styrene oxide

H312: Harmful in contact with skin [Warning Acute toxicity, dermal]

H319: Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H350: May cause cancer [Danger Carcinogenicity]

P203, P264+P265, P280, P302+P352, P305+P351+P338, P317, P318, P321, P337+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

This chemical does not meet GHS hazard criteria for 4.3% (16 of 374) of reports.

H311 (15%): Toxic in contact with skin [Danger Acute toxicity, dermal]

H312 (80.7%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H315 (57.2%): Causes skin irritation [Warning Skin corrosion/irritation]

H317 (57%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H319 (95.7%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H331 (57%): Toxic if inhaled [Danger Acute toxicity, inhalation]

H340 (42.2%): May cause genetic defects [Danger Germ cell mutagenicity]

H341 (25.1%): Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H350 (95.7%): May cause cancer [Danger Carcinogenicity]

P203, P261, P262, P264, P264+P265, P270, P271, P272, P280, P302+P352, P304+P340, P305+P351+P338, P316, P317, P318, P321, P332+P317, P333+P317, P337+P317, P361+P364, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 374 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 16 of 374 reports by companies.

There are 10 notifications provided by 358 of 374 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

H227: Combustible liquid [Warning Flammable liquids]

H302: Harmful if swallowed [Warning Acute toxicity, oral]

H311: Toxic in contact with skin [Danger Acute toxicity, dermal]

H315: Causes skin irritation [Warning Skin corrosion/irritation]

H317: May cause an allergic skin reaction [Warning Sensitization, Skin]

H332: Harmful if inhaled [Warning Acute toxicity, inhalation]

H336: May cause drowsiness or dizziness [Warning Specific target organ toxicity, single exposure; Narcotic effects]

H341: Suspected of causing genetic defects [Warning Germ cell mutagenicity]

H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H370: Causes damage to organs [Danger Specific target organ toxicity, single exposure]

H401: Toxic to aquatic life [Hazardous to the aquatic environment, acute hazard]

H412: Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]

P203, P210, P260, P261, P262, P264, P264+P265, P270, P271, P272, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P308+P316, P316, P317, P318, P319, P321, P330, P332+P317, P333+P317, P337+P317, P361+P364, P362+P364, P370+P378, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

P210, P280, P370+P378, P403, and P501 (click each P-code to see the statement)

P273, and P501 (click each P-code to see the statement)

H373: May causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]

P203, P210, P260, P261, P262, P264, P264+P265, P270, P271, P272, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P316, P318, P319, P321, P330, P332+P317, P333+P317, P337+P317, P361+P364, P362+P364, P370+P378, P403, P403+P233, P405, and P501 (click each P-code to see the statement)

P203, P261, P264+P265, P272, P280, P302+P352, P305+P351+P338, P317, P318, P321, P333+P317, P337+P317, P362+P364, P405, and P501 (click each P-code to see the statement)

Fresh air, rest.

Remove contaminated clothes. Rinse and then wash skin with water and soap.

First rinse with plenty of water for several minutes (remove contact lenses if easily possible), then refer for medical attention.

Rinse mouth. Refer for medical attention .

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.

SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. IMMEDIATELY call a hospital or poison control center even if no symptoms (such as redness or irritation) develop. IMMEDIATELY transport the victim to a hospital for treatment after washing the affected areas.

INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. IMMEDIATELY call a physician and be prepared to transport the victim to a hospital even if no symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing.

INGESTION: DO NOT INDUCE VOMITING. Corrosive chemicals will destroy the membranes of the mouth, throat, and esophagus and, in addition, have a high risk of being aspirated into the victim's lungs during vomiting which increases the medical problems. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. IMMEDIATELY transport the victim to a hospital. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. Transport the victim IMMEDIATELY to a hospital.

OTHER: Since this chemical is a known or suspected carcinogen you should contact a physician for advice regarding the possible long term health effects and potential recommendation for medical monitoring. Recommendations from the physician will depend upon the specific compound, its chemical, physical and toxicity properties, the exposure level, length of exposure, and the route of exposure. (NTP, 1992)

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)

Use powder, foam, carbon dioxide. In case of fire: keep drums, etc., cool by spraying with water. NO direct contact with water.

... /Styrene oxide/ is a corrosive chemical that reacts vigorously with water ... .

Excerpt from ERG Guide 153 [Substances - Toxic and/or Corrosive (Combustible)]:

IMMEDIATE PRECAUTIONARY MEASURE: Isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids.

SPILL: Increase the immediate precautionary measure distance, in the downwind direction, as necessary.

