What is the role of carbon disulfide in the etiology of toxic neuropathy?

Updated: Dec 06, 2017
  • Author: Jonathan S Rutchik, MD, MPH, FACOEM; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Answer

Carbon disulfide is an agent used in the viscose rayon industry. Refer to Table 3 for its other uses.

Carbon disulfide has been deemed a peripheral neurotoxin in both animals and humans by the Agency for Toxic Substances and Disease Registry (ATSDR). Consistency has been established for effect (ie, neurophysiological impairment and pathologic changes) but not for dose. The pathophysiology for toxic neuropathy is an axonal neuropathy in a distal dying back pattern. Reduced or absent sensory nerve action potentials (SNAPs) are common. Conduction velocities are usually normal, but they may be borderline low owing to selective involvement of large fibers. Metabolic abnormalities from coexisting diseases may be associated with reduced conduction velocities and may contribute to electrophysiologic abnormalities.

In humans, neurophysiological effects have been demonstrated at low levels of occupational exposure. In 1974, Seppalainen and Tolonen demonstrated a decrease in maximal motor NCV in the median, ulnar, peroneal, and posterior tibial nerves in 118 viscose rayon workers who had exposure to an average of 10-20 parts per million (ppm) of carbon disulfide for an average of 15 years. No improvement was noted after removal from exposure, but a follow-up study by these authors demonstrated that fewer workers who had retired 10-15 years prior had decreased NCVs than those who had been removed from their work 0-4 years prior to the study. (These abnormalities were in workers who had no subjective complaints.) [17]

In 1990 and 1993, Ruitjen et al demonstrated that 44 viscose rayon workers exposed to 1-30 ppm of carbon disulfide for at least 10 years had somewhat slower slow motor fiber conduction velocities than 31 controls, based on the antidromic collision technique. Symptoms of clinical neuropathy related to cumulative exposures were absent in the patients in this study. This study revealed that a decrease in the conduction velocity occurs at low levels of exposure to carbon disulfide. Extrapolation of these results suggests that small effects may occur after a mean cumulative exposure of 165 ppm-years, which would be equivalent to a concentration of 4 ppm over an 8-hour time-weighted average (TWA). At this exposure level over a lifetime of employment, the observed effects would be expected.

The authors explained that the significance of these effects on health would be that these observed changes might reduce reserve capacity to cope with other noxious influences. They concluded that these changes are undesirable until they are shown to be not detrimental to health in the long term.

The second study to verify these findings reexamined these workers 4 years later and found a statistically significant decrease in velocities in the slow as well as the fast motor nerve fibers of the peroneal nerve. Weighted cumulative exposures correlated less well with the peripheral nerve indices and revealed no evidence that the effects were reversible. The authors reiterated their concerns for the neurotoxic effects of carbon disulfide at these exposure levels. [18, 19]

In 1983, Johnson et al examined 189 workers from a viscose rayon plant; 245 workers in polyester-nylon filament and staple plants were used as controls. [20] Confounding exposures were hydrogen sulfide, tin oxide, zinc oxide and sulfate, sodium hydroxide, and sulfuric acid. At no point in time did hydrogen sulfide levels exceed 1 ppm.

Carbon disulfide exposure was divided into high (median >7.1 ppm), medium (median 3-7.1 ppm), and low (median < 3 ppm). Exclusion criteria were alcohol consumption >35 U, blood glucose >110 mg/dL, or blood lead >40 mcg/L. Mean duration of exposure for all exposed subjects was 12.1 years; for the high-exposure group it was 13.6 years; for the medium-exposure group it was 12.3 years; and for the low-exposure group it was 10.5 years. The average age of exposed individuals was 38.5 years and of controls, 33.9 years.

The study assessed NCV of motor (ie, peroneal, ulnar) and sensory (ie, sural) nerves. A reduction in peroneal nerve mean conduction velocity (MCV) was found to be related, in a dose-response sense, to cumulative exposure to carbon disulfide.


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