ATSDR - CSEM - Benzene Toxicity: Environmental Medicine Case Study

This monograph is one in a series of

self-instructional publications designed

to increase the primary care provider’s

knowledge of hazardous substances in

the environment and to aid in the

evaluation of potentially exposed

patients. This course is also available

on the ATSDR Web site, www.atsdr.cdc.

gov/HEC/CSEM/. See page 3 for more

information about continuing medical

education credits, continuing nursing

education units, and continuing

education units.

Case Studies in

Environmental Medicine

Course: SS3039

Revision Date: June 2000

Original Date: October 1992

Expiration Date: June 30, 2006

BENZENE

TOXICITY

Environmental Alert

Benzene is an important commercial commodity that, because of its

frequent use, has become widespread in the environment of developed

countries.

In the United States, gasoline contains up to 2% benzene by volume;

in other countries, the benzene concentration in gasoline may be as

high as 5%.

Benzene in the workplace has been associated with aplastic anemia

and leukemia.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Toxic Substances and Disease Registry

Division of Toxicology and Environmental Medicine

Benzene Toxicity

Table of Contents

ATSDR/DHEP Revision Authors:

Diane Drew, RN, MPA; Deanna K.

Harkins, MD, MPH; Ralph O’Connor Jr,

PhD; Felicia Pharagood-Wade, MD,

FACEP; Pamela Tucker, MD

ATSDR/DHEP Revision Planners:

William Carter, MD; Diane Dennis-

Flagler, MPH; Patricia Drehobl, RN,

MPH (CDC/PHPPO); Kim Gehle, MD,

MPH; Darlene Johnson, RN, BSN, MA

Edited By: Pamela S. Wigington;

Beverly Harris

Original Contributors: Arthur L.

Frank MD, PhD; Sophie Balk, MD

Original Peer Reviewers: John

Ambre, MD; Charles Becker, MD;

Jonathan Borak, MD; Joseph

Cannella, MD; Richard J. Jackson,

MD, MPH; Howard Kipen, MD, MPH;

Jonathan Rodnick, MD; Brian A.

Wummer, MD

Disclaimer

The state of knowledge regarding

the treatment of patients potentially

exposed to hazardous substances

in the environment is constantly

evolving and is often uncertain. In

this monograph, ATSDR has made

diligent effort to ensure the accuracy

and currency of the information

presented, but makes no claim that

the document comprehensively

addresses all possible situations

related to this substance. This

monograph is intended as an

additional resource for physicians

and other health professionals in

assessing the condition and

managing the treatment of patients

potentially exposed to hazardous

substances. It is not, however, a

substitute for the professional

judgment of a health care provider.

The document must be interpreted

in light of specific information

regarding the patient and in

conjunction with other sources of

authority.

Use of trade names and commer-

cial sources is for identification only

and does not impy endorsement by

the Agency for Toxic Substances

and Disease Registry or the U.S.

Department of Health and Human

Services.

Case Study ............................................................................................. 5

Pretest .................................................................................................... 5

Who’s At Risk ........................................................................................ 6

Exposure Pathways ................................................................................ 7

Biologic Fate .......................................................................................... 8

Physiologic Effects ................................................................................ 10

Clinical Evaluation ................................................................................. 12

Treatment and Management .................................................................. 14

Standards and Regulations .................................................................... 15

Suggested Reading List ......................................................................... 17

Answers to Pretest and Challenge Questions ......................................... 19

Additional Sources of Information ......................................................... 21

Evaluation Questionnaire and Posttest ................................................... 23

Table

Table 1. Summary of Standards and Regulations for Benzene ................. 16

Each content expert for this case study indicated no conflict of interest

to disclose with the case study subject matter.

ATSDR Publication No.: ATSDR-HE-CS-2001-0003

Benzene Toxicity

Case Studies in Environmental Medicine

(CSEM): Benzene Toxicity

Goals and Objectives

Instructions

The goal of the CSEM is to increase the primary care provider’s knowledge

See page 4

of hazardous substances in the environment and to aid in the evaluation of

potentially exposed patients.

After completion of this educational activity, the reader should be able to

discuss the major exposure route for benzene, describe two potential

environmental and occupational sources of benzene exposure, give two

reasons why benzene is a health hazard, describe three factors contributing

to benzene poisoning, identify evaluation and treatment protocols for

persons exposed to benzene, and list two sources of information on

benzene.

Accreditation

Continuing Medical Education (CME)

The Centers for Disease Control and Prevention (CDC) is accredited by the

Accreditation Council for Continuing Medical Education (ACCME) to

provide continuing medical education for physicians. CDC designates this

educational activity for a maximum of 1.5 hours in category 1 credit toward

the American Medical Association (AMA) Physician’s Recognition Award.

Each physician should claim only those hours of credit that he/she actually

spent in the educational activity.

Continuing Nursing Education (CNE)

This activity for 1.5 contact hours is provided by CDC, which is accredited

as a provider of continuing education in nursing by the American Nurses

Credentialing Center’s Commission on Accreditation.

Continuing Education Units (CEU)

CDC has been approved as an Authorized Provider of continuing education

and training programs by the International Association for Continuing

Education and Training and awards 0.1 continuing education units (CEUs).

Benzene Toxicity

The response form must be completed and returned electronically,

by fax, or by mail for eligibility to receive continuing education credit.

Instructions for Completing CSEM Online

1. Read this CSEM, Benzene Toxicity; all answers are in the text.

2. Link to the MMWR/ATSDR Continuing Education General Information page (www.cdc.gov/atsdr/index.html).

3. Once you access this page, select the Continuing Education Opportunities link.

4. Once you access the MMWR/ATSDR site online system, select the electronic file and/or register and test for a

particular ATSDR course.

a. Under the heading “Register and Take Exam,” click on the test type desired.

b. If you have registered in this system before, please use the same login and password. This will ensure an

accurate transcript.

c. If you have not previously registered in this system, please provide the registration information requested.

This allows accurate tracking for credit purposes. Please review the CDC Privacy Notice (www.cdc.gov/

privacy.htm).

d. Once you have logged in/registered, select the test and take the posttest.

5. Answer the questions presented. To receive continuing education credit, you must answer all of the questions.

Some questions have more than one answer. Questions with more than one answer will instruct you to “indicate

all that are true.”

6. Complete the course evaluation and posttest no later than June 29, 2006.

7. You will be able to immediately print your continuing education certificate from your personal transcript.

Instructions for Completing CSEM on Paper

1. Read this CSEM, Benzene Toxicity; all answers are in the text.

2. Complete the evaluation questionnaire and posttest, including your name, mailing address, phone number, and

e-mail address, if available.

3. Circle your answers to the questions. To receive your continuing education credit, you must answer all of the

questions.

