Trichloroethylene Toxicity

Trichloroethylene toxicity is injury from inhaling, absorbing or ingesting trichloroethylene, a chlorinated solvent. It causes acute central nervous system depression and arrhythmia, chronic neurological and hepatorenal disease, a severe hypersensitivity syndrome, and cancer.

Exposure. Metal degreasing, dry cleaning, adhesives, paint strippers, correction fluids and historically as an anaesthetic. Contaminated groundwater is a non-occupational source.

Epidemiology. Reduced in many regions through restriction. Hypersensitivity syndrome has occurred in clusters in factories, with genetic susceptibility.

Distinctive effects. Degreaser's flush (vasodilatory flush with alcohol), trigeminal neuropathy, and cardiac sensitisation to catecholamines.

Cancer. Strong association with renal cell carcinoma, with possible links to non-Hodgkin lymphoma and liver cancer.

Pathophysiology.

Trichloroethylene is metabolised by cytochrome P450 and glutathione conjugation to trichloroacetic acid, trichloroethanol and reactive intermediates. Conjugation products are nephrotoxic and mutagenic.

Dichloroacetylene formed on heating with alkali damages cranial nerves. Inhibition of aldehyde dehydrogenase causes the alcohol flush. In hypersensitivity syndrome, T cell mediated immune reactions are associated with the HLA-B*13:01 allele in several populations.

• Acute: headache, dizziness, nausea, drunkenness, confusion, coma, arrhythmia, and skin and eye irritation.
• Chronic: fatigue, memory and mood disturbance, peripheral and trigeminal neuropathy, and hearing loss.
• Degreaser's flush: red face and trunk within minutes of alcohol ingestion.
• Hypersensitivity syndrome: fever, widespread rash (often with erythema multiforme or toxic epidermal necrolysis features), hepatitis, lymphadenopathy and eosinophilia, weeks after starting exposure.

Red flags.

• Arrhythmia, syncope or coma.
• Skin blistering or mucosal erosions with fever.
• Jaundice, oliguria or haematuria.

• Exposure history and timing, including alcohol interaction and skin contact.
• ECG, liver enzymes, renal function, urinalysis (protein, blood), full blood count with eosinophils.
• Urinary trichloroacetic acid at the end of the working week shows exposure; about 15 mg/L is the usual workplace reference. Trichloroethanol in blood reflects recent exposure.
• Neurological examination of cranial nerves (facial sensation) and peripheral nerves.
• Skin biopsy and liver assessment in hypersensitivity syndrome; HLA testing where available and relevant.
• Imaging of the kidneys for haematuria in long term exposed workers.

Differential diagnosis. Other solvent toxicity, alcohol intoxication, drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, viral hepatitis, trigeminal neuralgia, carbon monoxide poisoning, primary arrhythmia.

• Remove from exposure; remove contaminated clothing and wash skin; irrigate eyes with water.
• Acute poisoning: oxygen, airway support and continuous ECG monitoring. Avoid adrenaline and other catecholamines. Do not induce vomiting after ingestion because of aspiration risk.
• Ventricular tachyarrhythmia: propranolol 1 mg intravenously over 1 minute, repeated every 2 to 5 minutes as needed to a maximum of 5 mg in one episode, with continuous ECG and blood pressure monitoring. Avoid in asthma, bradycardia, heart block and hypotension; use caution in hepatic impairment and heart failure; no renal adjustment.
• Hypersensitivity syndrome: stop exposure, admit, and give supportive care with liver and skin management. Prednisolone 0.5 to 1 mg/kg orally once daily, maximum 60 mg daily, then taper over 4 to 6 weeks as liver enzymes and skin improve. Evidence is limited. Monitor glucose, blood pressure and infection; caution in diabetes and peptic ulcer; no renal adjustment. Specialist dermatology and hepatology direction.
• Advise against alcohol during exposure.
• Renal cell carcinoma screening by imaging when risk is high and hematuria appears.

Monitoring. Liver and renal function and urinalysis yearly in exposed workers; neurological review for persistent symptoms.

Referral and escalation. Toxicology; dermatology and hepatology for hypersensitivity syndrome; urology for haematuria; occupational physician for process review and cluster investigation; notification and compensation where required.

Special groups. Pregnancy: avoid exposure because of foetal cardiac and developmental concerns. Liver or renal impairment: lower the threshold for specialist review.