FIRE: If tank, rail tank car or highway tank is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2024)

Personal protection: chemical protection suit including self-contained breathing apparatus. Collect leaking liquid in covered containers. Absorb remaining liquid in sand or inert absorbent. Then store and dispose of according to local regulations.

PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Incineration: Liquids should be atomized into an incinerator and combustion may be improved by mixing with a more flammable solvent (acetone or benzene). Solids should be combined with paper or other flammable material. An alternate procedure is to dissolve the solid in a flammable solvent and spray the soln into the fire chamber.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for STYRENE-7,8-OXIDE (8 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking, eating, storage of food or of food & beverage containers or utensils, & the application of cosmetics should be prohibited in any laboratory. All personnel should remove gloves, if worn, after completion of procedures in which carcinogens have been used. They should ... wash ... hands, preferably using dispensers of liq detergent, & rinse ... thoroughly. Consideration should be given to appropriate methods for cleaning the skin, depending on nature of the contaminant. No standard procedure can be recommended, but the use of organic solvents should be avoided. Safety pipettes should be used for all pipetting. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": In animal laboratory, personnel should remove their outdoor clothes & wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... clothing should be changed daily but ... discarded immediately if obvious contamination occurs ... /also,/ workers should shower immediately. In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. If gowns are of distinctive color, this is a reminder that they should not be worn outside of lab. /Chemical Carcinogens/

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.

PRECAUTIONS FOR "CARCINOGENS": ... operations connected with synth & purification ... should be carried out under well-ventilated hood. Analytical procedures ... should be carried out with care & vapors evolved during ... procedures should be removed. ... Expert advice should be obtained before existing fume cupboards are used ... & when new fume cupboards are installed. It is desirable that there be means for decreasing the rate of air extraction, so that carcinogenic powders can be handled without ... powder being blown around the hood. Glove boxes should be kept under negative air pressure. Air changes should be adequate, so that concn of vapors of volatile carcinogens will not occur. /Chemical Carcinogens/

For more Preventive Measures (Complete) data for STYRENE-7,8-OXIDE (12 total), please visit the HSDB record page.

SMALL SPILLS AND LEAKAGE: If you spill this chemical, FIRST REMOVE ALL SOURCES OF IGNITION. Then, use absorbent paper to pick up all liquid spill material. Your contaminated clothing and absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Solvent wash all contaminated surfaces with 60-70% ethanol followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.

STORAGE PRECAUTIONS: You should store this chemical under refrigerated temperatures, and protect it from moisture. Keep it away from oxidizing materials, acids and bases. (NTP, 1992)

Separated from acids, bases and food and feedstuffs. Ventilation along the floor.

... PRECAUTIONS SHOULD BE TAKEN TO PREVENT EXCESSIVE PRESSURE UNDER STORAGE OR REACTION CONDITIONS & TO RELIEVE SUCH PRESSURE SHOULD IT OCCUR.

PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practicable to lab in which carcinogens are to be used, so that only small quantities required for ... expt need to be carried. Carcinogens should be kept in only one section of cupboard, an explosion-proof refrigerator or freezer (depending on chemicophysical properties ...) that bears appropriate label. An inventory ... should be kept, showing quantity of carcinogen & date it was acquired ... Facilities for dispensing ... should be contiguous to storage area. /Chemical Carcinogens/

0.33 [ppm]

3.6 [ppm]

21 [ppm]

1.0 [ppm]

1 ppm as TWA; (skin); (DSEN); A3 (confirmed animal carcinogen with unknown relevance to humans)

1 ppm (4.9 mg/m³) [2020]

No indication can be given about the rate at which a harmful concentration of this substance in the air is reached on evaporation at 20 °C.

The substance is irritating to the eyes and skin. The substance may cause effects on the central nervous system. Exposure could cause lowering of consciousness.

This substance is probably carcinogenic to humans.

MINIMUM PROTECTIVE CLOTHING: If Tyvek-type disposable protective clothing is not worn during handling of this chemical, wear disposable Tyvek-type sleeves taped to your gloves.

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with a combination filter cartridge, i.e. organic vapor/acid gas/HEPA (specific for organic vapors, HCl, acid gas, SO2 and a high efficiency particulate filter). Splash proof safety goggles should be worn while handling this chemical. Alternatively, a full face respirator, equipped as above, may be used to provide simultaneous eye and respiratory protection. (NTP, 1992)

Wear protective gloves & goggles.

PRECAUTIONS FOR "CARCINOGENS": ... dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/

NO open flames. NO contact with acids or bases. Above 76 °C use a closed system and ventilation.

AVOID ALL CONTACT!

Use local exhaust or breathing protection.

Protective clothing. Protective gloves.

