IPCS INCHEM Home

Benzene

1. NAME
   1.1 Substance
   1.2 Group
   1.3 Synonyms
   1.4 Identification numbers
      1.4.1 CAS number
      1.4.2 Other numbers
   1.5 Main brand names/main trade names
   1.6 Main manufacturers/main importers:
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
   3.1 Origin of the substance
   3.2 Chemical structure
   3.3 Physical properties
      3.3.1 Colour
      3.3.2 State/form
      3.3.3 Description
   3.4 Hazardous characteristics
4. USES
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances of poisoning
   4.3 Occupationally exposed populations
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. TOXICOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
      7.2.4 Workplace standards
      7.2.5 Acceptable Daily Intake (ADI)
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological analyses and their interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple qualitative test(s)
         8.2.1.2 Advanced qualitative confirmation test(s)
         8.2.1.3 Simple quantitative method(s)
         8.2.1.4 Advanced quantitative method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple qualitative test(s)
         8.2.2.2 Advanced qualitative confirmation test(s)
         8.2.2.3 Simple quantitative method(s)
         8.2.2.4 Advanced quantitative method(s)
         8.2.2.5 Other dedicated method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
9. CLINICAL EFFECTS
   9.1 Acute poisoning
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central Nervous System (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Hematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Others
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from the literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR, REVIEWER(S), DATES (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    BENZENE

    International Programme on Chemical Safety
    Poisons Information Monogaph 63
    Chemical

    1.  NAME

        1.1  Substance

             Benzene

        1.2  Group

             Aromatic hydrocarbons

        1.3  Synonyms

             Annulene;
             benzeen;
             benzen;
             benzol;
             benzole;
             benzolene;
             benzolo;
             bicarburet of hydrogen;
             carbon oil;
             coal naphtha;
             cyclohexatriene;
             fenzen;
             mineral naphtha;
             phene;
             phenyl hydride;
             pyrobenzol;
             pyrobenzole

        1.4  Identification numbers

             1.4.1  CAS number

                    71-43-2

             1.4.2  Other numbers

                    UN: 1114
                    NCI: C55276
                    RTECS (NIOSH): CY-1400000

        1.5  Main brand names/main trade names

             Polystream (IARC, 1982)

        1.6  Main manufacturers/main importers: 

    2.  SUMMARY

        2.1  Main risks and target organs

             Acute exposure to high concentrations of benzene in air
             results in neurological toxicity and may sensitize the
             myocardium to endogenous catecholamines.  Acute ingestion of
             benzene causes gastrointestinal and neurological
             toxicity.
    
             Chronic exposure to benzene results primarily in
             haematotoxicity, including aplastic anemia, pancytopenia, or
             any combination of anaemia, leukopenia, and thrombocytopenia. 
             Chronic benzene exposure is associated with an increased risk
             of leukemia.

        2.2  Summary of clinical effects

             Acute neurological toxicity from benzene exposure may
             cause headache, dizziness, drowsiness, confusion, tremors,
             and loss of consciousness.  Exposure to high concentrations
             may have effects on multiple organ systems.  Sudden deaths
             occurring below anesthetic concentrations of benzene are
             apparently due to cardiac dysrhythmias.  With ingestion,
             toxic signs and symptoms may include nausea, vomiting, and
             abdominal pain as well neurological toxicity.  Chronic
             haematological effects include anaemia, thrombocytopenia,
             leukopenia, pancytopenia, chromosomal abberations, and
             leukemia.  Dermal exposure may cause skin irritation.

        2.3  Diagnosis

             The diagnosis of acute benzene toxicity depends on a
             history of benzene exposure and associated neurological
             symptoms improving with removal from exposure, or both
             gastrointestinal and neurologic symptoms in the case of
             ingestion.  Benzene has a sweet aromatic odour which may help
             in its detection.  Laboratory testing for excess phenol in
             the urine will support the diagnosis.  Benzene may also be
             detected in blood for a short period of time after exposure,
             and it may be measured in exhaled breath.  Haematological
             abnormalities, especially anemia, leukopenia,
             thrombocytopenia, pancytopenia, or acute myelogenous
             leukemia, associated with chronic use of benzene suggest
             benzene poisoning.

        2.4  First-aid measures and management principles

             Treatment for acute benzene toxicity is supportive.  The
             patient should be removed from exposure and additional oxygen
             administered as necessary.  For ingestion of large
             quantities, aspiration of stomach contents with a nasogastric
             tube and administration of activated charcoal may be
             beneficial, especially in suspected combined ingestions. 
             Emesis is not recommended because of the risk of aspiration,
             sudden loss of consciousness, or seizures.  Severe poisonings
             may required intubation and assisted ventilation.  Treatment
             of chronic poisoning is supportive care and removal from
             exposure.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Benzene occurs naturally but is primarily produced from
             petroleum products (ATSDR, 1993).  Benzene is produced
             commercially through catalytic reforming of light naphtha,
             dealkylation of toluene, and as a coking by-product in steel
             mills (Weaver et al., 1983).

        3.2  Chemical structure

             C6H6
    
             Molecular weight 78.11

        3.3  Physical properties

             3.3.1  Colour

                    Clear (Budivari, 1996)

             3.3.2  State/form

                    Normal state at 25C: liquid (Budivari, 1996)

             3.3.3  Description

                    Odour:  sweet, aromatic (Budivari, 1996)
                    Odour threshold: 1.5 to 4.7 ppm (ATSDR, 1993)
                    Taste threshold:  0.5 to 4.5 ppm (ATSDR, 1993)
                    Specific gravity:  0.8787 at 15C (Budivari, 1996)
                    Viscosity (at 20C):  0.6468 cP (IARC, 1982)
                    Vapour pressure (at 25C): 95.2 mmHg (OHMS/TADS, 1990)
                    Solubility in water (at 25C): 1.8 g/L (IARC, 1982)
                    Soluble in alcohol (Budivari, 1996)
                    Soluble in ether (Budivari, 1996)
                    Flammability:  high (HSDB, 1992)

                    Flash point: -11C (HSDB, 1992)
                    Melting point:  5.5C (HSDB, 1992)
                    Boiling point:  80.1C (HSDB, 1992)
                    Conversion factor:  1 ppm = 3.25 mg/m3

        3.4  Hazardous characteristics

             Stability:  stable, combustible (IARC, 1982)
             Reactivity undergoes substitution, addition, and cleavage of
             the ring (IARC, 1982)
             Explosive limits:  1.3% to 7.1% (OHMS/TADS, 1990)
             Autoignition temperature:  580C (OHMS/TADS, 1990))
             Safe disposal:  incineration (ATSDR, 1993)

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Benzene is used as an intermediate in the
                    manufacture of a number of chemicals, including
                    ethylbenzene (used in the synthesis of styrene),
                    cumene (used in the synthesis of phenol and for the
                    manufacture of phenolic resins and nylon
                    intermediates), cyclohexane (used to make nylon
                    resins), and nitrobenzene (used in the synthesis of
                    aniline).  Benzene is also a precursor in the
                    manufacture of urethanes, chlorobenzene, and maleic
                    anhydride.  Benzene was previously used widely as a
                    solvent, but this use has decreased in many countries
                    due to the concern over carcinogenic effects.  Benzene
                    is a naturally occurring component of petroleum and is
                    present in gasoline (ATSDR, 1993).  In the United
                    States benzene averages less than 2% by volume in
                    gasoline, and in Europe the concentration is often 4
                    to 5% by volume and may exceed these concentrations
                    with certain blends.  Environmental contamination from
                    benzene occurs from automobile exhaust, chemical
                    plants, gasoline spills, and emissions from coke ovens
                    (Haley, 1977).  In some countries, benzene continues
                    to be used as a household cleaner.  Benzene has also
                    been reported to be abused by sniffing (Winek et al.,
                    1967).

        4.2  High risk circumstances of poisoning

             The most common form of exposure to benzene is
             occupational, and both occupational and environmental
             exposures to benzene are overwhelmingly through inhalation. 

             Dermal contact is most often only a minor source of exposure. 
             Environmental exposure is greatest in areas of heavy
             automobile use due to the presence of benzene in tailpipe
             emissions, near service stations, and from tobacco smoke
             (ATSDR, 1993).  In the United States, smoking accounts for
             approximately half of the total population exposure to
             benzene (Wallace, 1989).  In countries where benzene is used
             as a household cleaner, accidental or suicidal ingestion may
             occur.

        4.3  Occupationally exposed populations

             Individuals working in industries involved with benzene
             production (petrochemical industry, coke manufacturing),
             rubber tire or cast rubber film manufacturing, transport or
             storage of benzene or benzene-containing products, and gas
             station employees all are at risk for excess benzene exposure
             (ATSDR, 1993).  Although in the United States benzene has
             been removed from commercial solvents, the use of industrial
             solvents may still be a source of exposure.  Historically,
             benzene used as a solvent in printing inks in the rotogravure
             industry (Vigliani & Forni, 1976) and adhesives by shoemakers
             (Aksoy et al., 1971) led to a high degree of exposure in
             these industries.
    
