Retour à la description de la base de données

    * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
    *               HAZARDOUS SUBSTANCES DATA BANK (HSDB)               *
    *                                                                   *
    * Produced by : U.S. National Library of Medicine                   *
    * Provided by : Canadian Centre for Occupational Health and Safety  *
    * * * * * * * * * * * * * * * * * * * * *  Issue : 99-2 (May, 1999) * 

                     *** SUBSTANCE IDENTIFICATION ***

HSDB CHEMICAL NAME           : BENZENE
HSDB NUMBER                  : 35
LAST REVISION DATE           : 19990211
CAS REGISTRY NUMBER          : 71-43-2
SYNONYMS:
    AI3-00808 ; (6)ANNULENE ; BENZEEN (DUTCH) ; BENZEN (POLISH) ; BENZOL ; Benzol 90 [REF-1, p.20]; BENZOLE ; BENZOLO (ITALIAN) ; BICARBURET OF HYDROGEN ; Caswell no 077 ; COAL NAPHTHA ; CYCLOHEXATRIENE ; EPA pesticide chemical code 008801 ; FENZEN (CZECH) ; NCI-C55276 ; PHENE ; PHENYL HYDRIDE ; Polystream [REF-2, p.V29 93]; PYROBENZOL ; PYROBENZOLE 
MOLECULAR FORMULA            : C6-H6 
RTECS NUMBER                 : NIOSH/CY1400000
SHIPPING NUMBER/NAME:
    UN 1114; Benzene
    IMO 3.2; Benzene
STCC NUMBER/NAME:
    49 081 10; Benzene

                 *** DESCRIPTION AND WARNING PROPERTIES ***

COLOR/FORM:
    CLEAR, COLORLESS LIQ [REF-3, p.151]
    RHOMBIC PRISMS [REF-4, p.C-105]
    Colorless to light-yellow liquid [Note: à solid below 42 degrees F]. [QR] [REF-5, p.26]
ODOR:
    AROMATIC ODOR [REF-6, p.49-20]
    Aromatic odor. [QR] [REF-5, p.26]
TASTE:
    Taste threshold in water is 0.5-4.5 mg/l. [REF-7]
ODOR THRESHOLD:
    BENZENE HAS DISTINCTIVE /SRP: AROMATIC/ ODOR ... HOWEVER /WARNING PROPERTIES/ ARE INADEQUATE SINCE 100 PPM HAS IRRITATION RATING OF 0 & ODOR INTENSITY BETWEEN 1 & 2. [REF-8, p.1225]
    4.68 PPM [REF-9]
    In air: 4.9 mg/cu m (characteristic odor), in water: 2.0 mg/l. [REF-10, p.19]
SKIN, EYE, AND RESPIRATORY IRRITATIONS:
    Benzene is irritant to skin [REF-11, p.3262]

                   *** SAFETY HAZARDS AND PROTECTION *** 

DOT EMERGENCY GUIDELINES: 
  . Fire or explosion: Highly flammable: Will be easily ignited by heat, sparks or flames. Vapors may form explosive mixtures with air. Vapors may travel to source of ignition and flash back. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Some may polymerize (P) explosively when heated or involved in à fire. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water. [QR] [REF-12, p.G-130]
  . Health: May cause toxic effects if inhaled or absorbed through skin. Inhalation or contact with material may irritate or burn skin and eyes. Fire will produce irritating, corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff from fire control or dilution water may cause pollution. [QR] [REF-12, p.G-130]
  . Public safety: Call Emergency Response Telephone Number on Shipping Paper first. If Shipping Paper not available or no answer, refer to appropriate telephone number listed on the inside back cover. Isolate spill or leak area immediately for at least 50 to 100 meters (160 to 330 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate closed spaces before entering. [QR] [REF-12, p.G-130]
  . Protective clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Structural firefighters' protective clothing will only provide limited protection. [QR] [REF-12, p.G-130]
  . Evacuation: Large spill: Consider initial downwind evacuation for at least 300 meters (1000 feet). Fire: If tank, rail car or tank truck is involved in à fire, isolate for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. [QR] [REF-12, p.G-130]
  . Fire: Caution: All these products have à very low flash point: Use of water spray when fighting fire may be inefficient. Small fires: Dry chemical, CO2, water spray or regular foam. Large fires: Water spray, fog or regular foam. Do not use straight streams. Move containers from fire area if you can do it without risk. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. Always stay away from the ends of tanks. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn. [QR] [REF-12, p.G-130]
  . Spill or leak: Eliminate all ignition sources (no smoking, flares, sparks or flames in immediate area). All equipment used when handling the product must be grounded. Do not touch or walk through spilled material. Stop leak if you can do it without risk. Prevent entry into waterways, sewers, basements or confined areas. à vapor suppressing foam may be used to reduce vapors. Absorb or cover with dry earth, sand or other non-combustible material and transfer to containers. Use clean non-sparking tools to collect absorbed material. Large spills: Dike far ahead of liquid spill for later disposal. Water spray may reduce vapor; but may not prevent ignition in closed spaces. [QR] [REF-12, p.G-130]
  . First aid: Move victim to fresh air. Call emergency medical care. Apply artificial respiration if victim is not breathing. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. Wash skin with soap and water. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved, and take precautions to protect themselves. [QR] [REF-12, p.G-130]

                         ** FIRE AND REACTIVITY ** 

FIRE POTENTIAL: 
  . WHEN EXPOSED TO HEAT OR FLAME; CAN REACT VIGOROUSLY WITH OXIDIZING MATERIALS. SPONTANEOUS HEATING: NO [REF-13, p.362]

NFPA HAZARD CLASSIFICATION: 
  . HEALTH: 2. 2= MATERIALS HAZARDOUS TO HEALTH, BUT AREAS MAY BE ENTERED FREELY WITH SELF-CONTAINED BREATHING APPARATUS. [REF-6, p.49-20]
  . FLAMMABILITY: 3. 3= LIQUIDS WHICH CAN BE IGNITED UNDER ALMOST ALL NORMAL TEMPERATURE CONDITIONS. WATER MAY BE INEFFECTIVE ON THESE LIQUIDS BECAUSE OF THEIR LOW FLASH POINTS. [REF-6, p.49-20]
  . REACTIVITY: 0. 0= MATERIALS WHICH ARE NORMALLY STABLE EVEN UNDER FIRE EXPOSURE CONDITIONS & WHICH ARE NOT REACTIVE WITH WATER. NORMAL FIRE FIGHTING PROCEDURES MAY BE USED. [REF-6, p.49-20]

FLAMMABLE LIMITS:
    LOWER 1.3%; UPPER 7.1% [REF-6, p.49-20]

FLASH POINT:
    -11 DEG C CLOSED CUP [REF-3, p.151]

AUTOIGNITION TEMPERATURE:
    1044 deg F [REF-6, p.49-20]

FIRE FIGHTING PROCEDURES: 
  . USE DRY CHEMICAL, FOAM, OR CARBON DIOXIDE. WATER MAY BE INEFFECTIVE ... BUT WATER SHOULD BE USED TO KEEP FIRE-EXPOSED CONTAINERS COOL. IF à LEAK OR SPILL HAS NOT IGNITED, USE WATER SPRAY TO DISPERSE THE VAPORS AND TO PROTECT MEN ATTEMPTING TO STOP à LEAK. WATER SPRAY MAY BE USED TO FLUSH SPILLS AWAY FROM EXPOSURES. [REF-6, p.49-20]

OTHER FIRE FIGHTING HAZARDS: 
  . VAPOR IS HEAVIER THAN AIR ... & MAY TRAVEL CONSIDERABLE DISTANCE TO SOURCE OF IGNITION & FLASH BACK. [REF-6, p.49-20]

EXPLOSIVE LIMITS AND POTENTIAL: 
  . LOWER 1.4%, UPPER 8.0% [REF-13, p.361]

REACTIVITIES AND INCOMPATIBILITIES: 
  . Reacts violently with iodine pentafluoride. [REF-14, p.96]
  . Hydrogenation of benzene to cyclohexane was effected in à fixed bed reactor at 210-230 deg C, but à fall in conversion was apparent. Increasing the bed temp by 10 deg C & the hydrogen flow led to à large increase in reaction rate which the interbed cooling coils could not handle, & an exotherm to 280 deg C developed, with à hot spot around 600 deg C which bulged the reactor wall. [REF-15, p.587]
  . Benzene ... ignites in contact with /iodine heptafluoride/ gas ... [REF-15, p.1080]
  . Dioxygenyl tetrafluoroborate is à very powerful oxidant, addition of à small particle to small samples of benzene ... at ambient temp ... /caused/ ignition. [REF-15, p.60]
  . ... à 2% solution /dioxygen difluoride/ in hydrogen fluoride ignites solid benzene at -78 deg C. [REF-15, p.1064]
  . Simultanous contact of sodium peroxide with ... benzene ... causes ignition, (equivalent to contact with concn hydrogen peroxide). [REF-15, p.1327]
  . Interaction /of uranium hexafluoride/ with benzene ... is very vigorous, with separation of carbon ... [REF-15, p.1079]
  . Benzene ignites in contact with powdered chromic anhydride. [REF-6, p.491M-65]
  . AN EXPLOSION OF BENZENE VAPORS & CHLORINE (INADVERTENTLY MIXED) WAS INITIATED BY LIGHT. [REF-6, p.491M-53]
  . Reacts explosively with bromine pentafluoride, chlorine, chlorine trifluoride, diborane, nitric acid, nitryl perchlorate, oxygen (liquid), ozone, silver perchlorate. [REF-14, p.96]
  . Interaction of the pentafluoride & methoxide /from arsenic pentafluoride & potassium methoxide/ proceeded smoothly in trichlorotrifluoroethane at 30-40 deg C, whereas in benzene as solvent repeated explosions occurred. [REF-15, p.50]
  . The effects of the presence of moisture or benzene vapor in air on the spontaneously explosive reaction /of diborane/ have been studied. [REF-15, p.69]
  . Silver perchlorate forms solid complexes with aniline, pyridine, toluene, benzene & many other aromatic hydrocarbons. à sample of the benzene complex exploded violently on crushing in à mortar. [REF-15, p.7]
  . Interaction /of nitryl perchlorate/ with benzene gave à slight explosion & flash. ... [REF-15, p.936]
  . The solution of permanganic acid (or its explosive anhydride, dimanganese heptoxide) produced by interaction of permanganates & sulfuric acid, will explode on contact with benzene ... . [REF-15, p.1099]
  . Large-scale addition of too-cold nitrating acid to benzene without agitation later caused an uncontrollably violent reaction to occur when stirring was started. The vapor-air mixture produced was ignited by interaction of benzene & nitric acid at 100-170 deg C & caused an extremely violent explosion. [REF-15, p.1118]
  . Peroxodisulfuric acid ... /is/ à very powerful oxidant; uncontrolled contact with ... benzene ... may cause explosion. [REF-15, p.1171]
  . Mixtures of /liquid oxygen &/ benzene are specifically described as explosive. [REF-15, p.1350]
  . During ozonization of rubber dissolved in benzene, an explosion occurred. This seems unlikely to have been ... /due/ to formation of benzene triozonide (which separates as à gelatinous precipitate after prolonged ozonization), since the solution remained clear. à rubber ozonide may have been involved, but the benzene-oxygen system itself has high potential for hazard. [REF-15, p.1360]
  . Mixtures /of peroxomonosulfuric acid/ with ... benzene ... explodes. [REF-15, p.1170]
  . Certain metal perchlorates recrystallized from benzene or ethyl alcohol can explode spontaneously. [REF-6, p.491M-152]
  . Strong oxidizers, many flourides & perchlorates, nitric acid. [QR] [REF-5, p.26]

                  ** PROTECTIVE EQUIPMENT AND CONTROLS ** 

PROTECTIVE EQUIPMENT AND CLOTHING:

  . Protective clothing consisting of coveralls or other full body clothing should be worn and changed at least twice weekly. [REF-16, p.12]
  . Where there is à possibility of benzene contact to eyes or skin, safety showers, eye-wash fountains, and cleansing facilities shall be installed and maintained. [REF-17, p.13]
  . WHERE HIGH VAPOR CONCN ARE UNAVOIDABLE, FORCED AIR MASKS SHOULD BE USED. LIFELINE ATTENDED BY ... PERSON OUTSIDE CONTAMINATED ENCLOSURE IS MANDATORY. IF SKIN CONTACT IS UNAVOIDABLE, NEOPRENE GLOVES MUST BE WORN. [REF-18, p.193]
  . HYDROCARBON VAPOR CANISTER, SUPPLIED AIR OR à HOSE MASK; HYDROCARBON INSOLUBLE RUBBER OR PLASTIC GLOVES; CHEMICAL GOGGLES OR FACE SPLASH SHIELD; HYDROCARBON-INSOLUBLE APRON SUCH AS NEOPRENE. [REF-9]
  . 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 à reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/ [REF-19, p.8]
  . Performance data: For butyl rubber, natural rubber, neoprene, neoprene, neoprene/natural rubber, nitrile rubber, polyethylene, chlorinated polyethylene, polyurethane, and polyvinyl chloride give breakthrough times less (usually significantly less) than one hour reported by (normally) two or more testers. Vendor Recommendations: C or D ratings from three or more (apparently independent) vendors. [REF-20, p.58]
  . Wear appropriate personal protective clothing to prevent skin contact. [QR] [REF-5, p.26]
  . Wear appropriate eye protection to prevent eye contact. [QR] [REF-5, p.26]
  . Eyewash fountains should be provided in areas where there is any possbility that workers could be exposed to the substance; this is irrespective of the recommendation involving the wearing of eye protection. [QR] [REF-5, p.26]
  . Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is à possibility of exposure. [Note: It is intended that these facilities should provide à sufficient quantity or flow of water to quickly remove the substance from any body areas likely to be exposed. The actual determination of what constitutes an adequate quick drench facility depends on the specific circumstances. In certain instances, à deluge shower should be readily available, whereas in others, the availability of water from à sink or hose could be considered adequate.] [QR] [REF-5, p.26]
  . Recommendations for respirator selection. Condition: At concentrations above the NIOSH REL, or where there is no REL, at any detectable concentration. Respirator Class(es): Any self-contained breathing apparatus that has à full facepiece and is operated in à pressure-demand or other positive pressure mode. Any supplied-air respirator that has à full face piece and is operated in pressure-demand or other positive pressure mode in combination with an auxiliary self-contained breathing apparatus operated in pressure-demand or other positive pressure mode. [QR] [REF-5, p.26]
  . Recommendations for respirator selection. Condition: Escape from suddenly occurring respiratory hazards: Respirator Class(es): Any air-purifying, full-facepiece respirator (gas mask) with à chin-style, front- or back-mounted organic vapor canister. Any appropriate escape-type, self-contained breathing apparatus. [QR] [REF-5, p.26]

OTHER PREVENTATIVE MEASURES:

  . Contact lenses should not be worn when working with this chemical. [REF-21, p.57]
  . SRP: The scientific literature for the use of contact lenses in industry is conflicting. The benefit or detrimental effects of wearing contact lenses depend not only upon the substance, but also on factors including the form of the substance, characteristics and duration of the exposure, the uses of other eye protection equipment, and the hygiene of the lenses. However, there may be individual substances whose irritating or corrosive properties are such that the wearing of contact lenses would be harmful to the eye. In those specific cases, contact lenses should not be worn. In any event, the usual eye protection equipment should be worn even when contact lenses are in place. 
  . [SRP] Local exhaust ventilation should be applied wherever there is an incidence of point source emmissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. 
  . VENTILATION CONTROL: WHEREVER POSSIBLE, PLANT SHOULD BE TOTALLY ENCLOSED ... ENCLOSURES SHOULD BE SUPPLEMENTED BY EXHAUST VENTILATION ... ATMOSPHERE ... SHOULD BE TESTED PERIODICALLY ... [REF-8, p.1221]
  . 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/ [REF-19, p.8]
  . 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 à reminder that they should not be worn outside of lab. /Chemical Carcinogens/ [REF-19, p.8]
  . 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/ [REF-19, p.8]
  . PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow biological safety cabinets may be used for containment of in vitro procedures ... provided that the exhaust air flow is sufficient to provide an inward air flow at the face opening of the cabinet, & contaminated air plenums that are under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety cabinets, where filtered air is blown across the working area towards the operator, should never be used ... Each cabinet or fume cupboard to be used ... should be tested before work is begun (eg, with fume bomb) & label fixed to it, giving date of test & avg air-flow measured. This test should be repeated periodically & after any structural changes. /Chemical Carcinogens/ [REF-19, p.9]
  . PRECAUTIONS FOR "CARCINOGENS": Principles that apply to chem or biochem lab also apply to microbiological & cell-culture labs. ... Special consideration should be given to route of admin. ... Safest method of administering volatile carcinogen is by injection of à soln. Admin by topical application, gavage, or intratracheal instillation should be performed under hood. If chem will be exhaled, animals should be kept under hood during this period. Inhalation exposure requires special equipment. ... Unless specifically required, routes of admin other than in the diet should be used. Mixing of carcinogen in diet should be carried out in sealed mixers under fume hood, from which the exhaust is fitted with an efficient particulate filter. Techniques for cleaning mixer & hood should be devised before expt begun. When mixing diets, special protective clothing &, possibly, respirators may be required. /Chemical Carcinogens/ [REF-19, p.9]
  . PRECAUTIONS FOR "CARCINOGENS": When ... admin in diet or applied to skin, animals should be kept in cages with solid bottoms & sides & fitted with à filter top. When volatile carcinogens are given, filter tops should not be used. Cages which have been used to house animals that received carcinogens should be decontaminated. Cage-cleaning facilities should be installed in area in which carcinogens are being used, to avoid moving of ... contaminated /cages/. It is difficult to ensure that cages are decontaminated, & monitoring methods are necessary. Situations may exist in which the use of disposable cages should be recommended, depending on type & amt of carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/ [REF-19, p.10]
  . PRECAUTIONS FOR "CARCINOGENS": To eliminate risk that ... contamination in lab could build up during conduct of expt, periodic checks should be carried out on lab atmospheres, surfaces, such as walls, floors & benches, & ... interior of fume hoods & airducts. As well as regular monitoring, check must be carried out after cleaning-up of spillage. Sensitive methods are required when testing lab atmospheres for chem such as nitrosamines. Methods ... should ... where possible, be simple & sensitive. ... /Chemical Carcinogens/ [REF-19, p.10]
  . PRECAUTIONS FOR "CARCINOGENS": Rooms in which obvious contamination has occurred, such as spillage, should be decontaminated by lab personnel engaged in expt. Design of expt should ... avoid contamination of permanent equipment. ... Procedures should ensure that maintenance workers are not exposed to carcinogens. ... Particular care should be taken to avoid contamination of drains or ventilation ducts. In cleaning labs, procedures should be used which do not produce aerosols or dispersal of dust, ie, wet mop or vacuum cleaner equipped with high-efficiency particulate filter on exhaust, which are avail commercially, should be used. Sweeping, brushing & use of dry dusters or mops should be prohibited. Grossly contaminated cleaning materials should not be re-used. ... If gowns or towels are contaminated, they should not be sent to laundry, but ... decontaminated or burnt, to avoid any hazard to laundry personnel. /Chemical Carcinogens/ [REF-19, p.10]
  . PRECAUTIONS FOR "CARCINOGENS": Doors leading into areas where carcinogens are used ... should be marked distinctively with appropriate labels. Access ... limited to persons involved in expt. ... à prominently displayed notice should give the name of the Scientific Investigator or other person who can advise in an emergency & who can inform others (such as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/ [REF-19, p.11]
  . [SRP] Contaminated protective clothing should be segregated in such à 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. 
  . The worker should immediately wash the skin when it becomes contaminated. [QR] [REF-5, p.26]
  . Work clothing that becomes wet should be immediately removed due to its flammability hazard. [QR] [REF-5, p.26]

                    ** STORAGE, CLEANUP AND DISPOSAL ** 

STORAGE CONDITIONS: 
  . KEEP IN WELL CLOSED CONTAINERS IN COOL PLACE & AWAY FROM FIRE. [REF-3, p.151]
  . 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/ [REF-19, p.13]

CLEANUP METHODS: 
  . For spills on water, contain with booms or barriers, use surface acting agents to thicken spilled materials. Remove trapped materials with suction hoses. [REF-22]
  . Small spills of benzene can be taken up by sorption on carbon or synthetic sorbent resins. Flush area with water. For large quantities, if response is rapid, benzene can be skimmed off the surface. Straw may be used to mop slicks. [REF-23, p.8-1]
  . PRECAUTIONS FOR "CARCINOGENS": à 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/ [REF-19, p.15]