Wear safety goggles or eye protection in combination with breathing protection.

Do not eat, drink, or smoke during work. Do not eat, drink, or smoke during work. Wash hands before eating.

Styrene oxide is a clear colorless straw-colored liquid with a sweet pleasant odor. (NTP, 1992)

Colorless to light yellow liquid; [Hawley] Pleasant, sweet odor; [HSDB] Faintly yellow-green clear liquid; [MSDSonline]

COLOURLESS-TO-PALE-YELLOW LIQUID.

Clear colorless straw-colored liquid with a sweet pleasant odor.

Colorless to pale straw-colored liquid

Sweet, pleasant

381 °F at 760 mmHg (NTP, 1992)

194.1 °C

194.2 °C @760 [mm Hg]

-35 °F (NTP, 1992)

-35.6 °C

-36.7 °C

175 °F (NTP, 1992)

165 °F (74 °C) (Open cup)

76 °C c.c.

less than 1 mg/mL at 67.1 °F (NTP, 1992)

Completely soluble in acetone, benzene, carbon tetrachloride, ethyl ether, heptane, methanol

0.3% wt in water

Solubility in water, g/100ml at 25 °C: 0.3 (poor)

1.0523 at 61 °F (NTP, 1992) - Denser than water; will sink

1.0490 g/ cu cm at 25 °C

Styrene oxide (98 mole % pure) is available in USA with following specifications: density, 1.0490-1.0515 (25/25 °C); distillation range at 760 mm: fraction between 5 and 95% by vol shall boil within 3.0 °C range, which includes temp 194.1 °C; water, 0.25% by wt.

Relative density (water = 1): 1.05

1.046 @25 °C

4.14 (NTP, 1992) - Heavier than air; will sink (Relative to Air)

4.30 (Air = 1)

Relative vapor density (air = 1): 4.30

0.3 mmHg at 68 °F (NTP, 1992)

0.3 [mmHg]

0.3 mm Hg at 20 °C

Vapor pressure, Pa at 20 °C: 40

0.3 mmHg

0.3 [mm Hg] @20 °C

log Kow = 1.61

929 °F (498 °C)

1.99 cP at 20 °C

STYRENE OXIDE WILL POLYMERIZE EXOTHERMALLY. ...

Odor detection in air, 0.063 ppm (purity not specified)

Odor recognition in air, 0.400 ppm (purity not specified)

Odor low 0.3093 mg/cu m; Odor high 1.9640 mg/cu m

Insoluble in water.

Hydrocarbons, Aromatic

Epoxides

Polymerizable Compounds

Polymerizable

STYRENE OXIDE is incompatible with oxidizing agents. Also incompatible with acids and bases. Reacts with 4-(4'-nitrobenzyl)pyridine. Polymerizes exothermally and reacts vigorously with compounds possessing a labile hydrogen (e.g. alcohols and amines) in the presence of catalysts such as acids, bases and certain salts (NTP, 1992).

REACTS VIGOROUSLY WITH CMPD HAVING LABILE HYDROGEN, INCL WATER, IN PRESENCE OF CATALYSTS SUCH AS ACIDS, BASES, & CERTAIN SALTS

Evaluation: There is inadequate evidence in humans for the carcinogenicity of styrene-7,8-oxide. There is sufficient evidence in experimental animals for the carcinogenicity of styrene-7,8-oxide. Overall evaluation: Styrene-7,8-oxide is probably carcinogenic to humans (Group 2A).

Styrene-7,8-oxide: reasonably anticipated to be a human carcinogen.

Styrene-7,8-oxide

Group 2A: Probably carcinogenic to humans

Volume Sup 7: Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42, 1987; 440 pages; ISBN 92-832-1411-0 (out of print)

Volume 60: (1994) Some Industrial Chemicals

Volume 121: (2019) Styrene, Styrene-7,8-oxide, and Quinoline

NB Overall evaluation upgraded to Group 2A with supporting evidence from other relevant data

The substance can be absorbed into the body by inhalation, through the skin and by ingestion.

Dizziness. Drowsiness. Unconsciousness. Vomiting.

Redness. Pain.

Abdominal pain. Further see Inhalation.

Neurotoxin - Other CNS neurotoxin

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

Lacrimator (Lachrymator) - A substance that irritates the eyes and induces the flow of tears.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

IARC Carcinogen - Class 2: International Agency for Research on Cancer classifies chemicals as probable (2a), or possible (2b) human carcinogens.

NTP Carcinogen - Reasonably anticipated to be a human carcinogen.

ACGIH Carcinogen - Confirmed Animal.

