Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Benzene Toxicity
Answers to Pretest and Challenge Questions

Pretest Answers

1. The patient's problem list includes epistaxis, fatigue, ecchymoses and petechiae, and anorexia with concomitant weight loss. The differential diagnosis includes nose picking, external trauma, dry nasal mucosa with vascular fragility, foreign bodies, blood dyscrasias, neoplasms, infections, vitamin deficiencies, toxic metal exposures, septal deformities, telangiectasias, angiofibromas, and aneurysm ruptures.
2. Additional testing for the patient might include coagulation factors, blood smear evaluation for infectious agents, and assessment of nutrient status. Evaluation of the bone marrow should include a search for malignant cells.
3. The patient must be removed from exposure to benzene and other hematologic toxicants. His home water for drinking and personal purposes should be obtained from a source with levels of benzene below health screening values. Work exposure to toxic chemicals must be carefully evaluated. Adequate nutrients (e.g., vitamins and protein sources) in his diet should be assured. Care to prevent injury and bleeding must be exercised until proper blood coagulation (i.e., platelets and other factors) has returned, and the patient should be carefully monitored for infection in the event of severe granulocytopenia. Prophylactic antibiotics and blood transfusions should be avoided unless a significant deterioration of his condition becomes evident.

Challenge Answers

1. Some important areas to explore include amounts, intensity, frequency, and duration of exposure from the following sources:
   • water supply (e.g., ingestion or inhalation or dermal absorption during bathing, cooking, and laundering)
   • ambient air (e.g., fugitive emissions from the chemical plant during its operation and since it was abandoned 9 years ago)
   • occupation (e.g., activities, conditions, mixed exposures, and time spent as a diesel mechanic)
   • workplace conditions (e.g., cleaning of machinery parts, solvents used, protective equipment worn, and the adequacy of ventilation)
   • home environment (e.g., hobbies, yardwork, cleaning activities, use of consumer products that might contain benzene, and exposure to personal or passive cigarette smoke)
2. Theoretically, a person could be at increased risk of benzene's adverse effects if he or she encountered agents or conditions that increased the rate of formation of toxic benzene metabolites through induction of the MFO system. Potential agents include MFO-inducing drugs (e.g., phenobarbital and alcohol); conditions include those causing rapid synthesis of bone marrow. Because the patient only occasionally drinks beer and did not take medications before his illness, he avoids the risk factors of alcohol and medications. However, if the patient is suffering from a hematologic abnormality, as his symptoms and laboratory evaluation suggest, he will have increased risk if benzene exposure continues.
   
   Other persons in the case who may be at increased risk of benzene exposure are those who have had contact with the water supply for a prolonged period of time, although there are no data to quantify the risk; persons who have lived, worked, or visited for a prolonged time in the patient's household; and members of the community who share the water supply. Community and household members who are at increased risk of benzene's adverse effects theoretically include those with rapidly synthesizing bone marrows and persons with increased MFO-mediated metabolism (e.g., heavy drinkers). Take-home exposures could also put other persons at risk of exposure to benzene, especially if work clothes are laundered at home and showers are taken after leaving the work site.
3. The patient's problem list includes epistaxis, fatigue, ecchymoses and petechiae, and anorexia with concomitant weight loss. The differential diagnosis includes nose picking, external trauma, dry nasal mucosa with vascular fragility, foreign bodies, blood dyscrasias, neoplasms, infections, vitamin deficiencies, toxic metal exposures, septal deformities, telangiectasias, angiofibromas, and aneurysm ruptures.
4. Additional testing for the patient might include coagulation factors, blood smear evaluation for infectious agents, and assessment of nutrient status. Evaluation of the bone marrow should include a search for malignant cells.
5. The patient must be removed from exposure to benzene and other hematologic toxicants. His home water for drinking and personal purposes should be obtained from a source with levels of benzene below health screening values. Work exposure to toxic chemicals must be carefully evaluated. Adequate nutrients (e.g., vitamins and protein sources) in his diet should be assured. Care to prevent injury and bleeding must be exercised until proper blood coagulation (i.e., platelets and other factors) has returned, and the patient should be carefully monitored for infection in the event of severe granulocytopenia. Prophylactic antibiotics and blood transfusions should be avoided unless a significant deterioration of his condition becomes evident.
6. The prognosis is generally good for the resolution of the macrocytosis. Although this patient has a significant aplastic anemia, it is possible for his bone marrow to recover slowly if the damage has not reached an irreversible stage. Supportive treatment will be needed for many months. Because of the continued risk of leukemia, the patient should receive medical surveillance consisting of regularly scheduled examinations and appropriate testing of hematologic function. The peripheral smear and blood count will permit monitoring of early changes of the patient's condition. Bone marrow biopsy should be repeated in a few weeks to confirm initial findings and observe an expected bone marrow recovery.
7. One step in your quest to establish a causal relationship between benzene-contaminated home water and the patient's condition would be to investigate competing causes of low blood counts for this patient (e.g., drugs, radiation exposure, and family history), keeping in mind that most cases of aplastic anemia are idiopathic. You also need to explore the patient's potential exposure to chemicals other than benzene that might cause hematologic disorders. Finally, assuming the patient's condition is due to benzene exposure, you need to weigh the significance of benzene sources other than the drinking water. For example, the patient is a diesel mechanic and most likely has inhalation and dermal exposure to gasoline (which contains benzene) at work. You need to determine the amounts of benzene each source might have contributed to the patient's exposure.
   
   For the patient in the case study, as for most exposure cases, it will not be an easy matter to establish causality, and there is no precedent for a person developing hematologic abnormalities from benzene in drinking water.

Previous Section

Next Section