DISPOSAL METHODS: 
  . SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. 
  . Biodegradation, incineration: Benzene is biodegradable. Diluted aqueous soln, therefore, are drained into sewage treatment plants and decomposed there by anaerobic bacteria. Solvent mixtures and sludges of higher concn are burnt in special waste incinerators if à recovery process is uneconomical. [REF-24, p.100]
  . This flammable liquid burns with à very smoky flame. Dilution with alcohol or acetone is suggested to minimize smoke. Recommendable methods: Use as boiler fuel, incineration. Not recommendable: Landfill, discharge to sewer. [REF-24, p.100]
  . Incinerate or dispose of via à licensed solvent recycling or disposal company. [REF-14, p.101]
  . 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/ [REF-19, p.14]
  . PRECAUTIONS FOR "CARCINOGENS": Total destruction ... by 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 à first-stage combustion with à less than stoichiometric air:fuel ratio is followed by à 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/ [REF-19, p.15]
  . PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency particulate arrestor) filters ... can be disposed of by incineration. For spent charcoal filters, the adsorbed material can be stripped off at high temp & carcinogenic wastes generated by this treatment conducted to & burned in an incinerator. ... LIQUID WASTE: ... Disposal should be carried out by incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses of lab animals, cage litter & misc solid wastes ... should be disposed of by incineration at temp high enough to ensure destruction of chem carcinogens or their metabolites. /Chemical Carcinogens/ [REF-19, p.15]
  . PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As à general technique ... treatment with sodium dichromate in strong sulfuric acid can be used. The time necessary for destruction ... is seldom known ... but 1-2 days is generally considered sufficient when freshly prepd reagent is used. ... Carcinogens that are easily oxidizable can be destroyed with milder oxidative agents, such as sat soln of potassium permanganate in acetone, which appears to be à suitable agent for destruction of hydrazines or of compounds containing isolated carbon-carbon double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an oxidizing agent. /Chemical Carcinogens/ [REF-19, p.16]
  . PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are alkylating, arylating or acylating agents per se can be destroyed by reaction with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols & thiosulfate. The reactivity of various alkylating agents varies greatly ... & is also influenced by sol of agent in the reaction medium. To facilitate the complete reaction, it is suggested that the agents be dissolved in ethanol or similar solvents. ... No method should be applied ... until it has been thoroughly tested for its effectiveness & safety on material to be inactivated. For example, in case of destruction of alkylating agents, it is possible to detect residual compounds by reaction with 4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/ [REF-19, p.17]
  . Chemical Treatability of Benzene; Concentration Process: Biological Treatment; Chemical Classification: Aromatic; Scale of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater; Results of Study: 90-100% reduction; (treated by aerated lagoon). [REF-25, p.E-42]
  . Chemical Treatability of Benzene; Concentration Process: Biological Treatment; Chemical Classification: Aromatic; Scale of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater; Results of Study: 95-100% reduction; (completely mixed activated sludge process). [REF-25, p.E-42]
  . Chemical Treatability of Benzene; Concentration Process: Biological Treatment; Chemical Classification: Aromatic; Scale of Study: Respirometer Study; Type of Wastewater Used: Domestic Wastewater; Results of Study: 1.44-1.45 g of oxygen utilized/g of substrate added after 72 hr of oxidation. [REF-25, p.E-42]
  . Chemical Treatability of Benzene; Concentration Process: Biological Treatment; Chemical Classification: Aromatic; Scale of Study: Respirometer Study; Type of Wastewater Used: Domestic Wastewater; Results of Study: Oxygen uptake of 34 ppm oxygen/hr for 50 ppm chemical and 37 ppm oxygen/hr for 500 ppm chemical. [REF-25, p.E-42]
  . Chemical Treatability of Benzene; Concentration Process: Biological Treatment; Chemical Classification: Aromatic; Scale of Study: Full Scale; Type of Wastewater Used: Industrial Wastewater; Results of Study: 95-100% reduction; (Activated sludge process). [REF-25, p.E-42]
  . Chemical Treatability of Benzene; Concentration Process: Stripping; Chemical Classification: Aromatic; Scale of Study: Literature Review; Type of Wastewater Used: Unknown; Results of Study: Air and steam strippable. [REF-25, p.E-96]
  . Chemical Treatability of Benzene; Concentration Process: Stripping; Chemical Classification: Aromatic; Scale of Study: Continuous Flow, Pilot Scale; Type of Wastewater Used: Synthetic Wastewater; Results of Study: 95-99% reduction by steam stripping; (estimated cost of $3.35/1000 gal based on 0.03 MGD). [REF-25, p.E-96]
  . Chemical Treatability of Benzene; Concentration Process: Solvent Extraction; Chemical Classification: Aromatic; Scale of Study: Literature Review; Type of Wastewater Used: Unknown; Results of Study: Extractable with suitable solvent). [REF-25, p.E-111]
  . Chemical Treatability of Benzene; Concentration Process: Solvent Extraction; Chemical Classification: Aromatic; Scale of Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used: Industrial Wastewater; Results of Study: 290 ppm @ 3 gal/hr, 97% reduction; ( Extraction of wastewater from styrene manufacture using isobutylane (S/W= 0.107), RDC extractor used). [REF-25, p.E-111]
  . Chemical Treatability of Benzene; Concentration Process: Solvent Extraction; Chemical Classification: Aromatic; Scale of Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used: Industrial Wastewater; Results of Study: 71 ppm @ 4.6 gal/hr, 96% reduction; (exraction of ethylene quench wastewater using isobutylene (S/W= 0.101) RDC extractor used). [REF-25, p.E-111]
  . Chemical Treatability of Benzene; Concentration Process: Solvent Extraction; Chemical Classification: Aromatic; Scale of Study: Laboratory Scale, Continuous Flow; Type of Wastewater Used: Industrial Waste; Results of Study: 81 ppm @ 4.6 gal/hr, 97% reduction; (extraction of ethylene quench wastewater using isobutane (S/W= 0.097) RDC extractor used). [REF-25, p.E-111]
  . Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of Study: Pilot Scale, Continuous Flow; Type of Wastewater Used: Hazardous Material Spill Results of Study: 90% removal (to 0.1 ppb effluent conc) achieved in 8.5 min contact time; (Spilled material treated rising EPA's mobile treatment trailer). [REF-25, p.E-142]
  . Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results of Study: 0.7 mg/g carbon capacity. [REF-25, p.E-142]
  . Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results of Study: Isotherm kinetics were as follows: Carbon: K= 26.8, l/n= 1.305; Filtrasorb: K= 18.5 l/n= 1.158; carbon dose (mg/l) required to reduce 1 mg/l to 0.1 mg/l; Daro-678 Filtrasorb-705. [REF-25, p.E-142]
  . Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compound; Results of Study: 95% reduction, 21 ppm final concn, 0.080 g/g carbon capacity; (Carbon dose with 5 g/l Westvaco Nuchar). [REF-25, p.E-143]
  . Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of Study: Literature Review; Type of Wastewater Used: Industrial Wastewater; Results of Study: Effluent concn of 30 ppm TOC achieved; 98% removal; (at contact time of 55 min 0.15 MGD flow; pretreatment including pH adjustment). [REF-25, p.E-143]
  . Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of Study: Isotherm Test; Type of Wastewater Used: Pure Compund; Results of Study: Effluent Character (ppm): 500, 95% removal; 250, 91% removal; 50, 60% removal; (24 hr contact time, carbon dose was 10 times chemical concn). [REF-25, p.E-143]
  . Chemical Treatability of Benzene; Concentration Process: Activated Carbon; Chemical Classification: Aromatic; Scale of Study: Literature Review; Type of Wastewater Used: Unknown; Results of Study: 95% removal at 0.5% carbon dose. [REF-25, p.E-143]
  . à good candidate for liquid injection incineration at à temperature range of 650 to 1,600 deg C and à residence time of 0.1 to 2 seconds. à good candidate for rotary kiln incineration at à temperature range of 820 to 1,600 deg C and residence times of seconds for liquids and gases, and hours for solids. à good candidate for fluidized bed incineration at à temperature range of 450 to 980 deg C and residence times of seconds for liquids and gases, and longer for solids. [REF-26, p.3-11]
  . Full-scale activated carbon column treatment: Influent concn: 28,000 ug/l; Effluent concn: 1) < 10 ug/l with +99% removal, 2) 73 ug/l with 48-80% removal. [REF-27, p.336]

                  *** HEALTH HAZARDS AND TOXIC EFFECTS *** 

NON-HUMAN TOXICITY VALUES:
    LD50 MOUSE INTRAPERITONEAL 0.34 ML/KG 95% CONFIDENCE LIMITS 0.28 TO 0.42 [REF-28]

HUMAN TOXICITY EXCERPTS:
    
    Benzene is irritant to skin, & by defatting the keratin layer may cause erythema, vesiculation, & dry & scaly dermatitis. [REF-11, p.3262]
    
    AFTER ACUTE EXPOSURE TO à LARGE AMT OF BENZENE, BY INGESTION OR BY BREATHING CONCENTRATED VAPORS, THE MAJOR TOXIC EFFECT IS ON THE CNS. SYMPTOMS FROM MILD EXPOSURE INCL DIZZINESS, WEAKNESS, EUPHORIA, HEADACHE, NAUSEA, VOMITING, TIGHTNESS IN CHEST, & STAGGERING. IF EXPOSURE IS MORE SEVERE, SYMPTOMS PROGRESS TO BLURRED VISION, TREMORS, SHALLOW & RAPID RESP, VENTRICULAR IRREGULARITIES, PARALYSIS, & UNCONSCIOUSNESS. [REF-29, p.1638]
    
    Chronic exposure to benzene usually involves the inhalation of vapor. Signs and symptoms incl effects on CNS & the GI tract (headache, loss of appetite, drowsiness, nervousness, & pallor), but the major manifestation of toxicity is aplastic anemia. Bone marrow cells in early stages of development are most sensitive ... & arrest of maturation leads to gradual depletion of circulating cells. [REF-29, p.1638]
    
    BENZENE (BENZOL) ... HAS SPECIFIC TOXIC EFFECT ON BLOOD FORMATION, CAUSING APLASTIC ANEMIA & TENDENCY TO HEMORRHAGE. OCCASIONALLY HEMORRHAGES IN RETINA & IN CONJUNCTIVA ARE FOUND IN SYSTEMIC POISONING BY BENZENE. IN RARE INSTANCES NEURORETINAL EDEMA & PAPILLEDEMA HAVE BEEN DESCRIBED ACCOMPANYING RETINAL HEMORRHAGES. IT HAS NOT BEEN ESTABLISHED THAT BENZENE CAN INDUCE RETROBULBAR NEURITIS OR OPTIC NEURITIS ... [REF-30, p.140]
    
    PATHOLOGICAL FINDINGS FROM ... INHALATION INCL ACUTE GRANULAR TRACHEITIS, LARYNGITIS & BRONCHITIS, MASSIVE HEMORRHAGE OF LUNG, CONGESTIVE GASTRITIS, INFARCT OF SPLEEN, ACUTE CONGESTION OF KIDNEYS, & MARKED CEREBRAL EDEMA. [REF-31, p.906]
    
    Many acute deaths /from benzene exposure at high concn have been/ ... due to ventricular fibrillation ... /caused by exertion/ & release of epinephrine. This was probably the mechanism involved in the death of workers in tank cars which had contained benzene. Frequently, the man who went into the tank car to carry out an unconscious worker died during the effort of lifting the unconscious man up the ladder. [REF-32, p.124]
    
    ... à large number of workers exposed to but not seriously intoxicated by benzene /were studied & results showed/ that serum complement levels, IgG, & IgA, were depressed but that IgM levels did not drop & were in fact slightly higher (Lange et al 1973; Smolik et al 1973). ... These /& other/ observations, taken together with well-known ability of benzene to depress leukocytes ... may explain why benzene-intoxicated individuals readily succumb to infection & why terminal event in severe ... toxicity is often an acute, overwhelming infection. [REF-2, p.V29 116]
    
    IN EXPT IN VITRO, BENZENE DID NOT CHANGE THE NUMBER OF SISTER-CHROMATID EXCHANGES OR THE NUMBER OF CHROMOSOMAL ABERRATIONS IN HUMAN LYMPHOCYTES. [REF-33]
    
    THE MUTAGENIC ACTIVITY UPON HUMAN LYMPHOCYTES WAS STUDIED AFTER ITS ADDN TO CULTURE ON THE 28TH HR OF CULTIVATION (G1-S PERIODS). CONCN OF 1, 10, 25, 50, 100, & 250 UG/ML WERE STUDIED. BENZENE IS à WEAK MUTAGEN. IT CAUSED ELONGATION OF CENTROMERE PORTIONS OF CHROMOSOMES & CHROMOSOMAL ABERRATIONS WERE MAINLY OF SINGLE & PAIRED FRAGMENT TYPE. MUTAGENIC ACTIVITY WAS ABOUT THE SAME IN THE G0 & G1-S PERIODS. [REF-34]
    
    à major concern is the relationship between chronic exposure to benzene & leukemia. Epidemiological studies have been conducted on workers in the tire industry (McMichael et al, 1975), & in the shoe factories (Aksoy et al, 1974), where benzene is used extensively. Among workers who died from exposure to benzene, death was caused by either leukemia or aplastic anemia, in approx equal proportions. [REF-29, p.1638]
    
    CHRONIC BENZENE TOXICITY IS EXPRESSED AS BONE MARROW DEPRESSION RESULTING IN LEUCOPENIA, ANEMIA, OR THROMBOCYTOPENIA (LEUKEMOGENIC ACTION). WITH CONTINUED EXPOSURE THE DISEASE PROGRESSES TO PANCYTOPENIA RESULTING FROM BONE MARROW APLASIA. EVIDENCE HAS ACCUM IMPLICATING BENZENE IN THE ETIOLOGY OF LEUKEMIAS IN WORKERS IN INDUSTRIES WHERE BENZENE WAS HEAVILY USED. IT HAS BEEN SUGGESTED THAT LEUKEMIA IS AS FREQUENT à CAUSE OF DEATH FROM CHRONIC BENZENE EXPOSURE AS IS APLASTIC ANEMIA. [REF-35]
    
    MANY CASES OF ACUTE LEUKEMIA DEVELOPING AS TERMINAL STAGE OF APLASTIC ANEMIA RESULTING FROM EXPOSURE TO BENZENE MAY HAVE BEEN MISSED BECAUSE BONE MARROW PUNCTURE WAS NOT PERFORMED. BENZENE LEUKEMIA IS ACUTE STEM CELL OR MYELOBLASTIC LEUKEMIA, SOMETIMES ALEUKEMIA. THERE MAY BE à LATENT PERIOD EXTENDING OVER SEVERAL YEARS BETWEEN CESSATION OF EXPOSURE WITH MORE OR LESS PRONOUNCED ANEMIA, & THE ONSET OF LEUKEMIA. [REF-36]
    
    à dose-related increase in the number of cells with chromosomal aberrations occurred in human lymphocyte cultures treated with 4X10-5 M and 3.0X10-3 M benzene for 53 hr prior to metaphase analysis. Cells in late G2 stage were the most susceptible to the effect of benzene. [REF-37]
    
    Epidemiological studies (exposure to high concn is associated with hematotoxicity and acute myelocytic leukemia in humans ...) [REF-38, p.44]
    
    Italian shoemakers exposed to 200-500 ppm benzene in inks and glues showed an incidence of leukemia of 1 per 1,000. [REF-39]
    
    Follow up study at Massachusetts rubber coating plants of 38 workers exposed over 1-24 yr at 5-50 ppm (140 ppm peak) showed no evidence of blood dyscrasias or leukemia. [REF-40]
    
    à significantly incr frequency of chromatid and isochromatid breaks in the cultured lymphocytes of workers in chemical laboratories and in the printing industry has been reported. [REF-41, p.C-46]
    
    à significant incr of peripheral blood lymphocyte chromosomal aberrations in workers exposed to benzene was reported, but not in those exposed to toluene and xylene. [REF-42, p.C-46]
    
    à report on 52 workers exposed to benzene found chromosomal aberrations (chromosome breaks, dicentric chromosomes, translocations, and exchange figures) in peripheral lymphocytes at 2-3 times the rates found in controls. The 8 hr TWA exposure was 2-3 ppm, the average concn determined by 15 min sampling was 25 ppm, and the peak concn was 50 ppm. [REF-43, p.C-47]
    
    An epidemiological study implicating benzene as à leukemogen (acute myelocytic leukemia) followed 748 white males exposed to benzene in the manufacture of à rubber product from 1940-1949. à statistically significant (p < or = 0.002) excess of leukemia was found when compared against two control populations. There was à 5 fold excessive risk of all leukemias and à 10 fold excessive risk of myelocytic and monocytic leukemias combined. [REF-44, p.C-58]
    
    à hematological investigation was carried out on 147 workers (employed for +10 years) exposed to high benzene levels (320-470 ppm). Abnormalities were noted in at least one parameter in 73%, the most common one being thrombocytopenia, which occurred in 62% followed by anemia (35%) and leucopenia (32%). Pancytopenia occurred in 21% of the workers. During the 3 months following removal from exposure, hematological parameters returned to normal in 120 workers, and one subject died. After one year, 20 of the remaining workers had only minor abnormalities, six were still off work, and one was still hospitalized. [REF-45]
    
    à retrospective mortality study of à cohort of 594 men exposed to benzene at levels ranging between 2 and 25 ppm (TWA) was carried out at the Dow Chemical Co between 1940-1973. No incr in total mortality was noted with 102 observed/128 expected (Standard Mortality Ratio (SMR) 80). à slight increase was noted in total deaths due to malignancies (30 observed/22.8 expected, SMR 132) and suicide (5 observed/3.2 expected, SMR 147) as well as deaths from leukemia (3 observed/0.8 expected) and cancers of the digestive organs and peritoneum (9 observed/6.9 expected, SMR 125). If 53 workers exposed to other chemicals are excluded from malignancies, the results would then be 24 observed/20.3 expected, SMR 108. [REF-46]
    
    /A subset of 292 men of the 594 in the benzene exposure of Dow cohort who were still employed in 1967/ had an examination of the health status /evaluation/ carried out between 1967-1974 and compared to à control population selected from employees not exposed to benzene, using à matched pair design (matched for age, cigarette smoking habits and length of employment). No clinically significant differences were reported although slight decr in total bilirubin levels and red blood cell counts were noted. [REF-47]
    
    Thirty two patients who had recovered from à blood disease (bone marrow impairment) caused by benzene poisoning had significantly increased rates of "unstable" and "stable" chromosomes. Aberrations of chromosomes were present for several years after cessation of the exposure and after recovery from poisoning. Persistence of an increase of the "stable" changes was particularly remarkable. [REF-48, p.214]
    
    NUMEROUS STUDIES HAVE BEEN CARRIED OUT ON THE CHROMOSOMES OF BONE-MARROW CELLS & PERIPHERAL LYMPHOCYTES FROM PEOPLE KNOWN TO HAVE BEEN EXPOSED TO BENZENE (DEAN 1978). ... IN MANY OF THESE STUDIES, SIGNIFICANT INCR IN CHROMOSOMAL ABERRATIONS HAVE BEEN SEEN, WHICH IN SOME CASES HAVE PERSISTED FOR YEARS AFTER CESSATION OF EXPOSURE. ... BONE-MARROW CELLS & PERIPHERAL LYMPHOCYTES /HAVE BEEN EXAM/ FROM WORKERS WITH CURRENT SEVERE BLOOD DYSCRASIAS, & ... /FOLLOW-UP STUDIES HAVE BEEN DONE ON/ SEVERAL WORKERS BY REPEATED CYTOGENETIC STUDIES UP TO 12 YR AFTER RECOVERY FROM BENZENE-INDUCED PANCYTOPENIA. GROSS CHROMOSOMAL ABNORMALITIES WERE CHARACTERISTIC OF THESE CELLS; 70% OF THE BONE-MARROW CELLS & LYMPHOCYTES IN PT WITH ACUTE POISONING SHOWED KARYOTYPIC ABNORMALITIES (POLLINI & COLOMBI 1964). THE AUTHORS COULD NOT RELATE THE FREQUENCY OR TYPE OF CHROMOSOMAL ALTERATIONS TO THE SEVERITY OF BLOOD DYSCRASIA (POLLINI ET AL 1964). FIVE YR AFTER POISONING, ALL ... 5 PATIENTS STUDIED STILL SHOWED STABLE (Cs) & UNSTABLE (Cu) CHROMOSOMAL ABERRATIONS IN ... LYMPHOCYTES, ALTHOUGH ONLY 40% OF CELLS WERE NOW ABNORMAL (POLLINI ET AL 1969). BY 12 YR ... NO CYTOGENETIC ABNORMALITIES REMAINED IN THE 4 PT STUDIED (POLLINI & BISCALDI 1977). [REF-2, p.V29 118]
    
    METABOLIC ACTIVATION OF BENZENE BY RAT LIVER MICROSOMES & à REDUCED NADP-GENERATING SYSTEM (S-9 MIX) INDUCED SISTER CHROMATID EXCHANGES (SCE) & CELL DIVISION DELAYS IN CULTURED HUMAN LYMPHOCYTES. THERE WERE OPTIMAL CONCN OF S
    9 MIX FOR THE CONVERSION OF BENZENE INTO THE ACTIVE METABOLITES THAT EXERTED THESE CYTOTOXIC EFFECTS. [REF-49]
    
    ... INCIDENCE OF ACUTE LEUKEMIA OR 'PRELEUKEMIA' AMONG 28,500 SHOE-WORKERS IN TURKEY /WAS ESTIMATED/ ON BASIS OF CASE ASCERTAINMENT BY CONTACT WITH MEDICAL CARE. THIRTY FOUR CASES WERE IDENTIFIED. ... INCIDENCE OF ACUTE LEUKEMIA WAS SIGNIFICANTLY GREATER AMONG WORKERS CHRONICALLY EXPOSED TO BENZENE, WHICH WAS USED AS à SOLVENT BY THESE WORKERS, THAN IN THE GENERAL POPULATION. OCCUPATIONAL EXPOSURES WERE DETERMINED BY WORK HISTORIES & BY ENVIRONMENTAL MEASUREMENTS. THERE WAS SAID TO BE EXPOSURE ONLY TO BENZENE IN SMALL, POORLY VENTILATED WORK AREAS; PEAK EXPOSURES ... WERE REPORTED TO BE 210-650 PPM (670-2075 MG/CU M). DURATION ... WAS EST TO HAVE BEEN 1 TO 15 YR (MEAN 9.7 YR). ANNUAL INCIDENCE WAS EST TO BE 13/100000, GIVING APPROX RELATIVE RISK OF 2 WHEN COMPARED WITH ANNUAL EST FOR GENERAL POPULATION, 6/100000 (AKSOY ET AL 1974; AKSOY 1977). (THESE EST ARE LIMITED BY STUDY DESIGN CHARACTERISTICS & BY UNCERTAINTY ABOUT THE WAY IN WHICH CASES WERE ASCERTAINED, & HOW MANY OF THE STUDY POPULATION WERE EXPOSED & HOW MANY UNEXPOSED). [REF-2, p.V29 121]
    
    OCCUPATIONAL EXPOSURES WERE IDENTIFIED IN ROTOGRAVURE PLANTS & SHOE FACTORIES. BENZENE CONCN NEAR ROTOGRAVURE MACHINES WERE 200-400 PPM (640-1280 MG/CU M), WITH PEAKS UP TO 1500 PPM (4800 MG/CU M); BENZENE CONCN IN AIR NEAR WORKERS HANDLING GLUE IN SHOE FACTORIES WERE 25-600 PPM (80-1920 MG/CU M), BUT WERE MOSTLY AROUND 200-500 PPM (640-1600 MG/CU M). EST LATENCY (YEARS FROM START OF EXPOSURE TO CLINICAL DIAGNOSIS OF LEUKEMIA) RANGED FROM 3-24 YR (MEDIAN, 9 YR). ... THE RELATIVE RISK OF ACUTE LEUKEMIA WAS /EST TO BE/ AT LEAST 20:1 FOR WORKERS HEAVILY EXPOSED TO BENZENE IN ROTOGRAVURE & SHOE INDUSTRIES IN THE PROVINCES STUDIED, WHEN COMPARED WITH GENERAL POPULATION (VIGLIANI 1976). (THE RELATIVE RISK IS BASED ON à NON-VALIDATED ESTIMATE). [REF-2, p.V29 122]
    
    à HISTORICAL COHORT MORTALITY STUDY WAS CONDUCTED OF 259 MALE EMPLOYEES OF à CHEM PLANT WHERE BENZENE HAS BEEN USED IN LARGE QUANTITIES. THE STUDY GROUP INCL ALL PERSONS WHO WERE EMPLOYED BY THE COMPANY ANY TIME BETWEEN JAN 1, 1947 & DEC 31, 1960. THE COHORT WAS FOLLOWED THROUGH DEC 31, 1977 AT WHICH TIME 58 KNOWN DEATHS WERE IDENTIFIED. THE ONLY UNUSUAL FINDING WAS FOUR DEATHS FROM LYMPHORETICULAR CANCERS WHEN 1.1 WOULD HAVE BEEN EXPECTED ON THE BASIS OF NATIONAL MORTALITY RATES. THREE OF THE DEATHS WERE DUE TO LEUKEMIA & 1 WAS CAUSED BY MULTIPLE MYELOMA. IN ADDN, 1 OF THE LEUKEMIA DEATHS HAD MULTIPLE MYELOMA LISTED ON THE DEATH CERTIFICATE. THE FINDINGS ARE CONSISTENT WITH PREVIOUS REPORTS OF LEUKEMIA FOLLOWING OCCUPATIONAL EXPOSURE TO BENZENE & RAISE THE POSSIBILITY THAT MULTIPLE MYELOMA COULD BE LINKED TO BENZENE, ALSO. [REF-50]
    
    HEMATOLOGIC & IMMUNOCHEMICAL INVESTIGATIONS CARRIED OUT IN 270 WORKERS WITH CHRONIC EXPOSURE TO BENZENE DEMONSTRATED CHANGES OF THE NUCLEOLOGRAM & OF THE AREA OF LYMPHOCYTE NUCLEOLI & DISORDERS OF THE HUMORAL IMMUNE RESPONSE REVEALED BY RADIAL IMMUNODIFFUSION. THE NUMERICAL RISE OF BI- & POLYNUCLEOLATED CELLS, OF CELLS WITH IRREGULAR MACRONUCLEOLI & AN ENLARGEMENT OF THE NUCLEOLAR AREA REFLECTED INCR ENDOLYMPHOCYTIC AMT OF RNA. AN INCR CAPACITY OF IG FORMATION, PARTICULARLY OF IGM, WAS ALSO OBSERVED. [REF-51]
    
    SOME ASPECTS OF QUANTITATIVE CANCER RISK ESTIMATION: ... RISK IS GREATEST AMONG THOSE WITH LONGEST EXPOSURE, RELATIVE RISKS OF APPROX 2, 14 & 32 BEING OBSERVED FOR EXPOSURES OF LESS THAN 5 YR (2 CASES), 5-9 YR (2 CASES) & 10+ YR (3 CASES), RESPECTIVELY. THE RELATIVE RISK ASSOC WITH AT LEAST 5 YR OF EXPOSURE IS THUS LIKELY TO BE LOWER BOUND FOR RISK ASSOC WITH LIFETIME EXPOSURE AT SIMILAR LEVELS. FOR THOSE WITH AT LEAST 5 YR EXPOSURE, 5 CASES WERE OBSERVED COMPARED WITH AN EXPECTED NUMBER OF 0.237, GIVING à RELATIVE RISK OF 21.1. SINCE THE EXPECTED CUMULATIVE MALE ADULT LIFETIME (FROM 20 YR TO END OF LIFE, TAKEN AS AGE 75) PROBABILITY OF DYING FROM LEUKEMIA IS APPROX 7 PER 1000 IN THE GENERAL POPULATION OF THE USA, AN EXPECTED RELATIVE RISK OF 21.1 WOULD GIVE AN EXTRA (21.1-1.0)X7= 141 CASES OF LEUKEMIA PER 1000 EXPOSED POPULATION. [REF-2, p.V29 395]
    