4. Sign and date the posttest.

5. Return the evaluation questionnaire and posttest, no later than June 1, 2006, to ATSDR by mail or fax:

Mail or Fax

Continuing Education Coordinator 770-488-4178

Division of Toxicology and Environmental Medicine ATTN: Continuing Education Coordinator

Agency for Toxic Substances and Disease Registry

4770 Buford Hwy, NE (Mail Stop F-32)

Atlanta, GA 30341-3717

6. You will receive an award certificate within 90 days of submitting your credit forms. No fees are charged for

participating in this continuing education activity.

Benzene Toxicity

Case Study

A 50-year-old man is prompted to visit your office because of a nosebleed

that has been recurring for 2 days. He says that this is the third episode of

nosebleeds in the last 6 months. He expresses concern that he becomes

easily fatigued at work, and 2 months ago he began noticing bruises on his

arms and legs, although he does not recall the causes. He has lost more than

12 pounds in the last 2 years, which he attributes to loss of appetite.

History of previous illness includes a fractured arm in childhood. In the past

2 years he has had three bad colds that lasted for more than a week and

included coughing and breathing difficulty. The patient occasionally drinks

beer; he quit smoking cigarettes 4 years ago. He does not have allergies and

is taking no medications at this time. Review of systems: patient admits to

fatigue, headache, dizziness, nausea and loss of appetite, loss of weight, and

weakness.

On examination, blood pressure is 138/84; heart rate is 94 and regular;

respiratory rate is 20, temperature 98.9°; skin exam reveals pale and dry

skin. A head, ear, nose, and throat exam shows a hyperemic inflamed

pharynx, bleeding gums, and pale conjunctivae. The lung exam is clear to

auscultation and the cardiovascular exam shows a regular rate and rhythm.

The abdominal exam indicates no hepatosplenomegaly; the genitourinary

exam is unremarkable; and the neurologic exam shows a normal gait,

Glasgow coma scale 15. The extremity exam finds numerous ecchymoses

and petechiae in variable stages of healing on the upper and lower

extremities, although the extremities have good range of movement. The

lymph node exam reveals prominent, palpable cervical nodes, and the rectal

exam stool guaiac is negative.

On further questioning, you learn that the patient is a diesel mechanic and

has worked on trucks for the same employer for the previous 12 years. He

and his wife divorced 8 years ago; his wife became nervous and withdrawn

after two miscarriages. There was marital stress. He has lived in his home

for the past 16 years. He has a daughter, age 16, who lives with his ex-wife.

Laboratory studies reveal the following: glucose, blood urea nitrogen, and

bilirubin within normal limits; hemoglobin (Hgb) 10.2 grams/deciliter (normal

14.0–18.0); hematocrit (Hct) 32.6% (44.8–52.0); red blood cell count

3.32 million per millimeter cubed (mm

) (4.3–6.0); mean corpuscular

volume (MCV) 98 femtoliters (80–100); mean corpuscular hemoglobin

(MCH) 31 picograms (26–31); mean corpuscular hemoglobin

concentration (MCHC) 31% (31–36); white blood cell count 1,500/mm

(5,000–10,000); segmented cells 60% (40–60); bands 1% (0–5);

lymphocytes 31% (20–40); monocytes 8% (4–8); platelets 50,000/mm

(150,000–400,000). A chest radiograph is remarkable for hyperlucency.

There are no infiltrates, effusions, or other abnormalities noted;

electrocardiogram is within normal limits. Urine was negative for blood.

A 50-year-old diesel mechanic

has recurring nosebleeds,

fatigue, and weight loss

Pretest

(a) What is the problem list for

this patient? What is the

differential diagnosis?

(b) What additional testing would

you recommend?

take to manage the case and

treat this patient?

Benzene Toxicity

Two to three million U.S.

workers are at risk of benzene

exposure.

Alcohol and other drugs that

induce the mixed-function

oxidase enzymes may potentiate

those effects of benzene that

depend on metabolism.

Although benzene-induced

central nervous system (CNS)

depression is probably not

dependent on metabolism,

alcohol and other CNS

depressants might act

cumulatively.

Who’s At Risk

Workers employed in industries using or producing benzene (i.e.,

petrochemical companies; petroleum refining and coke and coal chemical

manufacturing; rubber tire manufacturing; and companies involved in the

storage or transport of benzene and petroleum products containing benzene)

have the greatest likelihood of exposure. The Occupational Safety and

Health Administration (OSHA) estimates that approximately 238,000

workers in the United States may be exposed to benzene during refining

operations; gasoline storage, shipment, and retail operations; chemical

manufacturing; and plastics and rubber manufacturing. Of these workers,

only 10,000 (4%) were above an 8-hour time-weighted average (TWA) of

1 ppm and only 0.2% were above 10 ppm. Other workers who may be

exposed to benzene because of their occupations include steel workers,

printers, rubber workers, shoe makers, laboratory technicians, and gas

station employees.

Atmospheric benzene levels of up to 6.6 ppm and 6-hour TWAs of 0.1 ppm

have been measured during gasoline pumping. This risk has been lowered by

installing vapor recapture devices on delivery hoses. These devices, if used

properly, significantly reduce exposure. Catalytic converters have

significantly reduced the benzene in automobile emissions.

Benzene is converted to toxic metabolites mostly by mixed-function oxidases

(MFOs) in the liver and bone marrow. MFO-inducing drugs (e.g.,

phenobarbital and ethanol) and certain chemicals (e.g., chlordane and

parathion) may increase the rate at which toxic metabolites of benzene are

formed. It also seems likely that persons who have bone marrow that is

metabolically hyperactive (e.g., fetuses, infants and children, and those

persons with hemolytic anemia) are at increased risk of benzene toxicity

because the cells are rapidly dividing. Persons with compromised

hemoglobin, such as those with B-thalassemia or viral hepatitis, may be at

increased risk for benzene-induced aplastic anemia. Exposure to benzene

may also stimulate specific CYP (or P450) enzymes, which are responsible

for oxygenation of benzene and have a propensity to generate oxygen

radicals. These radicals are a major cause of benzene toxicity.

Challenge

(1) Does the patient in the case study have any risk factors for the

adverse effects of benzene? Is anyone else in the case at risk of

benzene exposure or its adverse effects?

Benzene Toxicity

Exposure Pathways

Benzene (C

) is the first member of a series of aromatic hydrocarbons

recovered from refinery streams during catalytic reformation and other

petroleum processes. It is a clear, colorless, highly flammable liquid at room

temperature. Its vapor is heavier than air and can travel to a source of

ignition and flash back. It has a pleasant, aromatic odor detectable at

concentrations of 1.5 to 4.7 parts per million (ppm). (The workplace

permissible exposure level [PEL] is 1 ppm). Common synonyms for benzene

include benzol, cyclohexatriene, phenyl hydride, and coal tar naphtha.

Benzene is one of the world’s major commodity chemicals. Its primary use

(85% of production) is as an intermediate in the production of other

chemicals, predominantly styrene (for styrofoam and other plastics), cumene

(for various resins), and cyclohexane (for nylon and other synthetic fibers).