LCLo (rat) = 500 ppm/4h

LD50 Rat oral 3000 mg/kg

LD50 Rat percutaneous 930 mg/kg

LD50 Rat intraperitoneal 460-610 mg/kg

LD50 Rabbit percutaneous 930 mg/kg

LD50 Chicken (embryo) 1.5 umol/egg /Styrene oxide (purum grade) dissolved in ethanol/

Doses of 0.8 umol/egg styrene oxide (purity, 97%) dissolved in vegetable oil were injected into the air space of White-Leghorn "mittari" & SK 12 chicken eggs on day 3 of incubation. In addnl groups, 0.1 umol trichloropropylene oxide, an inhibitor of epoxide hydrolyase, was injected simultaneously with styrene oxide as a check on the effects of metabolism on embryotoxicity. Embryos were examined on day 14 of incubation. Styrene oxide treatment alone resulted in embryolethality & malformations; addition of trichloropropylene oxide to the styrene oxide treatment augmented these effects.

Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand-valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR as necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Aromatic hydrocarbons and related compounds/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool. Administer activated charcoal ... . /Aromatic hydrocarbons and related compounds/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Consider drug therapy for pulmonary edema ... . Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias if necessary ... Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... .Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Aromatic hydrocarbons and related compounds/

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/

/SIGNS AND SYMPTOMS/ Tests with laboratory animals and human subjects indicate that styrene oxide is capable of causing moderate skin irritation and skin sensitization. These effects may result from single or repeated contact with undiluted material and with solutions as dilute as 1%. Experience indicates that persons who have become hypersensitive may react rather severely to contact with the vapor as well as with the liquid material. There is some evidence that styrene oxide is absorbed slowly through the skin. This absorption could be significant only from exposures that produced extensive and serious injury to the skin.

/GENOTOXICITY/ A cross-sectional study was carried out on 48 workers exposed to styrene and 14 unexposed healthy controls in order to investigate the genotoxic potential of styrene exposure. DNA damage was assessed in peripheral blood leukocytes (WBCs) by the comet assay. Polymorphisms in glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) and the gene encoding microsomal epoxide hydrolase (EPHX) were characterized to assess their possible modifying role in styrene metabolism and subsequent DNA damage. Exposed workers showed significantly higher levels of DNA damage compared to controls. Among workers, the GSTM1 and GSTT1 polymorphisms significantly affected comet parameters. Subjects bearing a GSTM1pos genotype showed a significantly higher proportion of damaged nuclei compared to people lacking GSTM1-1 expression (GSTM1null), whereas GSTT1pos workers showed significantly lower DNA damage than GSTT1null individuals. Styrene-7,8-oxide (SO)-induced DNA damage was assessed in vitro in WBCs isolated from the healthy controls. A clear dose-response relationship at micromolar doses of SO was found for the whole group. WBCs collected from subjects bearing the homozygous wildtype GSTP1 genotype showed a significant protection compared to cells from subjects bearing at least one GSTP1 variant allele. The field survey confirms that styrene exposure is associated with increased DNA damage and indicates a modulating role for GSTM1 and GSTT1 genotypes. In vitro experiments suggest that the extent of SO-induced DNA strand breaks depends, at least in part, on interindividual differences in GSH-conjugation capabilities.

/GENOTOXICITY/ ... Occupational exposure to styrene in lamination workers /was examined by a/ battery of parameters /that/ included markers of external and internal exposure and biomarkers of biological effects and susceptibility. DNA repair capacities have been determined in both exposed and control groups. Styrene workplace concentration significantly correlated with styrene concentration in blood, exhaled air and urinary mandelic acid. Hemoglobin and O(6)-styrene oxide (SO)-guanine DNA adducts were significantly higher in exposed subjects as compared to controls and correlated with exposure parameters. In styrene-exposed workers 1-SO-adenine DNA adducts were detected (2.6 per 10+9 dNp), while in controls these adducts were below the detection limit. 1-SO-adenine adduct levels were affected by both acute and cumulative exposure (P=0.001, F=86.0 and P=0.017, F=59.0, respectively) and associated with cytochrome P450 2E1 (CYP2E1) polymorphisms (R(2)=0.442). Mutant frequencies (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus appeared to accumulate with exposure over time and were associated with glutathione S-transferase P1 (GSTP1) polymorphism. DNA repair capacity increased with the exposure, except for the group exposed to the highest styrene concentration. In this particular group, increased DNA repair capacity to remove oxidative DNA damage was found.