    The hematotoxicity of benzene is expressed primarily as à bone marrow effect leading eventually to complete destruction of myeloid and erythroid marrow components. This is manifested as à marked decrease in circulating formed elements, ie red blood cells, and platelets. The resultant aplastic anemia is à potentially fatal disorder which in its severe form has better than à fifty percent mortality rate. In both man and laboratory animals the extent of bone marrow damage appears proportional to the dose of benzene. Lesser degrees of bone marrow toxicity than aplastic anemia are more common in occupational exposure situations. Classically, the discovery of one individual with significant bone marrow toxicity has led to evaluation of the exposed work force and the finding of à wide variation in the extent of hematotoxicity. This has ranged from clinically significant pancytopenia, in which are decreases in white blood cells (leukopenia), red blood cells (anemia), and platelets (thrombocytopenia) to à situation in which only one of these is slightly below normal range. In the latter case it is of course difficult to distinguish à benzene effect from that due to the extremes of normal variation or to mild intercurrent disease. [REF-52, p.52]
    
    The type of leukemia most commonly associated with benzene is acute myelogenous leukemia and its variants, including erythroleukemia and acute myelomonocytic leukemia. Acute myelogenous leukemia is the adult form of acute leukemia and, until recent advances in chemotherapy, it was à rapidly fatal disease. The other major acute form of leukemia, acute lymphocytic leukemia, has been reported to be associated with benzene exposure but evidence of à causal association is weak. There is à somewhat stronger, although still inconclusive, association in the literature between benzene exposure and the two common forms of chronic leukemia: chronic myelogenous leukemia and chronic lymphocytic leukemia. Other hematological disorders possibly associated with benzene exposure include Hodgkin's disease, lymphocytic lymphoma, myelofibrosis and myeloid metaplasia, paroxysmal nocturnal hemoglobinuria, and multiple myeloma. [REF-52, p.52]
    
    An acute hemorrhagic pneumonitis is highly likely if ... aspirated into lung. [REF-53, p.III-398]
    
    Three cases of chronic leukemia were presented which had à history of chronic benzene exposure. These three patients were part of à larger group of 58 leukemia patients with benzene exposure histories. Case 1 presented at age 43 due to cardiac complaints. The patient owned à printing shop at which he mixed pigmented dyes with solutions of toluene or methyl alcohol ketone. The individual had à practice of sniffing the solutions as control measure. The toluene solution on analysis was shown to contain 2.8% benzene 95.3% toluene. Blood and bone marrow examination revealed chronic lymphatic leukemia. Case 2 was à 51 year old man with pain in the right quadrant. This individual had owned à small plastics facility between 1955 and 1965 where he was intermittently exposed to thinners containing 27.3% benzene. Subsequent exposure included cleaning solutions without benzene. He was also diagnosed with chronic lymphatic leukemia. The third case was à 50 year old manager of à plastic facility who was diabetic for 15 years and was hospitalized due to recurrent gluteal and inguinal furunculosis during the last 3 years. He had been heavily exposed to benzene between 1957 and 1965. He admitted having removed the dirt from his hands using thinners containing benzene. Hairy cell leukemia was diagnosed. The data suggests that differences in distribution of acute or chronic leukemias in chronic benzene exposure may be related to exposure levels, mode of exposure, or exposure to benzene homologs or other chemicals. [REF-54]
    
    à study conducted to measure the concentration of benzene in the air and solvents at 40 small and large workplaces in Turkey where workers had contracted leukemia and lymphoma. In addition, hematological examinations were performed on the 231 workers employed at the facilities. The facilities manufactured and repaired shoes, tires, leather works, automobiles, and farm equipment. The age of the workers ranged from 14 to 57 years and the mean duration of exposure was 8.8 years (range 1 month to 40 years). Case reports were presented for five workers with 2 to 15 years of exposure who had developed acute myeloblastic leukemia, acute lymphoblastic leukemia, acute myelomonocytic leukemia, Hodgkin's disease and poorly differentiated lymphoma. Benzene concentrations in the solutions and thinners used ranged from 3 to 7.5%. The concn of benzene in air samples from the plants ranged from 0 to 110 ppm while 76.4% of solvents contained more than 1% of benzene. Hematological examinations of the workers showed that 32% of them had abnormal values. There has been à decline in the use of benzene in Turkey since an earlier study in 1972, but that the percentages of benzene in most of the materials are still above permissible limits. [REF-55]
    
    Benzene is widely recognized as à leukemogen, and the Occupational Safety and Health Administration is currently attempting to limit exposure to it more strictly. The proposed new regulation is à limit of an eight hr time-weighted average of 1 ppm in place of the current limit of 10 ppm. The fundamental rationale for the change is à perception that the current standard is associated with an inordinate excess of leukemia. The epidemiologic literature on benzene and leukemia supports the inference that benzene causes acute myelocytic leukemia. However, the available data are too sparse, or /have/ other limitations, to substantiate the idea that this causal association applies at low levels (ie, 1-10 ppm) of benzene. Nonetheless, under the assumption that causation does apply at such low levels, à number of researchers have perfomed risk assessments using similar data but different methodologies. The assessments that is considered acceptable suggest that, among 1,000 men exposed to
    benzene at 10 ppm for à working lifetime of 30 years, there would occur about 50 excess deaths due to leukemia in addition to the baseline expectation of seven deaths. However, this estimate is speculative and whether or not enough confidence can be placed in it to justify à lower occupational benzene standard remain à decision for policy makers. [REF-56]
    
    Results of epidemiologic studies indicating an association between solvent exposure and the development of malignancies affecting hematopoietic and lymphatic tissues are reviewed. Clinical and cytogenetic data supporting this association are discussed. à variety of malignant disorders have been associated with solvent exposure, ie acute leukemia, Hodgkin's disease (odds ratio 2.8-6.6), non-Hodgkin's lymphoma (odds ratio 3.3) and myeloma, and there are some indications that solvent exposure may be à risk factor myelofibrosis. The carcinogenic effect of benzene is epidemiologically and experimentally well documented and there are some indications that other solvents may also be hazardous. Possible mechanisms bringing about malignant transformation are discussed. The need for further epidemiologic, cytogenetic and clinical studies on the association between solvent exposure and malignant diseases is emphasized. [REF-57]
    
    Currently the most applied technique for monitoring biological effects of exposure to genotoxic chemicals in industrial workers is the measurement of chromosome aberrations in peripheral blood lymphocytes. In the Shell petrochemical complex in the Netherlands cytogenetic monitoring studies have been carried out from 1976 till 1981 inclusive, in workers potentially exposed to à variety of genotoxic chemicals, ie vinyl chloride, ethylene oxide, benzene, epichlorohydrin, epoxy resins. Average exposure levels to these chemicals were well below the occupational exposure limits. Results of thesse studies indicate that no biologically significant increase in the frequencies of chromosome aberrations in the exposed populations occurred compared with control populations. ... Experience with this methodology has shown that the results of chromosome analyses are difficult to interpret, due to the variable and high background levels of chromosome aberrations in control populations and in individuals. It is concluded that the method is not sufficiently sensitive for routine monitoring of cytogenetic effect in workers exposed to the low levels of genotoxic compounds. [REF-58]
    
    The possibility of there being à link between the apparent predominance of men with specific on the job exposures to toxic materials among patients with hairy cell leukemia was explored. Of à total of 105 hairy cell leukemia patients, eight were in the medical profession (two X-ray technicians, one radiologist, two pneumologists, two orthopedists, and one internist), 21 were garage mechanics or divers of trucks or other heavy vehicles, eight worked in construction as painters, decorators or masons, three were in the printing industry as photogravure and equipment maintenance workers, ten were farmers, six were engineers and 49 held various technical or office positions. Interviews were conducted with 69 of the patients. All those in medicine had used radioscopy for periods exceeding 10 years. Exposure to petroleum derived substances was high not only among the garage mechanics and drivers, but among those 49 individuals whose occupations did not have particular exposure, but whose hobbies and paraprofessional activities involved use of benzene or other solvents. Of the 69 interviewed, 52 were able to document exposure to benzene or other solvents. [REF-59]
    
    The case of à 55 year old male with hairy cell leukemia associated with chronic exposure to benzene in an occupational setting was described. The subject had been employed as à coach paint sprayer for over 25 years at the time of diagnosis. When that patient was questioned, it was admitted that at the job site he did not usually take the normal protective measures to prevent exposure to the chemicals in the paints. The /investigators noted/ that spray painting is the one of the occupations which can involve exposure to benzene, due to the use of benzene containing solvents. The /researchers/ concluded that since three other cases of chronic leukemia have been previously associated with exposure to benzene, more retrospective demographic studies which take occupational exposures into account confirm the possible link between chronic benzene toxicity and leukemia, particularly the very rare hairy cell leukemia. [REF-60]
    
    The mutual metabolic suppression between benzene and toluene was studied. The subjects, 190 male Chinese workers employed in shoe manufacturing, printing, audio equipment manufacture, and automobile industries, were divided into four groups based on occupational exposure: 65 were exposed to benzene, 35 to toluene, 55 to both compounds, and 35 served as comparisons. The arithmetic mean exposure level of benzene was 31.9 and of toluene 44.7 ppm. The mixture contained benzene at 17.9 +/29.3 and toluene at 20.5 +/25.8 ppm. The exposure levels were measured using individual diffusive samplers. The geometric mean levels of the metabolites, phenol, catechol, hydroquinone, hippuric acid, and o-cresol, in unexposed workers were 6.9, 9.4, 4.8, 72.5, and 0.066 mg/l, respectively. Values corrected for creatinine and specific gravity were different from the values cited above. Multiple correlation coefficients for benzene exposure versus its three metabolites were for phenol, 0.740; for catechol, 0.629; and for hydroquinone, 0.762. Multiple correlation coefficients for toluene and its two metabolites were 0.649 for hippuric acid and 0.583 for o-cresol. The slopes of regression lines for the exposure to benzene in the presence of toluene were less than half of those obtained when the workers were exposed to benzene alone; however, the regression lines for benzene in mixture versus catechol were aout 80% of higher than the lines observed with benzene as the sole pollutant. The regression lines for toluene in the mixture and excretion level of hippuric acid adn hydroquinone showed reduced metabolic conversion compared to when exposure was limited to toluene alone. [REF-61]
    
    à retrospective cohort study was conducted in 233 benzene factories and 83 control factories in 12 cities in China. The benzene cohort and the control cohort consisted of 28,460 benzene exposed workers (178,556 person-years in 1972-81) and 28,257 control workers (199,201 person-years). Thirty cases of leukemia (25 dead and 5 alive) were detected in the former and four cases (all dead) in the latter. The leukemia mortality rate was 14/100,000 person-years in the benzene cohort and 2/100,000 person-years in the control cohort; the standardized mortality ratio was 5.74 (p less tha 0.01 by U test). The average latency of benzene leukemia was 11.4 years. Most (76.6%) cases of benzene leukemia were of the acute type. The mortality due to benzene leukemia was high in organic synthesis plants followed by painting and rubber synthesis industries. The concentration of benzene to which patients with à leukemia were exposed ranged from 10 to 1000 mg/cu m (mostly from 50 to 500 mg/cu m). Of the 25 cases of leukemia, seven had à history of chronic benzene poisoning before the leukemia developed. [REF-62]
    
    Cytogenetic and environmental factors in the etiology of acute leukemias in adults were discussed. Epidemiological aspects of leukemia were considered. The leukemias currently account for approximately 3% of the total cancer incidence and 4% of the cancer deaths in the USA. The average annual incidence is eight cases per 100,000 for females and 11 cases per 100,000 for males. Leukemia is more common in whites than nonwhites and more common in males. Acute nonlymphocytic accounts for about 30% of the total leukemia incidence and for over 85% of the acute leukemia seen in persons over 40 years of age. Recent mortality data show very little change in leukemia death rates except for acute nonlymphocytic leukemia which increased by 20% from 1969 to 1977. Genetic and environmental factors were considered. Chromosome disorders and à family history may be etiological factors in both acute nonlymphocytic luekemia and lymphocytic leukemia. Exposures to benzene, ionizing radiation, and antineoplastic agents are known to cause chromosomal aberrations and leukemia; however, no evidence of à causal sequence of events has been obtained. Environmental risk factors such as ionizing radiation, cigarette smoke, and chemicals were described. Benzene is considered the best known and most widely occurring human leukemogen. à number of case reports and cohort studies have linked benzene exposure and acute leukemias. Benzene associated relative risk for overall leukemia generally range from 1.5 to 2.0. Cytogenetic aspects of leukemia were considered. Some studies have shown that prior chemical exposures are associated with chromosome aberrations in acute nonlymphocytic leukemic patients. Suggestions for improving epidemiological studies of leukemia were discussed. [REF-63]
    
    à study of mortality in automobile mechanics and gasoline service station workers in New Hampshire was conducted. à proportionate mortality ratio analysis of all deaths occurring among male residents 20 years or older who lived in New Hampshire between 1975 and 1985 was performed. Occupation, industry, age, and date and cause of death were obtained from death certificates. à total of 37,426 deaths were recorded. Of these, 453 were automobile mechanics and 134 were persons who had been employed in the gasoline service station industry. Automobile mechanics had statistically significant proportionate mortality ratio elevations for suicide. Nonsignificant increases in proportionate mortality ratio for leukemia, cancers of the oral cavity, lung, bladder, rectum and lymphatic tissue, and nonmalignant blood dyscrasias and cirrhosis of the liver were observed. Workers in the gasoline service station industry had statistically significant increases in mortality from leukemia and mental and psychoneurotic and personality disorders, proportionate mortality ratio 328 and 394
     respectively; however, the number of deaths was small. Proportionate mortality ratio increases were also observed for emphysema and suicide. One or more of the exposures experienced by automobile mechanics and service station workers presents à carcinogenic risk. The finding of excess mortality from leukemia in both groups is consistent with exposure to benzene, à component of gasoline. ... Workers who pump gasoline should be informed of the potential cancer hazard. Gasoline should not be used as à solvent for removing grease and cleaning hands, and gasoline should not be siphoned by mouth. [REF-64]
    
    This paper presents à critical review more than 100 references on the possible leukemogenic (blastomogenic) effects of benzene, based upon clinical, epidemiological and experimental /studies/. /Evidence supports the conclusion that/ there exists reliable clinical and epidemiological /studies/, concerning increased leukemogenic risk on working place with high benzene concentrations in past years (tens and even hundreds of ppm). Most epidemiological studies, indicate now that this risk is also elevated in more favorable working conditions, although practical valuable dose-effect relationship between benzene concentrations and rate of leukemogenic risks is still unknown. Results of experimental investigations on problem of leukemogenic effects of benzene are contradictory. It was stated recently that there is à lack of adequate experimental models of benzene blastomogenesis. Taking into consideration increasing economic significance of benzene and existence of large contingents of workers dealing with benzene, it is necessary to continue appropriate experimental and epidemiological investigations. [REF-65]
    
    The possible association of thinner, à mixture of seven organic solvents used in the Mexican auto and paint industry, with the frequency of sister chromatid exchanges in the peripheral lymphocytes of 24 industrial workers was investigated. The subjects worked in à factory and three workshops in which no protective measures against inhalation of vapors were taken. à matched comparison group consisted of 24 administrative and outdoor workers. Use of cigarettes, alcohol, and medicines, and presence of viral infections within the 3 previous months were determined by questionnaire. Blood was cultured for 72 hr with phytohemagglutinin, with 5-bromodeoxyuridine added at 24 hr and colchicine at 70 hr. Sister chromatid exchanges were scored from 50 metaphases from each individual. Air samples to determine concentrations of thinner components in the working atmosphere were taken on the day of blood sampling and analyzed by gas chromatography. Solvent concentrations in the samples from the factory air were methyl isobutyl ketone 2.4 ppm, methanol 0.6 ppm, isopropanol 3.3 ppm, toluene 3.3 ppm, benzene 6.0 ppm, and hexane 3.3 ppm. The concentrations were below the limits recommended by NIOSH ... except for benzene which was six times to NIOSH limit. One way analysis of variance of the sister chromatid exchanges frequency for the exposed and comparison groups showed no differences for exposures of either 5 years or less of 6 to 35 years. However, à significant increase of sister chromatid exchanges was found for tobacco use in the exposed group but not for the comparison group. The implications of this result were discussed principally in relation to benzene. ... Working conditions should be improved by à ventilation system and that à benzene free thinner be substituted for the one being used. [REF-66]
    
    Dose response analyses for à cohort study of chemical workers exposed to benzene were reported. Exposure information included 8 hour time-weighted averages and peak exposures and was used to calculate the latency, duration of exposure, and peak exposure for several types of lymphatic and hematopoietic cancers. The cohort included 4,602 male chemical workers from seven companies who were occupationally exposed to benzene for at least 6 months between 1946 and 1975. à comparison group included 3,074 workers at the same plants who were employed for at least 6 months without exposure to benzene. Workers exposed to benzene 5 and 14 years showed an increased risk of lung cancer with à statistically significant enhancement of the standardized mortality ratio. Increased in reticulosarcoma and lymphosarcoma were related to the duration of continuous benzene exposure. Increased latency was related to à slight enhancement for all cancers among the exposed workers. Analysis by cumulative exposure demonstrated an increasing trend for death due to lymphatic and hematopoietic cancer, lymphosarcoma, reticulosarcoma, and leukemia. Workers with à cumulative exposure of 180 to 719 ppm month showed à significant increase in lung cancer. No dose response relation was detected for any other causes of death. [REF-67]
    
    à mortality study of 7,676 male chemical workers occupationally exposed to benzene was described. The subjects were employed at nine plants belonging to seven member companies of the Chemical Manufacturers Association. Workers were classified according to their benzene exposure into occupationally exposed or comparison groups. Occupationally exposed workers received at least 6 months of continuous or intermittent job exposure to benzene between 1946 and 1975. The comparison group comprised workers with at least 6 months of employment at the same plant with no benzene exposure. Approximately 40% of the cohort were not occupationally exposed to benzene, and about 46% of the cohort had received continuous exposure to benzene. The remaining 14% fell into the intermittent exposure group. The observed mortality of the cohort was compared with the expected based on the United States mortality rates appropriately standardized. Standardized mortality ratios were determined for lymphatic and hematopoietic cancer, leukemia, non Hodgkin's lymphoma, and non-Hodgkin's lymphopoietic cancer. The number of observed deaths in the continuous exposure group was slightly but not significantly greater than expected. Deaths from lymphatic and hematopoietic cancers and from leukemia were greater than expected in the continuous exposure group. The mortality of the intermittent exposure group was comparable to the expected mortality. The standardized mortality ratios of the total group were greater than the comparison group. Statistically significant associations were demonstrated between benzene exposure and both lymphopoietic cancer and leukemia. [REF-68]
    
    Comprehensive comparative studies were conducted on the three groups of 148 male and 167 female workers exposed to benzene toluene, or à combination of the two to evaluate subjective symptoms and hematologic effects of the compounds. Exposed workers were compared to 127 unexposed referents. The exposure intensity of the workers was estimated by diffusion dosimetry, and their subjective symptoms were obtained from questionnaires. The workers in the benzene group were engaged in shoe making and printing; the toluene group was engaged in shoe making and audio equipment production, and the mixed exposure group was employed in spray painting in automobile body shops. The mean age of the workers ranged from 26.7 to 39.0 years. The average 7 hr time weighted exposure to benzene was 33 and 59 ppm for men and women, respectively; the exposure concentrations of toluene were 46 and 41 ppm for men ad women, respectively. In the mixed exposure group, men were exposed to 14 ppm of benzene and 18 ppm of toluene; the female mixed exposure was 18 ppm of benzene and 21 ppm of toluene. Hematological examinations showed no significant differences between exposed and nonexposed workers, although leukocytes were marginally decreased. The prevalence of subjective symptoms was dose related and statistically significant for both men and women. The number of symptoms per person during work was at least ten fold higher in the exposed than in the nonexposed groups. The most frequent symptoms were dizziness, sore throat, and headache which occurred during work as well as during non work time. This study provides no indication of pancytopenia, ad that both liver and kidney functions are unchanged under exposure conditions. [REF-69]
    
    Of à total of 528,729 workers exposed to benzene or benzene mixtures in China, 508,818 (96.23%) were examined. Altogether 2,676 cases of benzene poisoning were found, à prevalence of 0.15%. à higher prevalence of benzene poisoning was found in the cities of Hangjou, Hefei, Nanjing, Shenyang, and Xian. The geometric mean concentration of benzene in 50,255 workplaces was 18.1 mg/cu m but 64.6% of the workplaces had less than 40 mg/cu m. There was à positive correlation between the prevalence of benzene poisoning and the concentration in shoemaking factories. The prevalence of benzene induced aplastic anemia in shoemakers was about 5.8 times that occurring in the general population. The results of this investigation show the need for à practicable hygiene standard to prevent benzene poisoning. [REF-70]
    
    ... CYTOGENETIC APPROACHES APPEAR TO BE NEAREST TO ROUTINE SURVEILLANCE IN DETECTING EARLY BIOLOGIC EFFECTS IN EXPOSED HUMANS. BENZENE SHOWED CONTRADICTORY RESULTS IN CHROMOSOME ABERRATION TESTS & WAS NEGATIVE FOR SISTER CHROMATID EXCHANGE. [REF-71]
    
    Investigations on the association between environmental hazards and the development of various /forms/ of leukemia are reviewed. Regarding acute non-lymphocytic leukemia exposure to ionizing radiation is à well documented risk factor. According to several recent studies exposure to strong electronmagnetic fields may be suspected to be of etiologic importance for acute non-lymphocytic leukemia. There is evidence that occupational handling of benzene is à risk factor and other organic solvents may be leukemogenic. Occupational exposure to petroleum products has been proposed to be à risk factor although the hazardous substances have not yet been defined. Results of cytogenic studies in acute non-lymphocytic leukemia suggest that exposure to certain environmental agents may be associated with relatively specific clonal chromosome aberrations. These results are of interest because it has been proposed
    that chromosomal rearrangements may play à role in the activation of cellular oncogens. Exposure in utero to ionizing radiation has been proposed to be à risk factor for acute lymphocytic leukemia in children. Unlike acute non-lymphocytic leukemia there seems at present to be little evidence that acute lymphocytic leukemia is related to exposure to some chemicals. Chronic myleoid leukemia may follow exposure to high doses of ionizing radiation whereas such exposure seems to be of insignificant importance in the development of chronic lymphocytic leukemia. According to some studies an abnormally high incidnece of chronic lymphocytic leukemia may be found among farmers in the USA. These results have not been confirmed in Scandinaavian studies. There seems to be little evidence that chronic myleoid leukemia or chronic lymphocytic leukemia are related to occupational handling of some chemicals. [REF-72]
    
    Personal air monitors and breath samples were used to measure benzene and other volatile compounds in the breath of 200 smokers and 322 nonsmokers in New Jersey and California during 12 hr sampling periods. The monitor measured only sidestream and exhaled mainstream smoke. Concentrations were also measured in à subsample of homes and outdoor air. Compared to nonsmokers, benzene was significantly higher in the breath of persons who had smoked tobacco the day they were monitored (p< 0.001); values for smokers were 12 to 16 ug/cu m, nearly 10 times the breath level of nonsmokers. Values for personal air samplers were not always significantly higher. Benzene in breath was related to number of cigarettes smoked. Based on direct measurements of mainstream smoke, it was calculated that the typical smoker inhales 2 mg/day compared to the nonsmokers' intake of <0.2 mg/day. Both smokers and nonsmokers exposed to passive smoking at home or work had increased levels of benzene compared to nonsmoking situations (p< 0.05). Indoor air levels in homes with smokers were significantly greater than in nonsmoking homes in fall and winter but not during spring and summer. [REF-73]

NON-HUMAN TOXICITY EXCERPTS:
    
    Inhalation of air saturated with benzene vapor resulted in ventricular extrasystole in the cat & primate, with periods of ventricular tachycardia that occasionally terminated in ventricular fibrillation. ... In rabbit, sudden death from ventricular fibrillation has also been observed. ... In acute inhalation by male rats, benzene-induced resp paralysis occurred, followed by ventricular fibrillation. [REF-11, p.3270]
    
    ... DOGS INHALING BENZENE ... DEVELOPED HYPERTENSION. THIS WAS SOON FOLLOWED BY PARALYSIS OF VASOMOTOR SYSTEM DUE TO EFFECT OF BENZENE ON SMOOTH MUSCLE OF BLOOD VESSELS. [REF-8, p.1221]
    
    Benzene in rabbit eye is à moderate irritant, causes conjunctival irritation, & ... transient slight corneal injury. [REF-11, p.3269]
    