Benzene is an important raw material for the manufacture of synthetic

rubbers, gums, lubricants, dyes, pharmaceuticals, and agricultural chemicals.

Benzene is a natural component of crude and refined petroleum. The

mandatory decrease of lead alkyls in gasoline has led to an increase in the

aromatic hydrocarbon content of gasoline to maintain high octane levels and

antiknock properties. In the United States, gasoline typically contains less

than 2% benzene by volume, but in other countries the benzene

concentration may be as high as 5%.

Because of its lipophilic nature, benzene is an excellent solvent. Its use in

paints, thinners, inks, adhesives, and rubbers, however, is decreasing and

now accounts for less than 2% of current benzene production. Benzene was

also an important component of many industrial cleaning and degreasing

formulations, but now has been replaced mostly by toluene, chlorinated

solvents, or mineral spirits. Although benzene is no longer added in significant

quantities to most commercial products, traces of it may still be present as a

contaminant.

Benzene is widespread in the environment. Airborne benzene is usually

produced by processes associated with chemical manufacturing or the

gasoline industry, including gasoline bulk-loading and discharging facilities

and combustion engines (e.g., automobiles, lawn mowers, and snow

blowers). Benzene is a component of both indoor and outdoor air pollution.

Benzene levels measured in ambient outdoor air have a global average of

6 micrograms per cubic meter (µg/m

) (range 2–9 µg/m

). In almost all

cases, benzene levels inside residences or offices are higher than levels

outside and still higher in homes with attached garages and those occupied

by smokers. Seasonal variations also affect benzene levels, with higher levels

found in the fall and winter when buildings are less well ventilated. People

Benzene is an important raw

material in chemical syntheses

and is a historically important

solvent.

Benzene is added to unleaded

motor fuels to increase fuel

performance.

Benzene is widespread in the

environment because of its use

in many industrial processes and

its presence in gasoline.

Benzene Toxicity

living around hazardous waste sites, petroleum-refining operations,

petrochemical manufacturing sites, or gas stations may be exposed to higher

levels of benzene in air. In addition to being inhaled, airborne benzene is

absorbed across intact skin in experimental animals. For most people, the

level of exposure to benzene through food, beverages, or drinking water is

not as high as their exposure through air.

Leakage from underground storage tanks and seepage from landfills or

improper disposal of hazardous wastes has resulted in benzene

contamination of groundwater used for drinking. Effluent from industries is

also a source of groundwater contamination. In addition to being ingested,

benzene in water can also be absorbed through wet skin and inhaled as it

volatilizes during showering, laundering, or cooking. Typical drinking water

contains less than 0.1 parts per billion (ppb) benzene. Benzene has been

detected in bottled water, liquor, and food.

Cigarette smoke is another common source of personal and environmental

benzene exposure, representing about half of the benzene to which the

general population is exposed. Persons who smoke one pack of cigarettes a

day inhale a daily dose of approximately 1 milligram (mg) of benzene, about

3 to 4% of the amount inhaled daily by a worker exposed at the current

occupational PEL. Nonsmokers who live with smokers and who are

passively exposed to environmental tobacco smoke typically experience

50% greater exposure to benzene than do nonsmokers who live in a smoke-

free environment.

Challenge

(2) Later, the patient in the case study tells you that his well water has

always tasted “funny” and smells like “solvent.” You learn that a

chemical plant was near his property until 9 years ago, when the

company moved. You are concerned about your patient’s description

of his drinking water, and you request that the state health

department investigate the problem. The investigator contacts the

chemical company that owns the abandoned site and learns that

benzene is stored at the site in tanks that are above and below

ground. Laboratory analyses of the patient’s well water reveal an

average concentration of 20 ppm benzene and traces of

1,1,1-trichloroethane and toluene.

What questions will you ask to gauge the extent of the patient’s

exposure to benzene?

Biologic Fate

Benzene is rapidly and extensively absorbed by inhalation and ingestion.

Absorption through the skin is rapid but not extensive, as most of it

Benzene Toxicity

evaporates quickly. In humans, approximately 50% of inhaled benzene is

absorbed after a 4-hour exposure to approximately 50 ppm benzene in air.

An in vivo study on human volunteers indicated that approximately 0.05% of

a benzene dose applied to the skin was absorbed, whereas in an in vitro

study of human skin, the absorption of benzene was consistently 0.2% after

exposure to doses ranging from 0.01 to 520 microliters per square

centimeter. Oral absorption has not been studied in humans. In animals, at

least 90% of benzene was absorbed following oral ingestion of a dose of

340 to 500 milligrams per kilogram per day (mg/kg/day).

After exposure, benzene is found throughout the body, but it preferentially

distributes into the bone marrow and tissues with either high perfusion rates

or high lipid content. Thus, autopsies of people who died after acute

exposure showed that lipid-rich tissues, such as the brain and fat, and well-

perfused tissues, such as the kidney and the liver, have higher levels of

benzene than other tissues.

Once absorbed, benzene is initially metabolized in the liver and later in the

bone marrow. Although the total quantity of metabolites is greater in blood

than marrow, the concentrations of those metabolites in the marrow can be

400 times greater than in blood. Benzene metabolism in the liver involves

oxidation, with phenol as the major metabolite. Further metabolic products

are formed in liver and in bone marrow by the enzymatic addition of

hydroxyl groups to the benzene ring. Such metabolites include hydroquinone,

catechol, and 1,2,4-trihydroxybenzene, which are further conjugated and

excreted in the urine. These hydroxylated metabolites can be further oxidized

to their corresponding quinones or semiquinones. Benzene oxide may also

be metabolized via glutathione conjugation to form S-phenyl mercapturic

acid. Additionally, urinary excretion of small amounts of muconic acid, a

straight-chain dicarboxylic acid, indicates that the benzene ring also is

opened during metabolism.

Bone marrow is the main target organ of chronic benzene toxicity. One or

more benzene metabolite is suspected to be responsible for the

hematogenous toxicity, although the identity of the ultimate toxicant is

unknown. In the marrow, the metabolites may bind covalently to cellular

macromolecules (e.g., proteins, DNA, and RNA), causing disruption of cell

growth and replication.

Approximately 17% of absorbed benzene is excreted unchanged via the

lungs after a 4-hour exposure to 52 to 62 ppm benzene. Respiratory

elimination is triphasic, with approximate half-lives of 1, 3, and greater than

15 hours. Urinary excretion of phenol conjugates is biphasic, with half lives

of 5.7 and 28 hours. Approximately 33% of absorbed benzene is excreted in

urine, primarily as phenol conjugates, muconic acid, and S-phenyl-N-acetyl

cysteine.

Benzene is absorbed rapidly

and extensively after inhalation

or ingestion.

Benzene is metabolized in the

liver and bone marrow.

