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Styrene

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
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 circumstance 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 ANALYSES 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
   8.6 References
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, ears, 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 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 literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventive measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    STYRENE

    International Programme on Chemical Safety
    Poisons Information Monograph 509
    Chemical

    1.  NAME

        1.1  Substance

             Styrene

        1.2  Group

             Aromatic hydrocarbons

        1.3  Synonyms

             Ethenylbenzene; styrol;
             styrolene; cinnamene;
             cinnamenol; cinnamol;
             phenylethylene; vinylbenzene;
             monomeric styrene; styrene monomer;
             styron; styropor; 

        1.4  Identification numbers

             1.4.1  CAS number

                    100-42-5

             1.4.2  Other numbers

                    79637-11-9 (Other CAS) 
                    2055 (PIN-UN Number)
                    WL3675000 (RTECS Number)

    2.  SUMMARY

        2.1  Main risks and target organs

             The principal acute hazards from human exposure to
             styrene are central nervous system depression and irritation
             of the skin, eyes, and upper respiratory tract. The compound
             is volatile and is readily absorbed following inhalation or
             dermal contact.
    
             Chronic exposure may produce skin, eye changes, and liver
             dysfunction. As birth defects have been noted, expectant
             mothers and women with ovulation and menstrual disorders
             should not work in conditions exposing them to styrene.
    

             Neurobehavioral abnormalities have been related to chronic
             exposure to styrene.
    
             Target organs are: central nervous system; skin; respiratory
             tract; eyes; liver.

        2.2  Summary of clinical effects

             Irritation of skin and mucous membranes: eye and nasal
             irritation occurred after exposure to 300 ppm of styrene.
             Skin contact resulted in acute and chronic dermatitis.  After
             inhalation of large doses patients experienced chest burning,
             wheezing, dyspnea, increased nasal secretion, metallic taste,
             and vertigo.  Headache, nausea, incoordination, muscular
             weakness, anorexia, depression, feeling of drunkeness result
             from CNS action. The clinical picture is also called "styrene
             sickness".

        2.3  Diagnosis

             Clinical features: Irritation of skin and mucous
             membranes. Nasal an eye irritation. Corneal burns after
             direct contact. Headache, fatigue, weakness, depression,
             feeling of drunkeness.  Chest burning, wheezing, dyspnea. 
             The exposure to styrene may be detected by determining the
             urinary styrene etabolites.

        2.4  First-aid measures and management principles

             Remove the victim from the area of exposure.  Discard
             contaminated clothing. Irrigate exposed eyes with copious
             amounts of water or saline. Wash skin with soap and copious
             amounts of water.
    
             Maintain a clear airway.
    
             Support ventilation.
    
             If breathing has stopped begin artificial respiration. 
             Administer oxygen for inhalation.  In case of ingestion do
             not induce vomiting.

    3.  PHYSICO-CHEMICAL PROPERTIES

        3.1  Origin of the substance

             Isolated from storax, a balsam obtained from the trunk
             of Liquidambar orientalis Mill., or L. styraciflua L.. 
             Synthesized from benzene and ethylene.

        3.2  Chemical structure

             Chemical name:                 Styrene
             Molecular weight:              104.14
             Molecular formula:             C8-H8
             Structural formula:            C6H5- C=CH2
             Relative molecular mass:       C 92,26%; H 7,74%

        3.3  Physical properties

             3.3.1  Colour

                    Clear, colourless to yellowish liquid.

             3.3.2  State/form

                    Volatile liquid.

             3.3.3  Description

                    Styrene is flammable, very refractive, with a
                    strong pungent but tolerable and quickly disappearing
                    odour at ambient air levels of 100 ppm. The odour
                    detection limit is around 5 ppm.
    
                    Boiling point:            145.2C
                    Melting point:            -30.6C
                    Flash point:              31C (87 F)
                    Autoignition temperature: 490C
                    Relative density:         0.9059 at 25C
                    Vapour pressure:          10 mm at 35C
                    Saturation vapour concentration: 6600 ppm at 20C
                    Solubility:
                    practically insoluble in water; 
                    soluble in alcohol, ether, methanol, acetone and
                    carbon disulfide.
                    Explosive limits in air: 1.1 to 6.1% by volume in air.