    IN SERIES OF CHRONIC STUDIES, BILATERAL CATARACTS WERE FOUND IN 50% OF RATS EXPOSED /TO/ ... 50 PPM FOR 600 HR ... [REF-74, p.689]
    
    Rats, guinea-pigs, & rabbits exposed to 80-88 ppm (256-281 mg/cu m) for 7 hr/day for 30-40 wk had incr testicular wt & degeneration of seminiferous tubules. ... Alteration of estrous cycles has been reported in rats exposed to 1.6 or 9.4 ppm (5 or 30 mg/cu m) for 4 mo ... but there was no effect on their subsequent fertility or litter size. ... In C3H(JAX) mice whose ovaries were painted directly ... & which were later mated, à high incidence of sc hemorrhages & tail defects was observed in offspring, which persisted through 4 generations. [REF-2, p.V29 111]
    
    ... STUDIES HAVE DEMONSTRATED THE INDUCTION OF CHROMOSOMAL ABERRATIONS IN BONE-MARROW CELLS FROM MICE, RATS, AND RABBITS TREATED WITH SINGLE OR MULTIPLE DAILY DOSES OF BENZENE RANGING FROM ABOUT 0.2 TO 2.0 ML/KG PER DAY & GIVEN EITHER SC OR IP. MOST OF THE INDUCED ABERRATIONS WERE BREAKS OR DELETIONS; BUT CHROMOSOME-TYPE ABERRATIONS ALSO OCCURRED (KISSLING & SPECK 1971; LYON 1976), PARTICULARLY AFTER PROLONGED EXPOSURE, WHEN TOXICITY, MANIFESTED BY à DROP IN PERIPHERAL BLOOD LEUCOCYTE COUNT, APPEARED (KISSLING & SPECK 1971). ... à SIGNIFICANT ELEVATED LEVEL OF ABERRATIONS ARE SEEN UP TO 8 DAYS AFTER à SINGLE IP INJECTION OF 0.5 ML/KG BODY WT IN RATS (LYON 1976), WHEREAS ABERRATIONS WERE SIGNIFICANTLY INCR IN MICE 24 HR BUT NOT 7 DAYS AFTER RECEIVING à SIMILAR DOSE, 0.5 ML/KG BODY WT (MEYNE & LEGATOR 1978). [REF-2, p.V29 115]
    
    ... 30 MALE AKR, DBA2, C3H OR C57BL6 MICE WERE GIVEN WEEKLY SC INJECTIONS OF 0.001 ML BENZENE IN 0.1 ML OLIVE OIL FOR LIFE. NO TUMORS WERE FOUND IN MICE OF DBA2, C3H OR C57BL6 STRAINS, THE MAX LIFESPAN BEING 730 DAYS. BETWEEN 7TH & 16TH MO OF TREATMENT 16/30 TREATED AKR MICE DIED WITH LEUKEMIA, IN ADDITION, 8 DIED BEFORE AGE OF 9 MO WITHOUT LEUKEMIA. HOWEVER, LEUKEMIA WAS ALSO OBSERVED IN 30/35 AKR UNTREATED MICE WHICH LIVED, ON AVG, LONGER THAN TEST ANIMALS (AMIEL 1960). [REF-75, p.V7 209]
    
    ... AFTER 5 TO 8 WK OF 5 HR/DAY, 5 DAYS/WK EXPOSURE AT 44 & 47 PPM, RATS DEVELOPED à MODERATE DEGREE OF LEUKOPENIA, BUT ... NONE RESULTED FROM 15 TO 31 PPM. ... DECR IN THE WHITE CELL COUNTS OF RATS /WAS OBSERVED/ FOLLOWING 756 HR OF EXPOSURE AT 50 PPM OF BENZENE ON à SCHEDULE OF 8 HR/DAY, 5 DAY/WK. REDUCED AMT OF DNA IN THE WHITE CELLS, à DEPRESSION IN MYELOCYTIC ACTIVITY, & AN INCR IN THE RELATIVE NUMBER OF RED CELL PRECURSORS IN THE BONE MARROW WERE ALSO OBSERVED. [REF-76, p.50]
    
    SPRAGUE-DAWLEY RATS WERE EXPOSED TO 100, 300, & 2200 PPM OF BENZENE VAPOR IN AIR FOR 6 HR DAILY ON DAYS 6-15 OF GESTATION. THE MEAN BODY WT & CROWN-RUMP LENGTH WERE LOWER THAN CONTROL GROUPS ONLY AT THE HIGHEST EXPOSURE LEVEL. SKELETAL EXAM SHOWED AN INCR IN THE NUMBER OF FETUSES WITH DELAYED OSSIFICATION OF STERNEBRAE IN THE 300- & 2200-PPM GROUPS. THE FEMALE OFFSPRING APPEARED TO BE AFFECTED TO à GREATER EXTENT THAN MALE FETUSES WITH RESPECT TO THE INCIDENCE OF DELAYED OSSIFICATION OF STERNEBRAE. LIFETIME EXPOSURE OF C57BL/6J MICE TO 100 OR 300 PPM (320 OR 958 MG/CU M) BENZENE PRODUCES ANEMIA, LYMPHOCYTOPENIA & NEUTROPHILIA ASSOC WITH à RELATIVE INCR IN THE NUMBER OF IMMATURE LEUCOCYTES & DECR IN MATURE LEUCOCYTES IN CIRCULATION. SC ADMIN BENZENE LED TO à SELECTIVE DEPRESSION IN B-LYMPHOCYTES IN RABBITS, WHEREAS T LYMPHOCYTES WERE MORE RESISTANT. [REF-77]
    
    Male Charles River CD-1 mice (number unspecified) were exposed for 6 hr/day, 5 days/wk, for life to atmospheres containing ... levels of 0 (control), 100 ppm (320 mg/cu m) or 300 ppm (958 mg/cu m). Two mice in high-exposure group develop myelogenous (myeloid) leukemia (Snyder et al 1978). ... There was no evidence of leukemic response in 45 male 6 wk old Sprague-Dawley rats exposed to ... 900 mg/cu m (300 ppm) ... for 6 hr/day, 5 days/wk, for life. Exposure was terminated at wk 99 when the last test animal died. Controls were 27 males of same strain & age (Snyder et al 1978). ... Sprague-Dawley rats & AKR mice exposed to benzene (300 ppm, 958 mg/cu m) for 6 hr/day, 5 days/wk for life had lymphocytopenia, with little evidence of anemia. AKR mice were more sensitive to benzene-induced leucopenia than ... rats (Snyder et al 1978). /Mice also displayed agranulocytosis & reticulocytosis. No evidence of leukemia was reported/. [REF-2, p.V29 108]
    
    Single sc injection of 3 ml/kg body wt ... on 1 of days 11-15 of gestation to CFI mice caused cleft palate, agnathia & micrognathia in offspring (Watanabe & Yoshida 1970). (No controls were used, & it is very likely that these effects were produced by stress of the injection). Several other studies in pregnant mice exposed to benzene, (2 & 4 ml/kg body wt sc (Matsumoto et al 1975), 0.3 to 1.0 ml/kg body wt orally (Nawrot & Staples 1979) or 500 ppm (1597 mg/cu m) by inhalation for 7 hr/day (Murray et al 1979)) all failed to show any teratogenic effect, although reduced fetal wt & occasional embryolethality were observed. Similarly, several inhalation studies in rats have shown embryolethality & reduced fetal wt but only occasional teratogenic effects: Sprague-Dawley rats exposed to 10, 50, or 500 ppm (32, 160 & 1600 mg/cu m) for 7 hr/day had low incidence of brain & skeletal defects but no embryolethality at 50 or 500 ppm, & no abnormality or embryolethality at lower levels (Kuna & Kapp 1981). No teratogenic effect was seen in pregnant rats exposed to 10 or 40 ppm (32 or 128 mg/cu m) for 6 hr/day (Murray et al 1979), to 313 ppm (1000 mg/cu m) for 24 hr/day (Hudak & Ungvary 1978) or for 6 hr/day (Green et al 1978) or to 400 mg/cu m (125 ppm) for 24 hr/day (Tatrai et al 1980). No teratogenic effect has been reported in rabbits injected sc with 0.25 ml/kg of à 40% benzene soln daily during pregnancy (Desoille et al 1963) or in rabbits exposed by inhalation to 500 ppm (1600 mg/cu m) for 7 hr/day on days 6-18 of pregnancy (Murray et al 1979). [REF-2, p.V29 111]
    
    Rabbits and rats injected subcutaneously with 0.2 mg/kg/day showed an incr frequency of bone marrow mitoses. [REF-78]
    
    Bone marrow cells from mice orally dosed with 56-2050 mg/kg on two successive days showed dose-related incr in incidences of chromosomal gaps and single breaks, multiple breaks at or above 139 mg/kg, pulverization at or above 348 mg/kg, and cytotoxicity at 2050 mg/kg. [REF-79]
    
    Mice orally dosed with 0.22-1.65 g/kg showed à positive dose-related increase in polychromatic erythrocytes in the micronucleus test. [REF-80]
    
    Rats exposed continuously to 209.7 ppm for 10 days prior to breeding showed à complete absence of pregnancy. 1/10 rats exposed to 19.8 ppm had resorbed embryos. Females showed an inverse relationship between dose (0.3-209.7 ppm) and number of offspring. [REF-81]
    
    Chromosomal abnormalities in bone marrow cells have been reported as à consequence of experimental benzene exposure in à number of species including rats, rabbits, mice, and amphibians. [REF-82, p.C-44]
    
    Chromatid deletions in metaphase chromosomes of bone marrow cells have been found in rats given single doses of subcutaneous benzene at 2 ml/kg and in rats given 1 g/kg/day for 12 days. [REF-82, p.C-44]
    
    After rats were dosed with 0.5 ml/kg intraperitoneally, no dominant lethality was found; however, incr chromatid and chromosomal aberrations were reported. [REF-82, p.C-44]
    
    Benzene is à mitotic poison, producing à decr in DNA synthesis in animal bone marrow cells in vitro. [REF-82, p.C-45]
    
    Weanling male C57BL/6N mice were subcutaneously injected twice weekly for 44 weeks and once weekly for the last 10 weeks, gradually incr the dose from 450 mg/kg to 1.8 g/kg. The mice were killed 104 weeks after the first injection, and no evidence of carcinogenic activity was found in either the benzene-treated mice or the negative controls. Butylnitrosourea induced leukemia, lymphomas, and/or intestinal neoplasms/were observed/ in almost all the positive controls. [REF-83, p.C-48]
    
    Numerous studies on the effects of skin application of benzene to mice have yielded negative results. [REF-82, p.C-49]
    
    TWO GROUPS OF 40 MALE C57BL/6J MICE, 6 WK OLD, WERE EXPOSED TO ATMOSPHERES CONTAINING 0 OR 900 MG/CU M (300 PPM) BENZENE FOR 6 HR/DAY, 5 DAYS/WK, FOR LIFE. THE EXPOSURE ENDED AFTER 488 DAYS WITH THE DEATH OF THE LAST TEST MOUSE. IN ADDN TO ANEMIA, LYMPHOCYTOPENIA, NEUTROPHILIA & BONE-MARROW HYPERPLASIA, 6 OF 40 MICE EXPOSED ... DEVELOPED LYMPHOCYTIC LYMPHOMA WITH THYMIC INVOLVEMENT (P< 0.01 FOR LYMPHOMAS, ACCORDING TO PETO'S LOG-RANK METHOD), 1 PLASMACYTOMA & 1 HEMATOCYTOBLASTIC LEUKEMIA. AVG SURVIVAL TIME OF THE 8 TUMOR-BEARING MICE WAS 262 DAYS. TWO OF THE 40 CONTROL ANIMALS DIED FROM LYMPHOCYTIC LYMPHOMA WITH NO THYMIC INVOLVEMENT AFTER 282 & 608 DAYS, RESPECTIVELY. DIFFERENCES IN INCIDENCE & INDUCTION TIME OF TUMORS BETWEEN THE GROUPS WERE STATISTICALLY SIGNIFICANT (SNYDER ET AL 1980). (THE WORKING GROUP NOTED THAT THYMUS WAS NOT EXAM ROUTINELY). [REF-2, p.V29 108]
    
    THREE GROUPS OF 30 OR 35 MALE & ... FEMALE SPRAGUE-DAWLEY RATS, 13 WK OLD, RECEIVED 50 OR 250 MG/KG BODY WT BENZENE (PURITY UNSPECIFIED) DISSOLVED IN PURE OLIVE OIL BY STOMACH TUBE ONCE DAILY ON 4 OR 5 DAYS EACH WK DURING 52 WEEKS. GROUPS OF 30 MALE & 30 FEMALE CONTROLS RECEIVED OLIVE OIL ONLY. THE RATS WERE ALLOWED TO LIVE UNTIL SPONTANEOUS DEATH OR WERE KILLED AT 144 WEEKS, THE END OF EXPT; AVG SURVIVAL TIMES WERE UNSPECIFIED. OF FEMALES OF THE CONTROL, LOW- & HIGH-DOSE GROUPS, 0/30, 2/30 & 8/32, RESPECTIVELY, DEVELOPED ZYMBAL GLAND CARCINOMAS (COCHRAN
    ARMITAGE TEST FOR POS TREND; P= 0.001; FISHER EXACT TEST FOR CONTROL VERSUS HIGH-DOSE GROUP: P= 0.003); 3/30, 4/30 & 7/32 DEVELOPED MAMMARY GLAND CARCINOMAS; & 1/30, 2/30 & 1/32 DEVELOPED LEUKEMIAS. NO SUCH TUMORS WERE FOUND IN MALES, EXCEPT THAT LEUKEMIAS OCCURRED IN 4/32 HIGH-DOSE MALES (COCHRAN-ARMITAGE TEST FOR POS TREND; P= 0.008; FISHER EXACT TEST: P< 0.069). BACKGROUND INCIDENCE OF ZYMBAL GLAND CARCINOMAS IN SEVERAL THOUSAND MALE & FEMALE RATS OF SAME STRAIN ... /WAS/ ABOUT 0.7%. AVG LATENT PERIOD OF MAMMARY GLAND CARCINOMAS WAS 88 WK IN EACH TEST GROUPS VERSUS 110 WK IN CONTROL ... (MALTONI & SCARNATO 1979). [REF-2, p.V29 106]
    
    BLUE CRAB JUVENILES WHEN EXPOSED TO SUBLETHAL CONCN OF BENZENE (0.1 OR 5.0 PPM) IN à STATIC SYSTEM SHOWED AN INCR IN THE TIME NEEDED TO COMPLETE à MOLT CYCLE (50 DAYS IN CASE OF BENZENE-EXPOSED CRAB, AS COMPARED TO 33 DAYS FOR CONTROLS), à SLOWER RATE OF GROWTH OF REGENERATING LIMB BUDS, & à DEPRESSED ACTIVITY OF ATPASE IN MITOCHRONDRIA. OXYGEN CONSUMPTION BY THE CRAB DECR FROM EXPOSURE TO 1.0 PPM BENZENE. [REF-84]
    
    Toxicity threshold (cell multiplication inhibition test): bacteria (Pseudomonas putida) 92 mg/l; algae (Microcystis aeruginosa) >1400 mg/l; green algae (Scenedesmus quadricauda) >1400 mg/l; protozoa (Entosiphon sulcatum) >700 mg/l, & (Uronema parduczi Chatton-Lwoff) 486 mg/l. Algae (Chlorella vulgaris) /showed/ 50% reduction of cell numbers versus controls after 1 day incubation at 20 deg C at 525 ppm. Inhibition of photosynthesis (of à freshwater, non axenic unialgal culture of Selenastrum capricornutum) at 10 mg/l, 95% carbon-14 fixation (versus controls); at 100 mg/l, 84% carbon-14 fixation (versus controls); at 1000 mg/l, 5% carbon-14 fixation (versus controls). ... Young Coho salmon /showed/ no significant mortalities up to 10 ppm after 96 hr in artificial sea water at 8 deg C ... /mortality was 12/20 at 50 ppm after 24 hr up to 96 hr & 30/30 at 100 ppm after 24 hr/. Herring & anchovy larvae (Clupea pallasi & Engraulis mordex) /studies showed that/ 35-45 ppm caused delay in development of eggs & ... /produced/ abnormal larvae; 10-35 ppm caused delay in development of larvae, decrease in feeding & growth, & increase in respiration. [REF-85, p.240]
    
    Groups of 5 to 10 pregnant Swiss-Webster mice were exposed to concentrations of 0, 5, 10, or 20 ppm benzene from days 6 through 15 of gestation and offspring of exposed dams were examined for untoward effects. Litter sizes, fetal weights, numbers of dead, resorbed, or malformed fetuses were within control limits. In the fetuses (day 16 of gestation), the number of mature erythroid precursor cells (CFU-E) was decreased at 20 ppm benzene. In the neonates, the number of CFU-E cells was increased at 20 ppm benzene. Granulocytic colony forming cells (GM-CFU-C) were affected by the 2 higher exposure concentrations. Adult mice treated in utero when re-exposed to benzene showed à more severe decrease in splenic GM-CFU-C than controls. [REF-86]
    
    The best evidence that benzene must be metabolized to produce bone marrow depression is based on: 1) the observation that benzene toxicity is prevented by coadministration of toluene, which inhibits benzene metabolism; and 2) that partial hepatectomy (which decreases benzene metabolism) also decreases benzene toxicity. [REF-87]
    
    Reports indicate that protection against benzene toxicity in phenobarbital treated animals reflects the fact that phenobarbital increased the detoxification rate of benzene in the liver. Inhibition of metabolism by toluene and by aminotriazole has been found to protect animals by decreasing the rate of formation of toxic metabolites. [REF-87]
    
    The principal hydroxy metabolites of benzene hydroquinone, catechol and phenol were assayed in tests for mitotic segregation induction in Aspergillus nidulans diploid strain 19. Hydroquinone was the most effective chemical, increasing the frequency of mitotic segregants up to 10 fold at 1-3 mM. Catechol was similarly active at 10-20 mM and phenol was weakly positive at 15 mM. Genetic characterization of induced abnormal segregating colonies by replating and complementary assays with haploid strain 35 suggest that gross chromosomal aberrations, instead of numerical abnormalities, are the primary genetic damages induced by hydroxybenzenes in Aspergillus. The protecting activity exerted by L-cysteine against equimolar concentrations of hydroquinone supports à free radical mechanism for hydroxy metabolite genotoxicity in Aspergillus nidulans. [REF-88]
    
    Benzene hematotoxicity and leukemogenesis were investigated to verify epidemiological estimates to the effect that leukemia had developed in human beings exposed to benzene for about 15% of their lifetime, and that the levels of exposure reached at times as high as 250 to 300 ppm for at least à portion of working day. Based on à review of the literature and ongoing studies, mice were exposed to benzene vapor for 6 hr/day, 5 days/week for 16 weeks. Exposure of male CBA/Ca mice to 300 ppm benzene proved to be highly carcinogenic and leukemogenic compared to unexposed controls. Male and female CBA/Ca mice exposed to 100 ppm benzene, according to the same schedule, showed 30% mortality as compared to 12% in controls, while for neoplasms the respective figures were 10% and 1%. In this case, exposure to benzene reduced the cellularity of the bone marrow and the number of stem cells, while DNA synthesis increased. /Data indicates/ that benzene is carcinogenic in both animals and man and although it is unlikely that the slope for animals and man would be the same, the investigation of the linearity of the response would be helpful. [REF-89]
    
    à review of recent advances in the metabolism and toxicity of benzene was presented. Metabolism of benzene was discussed including the microsomal metabolism of benzene, mitochondrial metabolism of benzene, effect and its metabolites on replication and transcription, and covalent binding of reactive metabolites of benzene with macromolecules. The toxicity of benzene, including genotoxicity, carcinogenicity, hematopoietic toxicity, and immunotoxicity, was reviewed. Mutagenicity and cytogenic toxicity were also covered. Effects on stem cells, progenitor cells, and on the stromal microenvironment were discussed. Cytogenetic effects observed in animals and humans following exposure to benzene were reviewed. Myeloclastogenic effects and clastogenic effects were covered. Leukemias and related diseases in humans, associated with repeated exposure to benzene at relatively high concentrations, were discussed. Aplastic anemia from benzene poisoning was also discussed. Progress made in understanding the bioactivation of benzene and in the elucidation of metabolites produced in the liver and bone marrow was discussed. [REF-90]
    
    Environmental exposure to benzene results in both myelotoxicity and immunotoxicity. Although benzene induced immunotoxicity has been well documented, no studies to date have addressed the possibility that benzene toxicity is due in part to altered differentiation of marrow lymphoid cells. The effect of acute exposure to the benzene metabolite, hydroquinone, on murine bone marrow B-lymphopoiesis was investigated. Bone marrow cell suspensions from B6C3F1 (C57BL/6J x C3H/HeJ) mice were depleted of mature surface IgM+ B cells and cultured for 0, 24, 48, or 72 hr and production of newly formed B cells was assayed both by mature surface expression and colony formation in soft agar cultures. One hr exposure of bone marrow cells to hydroquinone before culture reduced the number of mature surface cells generated in liquid cultures. Small pre-B cells (cytoplasmic mu heavy chain+, sIgM-) were numerically elevated as compared with control cultures. Hydroquinone exposure also decreased the number of adherent cells found in cultures of bone marrow cells. These results suggest that short-term exposure to hydroquinone, an oxidative metabolite of benzene, may in some way block the final maturation stages of B cell differentiation. This apparent differentiation block resulted in reduced numbers of B cells generated in culture and à corresponding accumulation of pre-B cells. Reduction of adherent cells in treated cultures may also suggest that toxicity to regulatory cells for the B lineage may be in part responsible for this aspect of hydroquinone myelotoxicity. [REF-91]
    
    Benzene is à potent bone marrow toxin in animals and man. Animal studies have shown that exposure to benzene can alter lymphocyte functions and decrease the resistance of animals to Listeria monocytogenes and transplanted tumor cells. Mononuclear phagocytes participate in host resistance to Listeria and tumor cells. The purpose of the studies presented here was to determine the effects of benzene and benzene metabolites on macrophage functions and the ability of macrophages to be activated for functions which are important in host defense. Benzene had no effects on macrophage function or activation for any of the functions tested. Conversely, metabolites of benzene, catechol, hydroquinone, benzquinone, and 1,2,4-benzenetriol had potent and varied effects on macrophage function and activation. Benzoquinone inhibited the broadest range of functions including release of hydrogen peroxide, Fc receptor-mediated phagocytosis, interferon gamma priming for tumor cell cytolysis, and bacterial lipopolysaccharide triggering of cytolysis. Benzoquinone was also the most potent metabolite causing inhibition at lower concentrations than the other metabolites. Hydroquinone inhibited hydrogen peroxide release and priming for cytolysis and 1,2,4-benzenetriol inhibited phagocytosis and priming for cytolysis. Catechol only inhibited the release of hydrogen peroxide. None of the compounds tested inhibited the induction of class II histocompatibililty antigens on the cell surface. All of the effects measured occurred using concentrations of compounds which did not disrupt the cell integrity or inhibit general functions such as protein synthesis. Taken together these data suggest that benzene metabolites alter macrophage function through several mechanisms including inhibition of output enzymes and disruption of signal transduction systems. [REF
    92]
    
    Female Wistar rats were exposed to various solvent vapors 8 hr/day for 7 days. The leukocyte suspension and serum were prepared from peripheral blood and utilized for the determination of alkaline phosphatase activity with disodium phenyl phosphate as à substrate (leukocyte alkaline phosphatase and serum assay). While the exposure to benzene at 20 or 50 ppm did not cause significant changes in leukocyte alkaline phosphatase assay activity, the exposure at 100 to 300 ppm resulted in à dose-dependent increase of leukocyte alkaline phosphatase assay activity up to more than 100% over the control. No further increase was observed at 1000 or 3000 ppm. Similar exposure at 300 ppm to either toluene, m-xylene, n-hexane, trichloroethylene, methyl ethyl ketone, ethyl acetate, or methyl alcohol did not induce any changes in leukocyte alkaline phosphatase assay activity. Thus, the increase in leukocyte alkaline phosphatase assay activity was considered to be specific to benzene exposure. When the animals were exposed to toluene (300 ppm) in combination with benzene (300 ppm), not only was the benzene induced leukopenia alleviated as previously reported, but the benzene induced increase in leukocyte alkaline phosphatase assay activity was no longer observed. The parallel inhibitory effects of toluene on benzene induced increase in leukocyte alkaline phosphatase assay and leukopenia suggest that à relation may exist between increase in leukocyte alkaline phosphatase assay activity and leukopenia. No changes in serum alkaline phosphatase assay activities were observed in the rats under the exposure conditions examined. [REF-93]
    
