Carbon disulfide exposure

Neurological and Physiological Effects of Carbon Disulfide Exposure Review and Evaluation,." Westinghouse Behavioral Safety Center, Interim Report, NI0SH Contract HSM-99-73-35. Columbia, MD (1973). 

Carbon disulfide itself can be measured in breath, urine, and blood. It breaks down in the body into other chemical substances called metabolites. These substances can be found and measured in the urine. After carbon disulfide enters your body, these substances reach higher levels than normally found. One chemical test using urine can be done to tell whether the levels of these breakdown substances from carbon disulfide are higher than normal. This test requires special equipment and is not routinely available in a doctor s office. The test is not specific for carbon disulfide exposure because other chemicals can also produce these metabolites. Therefore, it cannot be used to find out exactly how much carbon disulfide you were exposed to or to predict whether you ll be harmed. Also, the test can only be used if you have breathed in at least 16 ppm this test can be used for determining longer term exposure to carbon disulfide. A second test based on a specific metabolite is more sensitive and specific. It also requires special equipment and cannot tell you exactly how much carbon disulfide you were exposed to or predict whether you ll be harmed. Carbon disulfide leaves the body quickly in the breath and in the urine. See chapters 2 and 6 for more information on testing for carbon disulfide. 

Compared to age-matched controls, an increase in total cholesterol, HDL-Ch, and LDL-Ch was observed in women 40-49 years of age and 50-59 years of age (Stanosz et al. 1994b). The women were exposed to carbon disulfide at 5-7 ppm for 0.5 to greater than 20 years. Only HDL cholesterol and LDL cholesterol were increased when the values were examined by duration of carbon disulfide exposure. Rather than being a hepatic effect, the investigators suggest that the effect may be on hormone production by the ovaries resulting in altered lipid metabolism. 

Thus, carbon disulfide does affect liver enzymes, particularly those related to lipid metabolism. The increases in serum cholesterol that are sometimes seen following carbon disulfide exposure may be a result of increased hepatic cholesterol synthesis. 

Adverse ocular effects in workers of a viscose silk plant exposed 6 hours a day, 5 days a week, for 0.5-30 years to less than 3.2 ppm carbon disulfide were reported by Szymankova (1968). Disturbances were manifested as vascular or inflammatory degenerative changes in the retinas of 12 out of 75 (16%) of the exposed workers, which disappeared in 11 workers following cessation of carbon disulfide exposure. 

The only study located that specifically addressed a possible immunological effect of carbon disulfide exposure in humans reported data that indicated that the -lipoprotein isolated from carbon disulfide-exposed workers (presumably exposed via inhalation) is antigenically identical to lipoproteins isolated from healthy nonexposed controls (Bobnis et al. 1976). The authors concluded that these findings... 

No studies were located regarding immunological or lymphoreticular effects after carbon disulfide exposure in either humans or animals. 

Regional cerebral blood flow was examined using Doppler ultrasound in 15 workers exposed to 3.2-28.9 ppm carbon disulfide for a mean of 20 years (Aaserud et al. 1992). Studies were performed 4 years after exposure ended. Asymmetrical blood flow patterns were observed in 8/14 workers, all of whom had encephalopathies consistent with carbon disulfide exposure. However, when the results were corrected to adjust for a possible influence of pC02, the values did not differ between the exposed workers and referents. No clear conclusions about this study can be made because of the small number of exposed workers, lack of a current exposure group, possible selection bias, and age variation between cohort and referents. 

In a cross-sectional study of the chronic effect of carbon disulfide exposure on the central nervous system, researchers measured the brain stem auditory evoked potential (BAEP) in Japanese spinning workers from a viscose rayon factory (Hirata et al. 1992a). The workers were divided into three groups depending upon... 

The relationship between electric impulse transmission and visual stimuli was examined in a group of 21 patients with chronic carbon disulfide exposure in a rayon production plant for 20-36 years and control groups of 25 or 36 healthy unexposed males (Sikora et al. 1990). A significant correlation was observed in latency and amplitude of response. The correlations suggest cerebral dysfunction of the visual pathway and diminished ability to transform visual information to motor reaction at the level of the cortical association center. The study was limited by the lack of quantification of exposure levels and the variability in responses in the exposed group. 

A narcotic-like stupor was observed during carbon disulfide exposure of rats at 600 ppm 10 hours a day for 14 days (Wilmarth et al. 1993). By the end of the study, mild ataxia and moderate hind-limb splay... 

The chronic effect of carbon disulfide exposure on the central nervous system was examined by auditory brainstem responses (ABR) in female JC1 Wistar rats (Hirata et al. 1992b). Rats were exposed by inhalation to 200 or 800 ppm, 6 hours a day, 5 days a week, for 15 weeks. Auditory responses were measured before exposure, every 3 weeks during exposure, and in weeks 2 and 6 after exposure. The... 

Behavioral and neurotoxic effects in the offspring of rats exposed via inhalation have been reported. Perinatal mortality was shown to be dose related to prenatal carbon disulfide exposure levels (225 and 642 ppm) in rats (Lehotzky et al. 1985). Exposure to 642 ppm carbon disulfide throughout pregnancy for 2 hours daily produced no malformations of fetuses in rats or mice but did increase the death rates of the embryos at all stages of intrauterine development (Yaroslavski 1969). 