             In the petrochemical industry, benzene is presently used
             primarily in closed system operations, but high time-weighted
             average exposure concentrations were previously found in
             chlorobenzene and alkylbenzene production plants (Weaver et
             al., 1983).  In the 1970s, the mean benzene air concentration
             in 10 large US tire manufacturing plants was 1.1 ppm with a
             range of 0.01 to 16.5 ppm in selected work areas (Van Ert et
             al., 1980).  Exposure to benzene in industries with poor
             workplace controls may still pose a significant hazard to
             workers.

    5.  ROUTES OF ENTRY

        5.1  Oral

             Acute oral exposure is uncommon and usually results from
             accidental ingestion or attempted suicide.  Benzene may also
             be a contaminant in drinking water (ATSDR, 1993).

        5.2  Inhalation

             Inhalation is the primary route of exposure for benzene,
             both in the occupational and environmental setting (ATSDR,
             1993).  The relatively high vapor pressure of benzene creates
             a significant hazard when adequate workplace safeguards are
             not in place.

        5.3  Dermal

             Dermal exposure may occur in the occupational setting,
             although it is quantitatively less important than inhalation
             exposure (ATSDR, 1993).

        5.4  Eye

             Ocular exposure may occur through splashing or high
             vapour concentrations.

        5.5  Parenteral

             Unknown.

        5.6  Others

             Unknown.

    6.  KINETICS

        6.1  Absorption by route of exposure

             In humans absorption by inhalation ranges from 70 to 80%
             in the first 5 minutes and then decreases to approximately
             50% thereafter (Srbova et al.,1950).  In rodents the
             percentage of retained benzene decreased as the inhaled vapor
             concentration increased from 10 to 1000 ppm (Sabourin et al.,
             1987).  In animal models, benzene is well absorbed by the
             oral route, ranging from over 90% in rabbits (Parke &
             Williams, 1953) to over 97% in rats and mice (Sabourin et
             al., 1987).  In vitro dermal absorption in humans is 0.2%
             over a period of 13.5 hours (Loden, 1986).  For a worker
             exposed to 10 ppm of ambient benzene with his entire skin
             exposed, and 100 cm2 of skin exposed directly to 5% benzene
             (gasoline), the expected hourly absorption of benzene will be
             7.5 L from inhalation, 1.5 L from ambient skin absorption,
             and 7.0 L from direct skin contact with the liquid (Blank &
             McAuliffe, 1985).  At 1 ppm ambient benzene, an unprotected
             worker using 0.5% benzene in a rubber solvent could
             theoretically absorb 4 to 8 mg of benzene percutaneously as
             compared with 14 mg via inhalation (Susten et al.,
             1985).

        6.2  Distribution by route of exposure

             Following inhalation, benzene is distributed throughout
             the body, and animal data suggests it may distribute
             preferentially to adipose tissue due to its lipophilicity
             (Sato & Fujiwara, 1975; Rickert et al., 1979).  In human
             autopsies on individuals dying shortly after exposure, high
             levels of benzene were found in the brain, with lower levels
             in the fat, blood, kidneys, and liver (Tauber, 1970; Winek &

             Collom, 1971).  Exposure to 25 ppm of benzene for two hours
             produced an average maximum blood benzene concentration of
             0.2 mg/L (Sato & Fujiwara, 1975).  No human studies are
             available concerning distribution after oral or dermal
             exposure (ATSDR, 1993).

        6.3  Biological half-life by route of exposure

             After inhalation exposure, benzene elimination in humans
             appears to follow a two compartment model, with half-lives of
             around 1 hour and 24 hours (Sherwood & Carter, 1970).  The
             half life of exhaled benzene in humans varies depending on
             the benzene exposure concentration and duration.  Exposure to
             99 ppm for 1 hour resulted in an initial phase half-life of
             42 minutes, and exposure to 6.4 ppm for 8 hours resulted in
             an initial phase half-life of 72 minutes, with a terminal
             phase half-life (from 10 to 100 hours after exposure) of 23
             to 31 hours (Sherwood, 1988).  In analysis of exhaled benzene
             in rats, exposure to 500 ppm for 6 hours results in an
             initial phase half-life of 42 minutes and a secondary phase
             half-life of 13.1 hours (Rickert et al., 1979).

        6.4  Metabolism

             Benzene is both exhaled unchanged in the lungs and
             excreted as metabolites in the urine.  Metabolism occurs
             primarily in the liver.  The first step in benzene metabolism
             is the formation of benzene oxide, an epoxide, by cytochrome
             P-450 dependent mixed function oxidases.  There are at least
             two metabolic pathways proceeding from this intermediate. 
             The first involves hydroxylation of the epoxide to phenol,
             which is then excreted as a glucuronide or sulfate conjugate,
             or converted to hydroquinone and benzoquinone.  Phenol,
             hydroquinone glucuronide and hydroquinone sulfate serve as
             markers for this enzymatic pathway.  The second pathway
             involves conversion of benzene oxide to muconic dialdehyde
             through an NADPH mediated process, and further conversion to
             muconic acid.  Catechol is produced via this pathway through
             the intermediate benzene glycol, and is excreted as a
             glucuronide or sulfate conjugate (Henderson et al., 1989). 
             In rat bone marrow after a six hour exposure to 500 ppm
             inhaled benzene, phenol was initially the main metabolite
             followed by catechol and hydroquinine at later times (Rickert
             et al., 1979).

        6.5  Elimination by route of exposure

             In a human study 16.4 to 41.6% of retained benzene was
             eliminated through the lungs within five to seven hours after
             a two- to three-hour exposure to 47 to 110 ppm and only 0.07
             to 0.2% of the remaining benzene was excreted unchanged in
             the urine (Srbova et al., 1950).  After exposure to 63 to 405
             mg/m3 of benzene for 1 to 5 hours, 51 to 87% was excreted in

             the urine as phenol over a period of 23 to 50 hours (Hunter &
             Blair, 1972).  In another human study, 30% of absorbed
             dermally applied benzene was excreted as phenol in the urine
             (Hanke et al., 1961).  No human studies are available for
             oral exposure (ATSDR, 1993).
    
             In rabbits within two to three days after oral dosing of 340
             to 500 mg/kg of benzene, 43% of benzene was exhaled
             unchanged, 23.5% was excreted in the urine as phenol, 4.8% as
             quinol, and 2.2% as catechol with a number of other phenolic
             compounds excreted as well (Parke & Williams, 1953).

    7.  TOXICOLOGY

        7.1  Mode of action

             Acute benzene exposure produces central nervous system
             excitation and depression (Gosselin et al., 1984).  In
             chronic exposures, benzene metabolites are considered the
             toxic agents, not the parent compound (Parke & Williams,
             1953; Sammett et al., 1979; Morimoto et al., 1983).  The
             relative contribution of different benzene metabolic pathways
             may be dose related, with more toxic agents produced by high
             affinity low capacity pathways (Medinsky et al., 1989). 
             Chronic benzene exposure can cause bone marrow stem cell
             depression, apparently through a cytotoxic effect on all
             lineages of haematopoietic progenitor cells, although there
             is some evidence for a mechanism involving injury to marrow
             stromal cells.  Bone marrow macrophages have been shown to
             metabolize phenol to reactive compounds that bind
             irreversibly to protein and DNA (Kalf et al., 1989). 
             Hydroquinone and phenol are known haematotoxins (Eastmond et
             al., 1987).

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             Inhalation exposure at 20,000 ppm
                             for five to ten minutes may be fatal (Flury,
                             1928).  Exposure to 150 to 650 ppm for 4
                             months to 15 years caused pancytopenia (Aksoy
                             et al., 1972; Aksoy & Erdem, 1978).  Chronic
                             exposure of up to eight years at a mean
                             benzene concentration of 75 ppm was
                             associated with the development of anemia and
                             leukopenia, but no such association was found
                             at mean exposure concentrations of 15 to 20
                             ppm for up to 27 years (Kipen et al., 1989).

                             Acute ingestion of over 10 mL of benzene may
                             prove lethal (Thienes & Haley,
                             1972).

                    7.2.1.2  Children

                             No data is available for pediatric
                             exposure levels.

             7.2.2  Relevant animal data

                    The LC50 for rats is in the range of 13700 ppm
                    over a four hour exposure period (Drew & Fouts, 
                    1974).  In rats, the LD50 for oral ingestions in one
                    study ranged from 710 to 1230 mg/kg in nonfasted rats
                    to 690 to 950 mg/kg in fasted rats (Cornish & Ryan,
                    1965).

             7.2.3  Relevant in vitro data

                    None.

             7.2.4  Workplace standards

                    The Occupational Safety and Health
                    Administration (OSHA) permissible exposure limit (PEL)
                    is 1 ppm.  The National Institute for Occupational
                    Safety and Health (NIOSH) recommended exposure limit
                    (REL) is 0.1 ppm (NIOSH, 1990).  The American
                    Conference of Governmental Industrial Hygienists
                    (ACGIH) threshold limit value-time weighted average
                    (TLV-TWA) is 10 ppm (ACGIH, 1994).