    à review was presented of data for ... chemicals for which either ovarian toxicity or carcinogenicity, or both, have been documented in recent studies /conducted by/ the National Toxicology Program. In most cases, ovarian atrophy was commonly found after 90 days of exposure, and ovarian hyperplasia and neoplasia after longer periods. Benzene administered by gavage produced ovarian atrophy, cysts, hyperplasia and neoplasia in mice. [REF-94]
    
    Based on literature, the mechanism of multitoxic effects of benzene and lesions in the peripheral blood of affected animals were postulated. The effects of chronic benzene poisoning upon erythrocytes and erythropoiesis, granulocytes and granulopoiesis, lymphocytes and lymphopoiesis, thrombocytes and thrombopoiesis were presented. Differences were pointed out in toxic effects of benzene varying with the kind, concentration and administration route of benzene and quantitative and qualitative differences in the fodder given to animals during the experiment. [REF-95]
    
    The effect of à single dose of benzene (0.5 ml/kg body wt ip) on the heme saturation of tryptophan pyrrolase activity in liver was examined /in female albino rats/. There was à significant decrease in the heme saturation of hepatic tryptophan pyrrolase, suggesting depletion of regulatory heme. After benzene administration there was significant increase in delta-aminolevulinate synthetase activity while delta-aminolevulinate dehydratase activity was significantly decreased, however, ferrochelatase and heme oxygenase activities were unaltered. Administration of tryptophan to benzene pretreated rats showed à reversal of benzene effects on heme synthesizing enzymes: there is an increase in the heme saturation of tryptophan pyrrolase and decrease in delta-aminolevulinate synthetase. However, there was no significant alteration in the activity of delta-aminolevulinate dehydratase. [REF-96]
    
    The effects of five straight alkane petroleum hydrocarbons (nC6 to nC10), as well as benzene and toluene upon lysosomal enzymes of the lung were investigated. Pulmonary alveolar macrophages were obtained from adult male Sprague Dawley rats and from 3 month old New-Zealand white rabbits by bronchial lavage. These cells were cultured and subsequently exposed to hydrocarbons in Leighton tubes. All hydrocarbons examined were cytotoxic to cultured pulmonary alveolar macrophages in à dose dependent manner, with benzene and toluene being least toxic. The concentration of hydrocarbon producing death in 50% of treated rat cells was 1.0 millimolar (mM) for nC8, 2.0 mM for nC7, 5 mM for nC9, and about 10 mM for nC6, nC10, benzene and toluene. Concentrations of hydrocarbons that killed 50% of rabbit macrophages were about half those observed in the rat. Cathepsin-D and, to à lesser extent, cathepsin-B release were stimulated upon addition of hydrocarbons to the cell media. à similar but more pronounced release of cathepsins was observed in isolated lysosomes as well. à significant decrease in cell respiration rate and à time and dose dependent increase in lipid peroxidation were also observed following exposure of macrophages to the tested hydrocarbons, particularly nC7 and nC8 alkanes. These results support the concept of an association between chain length and cytotoxicity of hydrocarbons in pulmonary alveolar macrophages. [REF-97]
    
    ... Under the conditions of these 2 yr gavage studies, there was clear evidence of carcinogenicity of benzene for male F344/N rats, for female F344/N rats, for male B6C3F1 mice and for female B6C3F1 mice. For male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. For female rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas, and squamous cell carcinomas of the oral cavity. For male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), Harderian gland adenomas, and squamous cell carcinomas of the preputial gland. For female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benigh mixed tumors, carcinomas and carcinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcinomas. ... [QR] [REF-98]

EVIDENCE FOR CARCINOGENICITY:
    
    Classification of carcinogenicity: 1) evidence in humans: sufficient; 2) evidence in animals: sufficient; Overall summary evaluation of carcinogenic risk to humans is group 1: The chemical is carcinogenic to humans. /From table/ [REF-99, p.S7 120]
    
    Notice of Intended Changes (1993-94): These substances, with their corresponding values, comprise those for which either à limit has been proposed for the first time, for which à change in the "Adopted" listing has been proposed, or for which retention on the Notice of Intended Changes has been proposed. In all cases, the proposed limits should be considered trial limits that will remain in the listing for à period of at least one year. If, after one year no evidence comes to light that questions the appropriateness of the values herein, the values will be reconsidered for the "Adopted" list. A1. A1= Confirmed Human Carcinogen. [QR] [REF-100, p.37]
    
    A2. A2= Suspected Human Carcinogen (1987) [QR] [REF-100, p.13]
    
    WEIGHT OF EVIDENCE CHARACTERIZATION: Benzene is classified as à "known" human carcinogen (Category A) under the Risk Assessment Guidelines of 1986. Under the proposed revised Carcinogen Risk Assessment Guidelines (1996), benzene is characterized as à known human carcinogen for all routes of exposure based upon convincing human evidence as well as supporting evidence from animal studies. Epidemiologic studies and case studies provide clear evidence of à causal association bewteen exposure to benzene and acute nonlymphocytic leukemia and also suggest evidence for chronic nonlymphocytic leukemia and chronic lymphocytic leukemia. Other neoplastic conditions that are associated with an increased risk in humans are hematologic neoplasms, blood disorders such as preleukemia and aplastic anemia, Hodgkin's lymphoma, and myelodysplastic syndrome. These human data are supported by animal studies. The experimental animal data add to the argument that exposure to benzene increases the risk of cancer in multiple species at multiple organ sites ... . It is likely that these responses are due to interactions of the metabolites of benzene with DNA. Recent evidence supports the viewpoint that they are likely multiple mechanistic pathways leading to cancer and, in particular, to leukemogenesis from exposure to benzene. HUMAN CARCINOGENICITY DATA: Benzene is à known carcinogen based upon evidence presented in numerous occupational epidemiological studies. Significant increased risks of leukemia, chiefly myelogenous leukemia, have been reported in benzene-exposed workers in the chemical industry, shoe making and oil refineries. ... ANIMAL CARCINOGENICITY DATA: Although human epidemiological studies provide the bulk of the evidence reaffirming the classification of benzene as à category A, "known" human carcinogen, many experimental animal studies, both inhalation and oral, also support the evidence that exposure to benzene increases the risk of cancer in multiple organ systems, including the hematopoietic system, oral and nasal cavities, liver, forestomach, preputial gland, lung, ovary and mammary gland. ... [QR] [REF-101]

NATIONAL TOXICOLOGY PROGRAM REPORTS:
    
    Two yr toxicology and carcinogenesis studies of benzene (greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil (5 ml/kg) were administered by gavage to male rats, 5 days/wk for 103 wk. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 wk. ... Under the conditions of these 2 yr gavage studies, there was clear evidence of carcinogenicity of benzene for male F344/N rats, for female F344/N rats, for male B6C3F1 mice and for female B6C3F1 mice. For male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. For female rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas, and squamous cell carcinomas of the oral cavity. For male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), Harderian gland adenomas, and squamous cell carcinomas of the preputial gland. For female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benigh mixed tumors, carcinomas and carcinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcinomas. ... [QR] [REF-102]

IARC SUMMARY AND EVALUATION:
    
    Sufficient evidence of carcinogenicity in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 1: The agent is carcinogenic to humans. [REF-99, p.S7 58]

TSCA TEST SUBMISSIONS:
    
    An evaluation of fertility was made in female Charles River CD rats (26/group) exposed by inhalation to benzene at 0, 1, 10, 30 and 300 ppm for 6 hrs/day, 5 days/week during à 10 week pre-mating treatment period and ensuing mating period, and continued exposure for mated females daily for 6 hrs/day during gestation to day 20. Daily exposure was resumed on day 5 of lactation until weaning (day 21 of lactation). There were significant differences between treated and control animals in the following: decrease in pup survival index (for lactation day 4-21 at 10 ppm, no dose-response), decreased mean pup weights (days 14 and 21 of lactation for high-dose level), and decreased mean absolute liver weights (high-dose female pups). There were no significant differences between treated and control animals in the following: maternal mortality, body weights, in-life observations, pregnancy rates, mean number dead pups, mean liver weights (male pups at all levels), mean relative liver weights (female pups at all levels), mean relative and absolute kidney weights (all female pups), or gross postmortem examinations of adult females or pups. [REF-103]
    
    Teratogenic effects were evaluated in pregnant female Sprague Dawley rats (40/group) exposed via inhalation to benzene at 0 (two groups), 1, 10, 40 and 100 ppm for 6 hrs/day from days 6-15 of gestation. On day 20 of gestation, the dams were sacrificed and the fetuses removed by cesarean section. There were significant differences between treated and control groups only in the decreased mean fetal body weights of fetuses from dams exposed at the high-dose level. There were no significant differences between treated and control dams in the following: mortality, clinical observations, body weight data, maternal gross pathology, pregnancy rates, mean number of corpora and implantations, or implantation efficiencies. There were no significant differences between fetuses from treated and control dams in the following: mean incidence of fetal resorptions, mortality, mean percentage of male fetuses/litter, mean fetal body lengths, or fetal development. [REF-104]
    
    The mutagenicity of benzene was evaluated in dominant lethal assay using four groups of 20 male Sprague-Dawley rats receiving whole body exposures to nominal concentrations of test material at 1, 10, 30 and 300ppm in à dynamic air flow chamber for 6hours/day, 5days/week for ten consecutive weeks. Following exposure, each male was mated with two untreated females per week for two consecutive weeks. There was no effect of treatment for all dosed male rats as indicated by: mortality, body weight data and in-life physical observations. Pregnancy rates and implantation efficiency ratios of females mated to treated males was not significant different from control group females. Slight increases in the mean number of dead implantations and mean mutagenic ratios (i.e. no. dead implants/total implants) were noted for each week of the post treatment mating period for females mated to high dose males, but these differences were not statistically significant compared to controls. Males were sacrificed after à 10-week post mating period and microscopic examination of testis/epididymides revealed two-high dose males with testicular lesions. [REF-105]
    
    As part of subchronic inhalation study, the ability of benzene to cause chromosome aberrations was evaluated in bone marrow cells of (50/sex) CD-1 mice receiving whole body exposures to nominal concentrations of 0, 1, 10, 30 and 300ppm in dynamic air flow chamber for 6hours/day, 5days/week for 13 weeks. Following the last day of exposure, animals received à single intraperitoneal injection of colchicine and were sacrificed. Bone marrow slides of mice at the highest concentration (300ppm) exhibited statistically significant increases chromosome aberrations relative to the control. [REF-106]
    
    As part of subchronic inhalation study, the ability of benzene to cause chromosome aberrations was evaluated in bone marrow cells of (50/sex) Sprague Dawley rats receiving whole body exposures to nominal concentrations of 0, 1, 10, 30 and 300ppm in dynamic air flow chamber for 6hours/day, 5days/week for 13 weeks. Following the last day of exposure, animals received à single intraperitoneal injection of colchicine and were sacrificed. Bone marrow slides of female rats at all exposure levels exhibited statistically significant increases in chromosome aberrations relative to the control. No-exposure related cytogenic effects were apparent in any of the male rats. [REF-106]
    
    The ability of benzene to increase the incidence of micronucleated polychromatic erythrocytes was evaluated in male and female CD-1 mice receiving nominal concentrations of 1, 10, 30 and 300ppm for 6hours/day, 5days/week for 13 weeks (Micronucleus Test). Groups of 20 mice (10/sex/sample time) were sacrificed after 0, 15, 30, 60 and 90 days of exposure. Exposure to 300ppm benzene caused à significant increases in micronucleated polychromatic erythrocytes (PCEs) and monochromatic erythrocytes (NCEs) in male and female mice at all sample times. Male mice exhibited à greater response than female mice. The frequency of micronucleated PCEs and the frequency micronucleated NCEs achieved steady state by the 30 day sample time. The rate of erythropoiesis, as measured by per cent of polychromatic erythrocytes in the peripheral blood, was not significantly altered by treatment. [REF-107]
    
    The levels of benzene and it's metabolites in the blood were evaluated in twenty male Sprague-Dawley rats and eighty male Swiss albino mice receiving nominal concentration of benzene at 300ppm in à dynamic air flow chamber. Sixteen mice and four rats were removed from the chamber after 1, 2, 4, 8 and 12 hours for eye bleeding. The mean levels of benzene in the rat blood were < 1.0, 4.7, 4.8, 5.7, 5.3, and 7.1ppm at intervals of 0, 1, 2, 4, 8 and 12 hours respectively. No free metabolites (phenol, catechol & hydroquinone) were detected at any of the time intervals in rats. The mean levels of benzene in mouse blood were < 1.0, 3.7, 3.0, 2.4, 3.0 and 1.3ppm at intervals of 0, 1, 2, 4, 8 and 12 hours, respectively. The mean levels of free phenol in mouse blood were 2.0, 2.4, 2.2, 2.3, 2.5 and 2.3ppm at respective intervals. No free catechol or hydroquinone were detected at any of the time intervals in mice. Also determined were levels of conjugates in rat and mouse blood. The mean levels of conjugated phenol in rat blood were < 1.0, 3.0, 5.3, 4.2, 7.1 and 4.7ppm and the mean levels in the mouse blood were 2.7, 7.2, 8.7, 8.4, 9.1, and 3.7 at intervals 0, 1, 2, 4, 8 and 12 hours, respectively. No conjugated catechol or hydroquinone were detected at any of the time intervals in rats or mice. It was concluded, that its takes approximately one hour to achieve à steady state level of benzene in rat and mouse blood. [REF-108]
    
    The levels of benzene and its's metabolites in blood were evaluated in male Sprague Dawley rats (4/group) and male Swiss albino mice (16/group) receiving nominal concentrations of benzene at 0, 3, 30, 300 or 1000ppm in dynamic air flow chamber for 6 hours. The mean levels of benzene in rat blood were < 1.0, < 1.0, < 1.0, 8.3 and 33.6ppm at exposure levels 0, 3, 30, 300 and 1000ppm, respectively. No free metabolites (phenol, catechol & hydroquinone) were detected at any exposure level in rat blood. The mean levels of benzene in the mouse blood were < 1.0, < 1.0, < 1.0, 1.44 and 29.5ppm at exposure levels 0, 3, 30, 300 and 1000ppm, respectively. à mean level of 1.2ppm of free phenol was only detected at the high dose level in mice. No free catechol or hydroquinone were detected in mouse blood. Also determined were the levels of conjugates in rat and mouse blood. The mean level of conjugated phenol in rat blood were < 1.0, < 1.0, 1.7, 6.0 and 6.3ppm and the mean levels of conjugated phenol in mouse blood were < 1.0, 1.1, 2.9, 7.9 and 15.5ppm at exposure levels of 0, 30, 300 and 1000ppm, respectively. No conjugated catechol or hydroquinone were detected at any exposure level in rats or mice. It was concluded that there was à direct correlation between increased exposure to benzene and increased blood concentration levels of benzene and conjugated phenol. Mice exposed to 1000ppm benzene had double the concentration of conjugated phenol in the blood relative to the 300ppm mice. In contrast, this effect was not observed in rats. [REF-109]
    
    The concentration of benzene and it's metabolites were determined after 12, 24, 48 and 72 hours in the urine of five exposed male Sprague Dawley rats and 25 male Swiss albino mice which received à nominal concentration of benzene at 300ppm in dynamic air flow chamber for 6 hours. No level of benzene at or above the detection limit (1.0ppm) were detected in rat and mice urine at any of the sampling intervals. The level of free phenol in the rat urine were 2.0, 2.2, 1.7 and 3.2ppm and in mouse urine were 15.6, 4.7, 5.8 and 4.3ppm at 12, 24, 48 and 72 hours, respectively. The mean levels of free catechol in rat urine were < 2.0, 0.46, 0.32 and < 2.0ppm and in mouse urine were 1.09, 1.29, 1.56 and 7.76ppm at 12, 24, 48 and 72 hours, respectively. No free hydroquinone at or above the detection limit were determined in rat urine at any sampling time. The mean levels of free hydroquinone in mouse urine were 12.87, 1.49, 1.46 and 0.31ppm at 12, 24, 48 and 72 hours, respectively. The expired air of rats was bubbled through dichloromethane and the mean total levels of benzene detected were 440.6, 101.4, not detected and 22.2ug/sampling interval ending at 6, 12, 24 and 48 hours, respectively. Benzene in expired air of mice was only detected at the 48 hour sampling interval. [REF-110]
    
    The in vitro percutaneous absorption of 14C-benzene was evaluated in mammalian skin samples maintain in à dynamic culture system. C3H Mice (primary test subject), HRS mice, rabbit and guinea pig (strain not specified) dorsal skin, and human skin from elective surgery were all placed in culture medium chamber for penetration analysis. 14C-Benzene (20ul) was topically applied to cultured C3H mouse skin samples and radioactivity was detected in the effluent medium 15 minutes following
    treatment with no apparent lag phase. Penetration was linear and the rates were 2.97 +/- 0.03 and 3.70 +/- 0.03%/hr for metabolically viable (fresh skin) and nonviable skin (frozen skin), respectively. Analysis of the effluent medium indicated negligible conversion of benzene to phenol. Different rates of in vitro skin permeation were observed between male and female C3H mice, however this difference was not observed between sexes in similar studies with hairless HRS mice. In vitro penetration of benzene in hairless mice skin (2.44 +/- 0.07%) was lower than C3H mice. Additional in vitro penetration studies with 14C-benzene (20ul) were preformed with metabolically viable guinea pig, rabbit and human skin with rates of penetration of 0.04 +/- 0.01, 0.55 +/- 0.02 and 0.23 +/- 0.04%/hr, respectively. The lag phase of these additional studies were between 45-60 minutes and two hours from application followed by linear radioactivity. Toluene and unleaded gasoline containing 14C-benzene (20ul) produced rates of permeation of 2.32 +/- 0.04 and 2.81 +/- 0.4%/hr, respectively in C3H mice which appeared linear. [REF-111]
    
    The benzene uptake rate was evaluated in five male Sprague Dawley rats and twenty five male Swiss albino mice receiving benzene at à nominal concentration of 300ppm in à dynamic air flow chamber for 6 hours. Five individual rats were determined to have an internal mean benzene uptake rate of 152ml/min prior to conducting the six hour test and an mean pretest respiratory minute volume of 145ml/min. The mean benzene uptake rates as compared to pretest values for rats decreased to 33, 22 and 9% of the mean test value 1, 3 and 6 hours after administration, respectively. The mean minute volume for rats decreased to 85, 78 and 66% of the pretest at 1, 3 and 6 hours after administration, respectively. Rats had an estimated retained dose of 56mg/kg. Mice (5/group) had à mean total pretest benzene uptake rate of 188ml/min and à mean pretest total respiratory minute volume of 189ml/min. The mean total benzene uptake for the mice decreased 65, 76 and 81% of the pretest value, after 1, 3 and 6 hours of exposure, respectively. The mean total minute volume for groups of mice decreased 96, 84 and 69% of the pretest after 1, 3 and 6 hours, respectively. The mean total retained dose per mice was estimated to be 377mg/kg. [REF-112]

                        ** EMERGENCY TREATMENT ** 

MEDICAL SURVEILLANCE:
    
    IF INDIVIDUALS ARE KNOWN TO BE EXPOSED TO BENZENE VAPORS IN THEIR WORKING ENVIRONMENT PROPHYLACTIC MEASURES SHOULD BE TAKEN. ALL POSSIBLE METHODS SHOULD BE USED TO PROTECT SUCH PERSONS AGAINST BREATHING THE FUMES. THEY SHOULD HAVE PERIODIC PHYSICAL EXAM, INCL BLOOD STUDIES. IN ADDN THE URINE SHOULD BE EXAM AT INTERVALS TO DETERMINE EXTENT OF EXCRETION OF BENZENE CONJUGATION PRODUCTS. ONCE POISONING HAS DEVELOPED, IT IS ESSENTIAL TO PREVENT FURTHER EXPOSURE. [REF-31, p.906]
    
    Assessment of fitness should incl consideration of previous medical ... & occupational history. Occupational history should take into account any previous exposure to benzene, radiomimetic substances or ionizing radiations. Medical exam should incl thorough physical ... & hematological examination. The latter ... should cover hemoglobin determination, red cell, white cell & platelet counts, white cell differential count & red cell & leukocyte morphology. Protect young persons of either sex under 18 yr of age from exposure to benzene since ... adolescents have lower resistance to bone-marrow poisons. Pregnant women & nursing mothers should not be exposed ... & special precautions are necessary where women of childbearing age are exposed to benzene hazard. ... Subjects with liver diseases & ... microcytemia should not be exposed. ... Periodic exam should be carried out in same way as pre-employment examination. ... Particular attention should be paid to any hematological abnormalities found during 1st periodic examination. ... Whenever there is slightest suspicion of leukemia, à bone-marrow biopsy is warranted. [REF-113, p.260]
    
    Biological monitoring: The current required regular physical exam should incl blood pressure check, lung functions, blood chemistry, hematology, urinalysis & skin exam. [REF-11, p.3283]
    
    PRECAUTIONS FOR "CARCINOGENS": ... In relation specifically to cancer hazards, there are at present no health monitoring methods that may ensure the early detection of preneoplastic lesions or lesions which may preclude them. Whenever medical surveillance is indicated, in particular when exposure to à carcinogen has occurred, ad hoc decisions should be taken concerning additional tests that might become useful or mandatory. /Chemical Carcinogens/ [REF-19, p.23]

                   *** METABOLISM AND PHARMACOLOGY *** 

POPULATIONS AT SPECIAL RISK: 
    INDIVIDUALS WITH G6PD /GLUCOSE 6-PHOSPHATE DEHYDROGENASE/ DEFICIENCY HAVE ... BEEN FOUND TO BE MORE SUSCEPTIBLE TO HEMOLYTIC EFFECTS OF ... BENZENE ... [REF-114, p.139]
    
    ... /It has been observed/ that levels of leukocyte agglutins were elevated in selected individuals exposed to benzene. ... /This/ suggested that in some people benzene toxicity may be accounted for in part by an allergic blood dyscrasia. [REF-2, p.V29 117]

ABSORPTION, DISTRIBUTION, AND EXCRETION:
    
    BENZENE IS READILY ABSORBED VIA LUNG, & ABOUT 40-50% IS RETAINED. ... IT IS TAKEN UP PREFERENTIALLY BY FATTY & NERVOUS TISSUES, & ABOUT 30-50% ... IS EXCRETED UNCHANGED VIA LUNG; à 3-PHASE EXCRETION PATTERN IS SEEN AT ... /APPROX/ 0.7-1.7 HR, 3-4 HR, & 20-30 HR. [REF-75, p.V7 211]
    
    When benzene was placed on skin under closed cup it was absorbed at rate of 0.4 mg/sq cm/hr (Hanke et al 1961) ... [REF-2, p.V29 117]
    
    MICE TREATED SC WITH 2 ML (3)H-LABELED BENZENE/KG CONTAINED IRREVERSIBLY BOUND RADIOACTIVITY WITH DECREASING BINDING MAGNITUDE IN THE FOLLOWING ORGANS: LIVER, BRAIN, KIDNEY, SPLEEN, FAT. MICE TREATED WITH 2 DAILY SC DOSES OF 0.5 ML (3)H-BENZENE/KG FOR 1-10 DAYS SHOWED à RADIOACTIVITY BINDING WITH LIVER & BONE MARROW RESIDUES WHICH INCREASED WITH TREATMENT DURATION, EXCEPT IN THE CASE OF BINDING TO BONE MARROW WHICH DECREASED AFTER DAY 6. [REF-115]
    
    When administered to mice subcutaneously, 72% of dose is recovered in expired air. [REF-116]
    
    Pharmacokinetic studies of humans experimentally exposed to approximately 50-60 ppm of benzene for four hours indicated that the absorption rate from the lung was approximately 47% with 30% being retained and 17% being exhaled unchanged. [REF-117]
    
    Rats were exposed to 500 ppm benzene for 30 min to eight hr. Benzene concentrations reached steady state within four hr in blood (steady-state concn= 11.5 ug/g), six hr in fat (concn= 164.4 ug/g), and two hr in bone marrow (concn= 37.0 ug/g). Lesser concn were detected in the kidney, lung, liver, brain, and spleen. [REF-118]
    
    Benzene is absorbed from the gastrointestinal tract when ingested. [REF-119, p.936]
    