Benzene is excreted via the

lungs and urine.

Benzene Toxicity

Benzene primarily affects the

CNS and the hematopoietic

system.

At very high concentrations,

benzene rapidly causes CNS

depression, which can lead to

death.

All three blood cell lines may be

adversely affected by benzene.

Pluripotential stem cells and

lymphocytic cells are the

probable targets of benzene

toxicity.

Benzene-induced aplastic

anemia is caused by chronic

exposure at relatively high

levels.

Physiologic Effects

Benzene exposure affects the CNS and hematopoietic system and may

affect the immune system. Death due to acute benzene exposure has been

attributed to asphyxiation, respiratory arrest, CNS depression, or cardiac

dysrhythmia. Pathologic findings in fatal cases have included respiratory tract

inflammation, lung hemorrhages, kidney congestion, and cerebral edema.

Central Nervous System Effects

Acute benzene exposure results in classic symptoms of CNS depression

such as dizziness, ataxia, and confusion. These effects are believed to be

caused by benzene itself rather than its metabolites, because the onset of

CNS effects at extremely high doses is too rapid for metabolism to have

occurred.

Hematologic Effects

Benzene can cause dangerous hematologic toxicity such as anemia,

leukopenia, thrombocytopenia, or pancytopenia after chronic exposure.

These effects are believed to be caused by the metabolites of benzene,

which most likely damage the DNA of the pluripotential stem cells. All of the

blood’s components (i.e., erythrocytes, leukocytes, and thrombocytes

[platelets]) may be affected to varying degrees. The accelerated destruction

or reduction in the number of all three major types of blood cells is termed

pancytopenia. Potentially fatal infections can develop if granulocytopenia is

present, and hemorrhage can occur as a result of thrombocytopenia.

Paroxysmal nocturnal hemoglobinuria, a disorder in which the breakdown of

the red blood cells is accelerated and results in bleeding into the urine during

sleep when the condition is active, has been associated with benzene

exposure. Cytogenetic abnormalities of bone marrow cells and circulating

lymphocytes have been observed in workers exposed to benzene—

abnormalities not unlike those observed after exposure to ionizing radiation.

Myelodysplastic effects also can be seen in the bone marrow of persons

chronically exposed to benzene.

Anemia

Aplastic anemia is caused by bone marrow failure, resulting in hypoplasia

with an inadequate number of all cell lines. Severe aplastic anemia typically

has a poor prognosis and can progress to leukemia, whereas pancytopenia

may be reversible. Benzene-induced aplastic anemia is generally caused by

chronic exposure at relatively high doses. Fatal aplastic anemia following

benzene exposure was first reported in workers in the nineteenth century.

Benzene Toxicity

Leukemia

Several agencies (e.g., the U.S. Department of Health and Human Services,

the U.S. Environmental Protection Agency [EPA], and the International

Agency for Research on Cancer) classify benzene as a confirmed human

carcinogen. EPA estimates that a lifetime exposure to 4 ppb benzene in air

will result in, at most, 1 additional case of leukemia in 10,000 people

exposed. EPA has also estimated that lifetime exposure to a benzene

concentration of 100 ppb in drinking water would correspond to, at most,

1 additional cancer case in 10,000 people exposed.

Cohort studies of benzene-exposed workers in several industries (e.g.,

sheet-rubber manufacturing, shoe manufacturing, and rotogravure [a special

printing process]) have demonstrated significantly elevated risk of

leukemia—predominantly acute myelogenous leukemia, but also

erythroleukemia and acute myelomonocytic leukemia. The latency period for

benzene-induced leukemia is typically 5 to 15 years after first exposure.

Patients with benzene-induced aplastic anemia progress to a preleukemic

phase and develop acute myelogenous leukemia. However, a person

exposed to benzene may develop leukemia without having aplastic anemia.

Studies addressing the risk of leukemia associated with occupational

exposures to low levels of benzene (less than approximately 1 ppm) have

been inconclusive. Death certificates do not reveal increased leukemia

mortality among workers potentially exposed to low levels of hydrocarbons

and other petroleum products.

However, in recent case-control studies, significantly more patients with

acute nonlymphocytic leukemia were employed as truck drivers, filling

station attendants, or in jobs involving exposure to low levels of petroleum

products than were the controls.

Other Effects

Several reports relate benzene exposure to a variety of lymphatic tumors

including non-Hodgkin lymphoma and multiple myeloma. Although this is

plausible, there is no scientific proof of a causal relationship. The association

between exposure to benzene and development of nonhematologic tumors

remains inconclusive.

Information on the reproductive toxicity of benzene in humans is meager.

Some effects on the testes have been noted in animals exposed via

inhalation. Benzene has not been proven teratogenic in humans. In animals,

high levels of benzene have resulted in decreased fetal weights and minor

skeletal variants.

Benzene-induced leukemia has

a usual latency period of 5 to

15 years and, in many cases, is

preceded by aplastic anemia.

There is insufficient evidence to

indicate a causal relationship

between benzene and

nonhematologic tumors.

Benzene has not been shown to

be teratogenic in humans.

Benzene Toxicity

Acute benzene toxicity is

characterized by CNS

depression.

Symptoms may progress from

light-headedness, headache,

and euphoria to respiratory

depression, apnea, coma, and

death.

Benzene concentrations of

about 20,000 ppm are fatal to

humans within 5 to 10 minutes.

Ventricular fibrillation can occur

due to myocardial sensitization.

Symptoms of chronic benzene

exposure may be nonspecific,

such as fever, bleeding, fatigue,

and anorexia.

Clinical Evaluation

History and Physical Examination

In addition to a thorough medical history and physical examination,

important factors in evaluating a patient potentially exposed to benzene are a

detailed family history of blood dyscrasias including hematologic neoplasms,

genetic hemoglobin abnormalities, bleeding abnormalities, and abnormal

function of formed blood elements; an environmental history focusing on

activities and possible sources of benzene exposure at home; and an

occupational history, including past exposures to hematologic toxicants such

as solvents, insecticides, and arsenic. A history of ionizing radiation

exposure, medications, and smoking should also be explored.

Signs and Symptoms

Acute Exposure

“Benzol jag” is a term workers use to describe symptoms of confusion,

euphoria, and unsteady gait associated with acute benzene exposure.

Depending on the magnitude of the dose, persons who have ingested

benzene may experience these effects 30 to 60 minutes after benzene

ingestion. In one case report, an oral dose of 10 milliliters was reported to

produce staggering gait, vomiting, tachycardia, pneumonitis, somnolence,

delirium, seizures, coma, and death. Other symptoms include bronchial and

laryngeal irritation after inhalation. Pulmonary edema has been reported.

Ingestion may cause substernal pain; cough; hoarseness; and burning of the

mouth, pharynx, and esophagus shortly after ingestion. It may also cause

stomach pain, nausea, and vomiting.