/GENOTOXICITY/ ... In humans, styrene metabolism involves oxidation by cytochrome P450 monooxygenases (CYPs) to styrene-7,8-oxide, an epoxide thought to be responsible for the genotoxic effects of styrene exposure, and detoxification by means of epoxide hydrolase (mEH) and glutathione S-transferases (GSTs). The objective of this study was to investigate if genetic polymorphisms of metabolic enzymes modulate the level of urinary styrene metabolites and styrene oxide adducts with N-terminal valine of human globin (SO-Hb) in 75 workers occupationally exposed to styrene and 77 unexposed controls. The mean air concentration of styrene in the breathing zone of workers (30.4 ppm) was higher than the threshold limit value of 20 ppm recommended by the ACGIH and the biological exposure index adopted by the ACGIH for exposure to styrene prior to the next shift (MA+PGA = 400 mg/g creatinine) was exceeded, indicating that styrene exposure for this group of workers was higher than recommended. A highly significant correlation was observed between styrene concentration in the breathing zone and the MA+PGA in urine of workers (r = 0.85, P<0.001). The levels of SO-Hb adducts in exposed workers were significantly increased as compared with controls, although no difference was observed between subjects stratified as high and medium exposure categories based on MA+PGA excretion. Regarding the effect of the genetic polymorphisms /it was/ found that the level of SO-Hb adducts might be modulated by the predicted mEH enzymatic activity in the exposed workers. From /the data it was concluded/that SO-Hb adduct measurement is a complementary method to MA+PG measurement for assessing exposure to styrene at occupational and environmental levels, which reflects a more extensive exposure period.

For more Human Toxicity Excerpts (Complete) data for STYRENE-7,8-OXIDE (23 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ Inhaled styrene is known to be toxic to the nasal olfactory epithelium of both mice and rats, although mice are markedly more sensitive. In this study, the nasal tissues of mice exposed to 40 and 160 ppm styrene 6 hr/day for 3 days had a number of degenerative changes including atrophy of the olfactory mucosa and loss of normal cellular organization. Pretreatment of mice with 5-phenyl-1-pentyne, an inhibitor of both CYP2F2 and CYP2E1 completely prevented the development of a nasal lesion on exposure to styrene establishing that a metabolite of styrene, probably styrene oxide, is responsible for the observed nasal toxicity. Comparisons of the cytochrome P-450 mediated metabolism of styrene to its oxide, and subsequent metabolism of the oxide by epoxide hydrolases and glutathione S-transferases in nasal tissues in vitro, have provided an explanation for the increased sensitivity of the mouse to styrene. Whereas cytochrome P-450 metabolism of styrene is similar in rats and mice, the rat is able to metabolize styrene oxide at higher rates than the mouse thus rapidly detoxifying this electrophilic metabolite. Metabolism of styrene to its oxide could not be detected in human nasal tissues in vitro, but the same tissues did have epoxide hydrolase and glutathione S-transferase activities, and were able to metabolize styrene oxide efficiently.

/LABORATORY ANIMALS: Acute Exposure/ ... Pneumotoxicity caused by styrene or styrene oxide was measured by elevations in the release of gamma-glutamyltranspeptidase (GGT) and lactate dehydrogenase (LDH) into bronchoalveolar lavage fluid (BALF), while hepatotoxicity was measured by increases in serum sorbitol dehydrogenase (SDH) in non-Swiss Albino (Hsd:NSA) mice. Intraperitoneal administration of styrene at doses of 500-1000 mg/kg caused consistent dose-dependent increases in both sets of biomarkers with the hepatic effect appearing earlier than the pulmonary effect. Pyridine, phenobarbital, and beta-naphthoflavone, inducers of CYP2E1, CYP2B, and CYP1A, respectively, increased the toxicity of styrene. Pyridine and phenobarbital treatments increased mortality due to styrene. Styrene oxide exists in two enantiomeric forms: (R)- and (S)-styrene oxide, and the differential toxicities of the two enantiomers and racemic styrene oxide were compared. In all studies, (R)-styrene oxide caused greater toxicity than the (S) enantiomer, especially in the liver. Trichloropropene oxide, an epoxide hydrolase inhibitor, was used to inhibit styrene oxide detoxification and increased its hepatotoxicity, while buthionine sulfoxamine, a glutathione depletor, did not.