        3.4  Hazardous characteristics

             The technical material is usually 99.6% pure, and
             normally contains a very small amount (12 to 15 ppm) of
             tertiary butyl catechol as a polymerisation inhibitor. When
             heated to 200C it is converted into the polymer,
             polystyrene. Styrene can react violently with oxidizing
             agents such as peroxides, strong acids, and chlorates. Fires
             involving styrene may release dangerous by-products specially
             carbon dioxiode and carbon monoxide. Fires must be
             extinguished with carbon dioxide or dry chemical (Budavari,
             1989; Heiselman and Cannon, 1990).

    4.  USES

        4.1  Uses

             4.1.1  Uses

             4.1.2  Description

                    Several millions of tons of styrene are used
                    world-wide in the production of polystyrene,
                    styrene-butadiene co-polymer for synthetic rubber,
                    styrene-acrylonitrile polymer,
                    acrylonitrile-butadiene-styrene copolymer, polyester
                    resins for reinforced fiberglass products, paints,
                    coatings, in the manufacture of reinforced plastics,
                    and as insulators (O'Donoghue, 1985; Budavari,
                    1989).

        4.2  High risk circumstance of poisoning

             The most likely circumstance of poisoning consists of
             the inhalation of vapours of styrene, although skin exposure
             may occur. Pungent odour usually gives adequate warning but
             the odour disappears rapidly.

        4.3  Occupationally exposed populations

             Occupational exposure to styrene occurs during monomer
             manufacture, transportation, and polymerization. Styrene is
             absorbed through the skin and the respiratory tract.
             Ingestion is not a significant occupational hazard.
    
             "Styrene sickness" in industry describes a clinical picture
             after heavy exposure to styrene and other solvents
             (O'Donoghue, 1985).
    
             In occupational settings, exposure to styrene varies
             considerably, depending on the operations concerned. In some
             processes, styrene concentrations are less than 21 mg/m3,
             although occasional values of 210 mg/m3 (1 ppm=4.26 _g/m3) or
             more have been reported. During styrene-butadiene rubber
             production, styrene concentrations have been re-ported to
             range from 42 to 840 mg/m3. In all industrial applications
             high levels of exposure may occur during clean-up and
             maintenance procedures (IPCS, 1983).

    5.  ROUTES OF ENTRY

        5.1  Oral

             Liquid styrene is absorbed through the digestive system,
             but human cases have not been described.

        5.2  Inhalation

             Inhalation of vapours of styrene is a major route of
             entry. Inhalation is responsible for the majority of
             poisoning cases.

        5.3  Dermal

             Both liquid an vapour forms are absorbed through the skin.

        5.4  Eye

             Styrene may produce eye irritation.

        5.5  Parenteral

             Not relevant

        5.6  Others

             Not relevant

    6.  KINETICS

        6.1  Absorption by route of exposure

             Oral absorption: human information is not available, but
             animal toxicity data indicate that effects after ingestion
             may be similar to those described for inhalation. 
             Percutaneous absorption of styrene vapours is very small
             (only about 2%). Absorption of liquid styrene through skin is
             9 to 15 mg/cm2/h. Styrene vapours are absorbed through the
             lungs. (Proctor et al, 1988). It has been shown that 59 to
             88% of the dose is absorbed following inhalation of styrene
             at atmospheric concentrations in the range 20 to 200 ppm but
             it is greater at increased ventilations during exercise
             (Fielder and Lowing, 1981).

        6.2  Distribution by route of exposure

             Absorbed styrene is rapidly and extensively distributed
             throughout the body tissues (Fielder and Lowing, 1981).
             Experimentally, styrene tissue distribution after oral acute
             doses presented highest concentrations in fat, brain,kidney,
             liver, and pancreas. On repeated exposure styrene gradually
             accumulated in the adipose tissue but not in other tissues
             (IARC, 1979).

        6.3  Biological half-life by route of exposure

             It was reported that the biological half-life of
             styrene, as measured by the appearance of metabolites in
             urine (phenylglyoxylic acid and mandelic acid), was between

             eight and nine hours in humans (Bond, 1989). The styrene
             concentration in blood is found to decay in a biexponential
             fashion typical of a two compartment kinetics model. Blood is
             proposed as the first component and tissues including adipose
             tissue as the second "slow" compartment. The half-life for
             styrene in blood in the initial phase is 0.58 hours and in
             the terminal phase 13 hours (Guillemin and Bauer, 1979;
             Harkonen et al, 1978; Ramsey and Anderson, 1984; IPCS,
             1983).Studies of styrene in inspired air of volunteer
             subjects estimated the half-life of concentration in adipose
             tissue is two to four days (Engstrom et al, 1978).