             7.2.5  Acceptable Daily Intake (ADI)

                    The WHO drinking water standard is 0.01 mg/L
                    (ATSDR, 1993).

        7.3  Carcinogenicity

             In epidemiologic studies, chronic exposure to benzene is
             associated with the development of acute myelogenous leukemia
             and its variants including erythroleukemia (Vigliani & Saita,
             1964; Aksoy et al., 1976; Goldstein, 1977; Goldstein, 1988). 
             Other forms of leukemia including acute lymphoblastic anemia,
             acute monocytic leukemia, and preleukemia have also been
             reported following benzene exposure (Aksoy et al., 1976). 
             Other haematopoietic malignancies have been described in
             association with benzene exposure including malignant
             lymphoma, myeloid metaplasia, and multiple myeloma (Aksoy,
             1980).
    

             There are a number of studies of occupational benzene
             exposure demonstrating an increased incidence of leukemia. 
             In a retrospective cohort study of 28,460 workers in China
             exposed to benzene at varying concentrations from 10 to 1000
             mg/m3, the relative risk for leukemia was 6.97 times the
             risk in the unexposed group (Yin et al., 1987a).  A group of
             748 workers producing rubber hydrochloride exposed to benzene
             concentrations of 10 to 100 ppm for up to 9 years had a
             relative risk of 10 for acute myelogenous and acute monocytic
             leukemia (Infante et al., 1977).  680 workers exposed to
             benzene at concentrations exceeding 2 ppm for 30 years had a
             relative risk of 3.93 for leukemia and other lymphopoietic
             cancers (Wong, 1987).  In a study of 1165 workers in a rubber
             hydrochloride factory there were 9 deaths from leukemia. 
             Stratification for level of exposure gave a standard
             mortality ratio (SMR) for leukemia of 109 for workers with
             < 40 ppm-years of exposure, a SMR of 322 with 40 to 199
             ppm-years of exposure, a SMR of 1186 with 200 to 399
             ppm-years of exposure, and a SMR of 6637 with > 400
             ppm-years of exposure.  These ppm-years of exposure
             correspond to exposures of <1, 1 to 4.99, 5 to 9.99, and
             >10 ppm of benzene over a 40 year working lifetime (Rinsky
             et al., 1987).  A study of 454 workers exposed to less than 1
             ppm of benzene for up to 26 years did not find any deaths
             from leukemia out of a total of 34 death certificates, or any
             cases of leukemia in a smaller study population (Tsai et al.,
             1983).
    
             In a case report, one individual developed acute myelogenous
             leukemia after an occupational exposure to 2 ppm of benzene
             over an 18 month period, although he had previously worked in
             a saw mill which manufactured veneer (Ott et al.,
             1978).

        7.4  Teratogenicity

             Benzene crosses the placenta and is present in cord
             blood in concentrations equal to or greater than maternal
             blood (Dowty et al., 1976).  An increased frequency of
             chromatid and isochromatid breaks was found in 14 children of
             women exposed during pregnancy to a mix of benzene and other
             solvents in chemical laboratories and the printing industry
             (Funes-Cravioto et al., 1977).
    
             Animal experiments exposing pregnant mice and rats to inhaled
             benzene in general demonstrated increased fetal skeletal
             variants and reduced fetal weight, but failed to demonstrate
             consistent convincing evidence of teratogenecity.  Rats
             exposed to 313 ppm for 24 hours/day on days 9 to 14 of
             gestation demonstrated reduced fetal weight and increased
             skeletal variants (Hudak & Ungvary, 1978).  Mice exposed to
             500 ppm of benzene for 7 hours/day from days 6 to 15 of
             gestation had decreased mean fetal body weight and an

             increase in several minor skeletal variants.  The same
             exposure (500 ppm for 7 hours/day) in rabbits on gestational
             days 6 to 18 did not affect fetal body weight, rather a
             decrease in two minor skeletal variants (Murray et al.,
             1979).  In rats exposed to 100, 300, and 2200 ppm of benzene
             vapor for 6 hours/day on days 6 to 15 of gestation, an
             increase in skeletal variants was seen at all exposure
             concentrations, and only the highest exposure concentration
             resulted in decreased fetal weight (Green et al., 1978). 
             Exposure in utero to 20 ppm of benzene for 6 hr/day on days 6
             to 15 of gestation in mice resulted in haematopoietic
             abnormalities (Keller & Snyder, 1988).  Exposures in rats to
             less than 10 ppm of benzene during pregnancy did not cause
             adverse fetal changes (Kuna & Kapp, 1981).

        7.5  Mutagenicity

             In studies of occupational exposure, benzene was found
             to cause chromosome changes at concentrations that induced
             blood dyscrasias (Tough & Court Brown, 1965; Forni et al.,
             1971; Ding et al., 1983).  At concentrations below 31 ppm,
             workers exposed for 10 to 26 years had significantly more
             chromosome breaks and gaps in peripheral lymphocytes than
             found in controls, and 31 of the 33 workers had no other
             evidence of clinical or haematological effects (Sasiadek et
             al., 1989).  At exposure levels of less than 10 ppm over one
             month to 26 years, workers also had a significantly higher
             number of chromosomal aberrations in peripheral lymphocytes
             than did controls (Picciano, 1979).

        7.6  Interactions

             Ethanol can increase the extent of hematotoxicity from
             benzene exposure (Baarson et al., 1982; Nakajima et al.,
             1985; Nakajima et al., 1987).  Previous administration of
             phenobarbital may decrease benzene hematotoxicity (Ikeda &
             Ohtsuji, 1971; Nakajima et al., 1985).  Toluene reduces the
             metabolism of benzene and reverses the benzene-induced
             decrease in incorporation of iron into red blood cells
             (Andrews et al., 1976).  Hepatitis B may also increase the
             incidence of hematopoietic effects from benzene exposure
             (Aksoy, 1989).

    8.  TOXICOLOGICAL AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological analyses and their interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple qualitative test(s)

                    8.2.1.2  Advanced qualitative confirmation test(s)

                    8.2.1.3  Simple quantitative method(s)

                    8.2.1.4  Advanced quantitative method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple qualitative test(s)

                    8.2.2.2  Advanced qualitative confirmation test(s)

                    8.2.2.3  Simple quantitative method(s)

                    8.2.2.4  Advanced quantitative method(s)

                    8.2.2.5  Other dedicated method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                    8.3.1.2  Urine

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their
             interpretation

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations

             Sample collection
    
             Urine for phenol measurement should be collected at the end
             of the workshift in a standard plastic urinalysis cup in a
             volume of at least 50 mL.  The sample should be refrigerated. 
             Breath samples for benzene are collected in standard breath
             sampling tubes on a solid sorbent such as activated charcoal,
             silica gel, or Tenax GC (ATSDR, 1993).  Generally, breath
             samples are collected at the start of the next shift (ACGIH,
             1993).
    
             Biomedical analysis
    
             Measurement of urine phenol has been the standard bioassay
             for benzene exposure, despite the well described limitations
             of this test.  For a benzene time-weighted average (TWA)
             exposure of 10 ppm, an acceptable total phenol in urine
             concentration at the end of a workshift is < 50 mg/g
             creatinine (ACGIH, 1993).  Exposure to 25 ppm of benzene
             gives an average end of shift urinary phenol level of 200
             mg/L (Walkley et al., 1961).  In another study end-shift
             urine phenol levels corrected for either creatinine
             concentration or specific gravity correlated with exposure to
             greater than 10 ppm of benzene.  Urine phenol concentrations
             of less than 10 mg/L were found in the non-exposed groups

             (Inoue et al., 1986).  Chronic exposure to 0.5 to 4.0 ppm of
             benzene resulted in urine phenol levels that correlated with
             benzene exposure, but 5 of 52 workers had baseline levels of
             urinary phenol frequently > 30 mg/L (Roush & Ott, 1977).  At
             benzene exposure concentrations of 8 to 10 ppm or less, urine
             phenol monitoring may be of minimal value (Roush & Ott, 1977;
             Brief et al., 1980).  At exposure concentrations of less than
             1 ppm of benzene, urine phenol concentrations do not
             correlate with duration of exposure (Drummond et al., 1988;
             Perbellini et al., 1988).
    
             Ingestion or inhalation of a variety of substances may
             interfere with the use of urine phenol measurement as a
             marker for benzene exposure.  Certain household products such
             as Pepto-Bismol and Chloraseptic contain phenol and their use
             may increase urinary phenol levels (Baselt & Cravey, 1989). 
             Consumption of ethanol, diet, and smoking may also be
             potential confounders (Nakajima et al., 1987; Brugnone et
             al., 1989).  Exposure to toluene decreases the metabolism of
             benzene to phenol and quinol but not catechol (Inoue et al.,
             1988).
    
             Estimates of benzene exposure can also be made through
             measurement of urinary inorganic and organic sulfates. 
             Unexposed subjects have 80 to 95% of urinary sulfates in the
             inorganic form, mild exposure to benzene results in a
             decrease to 70 to 80%, higher exposures decrease the
             percentage to 60 to 70%, and extremely hazardous exposures
             result in a drop to 0 to 60%.  However, urinary sulfate
             levels are quite variable, nonspecific for benzene, and have
             not been used for low levels of benzene exposure (ATSDR,
             1993).
    