    BENZENE CROSSES THE HUMAN PLACENTA, & LEVELS IN CORD BLOOD ARE SIMILAR TO THOSE IN MATERNAL BLOOD. ... THE MOST FREQUENT ROUTE BY WHICH HUMANS ARE EXPOSED TO BENZENE IS VIA INHALATION. TOXIC EFFECTS IN HUMANS HAVE BEEN ATTRIBUTED TO COMBINED EXPOSURE BY BOTH RESPIRATION & THROUGH THE SKIN ... IT IS ELIMINATED UNCHANGED IN EXPIRED AIR ... IN MEN & WOMEN EXPOSED TO 52-62 PPM (166-198 MG/CU M) BENZENE FOR 4 HR, à MEAN OF 46.9% WAS TAKEN UP, 30.2% WAS RETAINED & THE REMAINING 16.8% EXCRETED AS UNCHANGED BENZENE IN EXPIRED AIR. ... WHEN HUMANS WERE EXPOSED TO 100 PPM (300 MG/CU M) BENZENE, IT WAS DETECTED IN EXPIRED AIR 24 HR LATER, SUGGESTING THAT IT IS POSSIBLE TO BACK-EXTRAPOLATE TO THE BENZENE CONCENTRATION IN THE INSPIRED AIR. [REF-2, p.V29 117]
    
    ... In female & male rats with large body fat content, benzene was eliminated more slowly & stored longer than in lean animals. ... Distribution in rabbit was highest in adipose tissue, high for bone marrow, & lower for brain, heart, kidney, lung, & muscle, although direct binding was higher in liver than in bone marrow. [REF-11, p.3279]
    
    The solubility characteristics of benzene are such that it is easily taken up by the stratum corneum. Once in the stratum corneum, it does not meet many restraining forces to impede its movement and diffuses easily. The permeability constant for benzene, as determined in vitro, is higher than that of many other small molecules, particularly those having one or more polar groups. ... Even though these uncertainties exist, and more data are needed to support the ... conclusion that there is good overall agreement between in vitro and in vivo data. ... An adult working in ambient air containing 10 ppm of benzene, with 100 cm of glaborous skin in contact with gasoline containing 5% benzene, and his entire skin (2 sq m) in contact with ambient air, will absorb in an hr, 7.5 ul of benzene from inhalation, 7.0 ul from contact with gasoline, and 1.5 ul from body exposure to ambient air. Since ... in vitro techniques measure the penetration of benzene through strongly hydrated stratum corneum, the calculated flux may be higher than under some in vivo conditions. Nevertheless, it seems that unless good hygiene is maintained and care is taken to prevent lengthy exposure to solvents containing benzene, significant amounts of benzene may enter the body through the skin. [REF-120]

METABOLISM/METABOLITES:
    
    ... In human system /benzene/ is metabolized through à variety of major & minor pathways. The primary site of action is liver, where benzene is oxidized to phenol (hydroxybenzene), catechol (1,2-dihydroxybenzene), or quinol (1,4-dihydroxybenzene). Phenol is subsequently conjugated with inorganic sulfate to phenylsulfate, the other hydroxybenzenes are conjugated to à lesser extent, & all excreted in urine. Minor pathways incl further oxidation of catechol to hydroxyhydroquinol (1,2,4-trihydroxybenzene) or catabolism to cis, cis- or trans, trans-muconic acids, & phenol conjugation with glucuronic acid to form glucuronides, or with cysteine to produce 2-phenylmercapturic acid. [REF-11, p.3273]
    
    METABOLIC PRODUCTS IN RAT ... ARE PHENOL, HYDROQUINONE, CATECHOL, HYDROXYHYDROQUINONE, & PHENYLMERCAPTURIC ACID. CONJUGATED PHENOLS HAVE BEEN REPORTED ... EXCEPT FOR à SMALL AMT OF FREE PHENOL, ALL THE PHENOLIC METABOLITES WERE EXCRETED IN CONJUGATED FORM. WHEN (3)H-BENZENE WAS ADMIN TO MICE, (3)H2O WAS ALSO RECOVERED FROM URINE. [REF-74, p.688]
    
    YIELDS N-ACETYL-S-PHENYL-CYSTEINE IN RAT: ZBARSKY SH, YOUNG L; J BIOL CHEM 151: 587 (1943). YIELDS BENZYL ALCOHOL IN GUINEA PIGS: SLOANE NH; BIOCHIM BIOPHYS ACTA 107: 599 (1965); GIBSON ET AL, BIOCHEMISTRY 9: 1631 (1974). ... YIELDS CIS-1,2-DIHYDRO-1,2-DIHYDROXYBENZENE IN PSEUDOMONAS: GIBSON ET AL; BIOCHEMISTRY 9: 1631 (1974); GIBSON ET AL; BIOCHEMISTRY 7: 2653 (1968). PHENOL IN PSEUDOMONAS & ACHROMOBACTER: CLAUS D; J GEN MICROBIOL 36: 1 (1964). YIELDS CIS,CIS-MUCONIC ACID IN RABBIT: PARK & WILLIAMS; BIOCHEM J 54: 231 (1953). /FROM TABLE/ [REF-121, p.B-4]
    
    In the rabbit, the major hydroxylation product of benzene was phenol, which along with some catechol and hydroquinone, was found in the urine conjugated with ethereal sulfate or glucuronic acid. [REF-82, p.C-11]
    
    Unconjugated phenol has been found in mouse and rat urine after benzene administration. [REF-82, p.C-11]
    
    The formation of benzene oxide, an epoxide of benzene is involved in the metabolism of benzene. This highly unstable intermediate rearranges non-enzymatically to form phenol. This step accounts for the occurrence of phenol as the major metabolite of benzene in urine. Catechol formation is thought to result from the hydration of benzene oxide by the enzyme epoxide hydratase followed by oxidation to catechol. It appears that catechol and phenol are formed by two distinctly different metabolic pathways. Hydroquinone is thought to result from à second passage of phenol through the mixed function oxidases. [REF-122, p.C-12]
    
    The metabolism of benzene in vitro can be altered by the use of enzyme inducers administered to animals prior to sacrifice or by the addition of inhibitors to the mixtures. Benzene, phenobarbital, 3-methylcholanthrene and dimethyl sulfoxide are all microsomal stimulants for the metabolism of benzene. Benzene metabolism in vitro can be inhibited by carbon monoxide, aniline, metyrapone, SKF-525A, aminopyrine, cytochrome c, aminotriazole, or toluene. [REF-82, p.C-12]
    
    Benzene, when administered sc at 880 mg/kg twice daily for 3 days, decreased erythropoiesis much more markedly in DBA/2 mice than in C57BL/6 mice. Total urinary benzene metabolites and the % of the dose excreted in the urine were the same in both strains. Although the metabolic profile differed between the two strains, it was very similar when equitoxic doses of benzene were administered. The levels of both free and covalently bound benzene were higher in all organs of the DBA/2 mice. Phenol, hydroquinone, resorcinol, and catechol had no effect on erythopoiesis. [REF-123]
    
    The urinary metabolites isolated by DEAE Sephadex A-24 anion-exchange chromatography from mice treated with radiolabeled benzene included phenol as the major component, as well as catechol, hydroquinone, and phenylmercapturic acid. The phenolic metabolites were excreted primarily as glucronides with the exception of à small amount of free phenol. [REF-124]
    
    Benzene reduced the incorporation of (59)Fe into red cells by 75% at the higher dose when administered at 440 or 880 mg/kg to mice pretreated with (59)Fe 48 hr earlier. However, when toluene was administered simultaneously with benzene in à ratio of 2:1, the depression of (59)Fe uptake was prevented. Toluene reduced the appearance of benzene metabolites to 45% of controls at the higher dose and 30% at the lower dose. Thus toluene appears to inhibit benzene metabolism and by so doing, alleviates its toxicity. [REF-125]
    
    à sensitive high performance liquid chromatography method is described which separates urinary metabolites from benzene-treated male CD-1 mice. Phenol, trans, trans-muconic acid and quino in the 48 hr urine, accounted, respectively for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the orally administered single dose of benzene (880, 440, and 220 mg/kg body wt). Catechol occurred in trace amounts. Trans, trans-muconic acid was identified and was unique to benzene as none was detected in urine of mice dosed orally with phenol, catechol, or quinol. The potential existence of à toxic metabolite in the form of an aldehyde precursor of muconic acid in vivo is discussed. [REF-126]
    
    In humans, phenol sulfate is the major metabolite of benzene until 400 mg/l levels are reached in the urine. Beyond than level, glucuronide conjugates are also present in the urine. [REF-10, p.19]
    
    Male Wistar rats were tested to determine the effect of enzymes with different kinetic characteristics on the metabolism of benzene, in vitro. Kinetic analysis of the enzymes in the liver of rats fed à normal diet revealed the presence of two benzene hydroxylases with low Michaelis constant values of 0.01 millimolar and 0.07 millimolar, respectively. After 1 day of food deprivation, the isozyme with à constant equal to 0.01 millimolar disappeared while the activity of the second isozyme increased. Following the administration of phenobarbital there was evidence of à third benzene metabolizing enzyme in the liver of the animals exposed to benzene in concentrations ranging from 0.0055 to 6.25 millimolar, in vitro; the value of the Michaelis constant for this enzyme was equal to 4.5 millimolar and was not evident in control animals. Treatment with phenobarbital failed to affect the activity of the other low Michaelis constants of benzene hydroxylases identified in the liver of normal rats. Treatment with ethanol resulted in significant increase in the activity of both normally occurring benzene hydroxylases in the normal liver. [REF-127]
    
    Mitoplasts (mitochondria with the outer membrane removed) from the bone marrow of rabbits were incubated sequentially with (3)H-labeled deoxyguanosine triphosphate and (14)C-labeled benzene to study the DNA adducts formed from benzene metabolites in mitochondria. Following isolation and isopycnic density gradient centrifugation in CsCl, the doubly labeled DNA was hydrolyzed to deoxynucleosides and separated on à Sephadex LH 20 column. At least seven deoxyguanosine adducts and one deoxyadenine adduct were present. [REF-128]

BIOLOGICAL HALF/LIFE:
    
    The excretion of unchanged benzene from the lung of rats was reported to be biphasic, suggesting à two-compartment model for distribution and à half-life of 0.7 hr. This agreed with experimental half-life values for various tissues that ranged from 0.4 to 1.6 hr. [REF-129, p.C-11]

MECHANISM OF ACTION:
    
    COVALENT INTERACTION OF à BENZENE METABOLITE WITH DNA WAS SHOWN IN VIVO, BUT NO INFORMATION WAS GIVEN ABOUT THE CHEM NATURE OF THIS METABOLITE. à LIKELY INTERMEDIATE IN BENZENE METABOLISM IS BENZENE OXIDE. IN NEUTRAL AQ MEDIA IT REARRANGES ONLY SLOWLY TO THE PHENOL SO THAT ITS LIFETIME COULD BE LONG ENOUGH FOR DIFFUSION FROM THE SITE OF ACTIVATION TO THE DNA. ALTERNATIVELY, THE METABOLIC APPEARANCE OF POLYHYDROXY DERIVATIVES SUGGESTS THE FORMATION OF à PHENOL EPOXIDE, SO THAT THE REACTIVE MOLECULE COULD BE à SECONDARY METABOLITE. [REF-130]
    
    THE AVAILABLE EVIDENCE SUPPORTS THE CONCEPT THAT BENZENE TOXICITY IS CAUSED BY ONE OR MORE METABOLITES OF BENZENE. ... BENZENE METABOLITES CONTAINING 2 OR 3 HYDROXYL GROUPS INHIBITED MITOSIS. TOLUENE, WHICH INHIBITS BENZENE METABOLISM, PROTECTED ANIMALS AGAINST BENZENE-INDUCED MYELOTOXICITY. BENZENE TOXICITY COULD BE CORRELATED WITH THE APPEARANCE OF BENZENE METABOLITES IN BONE MARROW. ALTHOUGH IT IS CLEAR THAT BENZENE CAN BE METABOLIZED IN BONE MARROW, THE OBSERVATION THAT PARTIAL HEPATECTOMY PROTECTS AGAINST BENZENE TOXICITY SUGGESTS THAT à METABOLITE FORMED IN LIVER IS ESSENTIAL FOR BENZENE TOXICITY. [REF-2, p.V29 113]
    
    ... IMPORTANCE OF POLYHYDROXYLATED DERIVATIVES OF BENZENE & THEIR SEMIQUINONES. ... /IT HAS BEEN/ SHOWN THAT HYDROQUINONE INHIBITS RAT BRAIN MICROTUBULE POLYMERIZATION; THAT HYDROQUINONE & PARA-BENZOQUINONE ARE THE MOST POTENT INHIBITORS OF T- & B-LYMPHOCYTE FUNCTION, AS MEASURED IN MOUSE SPLEEN CELLS IN CULTURE; THAT HYDROQUINONE INHIBITS LECTIN-STIMULATED LYMPHOCYTE AGGLUTINATION IN RAT SPLEEN PREPN IN VITRO; & THAT PARA-BENZOQUINONE IS THE METABOLITE MOST LIKELY TO BE RESPONSIBLE FOR SUPPRESSION OF LYMPHOCYTE TRANSFORMATION & MICROTUBULE ASSEMBLY IN RAT SPLEEN CELLS IN CULTURE. HOWEVER, ADMIN OF THESE CMPD TO ANIMALS DOES NOT PRODUCE THE TYPICAL PICTURE OF BENZENE TOXICITY ... ADMIN /OF/ MAJOR METABOLITES OF BENZENE TO MICE ... FAILED TO ... DECR ... RED BLOOD CELL PRODUCTION, USING THE (59)FE UPTAKE TECHNIQUE ... /IT'S BEEN/ SUGGESTED THAT RING-OPENING PRODUCTS MAY PLAY à ROLE IN BENZENE TOXICITY. ... IN MICE BENZENE TREATMENT SUPPRESSED SUBSEQUENT COLONY FORMING UNIT-C FORMATION FROM BONE-MARROW CELLS IN VITRO. TREATING THE ANIMALS WITH PHENOL, HYDROQUINONE OR BENZENE DIHYDRODIOL FAILED TO SUPPRESS COLONY FORMING UNIT-C. THUS, THE TOXIC METABOLITES OF BENZENE HAVE YET TO BE IDENTIFIED. [REF-2, p.V29 113]
    
    ... RADIOACTIVITY /HAS BEEN DEMONSTRATED/ IN à NUCLEIC ACID FRACTION FROM RAT LIVER FOLLOWING ADMIN OF EITHER (3)H- OR (14)C-LABELLED BENZENE. IT HAS BEEN SHOWN THAT BENZENE BINDS COVALENTLY TO PROTEIN IN LIVER, BONE MARROW, KIDNEY, LUNG, SPLEEN, BLOOD, & MUSCLE. LESS COVALENT BINDING WAS OBSERVED TO THE PROTEIN OF BONE MARROW, BLOOD, & SPLEEN OF C57BL/6 MICE, WHICH ARE MORE RESISTANT TO THE BENZENE-INDUCED EFFECTS ON RED CELL PRODUCTION, THAN TO THAT OF SENSITIVE DBA/2 MICE. ... COVALENT BINDING OF BENZENE TO PROTEIN IN PERFUSED BONE-MARROW PREPN /HAS BEEN DEMONSTRATED/. ... à METABOLITE OF PHENOL BINDS TO LIVER PROTEIN MORE EFFICIENTLY THAN DOES BENZENE OXIDE, & THEY HAVE ELECTROPHORETICALLY SEPARATED HEPATIC PROTEINS TO WHICH BENZENE PREFERENTIALLY BINDS. ... COVALENT BINDING TO MITOCHONDRIA IS à PROMINENT FEATURE OF BENZENE METABOLISM. ... THERE IS RELATIVELY MORE RADIOACTIVITY IN à NUCLEIC ACID-RICH FRACTION OF à BENZENE METABOLITE ISOLATED FROM MOUSE BONE-MARROW CELLS THAN IN à SIMILAR FRACTION FROM LIVER. [REF-2, p.V29 113]
    
    EVIDENCE INDICATES THAT BENZENE MUST BE METABOLICALLY ACTIVATED IN ORDER TO EXCERT ITS CHARACTERISTIC TOXICITY ON BONE MARROW. SOME OF THE HYDROXYLATED BENZENE METABOLITES, PHENOL, CATECHOL, HYDROQUINONE, RESORCINOL & SOME TRIHYDROXYLATED DERIVATIVES IN URINE OF RABBITS ARE SUGGESTED TO BE THE TOXIC METABOLITES. [REF-131]
    
    MICE WERE GIVEN SINGLE DOSES OF BENZENE SC & ITS EFFECT ON (59)FE UPTAKE WAS EVALUATED. NO SUPPRESSION WAS FOUND AFTER 1 & 12 HR & ALSO 72 HR, WHEREAS DOSE-DEPENDENT INHIBITION OF (59)FE UPTAKE WAS OBSERVED 24 HR & 48 HR AFTER TREATMENT WITH 440 OR 2200 MG/KG DOSE. THUS, THE DATA CAN BE INTERPRETED TO SUGGEST THAT (1) BENZENE DID NOT INTERFERE WITH AN INCORPORATION OF IRON INTO HEME, (2) BENZENE INTERFERED WITH PROLIFERATION OF NORMOBLASTS & PRONORMOBLASTS, & (3) BENZENE DID NOT DAMAGE HEMOPOIETIC STEM CELLS WHICH WERE IN THE G0 STATE AT THE TIME OF BENZENE INJECTION. [REF-132]
    
    THE MECHANISM OF BENZENE OXYGENATION IN LIVER MICROSOMES & IN RECONSTITUTED ENZYME SYSTEMS FROM RABBIT LIVER WAS INVESTIGATED. THE RESULTS INDICATE THAT THE MICROSOMAL CYTOCHROME P450 DEPENDENT OXIDATION OF BENZENE IS MEDIATED BY HYDROXYL RADICALS FORMED IN à MODIFIED HABER-WEISS REACTION BETWEEN HYDROGEN PEROXIDE & SUPEROXIDE ANIONS & SUGGEST THAT ANY CELLULAR SUPEROXIDE-GENERATING SYSTEM MAY BE SUFFICIENT FOR THE METABOLIC ACTIVATION OF BENZENE & STRUCTURALLY RELATED COMPOUNDS. [REF-133]
    
    Animal expt show that benzene sensitizes the myocardium to epinephrine, so that the endogenous hormone may precipitate sudden & fatal ventricular fibrillation. [REF-53, p.III-398]
    
    When mitochondria are incubated in vitro with 2200 mg/kg of benzene there is an inhibition of RNA synthesis. Benzene also caused à dose-dependent inhibition of RNA synthesis in vitro in mitoplasts derived from cat and rabbit bone marrow mitochondria. Exogenous NADPH is required for inhibition of mitochondrial RNA synthesis in all these systems which suggests that benzene must be bioactivated within the organelle. Toluene does not inhibit RNA synthesis and the simultaneous addition of equimolar toluene and benzene results in protection against benzene inhibition. Both liver and bone marrow mitochondria incubated (3H) with benzene appear to activate benzene to à metabolite which can covalently bind to guanine residues of DNA. Benzene also inhibits mitochondrial translation. [REF-134]
    
    The protective effects of pyridine and xylene against benzene, benzo(a)pyrene, or cyclophosphamide clastogenicity were studied in mice. Swiss-ICR mice were treated orally with 220 to 880 mg/kg benzene, 150 mg/kg benzo(a)pyrene, or intraperitoneally with 50 mg/kg cyclophosphamide with or without 0 to 500 mg/kg pyridine or xylene. The mice were killed 24 to 72 hours later and the femurs were removed. The bone marrow was isolated and assayed for micronuclei. Xylene inhibited the induction of micronuclei of benzene only when given at an equimolar dose or greater. No delay in the peak micronuclei response was seen. Pyridine at 60 mg/kg completely blocked the induction of micronuclei by 880 mg/kg benzene of 24 hours. Pyridine at 25 mg/kg completely blocked the clastogenic effect of 440 mg/kg benzene at 36 to 76 hours and partially blocked micronuclei induction at 24 hours. The clastogenicity of benzo(a)pyrene was inhibited by pyridine only at doses of 100 mg/kg or more. Pyridine showed no protective effect against micronuclei induction by cyclophosphamide at any concn; micronuclei formation was enhanced by 60 to 260 mg/kg pyridine. Since the results suggested that the biological activation of benzene was due to different cytochrome p450 isozymes than the ones activating benzo(a)pyrene or cyclophosphamide, DBA/2 mice (aryl hydrocarbon hydrolase noninducible) and C57B1/6 mice with or without pretreatment with methylcholanthrene were dosed once or three times with benzene and the effects on bone marrow micronuclei were examined as before. Micronuclei formation was greater in DBA/2 mice. The effect was potentiated by methylcholanthrene. The cytochrome p450 isozyme involved in activating benzene is one of the enzymes induced by methylcholanthrene, independent of the high affinity aryl hydrocarbon hydrolase receptor. [REF-135]

INTERACTIONS:
    
    DMSO pretreatment enhances benzene metabolism and toxicity in male Wistar rats. [REF-136]
    
    BENZENE & ETHANOL INDUCED à COMMON CYTOCHROME P450 SPECIES IN RABBIT LIVER SPECIFICALLY EFFECTIVE IN HYDROXYL RADICAL-MEDIATED OXYGENATION OF ETHANOL. BENZENE OXIDATION BY THE BENZENE-INDUCIBLE FORM OF CYTOCHROME P450 WAS ALMOST COMPLETELY INHIBITED BY CATALASE, SUPEROXIDE DISMUTASE, DMSO, & MANNITOL. [REF-137]
    
    Simultaneous treatments with both benzene and toluene, or benzene and piperonyl butoxide, increased the excretion of unchanged benzene in the expired air. These compounds apparently act by inhibiting benzene metabolism. [REF-138]

                           ** PHARMACOLOGY ** 

THERAPEUTIC USES:
    
    MEDICATION (VET): DESTROYS SCREWWORM LARVAE IN WOUNDS /FORMER USE/ [QR] [REF-3, p.151]

             *** ENVIRONMENTAL FATE AND EXPOSURE POTENTIAL *** 

ENVIRONMENTAL FATE/EXPOSURE SUMMARY:
    
    Benzene will enter the atmosphere primarily from fugitive emissions and exhaust connected with its use in gasoline. Another important source is emissions associated with its production and use as an industrial intermediate. In addition, there are discharges into water from industrial effluents and losses during spills. If benzene is released to soil, it will be subject to rapid volatilization near the surface and that which does not evaporate will be highly to very highly mobile in the soil and may leach to groundwater. It may be subject to biodegradation based on reported biodegradation of 24% and 47% of the initial 20 ppm benzene in à base-rich para-brownish soil in 1 and 10 weeks, respectively. It may be subject to biodegradation in shallow, aerobic groundwaters, but probably not under anaerobic conditions. If benzene is released to water, it will be subject to rapid volatilization; the half-life for evaporation in à wind-wave tank with à moderate wind speed of 7.09 m/sec was 5.23 hrs; the estimated half-life for volatilization of benzene from à model river one meter deep flowing 1 m/sec with à wind velocity of 3 m/sec is estimated to be 2.7 hrs at 20 deg C. It will not be expected to significantly adsorb to sediment, bioconcentrate in aquatic organisms or hydrolyze. It may be subject to biodegradation based on à reported biodegradation half-life of 16 days in an aerobic river die-away test. In à marine ecosystem biodegradation occurred in 2 days after an acclimation period of 2 days and 2 weeks in the summer and spring, respectively, whereas no degradation occurred in winter. According to one experiment, benzene has à half-life of 17 days due to photodegradation which could contribute to benzene's removal in situations of cold water, poor nutrients, or other conditions less conductive to microbial degradation. If benzene is released to the atmosphere, it will exist predominantly in the vapor phase. Gas-phase benzene will not be subject to direct photolysis but it will react with photochemically produced hydroxyl radicals with à half-life of 13.4 days calculated using an experimental rate constant for the reaction. The reaction time in polluted atmospheres which contain nitrogen oxides or sulfur dioxide is accelerated with the half-life being reported as 4-6 hours. Products of photooxidation include phenol, nitrophenols, nitrobenzene, formic acid, and peroxyacetyl nitrate. Benzene is fairly soluble in water and is removed from the atmosphere in rain. The primary routes of exposure are inhalation of contaminated air, especially in areas with high traffic, and in the vicinity of gasoline service stations and consumption of contaminated drinking water. (SRC) 

