Styrene
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 number100-42-5 1.4.2 Other numbers79637-11-9 (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: 145.2°C Melting point: -30.6°C Flash point: 31°C (87 F) Autoignition temperature: 490°C Relative density: 0.9059 at 25°C Vapour pressure: 10 mm at 35°C Saturation vapour concentration: 6600 ppm at 20°C 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 200°C 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 disturbancesNo data available. 9.4.12.2 Fluid and electrolyte disturbancesNo data available. 9.4.12.3 OthersAlterations 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