        6.4  Metabolism

             The majority of the absorbed material (about 90%) in man
             is metabolised in the liver by oxidation of the vinyl side
             group to styrene oxide. Styrene oxide is the active
             metabolite (Baselt and Cravey, 1990). The resulting major
             metabolites which are excreted are mandelic acid (60-80%) and
             phenylglyoxylic acid (about 30%). Only very small quantities
             of hippuric acid are produced (Fielder and Lowing,
             1981).

        6.5  Elimination by route of exposure

             The main metabolites, mandelic acid and phenylglyoxylic
             acid, are excreted in the urine. Hippuric acid and
             4-vinylphenol are minor metabolites of styrene. About 1 to 2%
             of a dose is exhaled unchanged (Baselt and Cravey,1990). 
             Breath styrene concentrations represent about 25% of the
             corresponding air styrene concentration during constant
             exposure (Stewart and al, 1968).

    7.  TOXICOLOGY

        7.1  Mode of Action

             The exact mechanism of action is unknown.
    
             In acute exposures styrene, as other aromatic hydrocarbons,
             induces local irritation and central nervous system
             depression. These effects may be transient or persistent ones
             in the CNS - transient effects appear to be mediated directly
             by the action within the CNS and these transient changes in
             function are proportional to the measured concentrations
             within the brain in animal experiments. Persistent
             neurological effects have been associated with
             histopathological changes in neural tissue (Baker et al,
             1985).

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             Humans exposed at 376 ppm
                             experienced rapid onset of eye and nasal 
                             irritation. The level defined as immediately
                             dangerous to life or health is 5000 ppm
                             (Heiselman and Cannon, 1990). Inhalation
                             Lowest Lethal Concentration= 10000 ppm/30 
                             min. Inhalation Lowest Toxic Concentration =
                             600 ppm (Sax & Lewis, 1989).

                    7.2.1.2  Children

                             No data available.

             7.2.2  Relevant animal data

                    Oral, rat LD50:5000 mg/kg Inhalation, rat
                    LC50:24 mg/m3/4 h Intraperitoneal, rat LD50:1220 mg/kg
                    Oral, mouse LD50: 316 mg/kg Inhalation, mouse
                    LC50:2160 mg/m3/2h Intraperitoneal mouse LD50:660
                    mg/kg (Sax and Lewis, 1989)

             7.2.3  Relevant in-vitro data

                    Mutagenic test in-vitro present contradictory
                    conclusions, due to metabolic partial activation of
                    the compound to styrene 7,8-oxide, that is an
                    alkylating agent and mutagenic in many in-vitro test
                    systems (IPCS, 1983). Styrene vapour in hepatocyte
                    monolayers is not acutely toxic to the cells, even at
                    low oxygen tensions (Costa and Trudell, 1990). In an
                    in-vitro study on cytoskeletal apparatus, styrene
                    induced changes in the cytoskeletal elements (Malorni
                    et al, 1988). Styrene is mutagenic in animal and human
                    cells tests in vitro (IARC,1987).

             7.2.4  Workplace standards

                    Skin:
    
                    -TLV-TWA (Threshold Limit Values - Time Weighted
                    Average): 50 ppm (213 mg/m3)
    
                    -TLV - STEL (Threshold Limit Values - Short-Term
                    Exposure Limit): 100 pmm (426 mg/m3) (ACGIH,
                    1992)

             7.2.5  Acceptable daily intake (ADI)

                    Adopted biological exposure determinants:
    
                    Monitoring mandelic acid and phenylglyoxylic acid in
                    urine. Postshift urine samples of mandelic acid should
                    not exceed 800 mg per gram of creatinine. Prior to
                    next shift accepted value is 300 mg of mandelic acid
                    per gram of creatinine. Phenylglyoxylic acid in urine
                    in end of shift is 240 mg per gram of creatinine and
                    prior to next shift is 100 mg per gram of creatinine.
                    Accepted level of styrene in venous blood at the end
                    of shift is 0.55 mg/L and prior to next shift is 0.02
                    mg/L (ACGIH, 1992).
    