/LABORATORY ANIMALS: Acute Exposure/ Styrene causes both liver and lung damage in non-Swiss albino, CD-1, and other strains of mice. This is considered to be due to the bioactivation of styrene to styrene oxide by cytochromes P450, principally CYP2E1 and CYP2F2. If so, one would expect CYP2E1 knockout mice to be less susceptible to styrene-induced toxicity than wild-type mice. However, previous in vitro and in vivo studies demonstrated little difference in the metabolism of styrene to styrene oxide between wild-type and CYP2E1 knockout mice. These findings would suggest that there should be no difference in the toxic responses to styrene between these two strains. To determine which of these possibilities was correct, styrene (600 mg/kg) or styrene oxide (300 mg/kg) was administered ip 24 hr prior to measurement of serum sorbitol dehydrogenase as a biomarker of hepatotoxicity or lactate dehydrogenase activity, protein, and cells in bronchoalveolar lavage fluid as biomarkers for pneumotoxicity. Styrene was more hepatotoxic in the wild-type mice than in the knockout mice suggesting CYP2E1 activity is important. Strain differences were not observed with styrene oxide indicating no difference in intrinsic susceptibility. For lung, the response was similar in both strains to both styrene and styrene oxide supporting the idea that CYP2F2 is important in the bioactivation of styrene in this tissue and that there is no strain difference in susceptibility to the active metabolite.

/LABORATORY ANIMALS: Acute Exposure/ Styrene oxide causes corneal injury in rabbits, even with dilutions as low as 1%. Intradermal injection sensitized guinea pigs. One ip dose of 375 mg/kg bw ... caused significant decrease in activities of mixed-function oxidases and in glutathione content in vivo.

For more Non-Human Toxicity Excerpts (Complete) data for STYRENE-7,8-OXIDE (37 total), please visit the HSDB record page.

EC50; Species: Scenedesmus abundans (Green algae, 10+4 cells/mL); Conditions: freshwater, static, 22 °C; Concentration: 32000 ug/L for 96 hr; Effect: growth, general /97.0% purity/

LC50; Species: Daphnia magna (Water flea, age <24 hr neonate); Conditions: freshwater, renewal, 23.7 (23-24.5) °C, pH 8.34 (7.67-8.63), hardness 287.2 mgL CaCO3 (168-437 mg/L), alkalinity 174.2 mg/L CaCO3 (104-261 mg/L), dissolved oxygen 82.6% (75.9-95.3%); Concentration: 11600 ug/L for 48 hr (95% confidence interval: 10200-13100 ug/L) /97% purity/

LC50; Species: Pimephales promelas (Fathead minnow, age 30 days, length 17 mm, weight 0.082 g); Conditions: freshwater, flow through, 23.3 (22.5-24.8) °C, pH 6.9 (6.75-7.04), hardness 53.4 mgL CaCO3 (51.9-53.9 mg/L), alkalinity 40.5 mg/L CaCO3 (40-42 mg/L), dissolved oxygen 85.5% (72.9-92.3%); Concentration: 4540 ug/L for 96 hr /97% purity/

LC50; Species: Pimephales promelas (Fathead minnow, age 30 days, length 17 mm, weight 0.074 g); Conditions: freshwater, static, 22.3 (22-22.6) °C, pH 6.82 (6.53-7.12), hardness 53.2 mgL CaCO3 (49.9-57.9 mg/L), alkalinity 38 mg/L CaCO3 (31-42 mg/L), conductivity 120 (118-120) umhos/cm, dissolved oxygen 59.4% (25.6-73%); Concentration: 10700 ug/L for 96 hr /97% purity/

Styrene-7,8-oxide's production and use as an intermediate in the production of styrene glycol and its derivatives, use in the production of polystyrene glycols, and its use as a liquid diluent in the epoxy resin industry may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.3 mm Hg at 20 °C indicates styrene-7,8-oxide will exist solely as a vapor in the atmosphere. Vapor-phase styrene-7,8-oxide will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 3.2 days. Styrene-7,8-oxide does not contain chromophores that absorb at wavelengths >290 nm and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, styrene-7,8-oxide is expected to have very high mobility based upon an estimated Koc of 53. Volatilization from moist soil surfaces is expected based upon an estimated Henry's Law constant of 1.6X10-5 atm-cu m/mole. Hydrolytic half-lives of 0.17, 28 and 40.9 hours have been reported for styrene-7,8-oxide at pH 3, 7, and 9, respectively. Hydrolysis is likely to be a more important fate than volatilization from moist soils or transport through soil, particularly in acidic soils. Styrene-7,8-oxide is not expected to volatilize from dry soil surfaces based its vapor pressure. Styrene-7,8-oxide reached 80-82% of its theoretical BOD in 2 weeks using an activated sludge inoculum in the Japanese MITI test, suggesting that biodegradation is likely to be an important fate process for styrene-7,8-oxide; however, the test results might be for the hydrolysis product, styrene glycol. If released into water, styrene-7,8-oxide is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is expected based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 2.7 and 23 days, respectively. An estimated BCF of 3.5 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is likely to be a more important fate than volatilization from water surfaces and bioconcentration, particularly in acidic water. Occupational exposure to styrene-7,8-oxide may occur through inhalation and dermal contact with this compound at workplaces where styrene-7,8-oxide is produced or used. (SRC)