             Measurement of exhaled benzene has been used to monitor
             exposure, but is affected by smoking (Brugnone et al., 1989). 
             Given a benzene time-weighted average (TWA) exposure of < 10
             ppm, the American Conference of Governmental Industrial
             Hygienists (ACGIH) recommends exhaled breath monitoring prior
             to the next shift, with an acceptable maximum concentration
             of 0.08 ppm for mixed-exhaled breath and 0.12 ppm for
             end-exhaled breath.  However, these concentrations may be
             decreased markedly in light of the intended changes in
             acceptable workplace benzene levels for 1993 to 1994 (ACGIH,
             1993).  In one study of coke oven workers exposed to an
             average benzene concentration of 1.32 ppm, end-of shift
             exhaled breath analysis provided the most useful measurement
             of exposure, and measurement of exhaled breath collected just
             prior to the next shift was non-specific for smokers
             (Drummond et al., 1988).  In non-occupationally exposed urban
             subjects, average exhaled breath benzene concentrations were
             0.38 ppb in nonsmokers in a pristine rural setting, 2.5 ppb
             in nonsmokers in an urban area, and 6.8 ppb in smokers

             (Wester et al., 1986).  At an exposure level of 25 ppm of
             benzene in a sedentary individual, exhaled breath was found
             to contain 2 ppm of benzene at the end of a 4.5 hour exposure
             and 0.2 ppm 16 hours later (Sherwood & Carter, 1970).  At an
             exposure level of 4 to 7 ppm of benzene for 6 hours a day for
             5 days, 4 subjects had a maximum of < 0.05 ppm of benzene in
             exhaled breath the following morning (Berlin et al.,
             1979).
    
             Benzene concentrations may also be measured in blood, and are
             affected by smoking (Brugnone et al., 1989).  However,
             acceptable occupational limits for blood benzene levels are
             not commonly available.  The half-life of benzene in blood
             varies depending on the duration and magnitude of exposure,
             and the concentration may be different in venous and arterial
             blood (Schrenk et al., 1941).
    
             In order to detect the haematological effects of chronic
             benzene exposure, it is recommended to follow blood counts at
             regular intervals.  The Occupational Safety and Health
             Administration (OSHA) recommends monthly blood counts and
             removal from areas with high benzene exposure for white blood
             cell counts below 4,000/mm3 or erythrocyte counts below
             4,000,000/mm3 (OSHA, 1987).

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Large oral ingestions of benzene have resulted
                    in nausea, vomiting, ataxia, visual disturbances,
                    excitement, euphoria, somnolence, delirium, CNS
                    depression, loss of consciousness, nonreactive pupils,
                    tachycardia, and pneumonitis (Von Oetingen, 1940;
                    Thienes & Haley 1972).  A non-fatal ingestion 
                    resulted in an intense gastritis followed by pyloric
                    stenosis, and peripheral swelling and edema
                    (Greenburg, 1926).  Direct aspiration of liquid
                    benzene into the lungs has resulted in immediate
                    pulmonary edema and haemorrhage at the site of contact
                    (Gerarde, 1960).

             9.1.2  Inhalation

                    Acute exposure to 300 to 3000 ppm of benzene
                    may cause headache, dizziness, drowsiness, vertigo,
                    delirium, tremor, and loss of consciousness (Cronin,
                    1924; Greenburg, 1926; Flury, 1928).  Nausea,
                    paralysis, and coma may also occur with significant
                    exposure (Cronin, 1924; Greenburg, 1926; Tauber,

                    1970).  Additional symptoms may include excitement,
                    incoherent speech, flushed face, giddiness,
                    nervousness, insomnia, paresthesias, and fatigue which
                    may persist for more than two weeks (Hunter, 1978).
                    Acute benzene exposure has been reported to cause
                    systemic petechial haemorrhages, as well as
                    irritability and ataxia which may persist for several
                    weeks (Gerarde, 1960).  One case of sudden fatality
                    was suggested to be a result of dysrhythmias from the
                    benzene-sensitized myocardium (Tauber, 1970).

             9.1.3  Skin exposure

                    Dermal exposure to benzene may cause erythema,
                    vesiculation, dry and scaly dermatitis, and blistering
                    (Gerarde, 1960; Sandmeyer, 1981).

             9.1.4  Eye contact

                    Ocular burning and transient epithelial injury
                    may result from exposure to liquid.  Exposure to high
                    concentrations of benzene vapor may cause ocular
                    irritation (Grant & Schuman, 1993).

             9.1.5  Parenteral exposure

                    Unknown.

             9.1.6  Other

                    Unknown.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Historic usage of benzene to treat leukemia
                    resulted in anemia, leukopenia, and multiple
                    haemorrhages.  Dosages generally started at 3 g/day
                    and were increased to 5 g/day if necessary and
                    continued for months.  The patients developed multiple
                    hemorrhages and/or menorrhagia associated with anemia,
                    leukopenia, and purpura followed later by death
                    (Hunter, 1978).  Chronic ingestion studies in animals
                    have resulted in decreased numbers of erythrocytes and
                    lymphocytes (Hsieh et al., 1988; Huff et al.,
                    1989).

             9.2.2  Inhalation

                    Inhalation exposure to benzene over intervals
                    varying from several months to several years has
                    resulted in hematologic abnormalities including
                    pancytopenia, as well as deficits in specific cell
                    lines, aplastic anemia, and leukemia (Aksoy et al.,
                    1971; Aksoy et al., 1972; Aksoy et al., 1974; Aksoy &
                    Erdem, 1978; Aksoy, 1980; Aksoy et al., 1987; Yin et
                    al., 1987b; Kipen et al., 1989; Yin et al., 1989).
                    

             9.2.3  Skin exposure

                    No information is available on the effects of
                    chronic dermal exposure to benzene other than the
                    dermatitis discussed under the acute exposure section
                    9.1.3.

             9.2.4  Eye contact

                    Unknown.

             9.2.5  Parenteral exposure

                    Unknown

             9.2.6  Other

                    Not relevant.

        9.3  Course, prognosis, cause of death

             Most cases of acute benzene exposure resolve
             spontaneously or with supportive care without long-term
             sequela.  At extremely high benzene concentrations, death
             from acute exposure may occur immediately or within several
             hours after exposure (Hamilton, 1922; Cronin, 1924;
             Greenburg, 1926; Tauber, 1970).  Death may be due to CNS
             depression, asphyxiation, or respiratory or circulatory
             arrest (Hamilton, 1922; Greenburg, 1926).  In fatal cases
             autopsy has revealed haemolysis, cyanosis, and multiple organ
             haemorrhage.  In chronic benzene exposures, patients
             developing minor haematologic abnormalities usually recover
             completely when removed from the exposure.  In cases of
             benzene-induced pancytopenia, the patients may recover
             completely, die from complications of the pancytopenia, or
             develop leukemia at a later time (Aksoy & Erdem, 1978).

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Electrocardiographic studies in monkeys and
                    cats exposed to high concentrations of benzene
                    revealed ectopic beats and ventricular tachycardia,
                    which resolved upon excision of the adrenal glands and
                    stellate ganglion, and recurred with the subcutaneous
                    administration of adrenaline (Nahum & Hoff, 1934). 
                    One report of sudden death after running and acute
                    benzene exposure was felt to be due to benzene induced
                    myocardial sensitivity to endogenous catecholamines
                    (Tauber, 1970).

             9.4.2  Respiratory

                    Acute exposure may cause irritation, cough, and
                    hoarseness.  At high exposure concentrations
                    respiratory failure and pulmonary edema may occur
                    (Ellenhorn & Barceloux, 1988).

             9.4.3  Neurological

                    9.4.3.1  Central Nervous System (CNS)

                             Signs and symptoms from acute
                             exposure to benzene include headache,
                             dizziness, drowsiness, vertigo, delirium,
                             tremor, seizures, paralysis, and loss of
                             consciousness (Harrington, 1917; Cronin,
                             1924; Greenburg, 1926; Flury, 1928; Tauber,
                             1970).  A single case of acute transverse
                             myelitis was associated with chronic benzene
                             exposure, possibly due to spinal cord
                             haemorrhage (Herregods et al.,
                             1984).

                    9.4.3.2  Peripheral nervous system

                             Chronic exposure to mixed solvents
                             including benzene has been associated with
                             distal neuropathy of the upper extremities as
                             demonstrated by electromyographic (EMG) and
                             nerve conduction velocity (NCV) studies
                             (Baslo & Aksoy, 1982).

                    9.4.3.3  Autonomic nervous system

                             Not known.

                    9.4.3.4  Skeletal and smooth muscle

                             Exposure to mixed solvents including
                             benzene has been associated with global
                             atrophy of the lower extremities (Baslo &
                             Aksoy, 1982).

             9.4.4  Gastrointestinal

                    Acute benzene ingestion may cause nausea,
                    vomiting, and abdominal pain.  Ingestion of an unknown
                    amount of benzene resulted in gastritis followed by
                    pyloric stenosis (Greenburg, 1926).