ECOTOXICITY VALUES:

  . LC100 Tetrahymena pyriformis (ciliate) 12.8 mmole/l/24 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LC50 Palaemonetes pugio (grass shrimp) 27 ppm/96 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LC50 Cancer magister (crab larvae) stage 1, 108 ppm/96 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LC50 Crangon franciscorum (shrimp) 20 ppm/96 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LC50 Morone saxatilis (bass) 5.8 to 10.9 ppm/96 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LC50 Poecilia reticulata (guppy) 63 ppm/14 days /Conditions of bioassay not specified/ [REF-85, p.241]
  . LC50 Salmo trutta (brown trout yearlings) 12 mg/l/1 hr (static bioassay) [REF-85, p.241]
  . LC50 Ambystoma mexicanum (Mexican axolotl) (3-4 wk after hatching) 370 mg/l/48 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LC50 Clawed toad (3-4 wk after hatching) 190 mg/l/48 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LD50 Carassius auratus (goldfish) 46 mg/l/24 hr (modified ASTM D 1345) [REF-85, p.241]
  . LD50 Lepomis macrochirus (bluegill sunfish) 20 mg/l/24 to 48 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LD100 Lepomis macrochirus (bluegill sunfish) 34 mg/l/24 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . LD100 Lepomis macrochirus (bluegill sunfish) 60 mg/l/2 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . TLm Brine shrimp 66-21 mg/l/24 hr, 48 hr /Conditions of bioassay not specified/ [REF-85, p.241]
  . TLm Pimephales promelas (fathead minnow) 35.5 to 33.5 mg/l/24 hr, 96 hr (soft water) /Conditions of bioassay not specified/ [REF-85, p.241]
  . TLm Pimephales promelas (fathead minnow) 24.4 to 32 mg/l/24 hr, 96 hr (hard water) /Conditions of bioassay not specified/ [REF-85, p.241]
  . TLm Bluegill 22.5 mg/l/24 hr, 96 hr (soft water) /Conditions of bioassay not specified/ [REF-85, p.241]
  . TLm Carassius auratus (goldfish) 34.4 mg/l/24 hr, 96 hr (soft water) /Conditions of bioassay not specified/ [REF-85, p.241]
  . TLm Lebistes reticulata (guppy) 36.6 mg/l/24 hr, 96 hr (soft water) /Conditions of bioassay not specified/ [REF-85, p.241]
  . TLm Gambusia affinis (mosquito fish) 395 mg/l/24 hr, 96 hr /Conditions of bioassay not specified/ [REF-85, p.241]

ENVIRONMENTAL FATE:

  . TERRESTRIAL FATE: If benzene is released to soil it will be subject to rapid volatilization near the surface. That which does not evaporate will be highly to very highly mobile in soil and may leach to groundwater. The effective half-lives for volatilization without water evaporation from soil to benzene uniformly distributed to 1 and 10 cm in soil were 7.2 and 38.4 days, respectively(2). It may be subject to biodegradation based on reported biodegradation of 24% and 47% of the initial 20 ppm benzene in à based-rich para-brownish soil in 1 and 10 weeks, respectively(1). It may be subject to biodegradation in shallow, aerobic groundwaters, but probably not under anaerobic conditions. [REF-139]
  . AQUATIC FATE: If benzene is released to water, it will be subject to rapid volatilization; the half-life for evaporation in à wind-wave tank with à wind speed of 7.09 m/sec was 5.23 hrs(1); the estimated half-life for volatilization of benzene from à model river one meter deep flowing 1 m/sec with à wind velocity of 3 m/sec is estimated to be 2.7 hrs at 20 deg C(SRC). It will not be expected to significantly adsorb to sediment, bioconcentrate in aquatic organisms or hydrolyze. It may be subject to biodegradation based on à reported biodegradation half-life of 16 days in an aerobic river die-away test(2). In à marine ecosystem, biodegradation occurred in 2 days after an acclimation period of 2 days and 2 weeks in the summer and spring, respectively, whereas no degradation occurred in winter(3). [REF-140]
  . AQUATIC FATE: Evaporation was the primary loss mechanism in winter in à mesocosm experiment which simulated à northern bay where the half-life was 13 days(1). In spring and summer the half-lives were 23 and 3.1 days, respectively(1). In these cases biodegradation plays à major role and takes about 2 days(1). However, acclimation is critical and this takes much longer in the colder water in spring(1). According to one experiment, benzene has à half-life of 17 days due to photegradation(2) which could contribute to benzene's removal. In situations of cold water, poor nutrients, or other conditions less conducive to microbial, photolysis will play à important role in degradation(SRC). [REF-141]
  . ATMOSPHERIC FATE: If benzene is released to the atmosphere, it will exist predominantly in the vapor phase(3). Gas-phase benzene will not be subject to direct photolysis but it will react with photochemically produced hydroxyl radicals with à half-life of 13.4 days calculated using an experimental rate constant for the reaction. The reaction time in polluted atmospheres which contain nitrogen oxides or sulfur dioxide is accelerated with the half-life being reported as 4-6 hours(2). Products of photooxidation include phenol, nitrophenols, nitrobenzene, formic acid, and peroxyacetyl nitrate. Benzene is fairly soluble in water and is removed from the atmosphere in rain(1). [REF-142]

BIODEGRADATION:

  . No degradation of benzene as measured by BOD was reported in coarse-filtered (through 1 cm cotton layer) Superior harbor water incubated at 21 deg C for 12 days(1). Biodegradation half-lives of 28 and 16 days were reported in die-away tests for degradation of up to 3.2 ul/l benzene using groundwater and Lester River water, respectively, under aerobic conditions(2). The half-life in estuarine water was 6 days as measured by 14 C02 produced(3). In à marine ecosystem biodegradation occurred in 2 days after an acclimation period of 2 days and 2 weeks in the summer and spring, respectively, whereas no degradation occurred in winter(5). In à base-rich para-brownish soil, 20 ppm benzene was 24% degraded in 1 week, 44% in 5 weeks, and 47% in 10 weeks(4). [REF-143]
  . Benzene, in à mixture with toluene and xylenes, is readily biodegraded (total degradation of 7.5 ppm total mixture) in shallow ground water in the presence of oxygen in the unconfined sand aquifer at Canada Forces' Base Borden, Ontario; laboratory batch experiments demonstrated that the degradation could be attributed to biodegradation(1). Complete biodegradation in 16 days was reported under simulated aerobic groundwater conditions at 20 deg C(2). Reported metabolites of benzene using pure cultures of microorganisms include phenol and unidentified phenols(3), catechol and cis-1,2-dihydroxy-1,2-dihydrobenzene(4). [REF-144]
  . Benzene at 50 ppm was 90% degraded by industrial wastewater seed incubated at 23 deg C for 6 hrs(1). Benzene inhibited industrial seed at concn of 100 ppm and above and municipal seed at 50 ppm and above(1). In à bench scale activated-sludge reactor with an 8 hour retention time, complete degradation occurred with 0.5% of the benzene being lost by air stripping(2). In laboratory systems, low concentrations of benzene are degraded in 6-14 days(3,4). 44-100% removal occurred at à sewage treatment plant; percentage by evaporation and biodegradation were not determined(5). [REF-145]

ABIOTIC DEGRADATION:

  . Since gas-phase benzene(1) or benzene dissolved in cyclohexane(2) does not absorb light of 290 nm or longer, it will not be expected to directly photolize in sunlight in these media(SRC). However, slight shifts in wavelength of absorption might be expected in more representative environmental media, such as water(3); eg, à half-life of 16.9 days was reported for photolysis of benzene dissolved in deionized water saturated with air exposed to sunlight(4). The rate constant for the vapor phase reaction of benzene with photochemically produced hydroxyl radicals has been reported to be 1.2x10-12 cu cm/molecule-sec at 25 deg C(5) which corresponds to an atmospheric half-life of 13.4 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(SRC). [REF-146]
  . While benzene is considered to be relatively unreactive in photochemical smog situations (in the presence of nitrogen oxides), its rate of degradation is accelerated with about 16% decrease in concentration in 5 hr(1). à typical experiment in the presence of active species such as NOx and SO2 showed that benzene photodegradation was considerably accelerated above that in air alone(2). Its half-life in the presence of active species was 4-6 hr with 50% mineralization to CO2 in approximately 2 days(3). Products of degradation include phenol, 2-nitrophenol, 4-nitrophenol, 2,4-dinitrophenol, 2,6-dinitrophenol, nitrobenzene, formic acid, and peroxyacetyl nitrate(4-6). Hydrolysis is not à significant process for benzene(7). [REF-147]

BIOCONCENTRATION:

  . BCF: eels (Anguilla japonica) 3.5(1); pacific herring (Clupea harengus pallasi) 4.4(2); goldfish 4.3(3). Based on à reported log Kow of 2.13(4), à BCF of 24 was estimated(5,SRC). Based on the reported and estimated BCF, benzene will not be expected to bioconcentrate in aquatic organisms(SRC). [REF-148]

SOIL ADSORPTION/MOBILITY:

  . Koc: Woodburn silt loam 31(1); 31.7-143(4); 83(8). Leaches in soil, passes through soil during bank infiltration(2,3). Based on à reported log Kow of 2.13(5), à Koc of 98 was estimated(6,SRC). Based on the reported and estimated Koc values, benzene will be expected to exhibit very high to high mobility in soil(7) and therefore may leach to groundwater(SRC). [REF-149]

VOLATILIZATION FROM WATER/SOIL:

  . Half-lives for evaporation of benzene from seawater in à mesocosm simulating Narragansett Bay, RI, containing the associated planktonic and microbial communities, varied with the seasons: spring (15 Apr-18 Jun) half-life 23 days, summer (19 Aug-8 Sept) 3.1 days, winter (4 Mar-4 May) 13 days(1). The effective half-lives for volatilization without water evaporation of benzene uniformly distributed at à rate of 1 kg/ha to 1 and 10 cm in soil with an organic carbon content of 1.25% were 7.2 and 38.4 days, respectively(2). The half-life for evaporation in à wind-wave tank with à wind speed of 7.09 m/sec was 5.23 hr(3). [REF-150]
  . The estimated half-life for volatilization of benzene from à river one meter deep flowing 1 m/sec with à wind velocity of 3 m/sec is estimated to be 2.7 hrs at 20 deg C(2,SRC) based on à reported Henry's Law constant of 5.3X10-3 atm-cu m/mole(1). Based on à reported vapor pressure of 95.2 mm Hg at 25 deg C(3), evaporation of benzene from surface soil and other surfaces is expected to be rapid(SRC). [REF-151]

                     ** SOURCES AND CONCENTRATIONS ** 

NATURAL OCCURRING SOURCES: 
  . Volcano, natural constituent of crude oil, forest fires, plant volatile(1,2). [REF-152]

ARTIFICIAL SOURCES: 
  . Benzene enters the environment from production, storage, transport, venting, and combustion of gasoline; and from production, storage, and transport of benzene itself. Other sources result from its use as an intermediate in the production of other chemicals, and as à solvent, from spills, including oil spills; from its indirect production in coke ovens; from nonferrous metal manufacture, ore mining, wood processing, coal mining and textile manufacture; from cigarette smoke(1,2). [REF-152]
  . For late model cars it has been estimated that over 90% of automotive benzene comes from exhaust and less than 10% from fuel evaporation; this does not include any lost during tanker-to-station and station-to-car fuel transfers. [REF-85, p.238]
  . In 1976, an estimated 1.3 billion pounds of benzene were released into the atmosphere from 132 million stationary and mobile sources. This included an estimated 240 million pounds per year from the production, transport, storage and use of benzene; 1 billion pounds per year from the refueling and operation of motor vehicles; and 22 million pounds per year from oil spills. [REF-153, p.35]

WATER CONCENTRATIONS: 
  . DRINKING WATER: 113 public supplies, 1976, 7 sites pos, avg of positive sites <0.2 ppb(1). 5 USA cities, 1974-5, 0-0.3 ppb(2). Contaminated drinking water wells in NY, NJ, CT, 30-300 ppb; highest concn in drinking water from surface source, 4.4 ppb(3). 3 surveys of community water supplies: 0 of 111 pos; 7 of 113 pos, mean 4 ppb; 4 of 16 pos (0.95 ppb-max)(4). USA Groundwater Supply Survey (GWS, 1982, finished drinking water), 466 samples selected at random from 1000 in survey, 0.6% pos, 3 ppb median, 15 ppb max(5). Wisconsin drinking water wells, data through Jun 1984, 1174 community wells, 0.34% pos, 617 private wells, 2.9% pos(6). [REF-154]
  . GROUNDWATER: Chalk Aquifer (UK), 210 m from petrol storage, 1-10 ppb; Chalk Aquifer (UK), 120 m from petrol storage, >250 ppb; Chalk Aquifer (UK), 10 m from petrol storage, 1250 ppb; distances refer to benzene movement in groundwater(1). [REF-155]
  . SURFACE WATER: 14 heavily industrialized with basins, 1975-1976, 20% samples >1 ppb and between 1 and 7 ppb(1). Lake Erie, 1975-6, 0-1 ppb, 1 of 2 sites positive; Lake Michigan, 1975-6, 0-7 ppb, 5 of 7 sites positive(2). 700 random sites in US, 1975, 5.4 ppb avg(3). US EPA STORET database, 1,271 samples, 15.0% pos, 5.0 ppb median(4). [REF-156]
  . SEAWATER: 5-15 parts per trillion Gulf of Mexico, 1977, unpolluted areas; 5-175 parts per trillion, Gulf of Mexico, 1977, anthropogenic influence(1). [REF-157]
  . RAIN/SNOW: Detected in rainwater in Japan and in the UK (87.2 ppb)(1,2). [REF-158]
  . Benzene occurs in both ground water and surface public water supplies with higher levels occurring in ground water supplies. Based upon Federal drinking water surveys, approximately 1.3% of all ground water systems are estimated to contain benzene at levels greater than 0.5 ug/l. The highest level reported in the surveys for ground water was 80 ug/l. Approximately 3% of all surface water system are estimated to be contaminated at levels higher than 0.5 ug/l. None of the systems are expected to contain levels higher than 5 ug/l. [REF-10, p.19]

EFFLUENTS CONCENTRATIONS: 
  . Wastewater from coal preparation plants, 0.3-48 ppb(1); wastewater from plants which manufacture or use benzene <1-179 parts per trillion(1); stack emissions from coking plants (Czechoslovakia), 15-50 ppm(2); stack emission estimates from chemical plants using emissions and worst case modeling at 150 m from source, less than or equal to 5 ppm(3). Groundwater at 178 CERCLA hazardous waste sites, 11.2% pos(4). US EPA STORET database, 1,474 samples, 16.4% pos, 2.50 ppb median(5). [REF-159]
  . Industries in which mean or max levels in raw wastewater exceeded 1 ppm are (number of samples, percent pos, mean, max, in ppm): raw wastewater: auto and other laundries (20 samples, 70% pos, <1.4 ppm mean, 23 ppm max), iron and steal manufacturing (mfg) (9 samples, 77.8% pos, <8.0 mean, 46 max), aluminum forming (32 samples, 56.2% pos, 0.70 mean, 2.1 max), photographic equipment/supplies (48 samples, 54.2% pos, 0.16 mean, 2.1 max), pharmaceutical mfg (9 samples, 100% pos, 12 mean, 87 max), organic chemical/plastics mfg (number of samples not reported (NR), 63 detections, 22, NR), paint and ink formulation (36 samples, 63.9% pos, 1.2 mean, 9.9 max), petroleum refining (11 samples, number of pos NR, <0.10, 2.4), rubber processing (4 samples, 100% pos, 0.60 mean, 3.4 max), timber products processing (14 samples, 92.9% pos, 0.2 mean, 2.8 max); treated wastewater: auto and other laundries (4 samples, 50% pos, 0.1 ppm mean, 0.2 ppm max), iron and steal manufacturing (mfg) (13 samples, 76.9% pos, <14 mean, 120 max), aluminum forming (21 samples, 81.0% pos, <0.0058 mean, 0.040 max), photographic equipment/supplies (4 samples, 100% pos, 0.016 mean, 0.021 max), pharmaceutical mfg (6 samples, 100% pos, 1.8 mean, 10 max), organic chemical/plastics mfg (number of samples not reported (NR), 42 detections, 26, max NR), paint and ink formulation (24 samples, 62.5% pos, 0.39 mean, 3.8 max), petroleum refining (13 samples, NR, NR, 0.012), rubber processing (5 samples, 100% pos, <0.0077 mean, 0.010 max), timber products processing (5 samples, 60% pos, 0.010 mean, 0.033 max)(1). [REF-160]
  . Industrial sources of wastewater pollution from benzene in ug/l (avg; range): coal mining (2.6; 0-15), textile mills (<5; 0-200), timber products processing (350; 0-2,800), petroleum refining (>100; ND), paint and ink formulation (1,200; 0-9,900), gum and wood chemicals (180; 0-710), rubber processing (610; 0-3,400), auto and other laundries (840; 0-23,000), pharmaceuticals (220; 0-2,100), ore mining and dressing (2.1; 0-4.2), steam electric power (45, ND), foundries (200; ND), leather tanning and finishing (19; 0-150), nonferrous metals (11; 0-160), iron and steel (2,000; 0-43,000). /From table/ [REF-27, p.309]

SEDIMENT/SOIL CONCENTRATIONS: 
  . SEDIMENT: Surface sediments in Walvis Bay (off Capetown, SA)0-20 ppb(2). US EPA STORET database, 355 samples, 9% pos, <5.0 ppb median(3). SOIL: Soil near factories where benzene was used or produced, 2-191 ug/kg(1). [REF-161]

ATMOSPHERIC CONCENTRATIONS: 
  . BACKGROUND: Rural background avg concn 0.1-17 ppb(3). Multilatitude background concn (ppb/deg North (deg N): Atlantic Ocean 0.07/35 deg N, Pacific Ocean 0.23/45 deg N, Niwot Ridge (Colorado Rockies) 0.16-0.24 ppb(4); Pacific Ocean: Northern hemisphere 0.05, Southern hemisphere 0.01, Pacific Ocean, 0.581, Pullman, WA, 0.226, Cape Meares, OR, 0.230, Norwegian Arctic, 0.066(5). RURAL/REMOTE: US 1977-1980, 100 samples, 1.4 ppb avg(1). Barrows Alaska, 1967, 24 hr avg is 0.16 ppb in 5 of 25 samples(2). Remote tropical sites: 5 sites, range not detected to 1.8 ppb, range of avg 0.07-0.65 ppb(6). [REF-162]
  . SUBURBAN/URBAN: US 1977-1980, 2292 samples, 2.8 ppb avg(1). Toronto, 1971, 98 ppb max, 13 ppb avg, Los Angeles, 1966, 57 ppb max, 15 ppb avg(2). USA cities, 24 hr sampling for 2 weeks in 1979 (ppb): Los Angeles, Apr, 0.72-27.87, 6.04 avg, Phoenix, AZ, Apr-May, 0.39-59.89, 4.74 avg, Oakland, Jun-Jul, 0.06-4.63, 1.55 avg(3). New Jersey, 1978 (ppb): Rutherford, 149 samples, 107 max, 3.8 avg, Newark, 110 samples, 24 max, 2.6 avg, Piscataway/Middlesex, 18 samples, 1.9 max, 1.0 avg, Somerset county, 30 samples, 33 max, 5.6 avg, Bridgewater Township, 22 samples, 7.9 max, 1.4 avg(4). The general urban atmosphere, estimated avg, 0.02 ppm(5). [REF-163]
  . SOURCE DOMINATED: USA 1977-1980, 487 samples, 3.0 ppb avg(1). Concn near USA chemical factories where benzene is used 0.6-34 ppb; service stations 0.0003-3.2 ppm; cigarette smoke 57-64 ppm(3). Traffic tunnel in London, poorly ventilated, approx 0.010-0.21 ppb(2). [REF-164]
  . Ambient air samples from 44 sites in 39 USA urban areas were collected in electropolished, stainless steel canisters on week days from 6 to 9 am during June through September of 1984, 1985, and 1986. Not all sites were sampled all years. Samples were analyzed by capillary gas chromatography with flame ionization detection to determine C2 to C12 volatile hydrocarbon composition. Benzene ... was present in every sample. Individual sample concentrations median concentrations by site and year ranged from 4.8 ppb to 35.0 ppb with the overall median being 12.6 ppb. [REF-165, p.i]

FOOD SURVEY VALUES: 
  . Heat treated or canned beef 2 ug/kg; Jamaican rum 120 ug/kg; eggs 500-1900 ug/kg; detected in fruits, nuts, vegetables, dairy products, meat, fish, poultry, eggs, and beverages(1). [REF-166, p.C-5]

PLANT CONCENTRATIONS: 
  . Plant volatile(1). 2 species of macroalgae - 20 ppb(2). [REF-167]

FISH/SEAFOOD CONCENTRATIONS: 
  . Lake Pontchartrain, LA seafood (ppb wet weight): oysters (Crassostra virginica), from the Inner Harbor Navigational Canal, avg of 5 samples, 220, clams composite samples (Rangia cuneata): from Chef Menteur Pass, 260, from The Rigolets, not detected(1). [REF-168]

MILK CONCENTRATIONS: 
  . Detected in all 8 samples of mothers milk from 4 USA urban areas(1). [REF-169]

                    ** HUMAN ENVIRONMENTAL EXPOSURE ** 

PROBABLE ROUTES OF HUMAN EXPOSURE: 
  . Human populations are primarily exposed to benzene through inhalation of contaminated ambient air particularly in areas with heavy traffic and around filling stations. In addition, air close to manufacturing plants which produce or use benzene may contain high concentrations of benzene(1,2). Another source of exposure from inhalation is from tobacco smoke(1). Although most public drinking water supplies are free of benzene or contain <0.3 ppb, exposure can be very high from consumption of contaminated sources drawn from wells contaminated by leaky gasoline storage tanks, landfills, etc(SRC). Although benzene has been detected in various food items, data is too scant to estimate exposure from ingestion of contaminated food(SRC). [REF-170]
  . Human Exposure to Atmospheric Benzene from Emission Sources: Chemical manufacturing: numbers in parenthesis are annual average concentration levels in ppb, multiply these concentrations by 10 to get 8 hr worst case levels. 7,497 (0.1-1.0), 970,000 (1.1-2.0), 453,000 (2.1-4.0), 644,000 (4.1-10.0), 319,000 (>10.0), 9,883,000 (total). Coke ovens: 15,726,000 (0.1-1.0), 521,000 (1.1-2.0), 50,000 (2.1-4.0), 2,000 (4.1-10.0), 16,299,000 (total). People using gasoline service stations: 37,000,000 (total) - 245 ppb for 1.5 hr/yr/person. People residing near gasoline service stations: 87,000,000 (0.1-1.0), 31,000,000 (1.1-2.0), 118,000,000 (total). Petroleum refineries: 6,529,000 (0.1-1.0), 64,000 (1.1-2.0), 4,000 (2.1-4.0), <500 (4.1-10.0), 6,597,000 (total). Solvent operations (rubber related industries): 208,000 (0.1-10), 5,000 (1.1-2.0), 2,000 (2.1-4.0), 215,000 (total). Storage and Distribution: very few exposures (<0.1 ppb). Urban exposure (auto emissions): 68,337,000 (0.1-1.0), 45,353,000 (1.1-2.0), 113,690,000 (total)(1). [REF-171]
  . NIOSH (NOES Survey 1981-1983) has statistically estimated that 35,577 workers are exposed to benzene in the USA(1). NIOSH (NOHS Survey 1972-1974) has statistically estimated that 1,495,706 workers are exposed to benzene in the USA(2). [REF-172]
  . As estimated 3 million workers may possibly be exposed to benzene. Exposure may occur during the production of benzene or during the use of substances containing the chemical as an ingredient or contaminant. ... Because of the ubiquitous nature of benzene, more than 75 percent of the population probably has been exposed to the chemcial. [REF-153, p.35]
  . Estimates indicate that possibly 800,000 persons may be exposed to benzene from coke oven emissions at levels greater than 0.1 ppm; 5 million persons may be exposed to benzene from petroleum refinery emissions at levels of 0.1 to 1.0 ppm. [REF-153, p.35]

AVERAGE DAILY INTAKE: 
  . Avg exposure for urban/suburban residents: AIR INTAKE (assume typical range of concn 2.8-20 ppb(1,2)) 182-1300 ug; WATER INTAKE: (assume typical concn 0.1 ppb(3)) 0.2 ug; FOOD INTAKE: Insufficient data. [REF-173]

