Ethylene Oxide Toxicity

Ethylene oxide toxicity is injury from exposure to ethylene oxide, a flammable, colourless gas used to sterilise heat sensitive equipment and to make glycols and surfactants. Acute exposure injures the airway, eyes, skin and nervous system. Chronic exposure causes neuropathy and cancer.

Exposure. Hospital and device sterilisation, chemical manufacture, spice and cosmetic fumigation. Workplace limits are about 1 ppm as an eight hour average. The odour threshold is several hundred ppm, so smell gives no warning.

Epidemiology. Acute poisoning follows leaks and faulty sterilisers. Chronic effects follow years of low to moderate exposure.

Chronic effects. Peripheral neuropathy, cognitive impairment, cataract, spontaneous abortion, and excess lymphohaematopoietic and breast cancer.

Liquid contact. Liquid and cold vapour cause burns and freezing type skin injury, with delayed blistering.

Pathophysiology.

Ethylene oxide is a direct alkylating agent. It forms adducts on DNA and on haemoglobin (hydroxyethylvaline), and it is mutagenic and carcinogenic.

Alkylation of proteins and glutathione depletion cause airway epithelial injury, with delayed pulmonary oedema, and distal axonal degeneration.

• Acute: eye, nose and throat irritation, cough, dyspnoea, headache, nausea, vomiting and drowsiness; seizures and coma at high levels.
• Delayed pulmonary oedema up to 24 hours after exposure.
• Skin: erythema and blistering, sometimes delayed by hours.
• Chronic: distal numbness, weakness, memory and concentration problems, and lens opacity.

Red flags.

• Worsening dyspnoea, hypoxaemia or frothy sputum within 24 hours.
• Seizures or reduced consciousness.
• Persistent eye pain or visual loss.

• Exposure history, leak events and co-worker symptoms.
• Oxygen saturation, arterial gas, chest radiograph, ECG and electrolytes after acute exposure.
• Haemoglobin hydroxyethylvaline adducts show cumulative exposure over about 4 months; ethylene glycol and chlorohydrin metabolites are non-specific.
• Nerve conduction studies for neuropathy; slit lamp examination; full blood count yearly in exposed workers.

Differential diagnosis. Other irritant gas inhalation, carbon monoxide poisoning, other toxic neuropathy, viral pneumonitis, cardiogenic pulmonary oedema, other causes of cataract.

• Remove from exposure; remove contaminated clothing; wash skin and irrigate eyes with water for at least 15 minutes.
• Oxygen to keep saturation at 94 to 98%; airway support. No antidote exists.
• Observe for 24 hours after significant inhalation. Admit for hypoxaemia, abnormal radiograph or respiratory distress; manage pulmonary oedema with oxygen and ventilatory support.
• Bronchospasm: salbutamol 100 microgram metered dose through a spacer, 4 to 10 puffs, repeated every 20 minutes for the first hour, then every 4 hours as needed. Maximum 10 puffs each dose. Monitor heart rate, potassium and oxygen saturation. Caution in arrhythmia and hyperthyroidism.
• Seizures: lorazepam 4 mg intravenously over 2 minutes, repeated once after 10 minutes if seizures continue. Maximum 8 mg. Monitor breathing and blood pressure; have airway support ready. Use caution in respiratory depression and hepatic impairment; no renal adjustment.
• Liquid contact injury: give burn and freezing injury care; tetanus immunisation by status.
• Chronic neuropathy: remove from exposure and give supportive care; neuropathic pain with pregabalin if needed under specialist direction.

Monitoring. Respiratory observation for 24 hours; nerve conduction studies and neurological review at 3 and 6 months after significant exposure.

Referral and escalation. Toxicology and respiratory care for significant inhalation; ophthalmology for eye injury; occupational physician for leak investigation, monitoring and surveillance; notification and compensation where required.

Special groups. Pregnancy: remove from exposure because of the risk of spontaneous abortion.