The distribution of carbon disulfide following inhalation exposure has been studied in rabbits and rats (Toyama and Kusano 1953). In rabbits, blood equilibrium concentrations of carbon disulfide were reached after exposure to 20-150 ppm for 1.5-2.0 hours. In rats exposed to 60-350 ppm carbon disulfide, distribution was primarily to the brain, kidney, and liver. In contrast to rabbits, blood equilibrium concentrations for various carbon disulfide exposures in rats were not determined. Although carbon disulfide was rapidly eliminated from rat tissues during the first 6-8 hours after exposure, low concentrations of carbon disulfide were still detected in the tissues 20 hours after exposure. A separate study reported that equilibrium concentrations of carbon disulfide in blood were attained in dogs after 0.5-2.0 hours of exposure to 25-60 ppm carbon disulfide (McKee et al. 1943). Desaturation was largely complete within the first 30-60 minutes after inhalation exposure. Anesthetized male Sprague-Dawley... 

Following inhalation exposure, the primary route of excretion of unmetabolized carbon disulfide in humans is exhalation. In one study it was estimated that 6-10% of the carbon disulfide that was taken up was excreted by the lungs (McKee et al. 1943). In a study conducted on humans, carbon disulfide levels in the exhaled breath decreased rapidly on cessation of exposure (Soucek 1957). The excretion by the lung accounted for 10-30% of the absorbed carbon disulfide. Less than 1% was excreted unchanged in the urine. The remaining 70-90% of the dose was metabolized. The details regarding carbon disulfide exposure levels were not available. A correlation was established between carbon disulfide exposure of rayon workers and urinary excretion of a metabolite or metabolites that catalyzed the reaction of iodine with sodium azide (Djuric 1967). This test indicated exposures to carbon disulfide above 16 ppm but failed to identify specific urinary metabolites. The failure to detect carbon disulfide exposure below 16 ppm may be because of interference with the reaction by dietary sulfur-containing compounds. 

There are substantial data available on which to base conclusions regarding the potential health effects of carbon disulfide exposure in residents near hazardous waste sites and occupationally exposed individuals. The principal adverse health effects noted in humans exposed via inhalation are neurotoxic and... 

Endocrine Effects. The available data in humans provide conflicting evidence regarding the adverse effects of carbon disulfide exposure on thyroid function (El-Sobkey et al. 1979 Lancrajan et al. 1972 Wagar et al. 1981). Based on decreases in the urinary excretion of products of adrenal/gonadal or adrenal/sympathetic origin, exposure of workers to carbon disulfide may affect adrenal gland function (Cavalleri et al. 1967 Stanosz et al. 1994a). These studies also involved possible exposure to other chemicals and did not identify the precise exposure level. 

Dermal Effects. Dermal effects are limited to a report of blisters on the hands of viscose rayon workers presumably due to carbon disulfide exposure. This is borne out by studies in rabbits in which similar blisters could be induced by carbon disulfide exposure (Hueper 1936). This indicates that dermal contact from either occupational exposure or from contaminated soil or water near hazardous waste sites could cause adverse effects. 

Levels of carbon disulfide detected in exhaled breath, blood, urine, and milk as well as various metabolite concentrations in the urine of exposed individuals have been studied as biomarkers of carbon disulfide exposure. 

Carbon disulfide is also found in the saliva and sweat of exposed individuals in small quantities. These measurements have not been shown to quantitatively correlate with carbon disulfide exposure. The concentration of carbon disulfide in the feces is very low and therefore has also not been routinely used as a biological marker of exposure (Djuric 1967). 

Higher cholesterol levels (correlated with exposure levels), higher blood creatinine levels, marked disturbances of the hepatic cytochrome P-450 content and of the associated microsomal monooxygenase system, as well as the inhibition of succinic-oxidase enzyme activity, may also be considered as nonspecific biomarkers of carbon disulfide exposure. More research, however, needs to be done in order to determine whether a direct correlation exists between these parameters and carbon disulfide exposure. 

The following paragraphs describe reasonably specific biomarkers for carbon disulfide exposure in humans that correlate with exposure levels to varying degrees. 

Because of these confounding factors, results of breath tests for carbon disulfide exposure do not correlate well with its environmental levels. However, one might be able to detect carbon disulfide exposure more reliably if measurements of carbon disulfide were made during a second slower elimination phase and if a more sensitive detection technique were used. A quadrupole mass spectrometer makes the measurement of carbon disulfide in exhaled breath much more sensitive, detecting exposure levels as low as 1 ppm. In an investigation by Campbell et al. (1985), the short-term elimination of carbon disulfide was studied measuring uptake that had taken place 1-2 hours before the test. Carbon disulfide levels in the breath were found to fluctuate, but the value of next-day tests measuring the slower elimination phase of carbon disulfide by the breath should be explored. Nevertheless, the use of exhaled carbon disulfide remains an equivocal biomarker of exposure. 

As new red blood cells must be made to replace the damaged spectrin, the crosslinking of this protein may serve as a longer term biomarker of carbon disulfide exposure. 

Measuring the total concentration of urinary thio compounds (including glutathione conjugates, mercapturic acids, and other sulfur-containing carbon disulfide metabolites) can serve as a good marker of exposure. The level of total thio compounds correlates with carbon disulfide exposure levels and is a more sensitive biomarker of exposure than the iodine-azide test (Beauchamp et al. 1983 Van Doom et al. 

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