
Simultaneous analysis of urinary 2-thiothiazolidine-4-carboxylic acid and thiocarbamide as a biological exposure index for carbon disulfide exposure.
The objectives of this study were to develop optimal analytic methods for detecting urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) and thiocarbamide simultaneously and to evaluate the usefulness of these metabolites to a biological exposure index (BEI) for carbon disulfide (CS2) exposure. For this experiment, synthesized TTCA and thiocarbamide were used. The synthesized TTCA was identified by infrared spectrophotometer, nuclear magnetic resonance spectrometer and thin layer chromatography. The recovery rates of both metabolites were calculated to find the optimum analytical method. The amounts of urinary TTCA and thiocarbamide were measured by using an ultraviolet detector connected to high performance liquid chromatography (HPLC) after the administration of CS2 (350, 700 mg/kg) into Sprague-Dawley rats intraperitoneally. The maximum absorbance wave lengths for TTCA and thiocarbamide were 272 and 236 nm, respectively. Ethyl acetate extraction with NaCl as a salting-out reagent was used as a simultaneous extraction method for these metabolites. HPLC conditions for these metabolites included using a NH2 column, 50 mM KH2PO4: acetonitrile (85:15) and pH 3. Excreted amounts of urinary TTCA and thiocarbamide were increased significantly following CS2 administration. TTCA, which was already adopted as a BEI for CS2 by the American Conference of Governmental Industrial Hygienists (ACGIH), seems to be a more useful BEI for CS2 exposure than thiocarbamide. However further studies are needed to increase analytical efficiency before thiocarbamide can be adopted as a BEI and to apply this analytic method for simultaneous analysis of these metabolites in workers exposed to CS2. (+info
Toluene-3,4-dithiol analysis of blood for assessing carbon disulfide exposure.
Carbon disulfide is a neurotoxic compound used in the production of viscose rayon, and is a major decomposition product of dithiocarbamates used in industry, agriculture, and medicine. Methods used currently for assessing exposure to CS2 are limited in their ability to evaluate cumulative exposures and provide useful information for relatively short periods of time after exposure has ended. The present investigation evaluates a method for monitoring CS2 exposure that consists of cleaving the thiocarbonyl function of free CS2 or certain CS2-generated modifications on proteins using toluene-3,4-dithiol. The resulting toluene trithiocarbonate product is then quantified using reverse-phase high-performance liquid chromatography. The sensitivity, dose response, kinetics and specificity of this biomarker in blood were examined in rats administered CS2 by inhalation, intraperitoneal injection, or gavage for acute through subchronic periods. Dithiol reactive functions in plasma and hemolysate demonstrated a linear dose response over a wide range of exposure levels, were dependent upon the duration of exposure, and appeared to have an appropriate sensitivity for evaluating occupational levels of exposure. Elimination rates of dithiol reactive functions may also be dependent upon exposure duration and exhibit different kinetics for plasma and hemolysate suggesting that elimination rates may be useful for estimating cumulative exposure and intervals between exposure and sample procurement. Dithiol analysis, used in conjunction with previously established erythrocyte protein cross-linking biomarkers, may provide a means to characterize the internal dose of CS2 resulting from acute through chronic periods, and may provide insight into the level of CS2-mediated covalent protein modifications occurring within the nervous system. (+info
Indicators of cardiovascular risk among workers exposed to high intermittent levels of carbon disulphide.
The effects of exposure to carbon disulphide have been studied mostly among workers in the viscous rayon industry, where the usual exposure profile has been relatively steady exposure over work shifts. We investigated 13 workers in a small chemical company who were exposed to low levels, peaking intermittently to relatively high levels in the range of 100-200 ppm at the end of the work shift, a pattern that may change the risk profile. Our investigation was part of a compliance order that was fought by the company and our access and follow-up was limited. Two workers had burns on their bodies associated with exposure to caustic. Four had elevations in total serum cholesterol, one had elevated serum triglycerides and three had elevations in fasting blood glucose--two of them were known to be diabetics before employment and one had a history of unexplained peripheral neuropathy. No consistent pattern suggestive of a defined lipoprotein abnormality was obvious but several atherogenic profiles were observed. Five had abnormalities on electrocardiogram, four of whom appeared to be among the most heavily exposed. The presence of these changes taken together in this context may suggest accelerated atherosclerotic changes. Tests of liver and kidney function were within the normal range for all workers, as was a complete blood count. Four of the workers had evidence of a bilateral reduction in hearing threshold at 4,000 Hz. A complete set of recommendations was forwarded to the employer, emphasizing further control of exposure to carbon disulphide, personal protection requirements and a cardiovascular risk reduction programme. Conditions improved in the plant following modifications introduced in response to a stop work order from the provincial government's occupational health and safety agency. However, a fire in 1998 put the company out of business and ended further follow-up or interventions. We conclude that these findings, while difficult to interpret because of the circumstances of the investigation, are compatible with an atherogenic effect of exposure to peaking levels of carbon disulphide. The observation should be tested in a larger population with fewer confounding factors and greater control over the investigation. (+info
Characterization of carbon disulfide neurotoxicity in C57BL6 mice: behavioral, morphologic, and molecular effects.
Female C57BL6 mice were exposed to 0 or 800 ppm carbon disulfide (CS2), 6 h/d, 5 d/wk for 20 weeks. The neurologic function of all mice was assessed once at the end of exposures using a functional observational battery. General health effects included a decrease in body weight gain, piloerection, hunched body posture, and ptosis. Treatment-related effects included altered gait (uncoordinated placement of hind limbs and ataxia) and impaired function on an inverted screen test. In addition, rearing and locomotor movement were decreased in treated mice. Focal to multifocal axonal swelling was seen predominantly in the muscular branch of the posterior tibial nerve, and occasionally giant axonal swelling was detected in the lumbar segment of the spinal cord. Electron microscopic examination revealed swollen axons with massive accumulation of neurofilament proteins within the axoplasm. Covalent cross-linking of erythrocyte spectrin (surrogate protein to neurofilament protein) was demonstrated in mice exposed to CS2 but not in mice receiving filtered air. These data provide supportive evidence that covalent cross-linking of neurofilament proteins is a significant feature of the axonal swellings in mice produced by inhalation exposure to CS2. (+info
Behavioral toxicology of carbon disulfide and toluene.
Organic solvents are pervasive in the communal and industrial environments. Although many are potent central nervous system agents, clearly delineated behavioral effects have played only a minor role in the formation of exposure standards. A comprehensive behavioral pharmacology and toxicology of these compounds is one aim of US/USSR collaboration. The current report describes some actions of carbon disulfide and toulene. Earlier data about the actions of carbon disulfide on pigeon operant performance indicated disruption of schedule-controlled key-pecking. Primate data are now described from a situation designed to determine aversive thresholds to electrical stimulation. Effective concentrations of carbon disulfide produced both a rise in the amount of electric shock tolerated and a diminution of the response force exerted by the monkeys. In experiments with toluene, pigeons were shown to elevate key-pecking rate in an operant situation at certain concentrations. Toluene also was studied for its capacity to maintain self-administration in the same way as drugs of abuse. Monkeys worked to gain access to toulene vapor just as they work for opiates or amphetamines. The current experiments demonstrate how comprehensive the range of behavioral toxicology needs to be to deal with environmental health issues. (+info