Styrene-7,8-oxide's production and use as an intermediate in the production of styrene glycol and its derivatives, use in the production of polystyrene glycols, and its use as a liquid diluent in the epoxy resin industry(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a water solubility of 3,000 mg/L(2) and a regression-derived equation(3), indicates that styrene-7,8-oxide is expected to have very high mobility in soil(SRC). Volatilization of styrene-7,8-oxide from moist soil surfaces is expected(SRC) given an estimated Henry's Law constant of 1.6X10-6 atm-cu m/mole(SRC), derived from its vapor pressure, 0.3 mm Hg(2), and water solubility, 3,000 mg/L(2). Styrene-7,8-oxide is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 0.3 mm Hg(2). Hydrolytic half-lives of 0.17, 28 and 40.9 hours have been reported for styrene-7,8-oxide at pH 3, 7, and 9, respectively(4). Hydrolysis is likely to be a more important fate than volatilization from moist soil or transport through soils, particularly in acidic soils(SRC). Styrene-7,8-oxide (100 mg/L) reached 80-82% of its theoretical BOD in 2 weeks using an activated sludge inoculum (30 mg/L) in the Japanese MITI test(5), suggesting that biodegradation is likely to be an important fate process for styrene-7,8-oxide; however, the test results might be for the hydrolysis product, styrene glycol(SRC).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 53(SRC), determined from a water solubility of 3,000 mg/L(2) and a regression-derived equation(3), indicates that styrene-7,8-oxide is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is expected for styrene-7,8-oxide(3) based upon an estimated Henry's Law constant of 1.6X10-5 atm-cu m/mole(SRC), derived from its vapor pressure, 0.3 mm Hg(2), and water solubility, 3,000 mg/L(2). Using this Henry's Law constant and an estimation method(3), volatilization half-lives for a model river and model lake are 64 hours and 23 days, respectively(SRC). According to a classification scheme(4), an estimated BCF of 3.5(SRC), from its log Kow of 1.61(5) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolytic half-lives of 0.17, 28 and 40.9 hours have been reported for styrene-7,8-oxide at pH 3, 7, and 9, respectively(7). Hydrolysis is likely to be a more important fate than volatilization from water or bioconcentration in aquatic organisms, particularly in acidic water(SRC). Styrene-7,8-oxide (100 mg/L) reached 80-82% of its theoretical BOD in 2 weeks using an activated sludge inoculum (30 mg/L) in the Japanese MITI test(8), suggesting that biodegradation is likely to be an important fate process for styrene-7,8-oxide; however, the test results might be for the hydrolysis product, styrene glycol(SRC).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), styrene-7,8-oxide, which has a vapor pressure of 0.3 mm Hg at 20 °C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase styrene-7,8-oxide is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 3.2 days(SRC), calculated from its rate constant of 5.1X10-12 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Styrene-7,8-oxide does not contain chromophores that absorb at wavelengths >290 nm(4) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

AEROBIC: Styrene-7,8-oxide, present at 100 mg/L, reached 80-82% of its theoretical BOD in 2 weeks using an activated sludge inoculum at 30 mg/L and the Japanese MITI test(1); however, the test results might be for the hydrolysis product, styrene glycol(SRC).

The rate constant for the vapor-phase reaction of styrene-7,8-oxide with photochemically-produced hydroxyl radicals has been estimated as 5.1X10-12 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 3.2 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Hydrolytic half-lives of 0.17, 28 and 40.9 hours have been reported for styrene-7,8-oxide at pH 3, 7, and 9, respectively(2). Styrene-7,8-oxide does not contain chromophores that absorb at wavelengths >290 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3.5 was calculated in fish for styrene-7,8-oxide(SRC), using a log Kow of 1.61(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). Hydrolytic half-lives of 0.17, 28 and 40.9 hours have been reported for styrene-7,8-oxide at pH 3, 7, and 9, respectively(4). Hydrolysis is likely to be a more important fate than bioconcentration in aquatic organisms, particularly in acidic waters(SRC).

The Koc of styrene-7,8-oxide is estimated as 53(SRC), using a water solubility of 3,000 mg/L(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that styrene-7,8-oxide is expected to have very high mobility in soil. Hydrolytic half-lives of 0.17, 28 and 40.9 hours have been reported for styrene-7,8-oxide at pH 3, 7, and 9, respectively(4). Hydrolysis is likely to be a more important fate than transport through soils, particularly in acidic soils(SRC).