             9.4.5  Hepatic

                    No information is available on hepatic effects
                    in humans from benzene exposure.  In rats,
                    administration of 1.6 mg/kg/day of benzene for three
                    days resulted in increased liver weight and changes in
                    metabolic function (Pawar & Mungikar, 1975).

             9.4.6  Urinary

                    9.4.6.1  Renal

                             No information available.

                    9.4.6.2  Others

                             Chronic ingestion of benzene for
                             therapeutic purposes reportedly led to
                             bladder irritability and impotence in some
                             patients (Gerarde, 1960).

             9.4.7  Endocrine and reproductive systems

                    No data available.

             9.4.8  Dermatological

                    Acute dermal exposure to benzene may cause
                    erythema and blistering, and repeated or prolonged
                    exposures may cause a dry and scaly dermatitis
                    (Gerarde, 1960).  A non-fatal ingestion resulted in a
                    skin condition characterized by swelling and edema
                    (Greenburg, 1926).

             9.4.9  Eye, ear, nose, throat: local effects

                    Ocular burning and transient epithelial injury
                    may result from exposure to liquid.  Exposure to high
                    concentrations of benzene vapor may cause ocular
                    irritation.  There are reports of retrobulbar neuritis
                    or optic neuritis occurring after inhalation exposure
                    to benzene (Grant & Schuman, 1993).

             9.4.10 Hematological

                    Very little information is available
                    concerning acute effects of benzene on the
                    haematological system.  However, there are a multitude 
                    of studies on the haematological effects of
                    intermediate and chronic exposure, which include
                    aplastic anaemia, pancytopenia, and varying degrees of
                    thrombocytopenia and leukopenia mediated through bone
                    marrow toxicity.  Both hypoplasia and hyperplasia of
                    the bone marrow may be observed, and may vary in
                    frequency by sex (Hunter, 1978).
    
                    Exposure to concentrations of 150 to 650 ppm over a
                    period of 4 months to 15 years was associated with the
                    development of pancytopenia (Aksoy et al., 1972). 
                    Bone marrow aspirates in these patients demonstrated a
                    great range from acellularity to hypercellularity.  In
                    a follow-up study of 44 patients with the same
                    exposure range and duration, 23 (52%) had complete
                    remission, 14 (32%) died of complications of
                    pancytopenia, 6 (14%) developed leukemia after a
                    period of 6 months to 6 years, and one patient (2%)
                    with complete remission developed fatal myeloid
                    metaplasia (Aksoy & Erdem, 1978).  Chronic exposure of
                    1 to 25 years at benzene concentrations of 75 ppm has
                    been associated with the development of anemia and
                    leukopenia (Kipen et al., 1989).  Anemia and
                    leukopenia in a group of rubber hydrochloride workers
                    associated with mean exposures of 75 ppm of benzene
                    improved as the exposure concentration dropped (Kipen
                    et al., 1989).  A medical surveillance program of 303
                    workers exposed to less than 1 ppm of benzene for up
                    to 26 years as a group did not show any evidence of
                    changes in blood indices or any cases of leukemia
                    (Tsai et al., 1983).  Additional information on
                    hematological effects of benzene exposure is included
                    under sections 7.3 and 7.5.

             9.4.11 Immunological

                    Chronic benzene exposure has been shown to
                    affect both cellular and humoral immunity.  In a study
                    of 35 painters exposed to 3 to 49 ppm of benzene and
                    higher concentrations of toluene and xylene, increased
                    serum IgM, and decreased serum IgG and IgA were found
                    (Lange et al., 1973).  Decreases in cellular immunity
                    have been documented through leukopenia as described
                    under the hematological section 9.4.10.
    
                    Benzene administered to mice by intraperitoneal
                    injection resulted in a decreased cultured spleen cell
                    IgM production as demonstrated by plaque-forming cells
                    assays at a dose of 44 mg/kg for three days, and a
                    decreased lymphoproliferative response in cultured
                    spleen lymphocytes exposed to E. coli 
                    lipopolysaccharide or concanavalin A in animals
                    administered a dose of 264 mg/kg for three days.  The
                    number of circulating lymphocytes was decreased only
                    at dose of 440 mg/kg or higher (Irons et al., 1983). 
                    Mice given benzene contaminated water had significant
                    immunotoxic effects on both the humoral and cellular
                    immune responses at doses of 166 mg/L and higher for a
                    four week period (Hsieh et al., 1988).

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             No data available.

                    9.4.12.2 Fluid and electrolyte disturbances

                             No data available.

                    9.4.12.3 Others

                             Not applicable.

             9.4.13 Allergic reactions

                    None reported.

             9.4.14 Other clinical effects

                    None reported.

             9.4.15 Special risks

                    Pregnancy: Benzene crosses the human placenta
                    and is present in cord blood in concentrations equal
                    to or greater than maternal blood (Dowty et al.,
                    1976).  However, effects of benzene exposure in
                    pregnant women is not well understood.  A review of 15
                    pregnant women exposed to benzene reported one
                    stillbirth and 7 miscarriages but no congenital
                    abnormalities, and another study recorded a prevalence
                    of 4.6% for spontaneous abortions and premature births
                    in women exposed to benzene and other aromatic
                    hydrocarbons (Schardein, 1985).  An increased
                    frequency of chromatid and isochromatid breaks was
                    found in children of women exposed during pregnancy to
                    a mix of benzene and other solvents in the printing
                    industry and chemical laboratories (Funes-Cravioto et
                    al., 1977).  One pregnant woman with4 pancytopenia
                    from occupational exposure to benzene delivered an
                    apparently normal boy and from a later pregnancy
                    delivered a normal girl (Forni et al., 1971).
    
                    Animal experiments exposing pregnant mice, rats, and
                    rabbits demonstrated fetotoxicity associated with
                    maternal toxicity, specifically fetal skeletal
                    variants and reduced fetal weight (Tatrai et al.,
                    1980).  Exposure in utero to 20 ppm of benzene for 6
                    hr/day on days 6 to 15 of gestation in mice resulted
                    in haematopoietic abnormalities (Keller & Snyder,
                    1988).  Exposures in rats to less than 10 ppm of
                    benzene during pregnancy did not cause adverse fetal
                    changes (Kuna & Kapp, 1981).
    
                    Breast feeding: No data available.
    
                    Enzyme deficiencies: No data available.

        9.5  Others

             Ethanol can increase the extent of hematotoxicity from
             benzene exposure (Baarson et al., 1982; Nakajima et al.,
             1985; Nakajima et al., 1987).  Previous administration of
             phenobarbital may decrease benzene hematotoxicity (Ikeda &
             Ohtsuji, 1971; Nakajima et al., 1985).  Toluene reduces the
             metabolism of benzene and reverses the benzene-induced
             decrease in incorporation of iron into red blood cells
             (Andrews et al., 1976).  Hepatitis B may also increase the
             incidence of hematopoietic effects from benzene exposure
             (Aksoy, 1989).

    10. MANAGEMENT

        10.1 General principles

             For inhalation exposures, it is important to move the
             patient to fresh air and administer humidified 100% oxygen as
             needed.  For ingestions of greater than 1 mL/kg body weight
             of benzene presenting less than two hours after ingestion,
             gastric aspiration may be useful.  Administration of
             catecholamines is not recommended due to the possibility of
             myocardial sensitization (HSDB, 1992).

        10.2 Life supportive procedures and symptomatic treatment

             Supportive treatment is adequate for most cases of
             benzene exposure.  As in all patients, adequate airway,
             breathing, and circulation should be assured.  The patient
             should be removed from the exposure and 100% oxygen
             administered as necessary.  In severe exposures, endotracheal
             intubation and mechanical ventilation may be necessary. 
             Intravenous crystalloid solutions should be administered for
             hypotension.  Cardiac monitoring is recommended for severe
             exposures, and routine blood tests such as a CBC and
             electrolytes should be ordered.  Abnormalities should be
             corrected.  Diazepam is the first line therapy for the
             treatment of seizures, and phenobarbital may be a useful
             adjunct.

        10.3 Decontamination

             No decontamination is required for pure inhalation
             exposure.  For dermal exposure, the patient's clothing should
             be removed and discarded.  Then the skin should be washed
             with soap and copious amounts of tepid water.  For oral
             exposures, gastric aspiration may be helpful for ingestion of
             large quantities of benzene, although there is a risk of
             pulmonary aspiration.  Gastric lavage should be considered
             for the patient who may have ingested other substances. 
             Ipecac should not be administered due to the risk of sudden
             decrease in mental status.  Administration of activated
             charcoal and sorbitol has not been demonstrated to be
             efficacious in humans, although activated charcoal decreased
             absorption of benzene into blood from the ligated small
             intestines of rats (Laass, 1980).  For ocular exposures,
             irrigate with copious amounts of water or normal
             saline.

        10.4 Enhanced elimination

             There are no proven means of increasing benzene
             elimination once it has been absorbed.

