Carbon Disulphide Toxicity

Carbon disulphide toxicity is multisystem poisoning from inhaling or absorbing carbon disulphide. It causes acute narcosis and psychosis, and chronic polyneuropathy, parkinsonism, cognitive decline, retinal and vascular disease.

Exposure. Viscose rayon and cellophane manufacture, rubber vulcanisation, carbon tetrachloride production, pesticide and fumigant use, and laboratory solvent use. Workplace limits are set at about 1 ppm as an eight hour average.

Fire risk. The liquid is extremely flammable with a flash point of about minus 30 degrees Celsius, and vapour can ignite at low temperature.

Epidemiology. Cases are now concentrated in regions with poorly controlled rayon and rubber industries. Cardiovascular risk is raised in long term exposed workers.

Spectrum. Acute: headache, dizziness, agitation, delirium, coma. Chronic: neurobehavioural, neuropathic, cardiovascular, ocular and reproductive disease.

Pathophysiology.

Carbon disulphide reacts with amino groups to form dithiocarbamates that cross-link proteins and chelate copper, inhibiting dopamine beta hydroxylase and other copper dependent enzymes. Catecholamine metabolism is disturbed.

Metabolism produces 2-thiothiazolidine-4-carboxylic acid, excreted in urine. Vascular injury and accelerated atherosclerosis and axonal damage follow.

• Acute: headache, dizziness, nausea, irritability, mania or psychosis, delirium, seizures and coma.
• Chronic neurological: distal polyneuropathy, cognitive slowing, parkinsonism, tremor and optic neuritis.
• Cardiovascular: hypertension, angina and increased coronary events.
• Eye: retinal microaneurysms and visual loss.
• Reproductive and endocrine: menstrual disturbance, reduced libido and impotence.

Red flags.

• Coma, seizures or respiratory depression after acute exposure.
• Acute psychosis or suicidal behaviour.
• Chest pain, rapid deterioration of vision or progressive weakness.

• Exposure history and symptom timing.
• Neurological examination, mini mental state or neuropsychological testing, and nerve conduction studies.
• Fundoscopy, with fluorescein angiography for retinal vascular change.
• Cardiovascular assessment: blood pressure, lipids, glucose and ECG.
• Urinary 2-thiothiazolidine-4-carboxylic acid at the end of the shift for exposure; about 0.5 mg/g creatinine is the usual workplace reference.
• Liver and renal function; MRI brain for parkinsonism or encephalopathy.

Differential diagnosis. Primary psychosis, Parkinson disease, diabetic and alcoholic neuropathy, other solvent toxicity, vascular dementia, primary hypertension, Wernicke encephalopathy, other toxic neuropathy.

• Remove from exposure and move to fresh air; remove contaminated clothing and wash skin; avoid ignition sources.
• Acute poisoning: oxygen, airway protection, ECG monitoring and supportive care. No specific antidote exists.
• Acute psychosis or agitation: olanzapine orally 5 to 10 mg once daily, increased as needed to a maximum of 20 mg daily. Monitor sedation, glucose, lipids, weight and QTc. Start at 5 mg in older adults, hepatic or renal impairment; avoid in dementia related psychosis unless essential.
• Chronic neuropathic pain: pregabalin orally, 75 mg twice daily, increased after 3 to 7 days to 300 mg daily and, if needed after a further 7 days, to a maximum of 600 mg daily. Review at 4 weeks and stop if there is no meaningful benefit; withdraw over at least 1 week. Monitor sedation, dizziness, peripheral oedema, weight gain, mood and misuse. Adjust for renal function: creatinine clearance 30 to 60 mL/min, 75 to 300 mg daily in 2 or 3 divided doses; 15 to 30 mL/min, 25 to 150 mg daily; under 15 mL/min, 25 to 75 mg daily. Avoid in pregnancy unless benefit outweighs risk.
• Control cardiovascular risk: blood pressure, lipids, glucose, smoking cessation and exercise.
• Rehabilitation and workplace redeployment; the neurological deficit may persist.

Monitoring. Neurological and cognitive review every 6 months for 2 years; yearly cardiovascular and eye assessment.

Referral and escalation. Toxicology and neurology; ophthalmology for retinal change; psychiatry for psychosis; occupational physician for process review; notification and compensation where required.

Special groups. Pregnancy: avoid exposure; risk of spontaneous abortion and menstrual disturbance. Reproductive review is needed for both sexes.