The Henry's Law constant for styrene-7,8-oxide is estimated as 1.6X10-5 atm-cu m/mole(SRC) derived from its vapor pressure, 0.3 mm Hg(1), and water solubility, 3,000 mg/L (1). This Henry's Law constant indicates that styrene-7,8-oxide is expected to volatilize from water surfaces(2). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 64 hours(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(2) is estimated as 23 days(SRC). Styrene-7,8-oxide's estimated Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). Hydrolytic half-lives of 0.17, 28 and 40.9 hours have been reported for styrene-7,8-oxide at pH 3, 7, and 9, respectively(3). Hydrolysis is likely to be a more important fate than volatilization from water or moist soil surfaces, particularly in acidic water or soils(SRC). Styrene-7,8-oxide is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure of 0.3 mm Hg at 20 °C(1).

In a comprehensive survey of wastewater from 4000 industrial and publicly owned treatment works (POTWs) sponsored by the Effluent Guidelines Division of the US EPA, styrene-7,8-oxide was identified in one discharge of the rubber processing industry at a level of 46.2 ppb(1). Styrene-7,8-oxide was also identified in effluent from a latex manufacturing plant in Louisville, KY and chemical manufacturing plants in Louisville and Memphis, TN(2).

Styrene-7,8-oxide has been tentatively detected, but not quantified, in air samples in the Los Angeles Basin as well as other, unspecified areas of the USA(1).

SOURCE DOMINATED: Concentrations of styrene-7,8-oxide ranging from <0.2 to 190 ppb were reported in air from various polymerization facilities(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 458 workers are potentially exposed to styrene-7,8-oxide in the US(1). The NIOSH National Occupational Hazard Survey (1972-1974) reported that the principal industry in which workers may be exposed to styrene-7,8-oxide was fabricated rubber products(2). Some exposure may also occur in the paints and allied products industry(2). Results from Scandinavia show that occupational exposure to styrene-7,8-oxide can also occur in the reinforced plastics industry(2). Breathing-zone air concentration during lamination processes in a Finnish plant was 0.2 and 0.6 mg/cu m during hand and spray application, respectively(2). Air concentration during the manufacture of reinforced polyester plastics in Norway ranged from <0.02 to 0.6 mg/cu m(2). Occupational exposure to styrene-7,8-oxide may occur through inhalation and dermal contact with this compound at workplaces where styrene-7,8-oxide is produced or used(SRC).

Styrene oxide has been detected in the venous blood of 4 workers exposed to styrene of unspecified purity(1).

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Incineration: Liquids should be atomized into an incinerator and combustion may be improved by mixing with a more flammable solvent (acetone or benzene). Solids should be combined with paper or other flammable material. An alternate procedure is to dissolve the solid in a flammable solvent and spray the soln into the fire chamber.

PRECAUTIONS FOR "CARCINOGENS": There is no universal method of disposal that has been proved satisfactory for all carcinogenic compounds & specific methods of chem destruction ... published have not been tested on all kinds of carcinogen-containing waste. ... summary of avail methods & recommendations ... /given/ must be treated as guide only. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/

For more Disposal Methods (Complete) data for STYRENE-7,8-OXIDE (8 total), please visit the HSDB record page.

PRECAUTIONS FOR "CARCINOGENS": Procurement ... of unduly large amt ... should be avoided. To avoid spilling, carcinogens should be transported in securely sealed glass bottles or ampoules, which should themselves be placed inside strong screw-cap or snap-top container that will not open when dropped & will resist attack from the carcinogen. Both bottle & the outside container should be appropriately labelled. ... National post offices, railway companies, road haulage companies & airlines have regulations governing transport of hazardous materials. These authorities should be consulted before ... material is shipped. /Chemical Carcinogens/

PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in a securely sealed, watertight container (primary container), which should be enclosed in a second, unbreakable, leakproof container that will withstand chem attack from the carcinogen (secondary container). The space between primary & secondary container should be filled with absorbent material, which would withstand chem attack from the carcinogen & is sufficient to absorb the entire contents of the primary container in the event of breakage or leakage. Each secondary container should then be enclosed in a strong outer box. The space between the secondary container & the outer box should be filled with an appropriate quantity of shock-absorbent material. Sender should use fastest & most secure form of transport & notify recipient of its departure. If parcel is not received when expected, carrier should be informed so that immediate effort can be made to find it. Traffic schedules should be consulted to avoid ... arrival on weekend or holiday ... /Chemical Carcinogens/

Do not transport with food and feedstuffs.

Symbol: T; R: 45-21-36; S: 53-45; Note: E