Chronic Exposure

Early symptoms of chronic benzene exposure are often nonspecific but

show marked individual variability. By the time a physician is consulted, the

bone marrow may have been significantly affected. For example, conditions

that first bring the patient to medical attention are typically fever due to

infection or manifestations of thrombocytopenia, such as hemorrhagic

diathesis with bleeding from the gums, nose, skin, gastrointestinal tract, or

elsewhere; fatigue; and anorexia.

The clinical picture of patients chronically exposed to benzene was well

described in 1938 in a cohort study of about 300 workers in the

rotogravure printing industry. At that time, ink solvents and thinners

containing 75 to 80% benzene by volume were used in the pressroom. Initial

physical examination of the workers was relatively unrevealing, but of those

tested, 22 persons had severe hematologic abnormalities. Followup of the

workers a year after cessation of exposure suggested that the effects of

Benzene Toxicity

benzene can persist or can evolve over time. However, most patients

recover after exposure ceases.

Laboratory Evaluation

The laboratory evaluation of benzene-exposed persons should include the

following: complete blood count with differential, Hct, Hgb, erythrocyte

count, erythrocyte indices (i.e., MCV, MCH, and MCHC), and platelet

count. Plasma folate and vitamin B12 levels may be used to rule out

megaloblastic anemia if the MCV is elevated. These laboratory tests will

detect hematologic abnormalities that have been associated with relatively

high levels of exposure to benzene. Persons with blood dyscrasias that

persist after removal from exposure should be evaluated by a hematologist.

Bone marrow aspiration and biopsy may be useful in narrowing the

differential diagnosis in some cases.

Direct Biologic Indicators

Measurement of benzene in breath and blood can be useful in certain

occupational settings. Because of benzene’s relatively short biologic half-life,

blood benzene levels reflect exposure during the preceding hours, not

cumulative body burden. A less invasive measurement of workplace

exposure is benzene concentration in end-expired air. A study has shown

that workers exposed to benzene at levels between 0.2 and 4.1 ppm had

measurable benzene vapor in their breath 16 hours after exposure and

showed a progressive buildup of benzene in their expired air during the

workweek.

Urinary phenol concentrations generally correlate well with benzene

exposure to concentrations above 10 ppm. Workplace exposure to 10 ppm

for 8 hours typically produces a postshift urinary phenol level of 45 to

50 mg/liter (mg/L), but excretion of phenol from dietary and other

background sources (e.g., Pepto-Bismol ) can obscure the contribution to

urinary phenol of exposure air levels below 10 ppm. Under circumstances of

such low-level exposure, urinary phenol levels are unreliable. Unexposed

persons rarely have urinary phenol levels greater than 20 mg/L. Other

benzene metabolites, such as muconic acid and phenyl mercapturic acid, are

also used as indicators of exposure to benzene. Analysis of urinary muconic

acid appears to be a better indicator than phenol for chronic, low-level

benzene exposure. However, it is not specific for benzene exposure.

Phenylmercapturic acid concentrations in the urine are highly specific

parameters, although data concerning a dose-response relationship between

phenylmercapturic acid production and benzene uptake in workers are not

yet available.

Hematologic abnormalities are

the primary concern in benzene

exposure.

Benzene measurements in blood

and breath are generally not

clinically useful in

nonoccupational settings.

Because of the contributions of

background exposure, urinary

phenol concentrations may not

accurately reflect low

occupational benzene exposures

(e.g., <10 ppm).

Benzene Toxicity

MCV and lymphocyte count

may aid in the diagnosis of

benzene toxicity.

A bone marrow aspiration and

biopsy will aid in identifying

aplastic anemia.

There is no antidote for acute

benzene poisoning.

Treatment for benzene toxicity

is supportive and symptomatic.

Indirect Biologic Indicators

An increase in MCV, a decrease in total lymphocytes, and decreases in red

blood cells and white blood cells may be early signs of benzene toxicity. A

finding of benzene-induced hematotoxicity in a patient should trigger

consideration that this represents a sentinel event, indicating that other

persons may have been similarly exposed.

If aplastic anemia is suspected, a bone marrow aspiration and biopsy should

be performed. Aspiration of the marrow space often produces no sample

(i.e., dry tap) in patients with aplastic anemia. However, a dry tap is not

diagnostic of aplastic anemia; therefore, a biopsy specimen also should be

obtained and examined for architecture and cellularity. In aplastic anemia,

only the empty reticular meshwork of the marrow is evident; fat cells replace

all or most of the hematopoietic tissues.

Islands of residual hematopoiesis may be seen, but the overall cellularity

typically is less than 25%. Chromosomal changes consistent with

myelodysplasia are seen on cytogenetic analysis.

Challenge

(3) What should be included in the problem list of the patient

described in the case study?

(4) What additional laboratory testing would you recommend?

Treatment and Management

Acute Exposure

There is no antidote for benzene poisoning; therefore, treatment for persons

acutely exposed to benzene is generally supportive and symptomatic.

Immediate removal of the patient from exposure, administration of oxygen,

and monitoring and treatment of cardiopulmonary status are the first

considerations. In cases of ingestion, respiratory distress may indicate

pulmonary aspiration of gastric contents.

Contaminated clothing and shoes should be removed from an exposed

person as soon as possible. If liquid benzene has contacted the skin or eyes,

immediately wash the exposed skin with soap and copious water, and

irrigate the eyes with running water for 3 to 5 minutes or until irritation

ceases.

In cases of ingestion, do not induce emesis. Care must be taken to avoid

aspiration of stomach contents during vomiting because benzene can

produce a severe chemical pneumonitis. Ensure that the patient’s airway is

properly controlled and maintained before initiating orogastric tube lavage.

Gastric lavage is indicated if large amounts of benzene have been ingested or

if the patient is seen more than 1 hour after ingestion. Activated charcoal

Benzene Toxicity

may be used; it decreases benzene absorption in experimental animals, and

the benefits are likely to be similar in humans. Monitor the cardiac status of

the patient: benzene is one of several solvents that may increase the

susceptibility of the myocardium to the dysrhythmogenic effects of

catecholamines.

Epinephrine should be used only in the setting of cardiac arrest or severe

refractory reactive airway disease because its use may lead to ventricular

fibrillation secondary to the irritability of the myocardium.

Chronic Exposure

In treating persons chronically exposed to benzene, the most important

actions are to remove the patient from the source of benzene exposure and

to prevent further exposure. Benzene-induced depression of blood elements

generally reverses after exposure is terminated. Chronically exposed patients

whose hematologic results do not return to normal despite removal from

exposure should be managed in consultation with a hematologist or

oncologist. Chemotherapy and bone marrow transplants are therapeutic

options for leukemia and aplastic anemia, respectively.

Challenge

(5) What are some key considerations in the treatment for the patient

in the case study?

(6) What is the prognosis for this patient? What follow-up care should

he receive?