                    Evaluation of EEG in exposed individuals (Heiselmann &
                    Cannon, 1990; Gosselin et al, 1984).

        7.3  Carcinogenicity

             Studies on styrene exposure in man are inconclusive. 
             Some evidence suggests that occurrence of leukemia and
             lymphoid tumors may be linked to styrene. IARC evaluation of
             carcinogenicity of styrene to humans is: inadequate evidence.
             Overall IARC evaluation of carcinogenic risk: Group 2B
             (possibly carcinogenic to humans (IARC,1987).

        7.4  Teratogenicity

             Styrene was not proven to be teratogenic in animals. Two
             cases of children with central nervous system defects were
             reported but the significance is not clear due to exposure of
             the women during the pregnancy to other chemicals (Holmberg,
             1977).

        7.5  Mutagenicity

             DNA damage was observed in blood cells of workers
             exposed to styrene. Styrene is mutagenic in animal tests (in
             vivo) and animal and human cells test in vitro
             (IARC,1987).

        7.6  Interactions

             There is a synergistic action between styrene and other
             volatile solvents (O'Donoghue,1985).

    8.  TOXICOLOGICAL ANALYSES 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
    
             Complete blood count. Liver function tests.Urinalysis.
             Determination of mandelic and phenylglyoxylic acid in urine.
             Serial measurements of potassium, calcium, magnesium, and
             phosphate should be performed. Liver and kidney function
             tests. Chest roentgenogram.
    
             Toxicological analysis
    
             Other investigations

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning

             9.1.1  Ingestion

                    Acute poisoning after ingestion has not been
                    described in humans. On the basis of the animals
                    studies nausea, vomitos and diarrhoea might be
                    expected.

             9.1.2  Inhalation

                    Inhalation is one of the most important routes
                    of styrene poisoning. Described symptoms are: 
                    conjunctivitis, throat irritation, increased nasal
                    secretion, metallic taste, drowsines, vertigo, ataxia,
                    nystagmus, loss of coordination and memory (Ellenhorn
                    and Barceloux, 1988).

             9.1.3  Skin exposure

                    Skin contact may produce skin irritation,
                    burns, and acute dermatitis. One single prolonged
                    exposure may not result in absorption of harmful
                    amounts (Baselt,1990).

             9.1.4  Eye contact

                    Conjunctival irritation was found in 22% of a
                    group of 345 workers and correlated with intensity of
                    exposure to styrene.  Splash contact has resulted in
                    moderate hyperaemia of the conjunctiva and slight
                    injury of the corneal epithelium (Grant,
                    1986).

             9.1.5  Parenteral exposure

                    Not described.

             9.1.6  Other

                    Not relevant.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Chronic poisoning by ingestion has not been
                    described.

             9.2.2  Inhalation

                    Some workers exposed to styrene showed symptoms
                    of CNS depression (decreased coordination and
                    concentration) and abnormal EEG patterns (O'Donoghue
                    1985). As to the respiratory system studies are not
                    conclusive. Forced expiration volume in one second
                    (FEV1) was significantly decreased in 20% of a group
                    of workers exposed to styrene (Stewart et al, 1968). 
                    "Styrene sickness" in industry describes a clinical
                    picture after heavy exposure to styrene and other
                    solvents (O'Donoghue, 1985).

             9.2.3  Skin exposure

                    Skin contact may produce persisting itching and
                    erythematous papular dermatitis (Browning, 1965;
                    Heiselman & Cannon, 1990)

             9.2.4  Eye contact

                    Chronic exposure was not related to significant
                    eye disease.  (Grant, 1986). Toxic retrobulbar
                    neuritis was suspected after chronic exposure to
                    styrene (Pratt Johnson, 1964)

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

                    No data available.

        9.3  Course, prognosis, cause of death

             Acute exposure to high concentrations may produce signs
             of upper respiratory irritation, followed by asphyxia,
             muscular weakness, coma and death from respiratory paralysis
             (ILO,1983). Effects of short term styrene inhalation on
             volunteers are according the vapor concentrations: around 350
             to 375 ppm for 0.5 to one hour reduction of manual dexterity
             and coordination and impairment of reaction time. Increasing
             concentrations (>800 ppm) cause central nervous system
             depression. The reversibility of these effects has not been
             studied but since reports of clinically evident impairment
             are rare, reversibility is likely (O'Donoghue, 1985).