        10.5 Antidote treatment

             10.5.1 Adults

                    No proven antidotal therapy is available. 
                    Administration of N-acetyl cysteine may theoretically
                    be of benefit in limiting haematotoxicity from acute
                    benzene exposure.  In mice, coadministration of
                    indomethacin (2 mg/kg body weight) with benzene
                    prevented the bone marrow depression and genotoxicity
                    seen with the benzene given alone, most likely through
                    a prostaglandin-mediated process (Kalf et al., 1989),
                    although use of this therapy has not been reported in
                    human poisonings.

             10.5.2 Children

                    Adult management guidelines should be followed
                    with appropriate adjustment of dosages for
                    children.

        10.6 Management discussion

             Since the treatment of acute exposure to benzene is
             limited to decontamination and supportive care, there are few
             controversies over treatment other than the usual discussion
             about the risks and benefits of lavage and/or activated
             charcoal.  The possible beneficial effects of administration
             of nonsteriodal antiinflammatory agents and the
             administration of N-acetyl cysteine deserve further
             investigation prior to their routine use in humans.  Further
             research should focus on the prevention of injury by blocking
             the toxic effects of benzene metabolites.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from the literature

             Tauber reported in 1970 on a fatality from acute
             benzene exposure (Tauber, 1970).  A 45 year old previously
             healthy male collapsed after running 325 feet to shut off an
             overflowing benzol plant tank.  The tank contained 67.7%
             benzene, 14.5% toluene, 5.7% xylene, 4.8% crude solvents, and
             7.3% other chemicals.  Autopsy was unremarkable except for
             elevated benzene levels: blood 0.38 mg%, brain 1.38 mg%, and
             liver 0.28 mg%.  The suspicion in this case was death from
             the benzene-sensitized myocardium and endogenous
             catecholamines, as the brain levels were not felt to be high
             enough to result in general anesthesia.
    

             A case of multiple fatalities resulted when workers were
             exposed to benzene from a previous cargo while opening a
             flange valve in the cofferdam of a chemical cargo ship. 
             Three workers collapsed and one was rescued.  The exposure
             lasted only a number of minutes.  At autopsy all victims had
             second degree chemical burns to the face, trunk, and limbs,
             confluent alveolar haemorrhages, and pulmonary edema.  Blood
             benzene levels ranged from 30 to 120 mg/L (Avis & Hutton,
             1993).
    
             Hamilton reported on a number of cases of acute benzene
             exposure from entry into confined spaces (Hamilton, 1922). 
             In several of these cases benzene containing tanks had been
             washed out thoroughly and in one case additional air was
             supplied through a pipe, but despite these precautions
             fatalities were reported.  In this same article, Hamilton
             also reported on nine women aged 15 to 20 years of age who
             developed purpura and haemorrhages from the mouth, stomach,
             nose or uterus after using benzene-based rubber cement for
             three weeks to four months in a velocipede tire factory. 
             Upon evaluation, they were found to have both marked anemia
             and almost complete leukopenia.

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             Benzene should be stored in sealed well marked
             containers in locked areas to avoid inadvertent exposure to
             children.  In occupational settings benzene should be used in
             closed-process systems, or in areas with adequate
             ventilation.  Otherwise appropriate respiratory protection
             should be worn at benzene concentrations above occupational
             exposure limits.  For occupational exposures, annual medical
             surveillance examinations including complete blood counts are
             recommended.

        12.2 Other

             No data available.

    13. REFERENCES

        ACGIH (1994)  1994-1995 Threshold Limit Values for Chemical
        Substances and Physical Agents and Biological Exposure Indices.
        American Conference of Governmental Industrial Hygienists,
        Cincinnati, OH.
    
        Aksoy M (1980)  Different types of malignancies due to
        occupational exposure to benzene: A review of recent observations
        in Turkey. Environ Res, 23: 181-190.
    
        Aksoy M (1989)  Hematotoxicity and carcinogenicity of benzene.
        Environ Health Perspect, 82: 193-197.
    
        Aksoy M, Dincol K, Akgun T, Erdem S & Dincol G (1971) 
        Haematological effects of chronic benzene poisoning in 217
        workers. Br J Ind Med, 28: 296-302.
    
        Aksoy M, Dincol K, Erdem S, Akgun T & Dincol G (1972)  Details of
        blood changes in 32 patients with pancytopenia associated with
        long-term exposure to benzene. Br J Ind Med, 29: 56-64.
    
        Aksoy M & Erdem S (1978)  Followup study on the mortality and the
        development of leukemia in 44 pancytopenic patients with chronic
        exposure to benzene. Blood, 52: 285-292.
    
        Aksoy M, Erdem S & Dincol G (1974)  Leukemia in shoe-workers
        exposed chronically to benzene. Blood, 44: 837-841.
    
        Aksoy M, Erdem S & Dincol G (1976)  Types of leukemia in chronic
        benzene poisoning. A study in thirty-four patients. Acta Haematol,
        55: 65-72.
    
        Aksoy M, Ozeris S, Sabuncu H, Inanici Y & Yanardag R (1987) 
        Exposure to benzene in Turkey between 1983 and 1985: a
        haematological study on 231 workers. Br J Ind Med, 44:
        785-787.
    
        Andrews LS, Lee EW, Witmer CM, Kocsis JJ & Snyder R (1976) 
        Effects of toluene on the metabolism, disposition and hemopoietic
        toxicity of [3H]benzene. Biochem Pharmacol, 26: 293-300.
    
        ATSDR (1993)  Toxicological Profile for Benzene. U.S. Department
        of Health and Human Services: Agency for Toxic Substances and
        Disease Registry, Atlanta, GA.
    
        Avis SP & Hutton CJ (1993)  Acute benzene poisoning: A report of
        three fatalities. J Forensic Sci, 38: 599-602.
    
        Baarson KA, Snyder CA, Green JD, Sellakumar A, Goldstein BD &
        Albert RE (1982)  The hematotoxic effects of inhaled benzene on
        peripheral blood, bone marrow, and spleen cells are increased by
        ingested ethanol. Toxicol Appl Pharmacol, 64: 393-404.
    

        Baselt RC & Cravey RH (1989)  Disposition of Toxic Drugs and
        Chemicals in Man. 3rd ed. Year Book Medical Publishers, Chicago,
        IL.
    
        Baslo A & Aksoy M (1982)  Neurological abnormalities in chronic
        benzene poisoning. A study of six  patients with aplastic anemia
        and two with preleukemia. Environ Res, 27: 457-465.
    
        Berlin M, Holm S, Knutsson P & Tunek A (1979)  Biological
        threshold limits for benzene based on pharmacokinetics of inhaled
        benzene in man. Arch Toxicol, 2S: 303-310.
    
        Blank IH & McAuliffe DJ (1985)  Penetration of benzene through
        human skin. J Invest Dermatol, 85: 522-526.
    
        Brief RS, Lynch J, Bernath T & Scala RA (1980)  Benzene in the
        workplace. Am Ind Hyg Assoc J, 41: 616-623.
    
        Brugnone F, Perbellini L, Faccini GB, Pasini F, Danzi B, Maranelli
        G, Romeo L, Gobbi M & Zedde A (1989)  Benzene in the blood and
        breath of normal people and occupationally exposed workers. Am J
        Ind Med, 16: 385-399.
    
        Budivari S (ed) (1996)  The Merck Index: An Encyclopedia of
        Chemicals, Drugs, and Biologicals. 12th ed., Merck & Co., Inc,
        Rahway, NJ, USA.  
    
        Cornish HH & Ryan RC (1965)  Metabolism of  benzene in nonfasted,
        fasted, and aryl-hydroxylase inhibited rats. Toxicol Appl
        Pharmacol, 7: 767-771.
    
        Cronin HJ (1924)  Benzol poisoning in the rubber industry. Boston
        Medical and Surgical Journal, 191: 1164-1166.
    
        Ding X-J, Li Y, Ding Y (1983)  Chromosome changes in patients with
        chronic benzene poisoning. Chin Med J, 96: 681-685.
    
        Dowty BJ, Laseter JL, Storer J (1976)  The transplacental
        migration and accumulation in blood of volatile organic
        constituents. Pediatr Res, 10: 696-701.
    
        Drew RT & Fouts JR (1974)  The lack of effects of pretreatment
        with phenobarbital and chlorpromazine on the acute toxicity of
        benzene in rats. Toxicol Appl Pharmacol, 27: 183-193.
    
        Drummond L, Luck R, Afacan  AS, Wilson HK (1988)  Biological
        monitoring of workers exposed to benzene in the coke oven
        industry. Br J Ind Med, 45: 256-261.
    

        Eastmond DA, Smith MT, Irons R (1987)  An interaction of benzene
        metabolites reproduces the myelotoxicity observed with benzene
        exposure. Toxicol Appl Pharmacol, 91: 85-95.
    
        Ellenhorn MJ & Barceloux DG (1988)  Medical Toxicology: Diagnosis
        and Treatment of Human Poisoning.  Elsevier, New York, NY.
    
        Flury F (1928)  Moderne gewerbliche vergiftungen. IIa: Moderne
        gewerbliche vergiftungen in pharmakologisch-toxikologisher
        hinsicht. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol, 138:
        65-82 (in German).
    
