Benzene Toxicity

Benzene toxicity is acute and chronic poisoning from inhaling or absorbing benzene. Acute exposure causes central nervous system depression and arrhythmia. Chronic exposure suppresses the bone marrow and causes leukaemia.

Exposure. Petrochemical and refinery work, petrol handling and distribution, coke oven and chemical manufacture, rubber and some adhesives, laboratory work, and tobacco smoke. Workplace limits are set at about 0.5 to 1 ppm as an eight hour average.

Epidemiology. Risk of marrow disease and leukaemia rises with cumulative dose, and effects occur at lower levels than once thought. Occupational cases have declined where limits are enforced.

Spectrum. Acute: dizziness, headache, confusion, coma. Chronic: anaemia, leucopenia, thrombocytopenia, pancytopenia, aplastic anaemia, myelodysplastic syndrome and acute myeloid leukaemia.

Latency. Marrow suppression can appear within months of heavy exposure, and leukaemia typically after 5 to 20 years.

Pathophysiology.

Benzene is metabolised in the liver by CYP2E1 to benzene oxide, phenol, catechol and hydroquinone. Hydroquinone is converted to reactive benzoquinone in the marrow by myeloperoxidase.

Metabolites cause DNA adducts, chromosomal damage, topoisomerase II inhibition and oxidative stress in haematopoietic stem and progenitor cells.

• Acute: headache, dizziness, nausea, euphoria, tremor, confusion, arrhythmia and coma; skin and eye irritation.
• Chronic: fatigue, pallor, bruising, bleeding, recurrent infection and exertional dyspnoea.
• Sometimes menstrual disturbance and reduced fertility.

Red flags.

• Arrhythmia, collapse or reduced consciousness after acute exposure.
• Fever with neutropenia.
• Bleeding, petechiae or severe pallor.

• Exposure history with process, duration, ventilation and tobacco use.
• Full blood count with film, reticulocyte count, and serial counts in exposed workers.
• Urinary S-phenylmercapturic acid (usual workplace reference about 25 micrograms/g creatinine at the end of the shift) and trans,trans-muconic acid (about 500 micrograms/g creatinine) show exposure. Urinary phenol is insensitive at low exposure.
• Marrow aspirate and trephine with cytogenetics when cytopenia is unexplained or persistent.
• ECG after acute exposure; liver and renal function.

Differential diagnosis. Aplastic anaemia from other causes, myelodysplastic syndrome, vitamin B12 or folate deficiency, drug induced cytopenia, viral marrow suppression, hypersplenism, other solvent toxicity.

• Remove from exposure and move to fresh air; remove contaminated clothing and wash skin; irrigate eyes.
• Acute poisoning: oxygen, airway protection and continuous ECG monitoring. No antidote exists. Avoid adrenaline and other catecholamines. Do not induce vomiting.
• Cytopenia: stop all benzene exposure permanently, refer to haematology, and avoid marrow toxic drugs.
• Transfuse red cells when haemoglobin is under 70 g/L (under 80 g/L with cardiovascular disease), 1 unit then reassess. Transfuse platelets for a count under 10 x 10^9/L, or under 20 x 10^9/L with fever or bleeding. Use leucodepleted, irradiated products when marrow failure is severe. Monitor haemoglobin and platelets, and for transfusion reactions and iron overload.
• Fever with neutropenia: start broad spectrum antibiotics within 1 hour of presentation by local sensitivity data.
• Smoking cessation and removal of other benzene sources, including petrol vapour.

Monitoring. Full blood count every 6 to 12 months in exposed workers, more often if counts are falling; urinary biomarkers to review exposure.

Referral and escalation. Haematology for any persistent cytopenia; occupational physician for workplace investigation and removal; emergency care for acute exposure with arrhythmia or coma; notification and compensation where required.

Special groups. Pregnancy: avoid exposure because of foetal risk. Children and smokers are exposed through petrol vapour and tobacco smoke.