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Acute: Cardiac arrhytmias. styrene being an
                    aromatic hydrocarbon may increase the risk of
                    sensitivity of the heart to exogenic
                    catecholamines.

             9.4.2  Respiratory

                    Acute and chronic: Upper respiratory
                    irritation. Burning sensation in the chest, wheezing,
                    dyspnea. Forced expiratory volume in one second (FEV1)
                    was changed in a group of workers.  Chemical
                    pneumonitis may follow ingestion.

             9.4.3  Neurological

                    9.4.3.1  Central Nervous System (CNS)

                             Headache, general weakness. 
                             Increased tiredness, lightheadedness,
                             dizziness, loss of coordination and balance,
                             vertigo and ataxia. Extreme exposures may
                             cause unconsciousness. Minor EEG
                             abnormalities in chronic exposure. Slight
                             effects on psychomotor performance. 
                             Persistent and premature dementia was
                             suspected to be caused in some workers, after
                             long-term exposures.

                    9.4.3.2  Peripheral nervous system

                             Peripheral neuropathy was seen only
                             in chronic exposure (Behari et al, 1986)
                             characterized by hypoesthesias and decreased
                             peroneal nerve conduction velocity.

                    9.4.3.3  Autonomic nervous system

                             No data available.

                    9.4.3.4  Skeletal and smooth muscle

                             Skeletal muscles may exhibit
                             weakness and tremors.

             9.4.4  Gastrointestinal

                    Loss of appetite, nausea, vomiting.

             9.4.5  Hepatic

                    Chronic: possible alterations in liver enzymes
                    and liver function tests.

             9.4.6  Urinary

                    9.4.6.1  Renal

                             No data available.

                    9.4.6.2  Others

                             No data available.

             9.4.7  Endocrine and reproductive systems

                    Congenital defects and increase in spontaneous
                    abortions have been described but the relationship to
                    styrene was not proven.

             9.4.8  Dermatological

                    Mild to moderate irritation. Repeated or
                    prolonged contact may cause dermatitis (itching,
                    drying, redness).

             9.4.9  Eye, ears, nose, throat: local effects

                    Eye irritation and conjunctivitis.
    
                    Irritation of nose and throat mean that increased
                    incidence of laryngeal carcinoma was suspected but not
                    proven.

             9.4.10 Hematological

                    No data available.

             9.4.11 Immunological

                    No data available.

             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

                             Alterations in glucose metabolism
                             have been noted (Guillemin and Bauer,
                             1979).

             9.4.13 Allergic reactions

                    No data available.

             9.4.14 Other clinical effects

             9.4.15 Special risks

                    Expectant mothers and women with ovular or
                    menstrual disorders shoud not work in conditions
                    exposing them to styrene.

        9.5  Others

             No data available.

    10. MANAGEMENT

        10.1 General principles

             Rapid, effective decontamination is essential in the
             management of styrene exposure. The evaluation of vital
             functions and life-supporting measures are the main
             principles in poisoning management. Maintain airway and
             respiration. Start artificial respiration at the first sign
             of respiratory failure. Administer oxygen if necessary. The
             removal from the work place of individuals with elevated
             values of styrene metabolites, found on repeated
             measurements, should be considered.

        10.2 Life supportive procedures and symptomatic treatment

             Make a proper assessment of airway, breathing,
             circulation and neurological status of the patient. Maintain
             a clear airway. Administer oxygen if necessary. Start
             artificial respiration for respiratory failure. Open and
             maintain at least one intravenous route.

        10.3 Decontamination

             Eye exposure: irrigate with water or isotonic saline
             immediately and continuously for 15 minutes. If pain or
             irritation persistsconsult an ophtalmologist. Skin exposure: 

             Remove all contaminated clothing and shoes. Immediately flush
             skin thoroughly with plenty of water for at least 15 minutes. 
             Water and non-abrasive soap can help remove styrene. Even in
             the absence of symptoms the patient must be evaluated
             medically. Inhalation: Move victim to fresh air. Begin
             artificial respiration if required.
    
             Ingestion:  Do not induce vomiting.  Gastric lavage may be
             considered in massive and recent ingestion.The use of
             activated charcoal is discussed. Do not allow the victim to
             ingest any fat, oils, etc which probably may increase
             absorption.