        Forni AM, Cappellini A, Pacifico E, Vigliani EC (1971)  Chromosome
        changes and their evolution in subjects with past exposure to
        benzene. Arch Environ Health, 23: 385-391.
    
        Funes-Cravioto F, Zapata-Gayon C, Kolmodin-Hedman B, Lambert B,
        Lindsten J, Nirberg E, Nordenskjold M, Olin R, Swensson A (1977) 
        Chromosome aberrations and sister-chromatid exchange in workers in
        chemical laboratories and a rotoprinting factory and in children
        of women laboratory workers. Lancet, 2: 322-325.
    
        Gerarde HW (1960)  Toxicity and Biochemistry of Aromatic
        Hydrocarbons.  Elsevier, New York.
    
        Goldstein BD (1977)  Hematotoxicity in humans. J Toxicol Environ
        Health, 2S: 69-105.
    
        Goldstein BD (1988)  Benzene toxicity. Occupational medicine:
        State of the Art Reviews, 3: 541-554.
    
        Gosselin RE, Smith RP, Hodge HC (1984)  Clinical Toxicology of
        Commercial Products. 5th ed. Williams & Wilkins, Baltimore.
    
        Grant WM & Schuman JS (Eds.) (1993) Toxicology of the Eye: Effects
        on the eyes and visual system from chemicals, drugs, metals and
        minerals, plants, toxins and venoms; also, systemic side effects
        from eye medications. 4th ed. Charles C. Thomas Publisher,
        Springfield, IL.
    
        Green JD, Leong BKJ, Laskin S (1978)  Inhaled benzene fetotoxicity
        in rats. Toxicol Appl Pharmacol, 46: 9-18.
    
        Greenburg L (1926)  Benzol  poisoning as an industrial hazard.
        Public Health Rep, 41: 1357-1375.
    
        Haley TJ (1977)  Evaluation of the health effects of benzene
        inhalation. Clin Toxicol, 11: 531-548.
    

        Hamilton A (1922)  The growing menace of benzene (benzol)
        poisoning in American industry. J Am Med Assoc, 78: 627-630.
    
        Hanke J, Dutkiewicz T, Piotrowski J (1961)  The absorption of
        benzene through the skin in men. Med Pr, 12: 413-426.
    
        Harrington TF (1917)  Industrial benzol poisoning in
        Massachusetts. Boston Medical and Surgical Journal, 177:
        203-206.
    
        Henderson RF, Sabourin PJ, Bechtold WE, Griffith WC, Medinsky MA,
        Birnbaum LS, Lucier GW (1989)  The effect of dose, dose rate,
        route of administration, and species on tissue and blood level of
        benzene metabolites. Environ Health Perspect, 82: 9-17.

        Herregods P, Chappel R, Mortier G (1984)  Benzene poisoning as a
        possible cause of transverse myelitis. Paraplegia, 22:
        305-310.
    
        HSDB (1992)  Hazardous Substances Data Bank. National Library of
        Medicine, National Toxicology Information Program, Bethesda,
        MD.
    
        Hsieh GC, Sharma RP, Parker RDR (1988)  Subclinical effects of
        groundwater contaminants I: Alteration of humoral and cellular
        immunity by benzene in CD-1 mice. Arch Environ Contam Toxicol, 17:
        151-158.
    
        Hudak A & Ungvary G (1978)  Embryotoxic effects of benzene and its
        methyl derivatives: toluene, xylene. Toxicology, 11: 55-63.
    
        Huff JE, Haseman JK, DeMarini DM, Eustis S, Maronpot RR, Peters
        AC, Persing RL, Chrisp CE & Jacobs AC (1989)  Multiple-site
        carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice. 
        Environ Health Perspect, 82: 125-163.
    
        Hunter CG & Blair D (1972)  Benzene: Pharmacokinetic studies in
        man. Ann Occup Hyg, 15: 193-199.
    
        Hunter D (1978)  The Diseases of Occupations. 6th ed. Hodder and
        Stoughton, London.
    
        IARC (1982)  IARC Monographs on the evaluation of the carcinogenic
        risk of chemicals to humans. Vol. 29: Some industrial chemicals 
        and dyestuffs. pp. 93-148. World Health Organization:
        International Agency for Research on Cancer, Lyon, France.
    

        Ikeda M & Ohtsuji H (1971)  Phenobarbital-induced protection
        against toxicity of toluene and benzene in the rat. Toxicol Appl
        Pharmacol, 20: 30-43.
    
        Infante PF, Rinsky RA, Wagoner JK, Young RJ (1977)  Leukaemia in
        benzene workers. Lancet, 2: 76-78.
    
        Inoue O, Seiji K, Kasahara M, Nakatsuka H, Watanabe T, Yin S-G, Li
        G-L, Jin C, Cai S-X, Wang X-Z, Ikeda M (1986)  Quantitative
        relation of urinary phenol levels to breathzone benzene
        concentrations: a factory survey. Br J Ind Med, 43: 692-697.
    
        Inoue O, Seiji K, Watanabe T, Kasahara M, Nakatsuka H, Yin S, Li
        G, Cai S, Jin C, Ikeda M (1988)  Mutual metabolic suppression
        between benzene and toluene in man. Int Arch Occup Environ Health,
        60: 15-20.
    
        Irons R, Wierda D, Pfeifer RW (1983) The immunotoxicity of benzene
        and its metabolites. In Mehlman MA (Eds.), Advances in Modern
        Environmental Toxicology Volume IV: Carcinogenicity and Toxicity
        of Benzene. (pp. 37-50).  Mobil Oil Corporation, Princeton,
        NJ.
    
        Kalf GF, Schlosser MJ, Renz JF, Pirozzi SJ (1989)  Prevention of
        benzene-induced myelotoxicity by nonsteroidal anti-inflammatory
        drugs. Environ Health Perspect, 82: 57-64.
    
        Keller KA & Snyder CA (1988)  Mice exposed in utero to 20 ppm
        benzene exhibit altered numbers of recognizable hematopoietic
        cells up to seven weeks after exposure. Fundam Appl Toxicol, 10:
        224-232.
    
        Kipen HM, Cody RP, Goldstein BD (1989)  Use of longitudinal
        analysis of peripheral blood counts to validate historical
        reconstructions of benzene exposure. Environ Health Perspect, 82:
        199-206.
    
        Kuna RA & Kapp RW (1981)  The embryotoxic/teratogenic potential of
        benzene vapor in rats. Toxicol Appl Pharmacol, 57: 1-7.
    
        Laass W (1980)  Therapy of acute oral poisonings by organic
        solvents: Treatment by activated charcoal in combination with
        laxatives. Arch Toxicol, 4S: 406-409.
    
        Lange A, Smolik R, Zatonski W, Szymanska (1973)  Serum
        immunoglobulin levels in workers exposed to benzene, toluene, and
        xylene. Int Arch Arbeitsmed, 31: 37-44.
    
        Loden M (1986)  The in vitro permeability of human skin to
        benzene, ethylene glycol, formaldehyde, and n-hexane. Acta
        Pharmacol Toxicol, 58: 382-389.
    

        Medinsky MA, Sabourin PJ, Lucier G, Birnbaum LS, Henderson RF
        (1989)  A physiological model for simulation of benzene metabolism
        by rats and mice. Toxicol Appl Pharmacol, 99: 193-206.
    
        Morimoto K, Wolff S, Koizumi A (1983)  Induction of
        sister-chromatid exchanges in human lymphocytes by microsomal
        activation of benzene metabolites. Mutat Res, 119: 355-360.
    
        Murray FJ, John JA, Rampy LW, Kuna RA, Schwetz BA (1979) 
        Embryotoxicity of inhaled benzene in mice and rabbits. Am Ind Hyg
        Assoc J, 40: 993-998.
    
        Nahum LH & Hoff HE (1934)  The mechanism of sudden death in
        experimental acute benzol poisoning. J Pharmacol Exp Ther, 50:
        336-345.
    
        Nakajima T, Okino T, Sato A (1987)  Kinetic studies on benzene
        metabolism in rat liver-possible presence of three forms of
        benzene metabolizing enzymes in the liver. Biochem Pharmacol, 36:
        2799-2804.
    
        Nakajima T, Okuyama S, Yonekura I, Sato A (1985)  Effects of
        ethanol and phenobarbital administration on the metabolism and
        toxicity of benzene. Chem Biol Interact, 55: 23-38.
    
        NIOSH (1990)  NIOSH Pocket Guide to Chemical Hazards, DHHS (NIOSH)
        Publication No, 90-117.  U.S. Department of Health and Human
        Services, Public Health Service, Centers for Disease Control,
        National Institute for Occupational Safety and Health, Washington
        D.C.
    
        OHMS/TADS (1990)  Oil and Hazardous Materials/Technical Assistance
        Data System. Chemical Information Systems, Inc, Baltimore, MD.
    
        OSHA (1987)  Occupational exposure to benzene. Final rule. US
        Department of Labor. Occupational Safety and Health
        Administration. Federal Register. 52, pp. 34460-34578. 
    