Standards and Regulations

Workplace

Air

In 1987, OSHA instituted a PEL for benzene of 1 ppm, measured as an

8-hour TWA, and a short-term exposure limit of 5 ppm (Table 1). These

legal limits were based on studies demonstrating compelling evidence of

health risk to workers exposed to benzene. The risk from exposure to

1 ppm for a working lifetime has been estimated as 5 excess leukemia

deaths per 1,000 employees exposed. (This estimate assumes no threshold

for benzene’s carcinogenic effects.) OSHA has also established an action

level of 0.5 ppm to encourage even lower exposures in the workplace.

The National Institute for Occupational Safety and Health (NIOSH)

recommends an exposure limit of 0.1 ppm as a 10-hour TWA. NIOSH also

recommends that benzene be handled in the workplace as a human

carcinogen. In 1997, the American Conference of Governmental Industrial

Hygienists lowered its TWA-threshold limit value to 0.5 ppm to reflect the

change in cancer classification to A1 (i.e., confirmed human carcinogen).

Once chronic exposure to

benzene ceases, hematologic

test results typically return to

normal.

The current PEL for benzene

is 1 ppm.

Benzene Toxicity

Table 1. Summary of Standards and Regulations for Benzene

Agency Focus Level

Comments

American Conference of Governmental Air (workplace) 0.5 ppm Advisory; TWA

†

; confirmed

Industrial Hygienists human carcinogen

2.5 ppm STEL (15-minute ceiling limit)

National Institute for Occupational Air (workplace) 0.1 ppm Advisory; 10-hour TWA

Safety and Health 1.0 ppm 15-minute ceiling limit

Occupational Safety and Health Air (workplace) 1 ppm Regulation; TWA

Administration 5 ppm 15-minute STEL

‡

0.5 ppm Action level TWA

U.S. Environmental Protection Agency Water (drinking) 5 ppb Regulation; maximum contaminant

level

Food and Drug Administration Food NA Regulation; may be used only as a

component of packaging

adhesives

ppb: parts per million; ppb: parts per billion.

†

TWA (time-weighted average): concentration for a normal 8-hour workday or

40-hour workweek to which nearly all workers may be repeatedly exposed.

‡

STEL (short-term exposure limit): a 15-minute TWA exposure that should not be exceeded at any time during the workday.

EPA restricts benzene emissions

from specific point sources.

The maximum contaminant level

of benzene in drinking water is

5 ppb.

Environment

Air

Under section 112 of the Clean Air Act, benzene is a hazardous air

pollutant. EPA has not promulgated a specific ambient air standard for

benzene but has imposed restrictions designed to lower industrial emissions

of benzene by 90% over the next 20 years. In addition, regulations have

been proposed that would control benzene emissions from industrial solvent

use, waste operations, transfer operations, and gasoline marketing. At gas

stations, proposed rules would require new equipment restricting benzene

emissions while dealers’ storage tanks are being filled. Under the Clean Air

Act Amendments of 1990, the use of clean (“oxygenated”) fuels was

mandated as a means of reducing motor vehicle emission-related air

pollutants. EPA predicts that this clean fuels program will decrease ambient

benzene levels by 33%.

Water

The National Primary Drinking Water Regulations promulgated by EPA in

1987 set a maximum contaminant level for benzene of 0.005 ppm (5 ppb).

This regulation is based on preventing benzene leukemogenesis. The

maximum contaminant level goal, a nonenforceable health goal that would

allow an adequate margin of safety for the prevention of adverse effects, is

zero benzene concentration in drinking water.

Benzene Toxicity

Food

Effective April 1988, FDA mandated that benzene can only be an indirect

food additive in adhesives used for food packaging.

Challenge

(7) The lawyer for the family of the patient in the case study

approaches you and asks you to establish causality between the

patient’s condition and the benzene in the drinking water.

The Food and Drug

Administration (FDA) prohibits

the use of benzene in foods.

How would you do so?

Suggested Reading List

Graber MA, Beaty L. 1999. Otolaryngology: nose. In: University of Iowa

Family Practice Handbook. 3rd ed. Chapter 19. Ames (IA): University of

Iowa.

Reviews

Austin H, Delzell E, Cole P. 1988. Benzene and leukemia. A review of the

literature and a risk assessment. Am J Epidemiol 127(3):419–39.

Goldstein BD. 1998. Benzene toxicity. State Art Rev Occup Med

3:541–54.

Marcus WL. 1987. Chemical of current interest-benzene. Toxicol Ind

Health 3(1):205–66.

Snyder R, Witz G, Goldstein BD. 1993. The toxicology of benzene. Environ

Health Perspect 100:293–306.

Hematologic Effects

Aksoy M. 1989. Hematotoxicity and carcinogenicity of benzene. Environ

Health Perspect 82:193–217.

Aksoy M. 1985. Benzene as a leukemogenic and carcinogenic agent. Am J

Ind Med 8:9–20.

Collins JJ, Conner P, Friedlander BR, et al. 1991. A study of the

hematologic effects of chronic low-level exposure to benzene. J Occup Med

33(5):619–26.

Dosemeci M, Li GL, Hayes RB, et al. 1994. Cohort study among workers

exposed to benzene in China. II: exposure assessment. Am J Ind Med

26(3):401–11.

Benzene Toxicity

Hayes RB, Yin S-N, Dosemeci M, et al. 1997. Benzene and the dose-related incidence of hematologic neoplasms in

China. J Natl Cancer Inst 89:1065–71.

Infante PF, Rinsky RA, Wagoner JK, et al. 1977. Leukemia in benzene workers. Lancet 2:76–8.

Infante PF, White MC. 1985. Projections of leukemia risk associated with occupational exposure to benzene. Am J

Ind Med 7:403–13.

Kwong YL, Chan TK. 1993. Toxic occupational exposures and paroxysmal nocturnal haemoglobinuria. Lancet

341:443.

Landrigan PJ. 1996. Benzene and blood: One hundred years of evidence [editorial]. Am J Ind Med 29:225–6.

Rothman N, Li G-L, Dosemeci M, et al. 1996. Hematotoxicity among Chinese workers heavily exposed to benzene.

Am J Ind Med 29:236–46.

Runion HE, Scott LM. 1985. Benzene exposure in the United States, 1978–1983: an overview. Am J Ind Med

7:385–93.

Snyder R, Kalf GF. 1994. A perspective on benzene leukemogeneis. Crit Rev Toxicol 24(3):177–209.

Ward E, Hornung R, Morris J, et al. 1996. Risk of low red or white blood cell count related to estimated benzene

exposure in a rubberworker cohort (1940–1975). Am J Ind Med 29:247–57.

Yin S-N, Hayes RB, Linet MS, et al. 1996. A cohort study of cancer among benzene-exposed workers in China:

overall results. Am J Ind Med 29:227–35.

Risk Assessment

Cox LA Jr, Ricci PF. 1992. Reassessing benzene cancer risks using internal doses. Risk Anal 12(3):401–10.