        10.4 Elimination

             A good urinary output is mandatory. No data available
             on the value of forced diuresis or dialysis. The use of
             cathartics is questionable.

        10.5 Antidote treatment

             10.5.1 Adults

                    There are no antidotes available.

             10.5.2 Children

                    There are no antidotes available.

        10.6 Management discussion

             Acute exposure: styrene is an irritant to the
             respiratory system and will cause CNS depression. These are
             the most important points in the management of acute
             episodes. Current management involves the classical
             decontamination and symptomatic treatment, after careful
             clinical evaluation.
    
             Chronic exposure: monitoring the work environment and urinary
             metabolites are the mandatory features concerning chronic
             poisoning. Personal protection to eyes and skin as suitable
             respiratory protection should be used when vapour
             concentration is unknown or exceeds exposure limits.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Moscato et al (1987) report two cases of occupational
             asthma due to styrene. Contact with styrene resulted in
             coughing, breathlessness and symptoms of asthma in the two
             subjects. The respiratory reaction in subject 1 was followed

             by a late cutaneous rash. When the subjects were not at work
             then the symptoms disappeared. In both subjects inhalation
             challenge with styrene resulted in an immediate
             bronchospastic reaction which was followed by the late
             cutaneous rash in subject 1. Prior administration of disodium
             cromoglycate (40 mg from a spinhaler) prevented the
             respiratory reactions completely, but failed to prevent the
             late skin response in subject 1. The complete disappearance
             of the symptoms followed the removal of the subjects from the
             source of the styrene. It was concluded that styrene can be a
             primary cause of occupational asthma.

    12. ADDITIONAL INFORMATION

        12.1 Specific preventive measures

             Inhalation: wear suitable respiratory protection if
             vapour concentration is unknown or exceeds exposure
             limits.
    
             Skin: wear gloves, pants, overalls, jacket, boots, as needed.
             Have a safety shower/eyewash fountain readily available in
             the immediate work area.
    
             Eyes: wear chemical-splash goggles or a face shield. Store
             styrene in properly grounded containers, in a cool area with
             adequate ventilation, away from sources of heat or sparks. In
             case of spills absorb on clay or sand. Extinguish fires with
             carbon dioxide or dry chemical (ILO, 1983).

        12.2 Other

             No data available.

    13. REFERENCES

        ACGIH - American Conference of Governmental Industrial
        Hygienists (1992) TLVs Threshold Limit Values for Chemical
        Substances and Physical Agents and Biological Exposure Indices for
        1992-1993 Cincinatti, ACGIH.
    
        Baker EL, Smith TJ, Landrigan PJ (1985) The neurotoxicity of
        industrial solvents: a review of the literature Am J Ind Med
        8:207-217.
    
        Baselt RC, Cravey RH (1990) Disposition of toxic drugs and
        chemicals in man. 3d ed. Chicago, Year Book Medical Publishers
        p.762-764.
    
        Behari M, Choudhary C, Roy S & Maheshwari MC (1986)
        Styrene-induced peripheral neuropathy. A case report. Eur. Neur.
        25(6): 424-7
    

        Bond JA (1989)Review of the the toxicology of styrene. CRC
        Critical Reviews in Toxicology 19(3):227-246.
    
        Browning E (1965) Toxicity and metabolism of industrial solvents.
        New York, American Elsevier, p.101.
    
        Budavari S ed. (1989) The Merck Index: an encyclopedia of
        chemicals, drugs and biologicals. 11th ed. Rahway, New Jersey,
        Merck and Co.Inc.
    
        Costa AK, Trudell JR (1990) Toxicity of styrene vapor in
        hepatocyte monolayers at low oxygen tensions. Environ Health
        Perspect 84:209-213
    
        Ellenhorn MJ & Barceloux DG (1988) Medical Toxicology.  Diagnosis
        and Treatment of Human Poisoning. New York, Elsevier, p. 957.
    
        Engstrom J, Bjustrom R, Astrand I, Ovrum P (1978) Uptake,
        Distribution and Elimination of Styrene in Man.Scand J Work
        Environ Health 4(4):324-329
    
        Fielder RJ, Lowing R et al (1981) Styrene. Toxicity review 1.
        London, Her Majesty's Stationery Service.
    
        Gosselin RE, Smith RP, Hodge HC (1984) Clinical Toxicology of
        Commercial Products. 5th ed. Baltimore, Williams & Wilkins,
        p.II-152.
    