        Ott MG, Townsend JC, Fishbeck WA, Langner RA (1978)  Mortality
        among workers occupationally exposed to benzene. Arch Environ
        Health, 33: 3-10.
    
        Parke DV & Williams RT (1953)  Studies in detoxication 49. The
        metabolism of benzene containing [14C1]benzene. Biochem J, 54:
        231-238.
    
        Pawar SS & Mungikar AM (1975)  Changes in the activities of
        hepatic drug metabolizing enzymes and lipid peroxidation caused by
        benzene and toluene. Indian J Biochem Biophys, 12: 133-135.
    
        Perbellini L, Faccini GB, Pasini F, Cazzoli F, Pistoia S,
        Rosellini R, Valsecchi M, Brugnone F (1988)  Environmental and
        occupational exposure to benzene by analysis of breath and blood.

        Br J Ind Med, 45: 345-352.
    
        Picciano D (1979)  Cytogenetic study of workers exposed to
        benzene. Environ Res, 19: 33-38.
    
        Rickert DE, Baker TS, Bus JS, Barrow CS, Irons RD (1979)  Benzene
        disposition in the rat after exposure by inhalation. Toxicol Appl
        Pharmacol, 49: 417-423.
    
        Rinsky RA, Smith AB, Hornung R, Filloon TG, Young RJ, Okun AH,
        Landrigan PJ (1987)  Benzene and leukemia.  An epidemiologic risk
        assessment. N Engl J Med, 316: 1044-1050.
    
        Roush GJ & Ott MG (1977)  A study of benzene exposure versus
        urinary phenol levels. Am Ind Hyg Assoc J, 38: 67-75.
    
        Sabourin PJ, Chen BT, Lucier G, Birnbaum LS, Fisher E, Henderson
        RF (1987)  Effect of dose on the absorption and excretion of [14C]
        benzene administered orally or by inhalation in rats and mice.
        Toxicol Appl Pharmacol, 87: 325-336.
    
        Sammett D, Lee EW, Kocsis JJ, Snyder R (1979)  Partial hepatectomy
        reduces both metabolism and toxicity of benzene. J Toxicol Environ
        Health, 5: 785-792.
    
        Sandmeyer EE (1981) Aromatic hydrocarbons. In Clayton GD & Clayton
        FE (Eds.), Patty's Industrial Hygiene and Toxicology. (pp.
        3253-3283). 3rd rev. ed. John Wiley & Sons, New York, NY.
    
        Sasiadek M, Jagielski J, Smolik R (1989)  Localization of
        breakpoints in the karyotype of workers professionally exposed to
        benzene. Mutat Res, 224: 235-240.
    
        Sato A & Fujiwara Y (1975)  Elimination of inhaled benzene and
        toluene in man. Sangyo igaku (Jap J Ind Health), 14: 224-225.
    
        Schardein JL (1985)  Chemically Induced Birth Defects.  Marcel
        Dekker, Inc, New York, NY.
    
        Schrenk HH, Yant WP, Pearce SJ, Patty FA, Sayers RR (1941) 
        Absorption, distribution, and elimination of benzene by body
        tissues and fluids of dogs exposed to benzene vapor. J Ind Hyg
        Toxicol, 23: 20-34.
    
        Sherwood RJ (1988)  Pharmacokinetics of benzene in a human after
        exposure at about the occupational limit. Ann N Y Acad Sci, 534:
        635-647.
    
        Sherwood RJ & Carter FWG (1970)  The measurement of occupational
        exposure to benzene vapour. Ann Occup Hyg, 13: 125-146.
    

        Srbova J, Teisinger J, Skramovsky S (1950)  Absorption and
        elimination of inhaled benzene in man. Arch Ind Hyg Occup Med, 2:
        1-8.
    
        Susten AS, Dames BL, Burg JR, Niemeler RW (1985)  Percutaneous
        penetration of benzene in hairless mice: An estimate of dermal
        absorption during tire-building operations. Am J Ind Med, 7:
        323-335.
    
        Tatrai E, Ungvary GY, Hudak A, Rodics K, Lorincz M, Barcza GY
        (1980)  Concentration dependence of the embryotoxic effects of
        benzene inhalation in CFY rats. J Hyg Epidemiol Microbiol Immunol,
        24: 363-371.
    
        Tauber J (1970)  Instant benzol death. J Occup Med, 12: 91-92.
    
        Thienes CH & Haley TJ (1972)  Clinical Toxicology. 5th Edition ed.
        Lea & Febiger, Philadelphia, PA.
    
        Tough IM & Court Brown WM (1965)  Chromosome aberrations and
        exposure to ambient benzene. Lancet, 1: 684.
    
        Tsai SP, Wen CP, Weiss NS, Wong O, McClellan WA, Gibson RL (1983) 
        Retrospective mortality and medical surveillance studies of
        workers in benzene areas of refineries. J Occup Med, 25:
        685-692.
    
        Van Ert M, Arp EW, Harris RL, Symons MJ, Williams TM (1980) 
        Worker exposure to chemical agents in the manufacture of rubber
        tires: Solvent vapor studies. Am Ind Hyg Assoc J, 41: 212-219.
    
        Vigliani EC & Forni A (1976)  Benzene and leukemia. Environ Res,
        11: 122-127.
    
        Vigliani EC & Saita G (1964)  Benzene and leukemia. N Engl J Med,
        271: 872-876.
    
        Von Oetingen WF (1940)  II. Toxicity and potential dangers of
        aliphatic and aromatic hydrocarbons. Public Health Bulletin, 255:
        66-97.
    
        Walkley JE, Pagnotto LD, Elkins HB (1961)  The measurement of
        phenol in urine as an index of benzene exposure. Am Ind Hyg Assoc
        J, 22: 362-367.
    
        Wallace LA (1989)  Major sources of benzene exposure. Environ
        Health Perspect, 82: 165-169.
    
        Weaver NK, Gibson RL, Smith CW (1983) Occupational exposure to
        benzene in the petroleum and petrochemical industries. In Mehlman
        MA (Eds.), Advances in Modern Environmental Toxicology Volume IV:

        Carcinogenicity and Toxicity of Benzene. (pp. 63-75).  Mobil Oil
        Corporation, Princeton, NJ.
    
        Wester RC, Maibach HI, Gruenke LD, Craig JC (1986)  Benzene levels
        in ambient air and breath of smokers and nonsmokers in urban and
        pristine environments. J Toxicol Environ Health, 18: 567-573.
    
        Winek CL, Collum WD, Wecht CH (1967)  Fatal benzene exposure by
        glue-sniffing. Lancet, March 25: 683.
    
        Winek CL & Collom WD (1971)  Benzene and toluene fatalities. J
        Occup Med, 13: 259-261.
    
        Wong O (1987)  An industry wide mortality study of chemical
        workers occupationally exposed to benzene. II Dose response
        analyses. Br J Ind Med, 44: 382-395.
    
        Yin S-N, Li G-L, Tain F-D, Fu Z-I, Jin C, Chen Y-J, Luo S-J, Ye
        P-Z, Zhang J-Z, Wang G-C, Zhang X-C, Wu H-N, Zhong Q-C (1987a) 
        Leukaemia in benzene workers: a retrospective cohort study. Br J
        Ind Med, 44: 124-128.
    
        Yin S-N, Li G-L, Tain F-D, Fu Z-I, Jin C, Chen Y-J, Luo S-J, Ye
        P-Z, Zhang J-Z, Wang G-C, Zhang X-C, Wu H-N, Zhong Q-C (1989)  A
        retrospective cohort study of leukemia and other cancers in
        benzene workers. Environ Health Perspect, 82: 207-213.
    
        Yin S-N, Li Q, Liu Y, Du C, Jin C (1987b)  Occupational exposure
        to benzene in China. Br J Ind Med, 44: 192-195.

    14. AUTHOR, REVIEWER(S), DATES (INCLUDING UPDATES), COMPLETE
        ADDRESS(ES)

        Author:     Dr J.L. Burgess
                    Washington Poison Center
                    P.O. Box 5371
                    Seattle, WA 98105-0371
                    USA
    
                    Tel:     1-206-5172357
                    Fax:     1-206-5268490
    
        Date:       May 1993
    
        Peer
        review:     Cardiff, United Kingdom, March 1995
                    (Group members: Mr J. de Kom, Dr R. Dowsett, Dr K.
                    Hartigan-Go, Dr H. Hentschel, Dr P. Myrenfors, Dr L.
                    Pinto Pereira, Dr M. Rizk, Dr E. Wickstrom)
    
        Editors:    Dr M.J. Ruse (April 1997)
                    Mrs J. Dumnil (June 1999)
    

        
        
        
    



    See Also:
       Toxicological Abbreviations
       Benzene (EHC 150, 1993)
       Benzene (ICSC)
       BENZENE (JECFA Evaluation)
       Benzene  (IARC Summary & Evaluation, Supplement7, 1987)
       Benzene (IARC Summary & Evaluation, Volume 7, 1974)
       Benzene (IARC Summary & Evaluation, Volume 29, 1982)