Crump KS. 1994. Risk of benzene-induced leukemia: a sensitivity analysis of the Pliofilm cohort with additional

follow-up and new exposure estimates. J Toxicol Environ Health 42(2):219–42.

Hallenbeck WH, Flowers RE. 1992. Risk analysis for worker exposure to benzene. Environ Manage

16(3):415–20.

Paxton MB, Chinchilli VM, Breet SM, et al. 1994. Leukemia risk associated with benzene exposure in the Pliofilm

cohort. II: Risk estimates. Risk Anal 14(2):155–61.

Rinsky RA, Smith AB, Hornung R, et al. 1987. Benzene and leukemia: an epidemiologic risk assessment. N Engl J

Med 316:1044–9.

Voytek PE, Thorslund TW. 1991. Benzene risk assessment: status of quantifying the leukemogenic risk associated

with the low-dose inhalation of benzene. Risk Anal 11(3):355–7.

Related Publications

Agency for Toxic Substances and Disease Registry. 1997. Toxicological profile for benzene (update). Atlanta: US

Department of Health and Human Services.

Benzene Toxicity

American Conference of Governmental Industrial Hygienists. 1999. Threshold limit values for chemical substances

and physical agents and biological exposure indices. Cincinnati (OH): American Conference of Governmental

Industrial Hygienists.

National Institute for Occupational Safety and Health. 1999. NIOSH pocket guide to chemical hazards. Cincinnati

(OH): National Institute for Occupational Safety and Health. Available from URL: www.cdc.gov/niosh/npg/

pgdstart.html.

National Library of Medicine. 2000. Hazardous Substances Database. Bethesda (MD): National Library of

Medicine. Available from URL: toxnet.nlm.nih.gov/.

US Environmental Protection Agency, Office of Ground Water and Drinking Water. 2000. Current drinking water

standards. Washington (DC): Environmental Protection Agency. Available from URL: www.epa.gov/safewater/

mcl.html.

US Environmental Protection Agency. 1998. Carcinogenic effects of benzene: an update. Washington (DC):

National Center for Environmental Health, Office of Research and Development. Report No. EPA/600/P-97/001F.

US Environmental Protection Agency. 1999. Extrapolation of the benzene inhalation unit risk estimate to the oral

route of exposure. Washington (DC): National Center for Environmental Health, Office of Research and

Development. Report No. NCEA-W-0517.

US Environmental Protection Agency. 1984. Health effects assessment for benzene. Cincinnati (OH): US

Environmental Protection Agency, Office of Health and Environmental Assessment. Report No. EPA/540/1-86/

037.

US Environmental Protection Agency. 2000. Integrated Risk Information System (IRIS) file for benzene.

Washington (DC): US Environmental Protection Agency.

US Environmental Protection Agency. 1985. Drinking water criteria document on benzene. Final draft. Washington

(DC): US Environmental Protection Agency, Office of Drinking Water. Report No. PB86-118122.

Answers to Pretest and Challenge

Questions

Pretest

(a) 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.

(b) 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.

Benzene Toxicity

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

(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.

Benzene Toxicity

(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.

Additional Sources of Information

More information on the adverse effects of benzene and the treatment and management of benzene-exposed

persons can be obtained from ATSDR, your state and local health departments, and university medical centers.

Case Studies in Environmental Medicine: Benzene Toxicity is one of a series. For other publications in this series

or for clinical inquiries, contact ATSDR, Division of Health Education and Promotion, Office of the Director, at 404-

498-0101.

Electronic databases are also available on the Internet as well as on CD-ROMs. Some CD-ROMs such as

TOMES Plus also contain environmental databases that can put current, peer-reviewed environmental data at the

physician’s fingertips. Most involve a charge, but updates are sent regularly after the initial purchase.

In addition to other resources, ATSDR has created a subregistry for benzene within the National Exposure Registry.

This subregistry is mandated by the Comprehensive Environmental Response, Compensation, and Liability Act of

1980. ATSDR, in cooperation with the states, will establish and maintain national registries of (1) persons exposed

to substances and (2) persons with serious illness or diseases possibly due to exposure. The registries will collect

information on the effects of low-level exposures of long duration (i.e., the exposures typically found in populations

surrounding hazardous waste sites) and the health outcomes for populations receiving one-time, high-level

Benzene Toxicity

environmental exposures (such as those experienced at chemical spill sites). The registries will facilitate the

identification and subsequent tracking of persons exposed to a defined substance at selected sites and will

coordinate the clinical and research activities involving the registrants.

For further information on the benzene subregistry, please contact ATSDR, Division of Health Studies, Office of the

Director, at 404-498-0105.

Notes

Benzene Toxicity

Case Studies in Environmental Medicine:

Benzene Toxicity

Evaluation Questionnaire and Posttest, Course Number SS3039

Course Goal: To increase the primary care provider’s knowledge of hazardous substances in the environment and

to aid in the evaluation of potentially exposed patients.

Objectives

Discuss the major exposure route for benzene.

Describe two potential environmental and occupational sources of benzene exposure.

State two reasons why benzene is a health hazard.

Describe three factors that contribute to benzene poisoning.

Identify evaluation and treatment protocols for persons exposed to benzene.

List two sources of information on benzene.

Tell Us About Yourself

Please carefully read the questions. Provide answers on the answer sheet (page 29). Your credit will be

awarded based on the type of credit you select.