        Grant WM (1986) Toxicology of the eye. 3d. ed. Springfield,
        Charles Thomas Publisher, p. 854.
    
        Guillemin MP and Bauer D (1979) Human exposure to styrene. Int
        Arch Occup Environ Health. 44:249-63.
    
        Harkonen H (1978) Styrene, its experimental and clinical
        toxicology. Scand J Work Environ Health. 4:104-13.
    
        Harkonen H, Lindstrom K, Sappalainan AM (1978) Exposure response
        relationship between styrene exposure and central nervous system
        functions. Scand J Work Environ Health 4:53-59.
    
        Heiselman DE and Cannon, LA (1990) Benzene and the aromatic
        hydrocarbons. In: Haddad LM & Winchester JF eds. Clinical
        management of poisoning and drug overdose. Philadelphia, W.
        Saunders Co. p. 1226-1227.
    
        Holmberg PC (1977) Central nervous system defects in two children
        of mothers exposed to chemicals in the reinforced plastics
        industry. Scand J Work Environ & Health. 3(4):212-214.
    

        IARC (1979) Monographs on the evaluation of carcinogenic risks to
        humans. Supplement 7, Lyon,IARC, p. 345-347.
    
        IARC (1987) Monographs on the evaluation of carcinogenic risks to
        humans. Supplement 6. Lyon, IARC. p.15-18; 498-501.
    
        ILO - International Labour Office (1983) Encyclopedia of
        Occupational Health and Safety. 3 ed Geneva, p.2115.
    
        IPCS (1983) Styrene. Environnemental Health Criteria Document no
        26. Geneva. World Health Organisation.
    
        Malorni W, Formisano G,Iosi F (1988) In vitro effects of styrene
        on cytoskeletal apparatus:an immunocytochemical study. Drug Chem
        Toxicol 11(4):419-431
    
        Moscato G, Biscaldi G, Cottica D, Pugliese F, Candura S and
        Candura F (1987) Occupational asthma due to styrene: two case
        reports. J Occup Med 29(12):957-960.
    
        O'Donoghue JL ed (1985) Aromatic Hydrocarbons. In: Neurotoxicity
        of industrial and commercial chemicals. Boca Raton, Florida. CRC,
        Press, Inc. vol II, p.127-137.
    
        Pratt-Johnson JA (1964) Case report. Retrobulbar neuritis
        following exposure to vinyl benzene (styrene). Can Med J
        90:975.
    
        Proctor Nh, Hughes JP, Fischman ML (1988) Chemical hazards of the
        workplace. 2d ed. Philadelphia, J.B.Lippincott Co., p.448-449.
    
        Ramsey JC and Anderson ME (1984) A physiologically based
        description of the inhalation pharmacokinetics of styrene in rats
        and humans. Toxicol Appl Pharmacol. 73:159-75
    
        Sax NI & Lewis RJ (1989) Dangerous properties of industrial
        materials, 7th ed. New York, Van Nostrand Reinhold, vol III,
        p.3127-3128.
    
        Stewart RD, Dodd HC, Baretta ED, Schaffer AW (1968) Human exposure
        to styrene vapor. Arch Environ Health 16:656-662.

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

        Author:    Alberto Furtado Rahde
                     Rua Riachuelo 677 ap 201
                     90010-270 Porto Alegre
                     BRAZIL
    
                     Tel: 55-51-2275419
                     Fax: 55-51-2246563/2299067/3391564
    

        Date:        November 1992
    
        Reviewer:    Dr J. Benitez
                     Toxicology Treatment Program
                     NE-583 Montefiore University Hospital
                     200 Lothrop Street
                     Pittsburgh, PA 15213-2582
                     USA
    
                     Tel: 1-412-6486800
                     Fax: 1-412-6922815
    
        Date:        February 1995
    
        Peer review: Cardiff, United Kingdom
    
        Date:       March 1995
    
        Finalised:  IPCS, September 1996
    








    See Also:
       Toxicological Abbreviations
       Styrene (EHC 26, 1983)
       Styrene (ICSC)
       Styrene (WHO Food Additives Series 19)
       STYRENE (JECFA Evaluation)
       Styrene (IARC Summary & Evaluation, Volume 60, 1994)
       Styrene (IARC Summary & Evaluation, Volume 82, 2002)