1. What type of continuing education credit do you wish to receive?

**Nurses should request CNE, not CEU. See note on page 28.

A. CME (for physicians)

B. CME (for non-attending)

C. CNE (continuing nursing education)

D. CEU (continuing education units)

E. [Not used]

F. [Not used]

G. [Not used]

H. None of the above

2. Are you a...

A. Nurse

B. Pharmacist

C. Physician

D. Veterinarian

E. None of the above

3. What is your highest level of education?

A. High school or equivalent

B. Associate, 2-year degree

C. Bachelor’s degree

D. Master’s degree

E. Doctorate

F. Other

Benzene Toxicity

4. Each year, approximately how many patients with benzene exposure do you see?

A. None

B. 1–5

C. 6–10

D. 11–15

E. More than 15

5. Which of the following best describes your current occupation?

A. Environmental Health Professional

B. Epidemiologist

C. Health Educator

D. Laboratorian

E. Physician Assistant

F. Industrial Hygienist

G. Sanitarian

H. Toxicologist

I. Other patient care provider

J. Student

K. None of the above

6. Which of the following best describes your current work setting?

A. Academic (public and private)

B. Private health care organization

C. Public health organization

D. Environmental health organization

E. Non-profit organization

F. Other work setting

7. Which of the following best describes the organization in which you work?

A. Federal government

B. State government

C. County government

D. Local government

E. Non-governmental agency

F. Other type of organization

Tell Us About the Course

8. How did you obtain this course?

A. Downloaded or printed from Web site

B. Shared materials with colleague(s)

C. By mail from ATSDR

D. Not applicable

Benzene Toxicity

9. How did you first learn about this course?

A. State publication (or other state-sponsored communication)

B. MMWR

C. ATSDR Internet site or homepage

D. PHTN source (PHTN Web site, e-mail announcement)

E. Colleague

F. Other

10. What was the most important factor in your decision to obtain this course?

A. Content

B. Continuing education credit

C. Supervisor recommended

D. Previous participation in ATSDR training

E. Previous participation in CDC and PHTN training

F. Ability to take the course at my convenience

G. Other

11. How much time did you spend completing the course, evaluation, and posttest?

A. 1 to 1.5 hours

B. More than 1.5 hours but less than 2 hours

C. 2 to 2.5 hours

D. More than 2.5 hours but less than 3 hours

E. 3 hours or more

12. Please rate your level of knowledge before completing this course.

A. Great deal of knowledge about the content

B. Fair amount of knowledge about the content

C. Limited knowledge about the content

D. No prior knowledge about the content

E. No opinion

13. Please estimate your knowledge gain after completing this course.

A. Gained a great deal of knowledge about the content

B. Gained a fair amount of knowledge about the content

C. Gained a limited amount of knowledge about the content

D. Did not gain any knowledge about the content

E. No opinion

Benzene Toxicity

Please use the scale below to rate your level of agreement with the following statements

(questions 14–25) about this course.

A. Agree

B. No opinion

C. Disagree

D. Not applicable

14. The objectives are relevant to the goal.

15. The tables and figures are an effective learning resource.

16. The content in this course was appropriate for my training needs.

17. Participation in this course enhanced my professional effectiveness.

18. I will recommend this course to my colleagues.

19. Overall, this course enhanced my ability to understand the content.

20. I am confident I can discuss the major exposure route for benzene.

21. I am confident I can describe two potential environmental and occupational sources of benzene

exposure.

22. I am confident I can state two reasons why benzene is a health hazard.

23. I am confident I can describe three factors that contribute to benzene poisoning.

24. I am confident I can identify evaluation and treatment protocols for persons exposed to benzene.

25. I am confident I can list two sources of information on benzene.

Benzene Toxicity

Posttest

If you wish to receive continuing education credit for this program, you must complete this posttest. Each question

below contains four suggested answers, of which one or more is correct. Choose the answer:

A if 1, 2, and 3 are correct

B if 1 and 3 are correct

C if 2 and 4 are correct

D if 4 is correct

E if 1, 2, 3, and 4 are correct

26. Which of the following statements about benzene exposure are true?

(1) Benzene vapor may emanate from products in the home.

(2) Possible routes of benzene exposure include dermal absorption.

(3) Benzene in the water supply could expose persons by ingestion, inhalation, and dermal absorption.

(4) In the United States, benzene is no longer found in commercial gasoline.

27. Smokers may be at increased risk of benzene exposure because

(1) carbon monoxide potentiates the effects of benzene

(2) cigarette smoke contains toluene, which is metabolized to benzene

(3) smokers drink less alcohol as they smoke

(4) inhaled cigarette smoke contains benzene

28. An appropriate biologic measure of high-dose benzene exposure may be

(1) blood benzene concentration

(2) benzene levels in end-expired air

(3) urinary phenol level

(4) thyroid function tests and tissue benzene concentration

29. Hematologic abnormalities associated with benzene toxicity may include all except

(1) leukopenia

(2) myelogenous leukemia

(3) aplastic anemia

(4) thrombocytopenia

30. Which of the following statements about benzene metabolism are true?

(1) The metabolic fate of absorbed benzene depends on the route of exposure.

(2) Benzene’s hematotoxicity is probably due to the effects of active metabolites.

(3) Only the liver can metabolize benzene.

(4) Benzene’s metabolites may bind covalently to cellular macromolecules.

31. Which of the following statements are true for benzene?

(1) Benzene is used as a solvent.

(2) Benzene is used is artisan work, shoe manufacturing, and chemical industries.

(3) Benzene can be inhaled from tobacco smoke and while pumping of handling gasoline.

(4) Benzene may cause leukemia, pancytopenia, or aplastic anemia.

Benzene Toxicity

32. Treatment of acute benzene toxicity would include

(1) immediate removal of the patient from the source of exposure

(2) administration of large doses of catecholamines

(3) symptomatic and supportive measures

(4) administration of hyperbaric oxygen, intravenous fluids and large doses of catecholamines

33. Benzene exposures have been reported to occur during

(1) shoe manufacturing

(2) manufacturing of certain synthetic polymers

(3) gasoline transfer

(4) rocket fuel formulating or blueprint drawing

Note to Nurses

CDC is accredited by the American Nurses Credentialing Center’s (ANCC) Commission on Accreditation.

ANCC credit is accepted by most State Boards of Nursing.

California nurses should write in “ANCC - Self-Study” for this course when applying for relicensure. A

provider number is not needed.

Iowa nurses must be granted special approval from the Iowa Board of Nursing. Call 515-281-4823 or e-mail

[email protected] to obtain the necessary application.

Benzene Toxicity

Case Studies in Environmental Medicine:

Benzene Toxicity

Answer Sheet, Course Number SS3039

Remember, you can access the

Instructions for submitting hard-copy answer sheet: Circle your

case studies online at

answers. To receive your certificate, you must answer all questions. Mail or

www.atsdr.cdc.gov/HEC/CSEM/

fax your completed answer sheet to

and complete the evaluation

Fax: 770-488-4178, ATTN: Continuing Education Coordinator

questionnaire and posttest

online at www2.cdc.gov/

Mail: Agency for Toxic Substances and Disease Registry

atsdrce/.

ATTN: Continuing Education Coordinator

Division of Toxicology and Environmental Medicine Online access allows you to

receive your certificate as soon

4770 Buford Hwy, NE (Mail Stop F-32)

as you complete the posttest.

Atlanta, GA 30341-3717

Be sure to fill in your name and address on the back of this form.

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Name: E-mail (not required):

Address:

Zip code:

Check here to be placed on the list to

pilot test new case studies

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Continuing Education Coordinator

Agency for Toxic Substances and Disease Registry

Division of Toxicology and Environmental Medicine

4770 Buford Hwy, NE (Mail Stop F-32)

Atlanta, GA 30341-3717

fold here second

Place

Stamp

Here

Access the case studies online at www.atsdr.cdc.gov/

HEC/CSEM/ and complete the evaluation question-

naire and posttest online at www2.cdc.gov/atsdrce/.

Online access allows you to receive your certificate

as soon as you complete the posttest.

tape or staple here

DEPARTMENT OF HEALTH

AND HUMAN SERVICES

Agency for Toxic Substances

and Disease Registry

Division of Toxicology and

Environmental Medicine

(MS F-32)

Atlanta, GA 30333

Official Business

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