BODY BURDENS: 
  . Detected in all 8 samples of mothers' milk from 4 USA urban areas(1). Breath of persons without specific exposure to benzene 8-20 ppb(2). Whole blood, 250 subjects (121 males, 129 females), not detected-5.9 ppb, 0.8 ppb avg(3). USA FY82 National Human Adipose Tissue Survey specimens, 46 composites, 96% pos, (>4 ppb, wet tissue concn), 97 ppb max(4). [REF-174]

                    *** STANDARDS AND REGULATIONS *** 

IMMEDIATELY DANGEROUS TO LIFE OR HEALTH (IDLH): 
  . NIOSH has recommended that benzene be treated as à potential human carcinogen. [QR] [REF-5, p.26]

ACCEPTABLE DAILY INTAKES: 
  . Insufficient data are available to calculate à one-day Health Advisory for benzene. The Ten-day Health Advisory (0.235 mg/l) is considered to be adequately protective for à one-day exposure as well. ... Longer-term Health Advisories have not been calculated because of the carcinogenic potency of benzene. [REF-10, p.20]

ALLOWABLE TOLERANCES: 
  . Benzene is exempted from the requirement of à tolerance when used in accordance with good agricultural practice as inert (or occasionally active) ingredient in pesticide formulations applied to growing crops. [REF-175]

OSHA STANDARDS: 
  . The employer shall assure that no employee is exposed to an airborne concentration of benzene in excess of one part of benzene per million parts of air (1 ppm) as an 8 hr TWA. The employer shall assure that no employee is exposed to an airborne concentration of benzene in excess of 5 ppm as averaged over any 15 min period. [QR] [REF-176]
  . Permissible Exposure Limit: Table Z-2 8-hr Time Weighted Avg: 10 ppm. (Note: This standard applies to the industry segments exempt from the 1 ppm 8 hr TWA and 5 ppm STEL of the benzene standard at 1910.1028) [QR] [REF-177]
  . Permissible Exposure Limit: Table Z-2 Acceptable Ceiling Concentration: 25 ppm. (Note: This standard applies to the industry segments exempt from the 1 ppm 8 hr TWA and 5 ppm STEL of the benzene standard at 1910.1028). [QR] [REF-177]
  . Permissible Exposure Limit: Table Z-2 Acceptable maximum peak above the acceptable ceiling concentration for an 8-hour shift. Concentration: 50 ppm. Maximum Duration: 10 minutes. (Note: This standard applies to the industry segments exempt from the 1 ppm 8 hr TWA and 5 ppm STEL of the benzene standard at 1910.1028.) [QR] [REF-177]

NIOSH RECOMMENDATIONS: 
  . NIOSH recommends that the benzene be treated as à potential human carcinogen. [REF-178, p.6S]
  . NIOSH recommends that benzene be regulated as à potential human carcinogen. [QR] [REF-5, p.26]
  . NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible concn. [QR] [REF-5, p.26]
  . 10 hr Time-Weighted avg: 0.1 ppm. [QR] [REF-5, p.26]
  . 15 min Short-Term Exposure Limit: 1 ppm. [QR] [REF-5, p.26]

THRESHOLD LIMIT VALUES: 
  . 8 hr Time Weighted Avg (TWA) 0.5 ppm; 15 min Short Term Exposure Limit (STEL): 2.5 ppm, skin. [QR] [REF-179, p.19]
  . BEI (Biological Exposure Indices): S-Phenylmercapturic acid in urine (end of shift): 25 ug/g creatinine. The determinant is usually present in à significant amt in biological specimens collected from subjects who have not been occupationally exposed. Such background levels are incl in the BEI value. [QR] [REF-179, p.98]

OTHER OCCUPATIONAL PERMISSIBLE LEVELS: 
  . Belgium: TWA (skin) 30 mg/cu m, 10 ppm (1978); Czechoslovakia: TWA 50 mg/cu m, Ceiling 80 mg/cu m/10 min (1976); Finland: TWA (skin) 32 mg/cu m, 10 ppm (1975); Hungary: TWA 20 mg/cu m, may be exceeded 5 times/shift as long as avg does not exceed value (1974); Poland: Ceiling (skin) 30 mg/cu m (1976); Romania: Maximum (skin) 50 mg/cu m (1975); Switzerland: TWA (skin) 6.5 mg/cu m, 2 ppm (1978); USSR: Ceiling (skin) 5 mg/cu m (1980); Yugoslavia: Ceiling (skin) 50 mg/cu m, 15 ppm (1971). [REF-2, p.V29 97]

ATMOSPHERIC STANDARDS: 
  . National emission standard for equipment leaks (fugitive emission sources) of benzene prohibit detectable benzene emissions from processing equipment (eg, pumps, valves) that contains materials which have à benzene concn of 10% or more by wt. [REF-180]
  . This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). These standards implement Section 111 of the Clean Air Act and are based on the Administrator's determination that emissions from the SOCMI cause, or contribute significantly to, air pollution which may reasonably be anticipated to endanger public health or welfare. The intended effect of these standards is to require all newly constructed, modified, and reconstructed SOCMI process units to use the best demonstrated system of continuous emission reduction for equipment leaks of VOC, considering costs, non air quality health and environmental impact and energy requirements. Benzene is produced, as an intermediate or final product, by process units covered under this subpart. These standards of performance become effective upon promulgation but apply to affected facilities for which construction or modification commenced after January 5, 1981. [REF-181]
  . Benzene, pursuant to section 112 of the Clean Air Act, has been designated as à hazardous air pollutant. [REF-182]
  . The actual standards, if applicable, are contained in 40 CFR Part 61 Subpart V (61.240-61.247), National Emission Standards for Equipment Leaks (Fugitive Emission Sources) and refer to standards of operation of process equipment. EPA regulations establish à national emission standard for equipment leaks of benzene. They apply to pumps, compressors, pressure relief devices, sampling connecting systems, open-ended valves or lines, valves, flanges and other connectors, product accumulator vessels, can control devices, or systems intended to operate in benzene service (ie containing or contacting à fluid that is at least 10 percent benzene by weight). Equipment in plants producing or using less than 1,000 metric tons of benzene per year is exempt. The regulations do not apply to sources located in coke by-product plants (40 CFR 61.110). [REF-183]
  . EPA 5 ug/l [REF-184]
  . (AZ) ARIZONA 5 ug/l [REF-184]
  . (CA) CALIFORNIA 1 ug/l [REF-184]
  . (FL) FLORIDA 1 ug/l [REF-184]
  . (NJ) NEW JERSEY 1 ug/l [REF-184]

STATE DRINKING WATER GUIDELINES: 
  . (AZ) ARIZONA 1.3 ug/l [REF-184]
  . (CT) CONNECTICUT 1 ug/l [REF-184]
  . (ME) MAINE 5 ug/l [REF-184]
  . (MN) MINNESOTA 10 ug/l [REF-184]

CLEAN WATER ACT REQUIREMENTS: 
  . Toxic pollutant designated pursuant to section 307(a)(1) of the Clean Water Act and is subject to effluent limitations. [REF-185]
  . Designated as à hazardous substance under section 311(b)(2)(A) of the Federal Water Pollution Control Act and further regulated by the Clean Water Act Amendments of 1977 and 1978. These regulations apply to discharges of this substance. [REF-186]

TRANSPORT METHODS AND REGULATIONS: 
  . 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/ [REF-19, p.13]
  . PRECAUTIONS FOR "CARCINOGENS": When no regulations exist, the following procedure must be adopted. The carcinogen should be enclosed in à securely sealed, watertight container (primary container), which should be enclosed in à 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 à 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/ [REF-19, p.13]
  . No person may /transport,/ offer or accept à hazardous material for transportation in commerce unless that person is registered in conformance ... and the hazardous material is properly classed, described, packaged, marked, labeled, and in condition for shipment as required or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./ [QR] [REF-187]
  . The International Air Transport Association (IATA) Dangerous Goods Regulations are published by the IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and constitute à manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials. [QR] [REF-188, p.106]
  . The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and à number of recommendations for good practice are included in the classes dealing with such substances. à general index of technical names has also been compiled. This index should always be consulted when attempting to locate the appropriate procedures to be used when shipping any substance or article. [QR] [REF-189, p.3058]

RCRA REQUIREMENTS: 
  . As stipulated in 40 CFR 261.33, when benzene, as à commercial chemical product or manufacturing chemical intermediate or an off-specification commercial chemical product or à manufacturing chemical intermediate, becomes à waste, it must be managed according to Federal and/or State hazardous waste regulations. Also defined as à hazardous waste is any residue, contaminated soil, water, or other debris resulting from the cleanup of à spill, into water or on dry land, of this waste. Generators of small quantities of this waste may qualify for partial exclusion from hazardous waste regulations (see 40 CFR 261.5). [REF-190]
    When benzene is à spent solvent, it is classified as à hazardous waste from à nonspecific source (F005), as stated in 40 CFR 261.31, and must be managed according to state and/or federal hazardous waste regulations. [REF-191]
    The Environmental Protection Agency is today amending its regulations concerning ground-water monitoring with regard to screening suspected contamination at land based hazardous waste treatment, storage, and disposal facilities. The amendments replace current requirements to analyze for all Appendix VIII constituents with new requirements to analyze for a specified core list of chemicals plus those chemicals specified by the Regional Administrator on a site-specific basis. ... These final regulations become effective on September 28, 1987 which is six months from the date of promulgation, as RCRA Section 3010(b) requires. ... /Benzene is included on this list./ ... The regulatory requirements pertain only to the list of substances. /Suggested SW-846 analytical methods and Practical Quantitation Limits (PQL's) are listed./ ... CAUTION: The methods listed are representative SW-846 procedures and may not always be the most suitable method(s) for monitoring an analyte under the regulations. PQL's are the lowest concentrations of analytes in ground waters that can be reliably determined within specified limits of precision and accuracy by the indicated methods under routine laboratory operating conditions. ... CAUTION: The PQL values in many cases are based only on a general estimate for the method and not on a determination for individual compounds. PQL's are not a part of the regulation. [REF-192]

FDA REQUIREMENTS: 
  . Benzene is an indirect food additive for use only as a component of adhesives. [REF-193]

                 *** MONITORING AND ANALYSIS METHODS *** 

SAMPLING PROCEDURES:

  . ANALYTE: BENZENE; MATRIX: AIR; RANGE: 13 TO 51.8 PPM; PROCEDURE: ADSORPTION ON CHARCOAL, DESORPTION WITH CARBON DISULFIDE, GC. PRECISION: COEFFICIENT OF VARIATION 0.059 FOR TOTAL ANALYTICAL & SAMPLING METHOD IN RANGE OF 13 TO 51.8 PPM. [REF-194, p.V3]
  . Analyte: Benzene by portable GC; Matrix: air; Sampler: air bag (Tedlar); Flow rate: 0.02 to 0.05 l/min or higher; Stability: approx 4 hr [REF-195, p.V1 3700-1]
  . Analyte: Benzene; Matrix: air; Sampler: Solid sorbent tube (coconut shell charcoal, 100 mg/50 mg); Flow rate: approx 0.20 l/min; Vol: max: 30 l; Stability: at least 2 wk; Bulk sample: 1 to 10 ml, ship in separate containers from samples. [REF-195, p.V2 1500-1]
  . Analyte; Benzene; Matrix: air; Sampler: Solid sorbent tube (coconut shell charcoal, 100 mg/50 mg); Flow rate: approx 0.20 l/min; Vol: max: 30 l; Stability: not determined; Bulk sample: 1 to 10 ml, ship in separate containers from samples. [REF-195, p.V2 1501-1]

ANALYTIC LABORATORY METHODS:

  . VAPOR-PHASE ORGANICS IN AMBIENT AIR NEAR INDUSTRIAL COMPLEXES & CHEMICAL WASTE DISPOSAL SITES WERE CHARACTERIZED BY CAPILLARY GAS CHROMATOGRAPHY/MASS SPECTROMETRY/COMPUTER. /VAPOR-PHASE ORGANICS/ [REF-196]
  . A SIMPLE METHOD BASED ON A SINGLE DILUTION STEP & QUANTIFICATION BY HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) HAS BEEN DEVELOPED FOR DETERMINATION OF BENZENE IN GASOLINE. THIS STUDY INDICATES THAT APART FROM BEING FASTER & DEMANDING LESS PRETREATMENT, THE HPLC METHOD IS LESS EXPOSED TO INTERFERENCES THAN THE HIGH-RESOLUTION CAPILLARY GAS CHROMATOGRAPHY (HRGC) METHOD. [REF-197]
  . ANALYSIS OF GROUNDWATER SAMPLES OF LANDFILL SITES FOR VOLATILE ORGANIC POLLUTANTS EG BENZENE, BY GAS CHROMATOGRPAHY (GC) USING THE PURGE & TRAP METHOD ARE DISCUSSED. [REF-198]
  . GC/FID method to determine benzene in landfill vapors & soil. Adsorb landfill vapors on carbon in glass tubes; desorb with carbon disulfide: (Colenutt BA, Davies DN; Int J Environ Anal Chem 7: 223-9 (1980)). Sparge soil sample with nitrogen; trap in Tenax GC tube; limit of detection 0.1 ug/kg. (Fentiman AF et al; Environmental Monitoring Benzene (PB-295 641) - prepared for USEPA by Battelle Columbus Lab, Springfield, Va, Natl Tech Info Ser, pp 9-15, 26-110 (1979)). [REF-2, p.V29 107]
  . Analyte: Benzene; Matrix: air; Procedure: Gas chromatography (portable), photoionization detector; Range: 0.1 to 500 ppm; Est LOD: 0.15 ng/injection (0.05 ppm for a 1 ml injection); Precision: 0.127; Interferences: any compound having the same or nearly the same retention time as benzene on the column in use. [REF-195, p.V1 3700-1]
  . Analyte: Benzene; Matrix: air; Procedure: Gas chromatography, FID; Desorption: 1 ml CS2, stand 30 min; Range: 0.09 to 0.35 mg; Est LOD: 0.001 to 0.01 mg/sample with capillary column; Precision: 0.036; Interferences: other volatile organic solvents (eg, alcohols, ketones, ethers, and halogenated hydrocarbons), corrected by using more polar column or changing column temp. At high humidity breakthrough volumes may be reduced by as much as 50%. [REF-195, p.V2 1500-1]
  . EPA Method 8020: Aromatic Volatile Organics. For the detection of aromatic volatile organics, a representative sample (solid or liquid) is collected in a standard 40 ml glass screw-cap VOA vial equipped with a Teflon-faced silicone septum. Sample agitation, as well as comtamination of the sample with air, must be avoided. Two vials are filled per sample location, then placed in separate plastic bags for shipment and storage. Samples may be analyzed by direct injection or purge-and-trap using gas chromatography, with detection achieved by a photo-ionization detector (PID). A temperature program is used in the gas chromatograph to separate the organic compounds. Column 1 is a 6-ft by 0.082-in ID #304 stainless steel or glass column packed with 5% SP-1200 and 1.75% Bentone-34 on 100/120 mesh Supelcort or equivalent. Column 2 is an 8-ft by 0.1-in stainless steel or glass column packed with 5% 1,2,3-Tris(2-cyanoethoxy)propane on 60/80 mesh Chromosorb W-AW or equivalent. Under the prescribed conditions, benzene has a detection limit of 0.2 ug/l, an average recovery range of four measurements of 10.0-27.9 ug/l, and a limit for the standard deviation of 4.1 ug/l. [REF-199]
  . EPA Method 8240: Gas Chromatography/Mass Spectrometry for Volatile Organics Method 8240 can be used to quantify most volatile organic commpounds that have boiling points below 200 C (vapor pressure is approximately equal to mm Hg @ 25 C) and that are insoluble or slightly soluble in water, including the title compound. Volatile water-soluble compounds can be included in this analytical technique, however, for the more soluble compounds, quantitation limits are approximately ten times higher because of poor purging efficiency. The method is also limited to compounds that elute as sharp peaks from a GC column packed with graphitized carbon lightly coated with a carbowax (6-ft by 0.1-in ID glass, packed with 1% SP-1000 on Carbopack-B (60/80 mesh) or equivalant). This gas chromatography/mass spectrometry method is based on a purge-and-trap procedure. The practical quantitation limit (PQL) for Method 8240 for an individual compound is approximately 5 ug/kg (wet weight) for wastes and 5 ug/l for ground water. PQLs will be proportionately higher for sample extracts and samples that require dilution or reduced sample size to avoid saturation of the detector. A representative sample (solid or liquid) is collected in a standard 40 ml glass screw-cap VOA vial equipped with a Teflon-faced silicone septum. Sample agitation, as well as contamination of the sample with air, must be avoided. Two vials are filled per sample location, then placed in separate plastic bags for shipment and storage. Under the prescribed conditions, benzene has an average recovery range for four samples of 15.2-26.0 ug/l with a limit for the standard deviation of 6.9 ug/l and a retention time of 17.0 min. [REF-200]
  . EPA Method 602 A purge and trap gas chromatography method for the determination of benzene in municipal and industrial discharges consists of a stainless steel column, 6 ft x 0.85 in ID, packed with Supelcoport (100/120) coated with 5% SP-1200/1.75% Bentone-34, with photoionization detection and helium as the carrier gas at a flow rate of 36 ml/min. A sample volume of 5.0 ml is used, the column temperature is held at 50 deg C for two minutes, then programmed at 6 deg C/min to a final temperature of 90 deg C. This method has a detection limit of 0.2 ug/l, an overall precision of 0.21 times the average recovery + 0.56 over a working range of 2.1 to 550 ug/l. [REF-201]
  . EPA Method 624 - Purgeables: Grab samples of water in industrial and municipal discharges must be collected in glass containers and extracted with methylene chloride. Analysis is performed by a purge and trap gas chromatography/mass spectrometry method. Using this procedure, benzene has a method detection limit of 4.4 ug/l and an overall precision of 0.25 times the average recovery - 1.33, over a working range of 5 to 600 ug/l. [REF-202]
  . EPA Method 1624 - Volatile Organic Compounds By GC/MS: Grab samples in municipal and industrial discharges are collected. If residual chlorine is present, add sodium thiosulfate. Extraction is performed by a purge and trap apparatus. An isotope dilution gas chromatography/ mass spectrometry method for the determination of volatile organic compounds in municipal and industrial discharges is described. Unlabeled benzene has a minimum level of 10 ug/l and a mean retention time of 1212 sec. This method has an initial precision of 9.0 ug/l, an accuracy of 13.0-28.2 ug/l, and a labeled compound recovery of >0-196%. [REF-202]

CLINICAL LABORATORY METHODS:

  . Volatile cmpd such as benzene are separated from blood or tissue homogenate directly on gas-chromatographic column & detected using a flame ionization detector. High volatility permits gas chromatograph to be operated at relatively low temp. The nonvolatile & high boiling components of the biological matrix are left behind in the injection port. This insures long column life & requires only occasional cleaning of the injection chamber: Baker RN et al; Toxic volatiles in alcoholic coma; Bull Los Angles County Neurol Soc 33: 140 (1968); Wallace JE, Dahl EV; Rapid vapor phase method for determining ethanol in blood & urine by gas chromatography; Am J Clin Pathol 46: 152 (1966). [REF-203, p.378]
  . GLC & colorimetric (phenol metabolite) methods are used to determine benzene in serum, urine, & breath. Conventional reference range: >1.0 mg/l (toxic concn) for serum; <10.0 mg/l as phenol, >75.0 mg/l (toxic concn) as phenol for urine. Internationally recommended conc reference range is: >13 umol/l (toxic concn) for serum; <106 umol/l as phenol, >795 umol/l (toxic concn) as phenol for urine. Substances producing phenol as a metabolite can interfere with color assay. [REF-204, p.76]
  . GC/MS method to determine benzene in adipose tissue, brain, kidney, liver, lung, muscle, pancreas, & spleen; treat sample with chlorobenzene, ethanol & water at 60 deg C; inject vapor phase into gas chromatograph: Nagata T et al; Koenshu-lyo Masu Kenkyukai 3: 77-82 (1978), (Chem Abstr 92: 192082X). [REF-2, p.V29 107]
  . The urinary metabolites isolated by DEAE Sephadex A-24 anion-exchange chromatography from mice treated with radiolabeled benzene included phenol as the major component, as well as catechol, hydroquinone, and phenylmercapturic acid. [REF-124]
  . A sensitive HPLC method is described which separates urinary metabolites from benzene-treated male CD-1 mice phenol, trans, trans-muconic acid and quinol in the 48 hr urine, accounted, respectively for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the orally administered single dose of benzene (880, 440, and 220 mg/kg body wt). [REF-205]

                 *** MANUFACTURING AND USE INFORMATION *** 

METHODS OF MANUFACTURING: 
  . Catalytic cracking, pioneered by Houdry Corporation (WC Dickerman Jr; J Inst Pet 39: 7651 (1953)) in the 1930s, was an early source of petroleum derived aromatics. ... Processes for dehydrogenation of cycloparaffins (naphthenes) using platinum or palladium catalysts were developed & commercialized prior to 1950. Since then, dehydrocyclization catalysts that convert paraffins to aromatics have been developed. These processes, together known as catalytic reforming, have become the primary source of aromatics. In catalytic reforming, a low sulfur naphtha-range petroleum fraction is catalytically reformed to produce a high-octane product. ... Benzene & other aromatic hydrocarbons can be removed from the reformate by solvent extraction & fractional distillation of the extract to produce pure compounds. Benzene originally present in the petroleum fraction remains essentially unchanged by the process. The total benzene obtained includes this benzene & benzene from various precursors such as cyclohexane, methylcyclohexane, methylcyclopentane, & in some cases hexane. [REF-206, p.V3(78) 750]
  . The production of benzene by reforming-separation processes is assoc with the production of toluene & xylene (BTX plants). The relative production of the various aromatic hydrocarbons is a function of the feedstock, reactor conditions, catalyst, &, primarily, of the boiling range of the prod fraction subjected to solvent extraction. ... In reforming processes, cycloparaffins, such as cyclohexane, methylcyclohexane, & dimethylcyclohexanes, are converted to benzene by dehydrogenation or by dehydrogenation & dealkylation, & methylcyclopentane & dimethylcyclpentanes are converted to benzene by isomerization, dehydrogenation, & dealkylation. Straight-chain paraffins such as hexane are converted to benzene by cyclodehydrogenation. The process conditions & the catalyst determine which reaction predominate & their kinetics (Hydrocarbon Process 55 (9): 171-8 (1976); & P Bonnifay & co-workers, Oil Gas J 74 (3): 48 (1976)). [REF-206, p.V3(78) 751]
  . Toluene can be converted to benzene & xylenes by transalkylation, also called disproportionation. The disproportionation processes incl xylenes-plus (ARCO), LTD (Mobile), & Tatory (Toray Ind, with UPO). ... The steam cracking of heavy naphthas or gas oils to produce ethylene yields a liq by-product high in unsaturated aliphatic & aromatic hydrocarbons valuable as gasoline or petrochemical feedstock. This material is known as pyrolysis gasoline or dripolene. Several integrated pyrolysis gasoline treatment processes are avail including Pyrotol (Houdry) ... /which/ is designed to produce benzene alone. [REF-206, p.V3(78) 754]
  . Benzene is one of the principal components of the light oil recovered from coal carbonization gases (M Sittig, Aromatic Hydrocarbons, Manufacture and Technology, Noyes Data Corp, NJ (1976) pp.26-56). ... /A miscellaneous source of benzene is recovery/ from coal tar. The lowest boiling distillate from coal tar is extracted with caustic soda to remove the tar acids. The extracted oil is fractionated, & the benzene-containing fraction is purified by hydrodealkylation. [REF-206, p.V3(78) 755]

IMPURITIES: 
  . Major impurities are toluene and xylene, others: phenol, thiophene, carbon disulfide, acetylnitrile, and pyridine. [REF-16, p.20]

FORMULATIONS/PREPARATIONS: 
  . Nitration grade > 99% purity. [REF-14, p.20]
  . "Benzol 90" contains 80-85% benzene, 13-15% toluene, 2-3% xylene. [REF-16, p.20]
  . Commercial grades of benzene: Refined benzene-535 (free of H2S and SO2, 1 ppm max thiophene, 0.15% max nonaromatics); Refined benzene-485, Nitration-grade (free of H2S and SO2); Industrial-grade benzene (free of H2S and SO2) [REF-206, p.3(78) 762]
  . Grade: crude, straw color; motor; industrial pure (2C); nitration (1C); thiophene-free; 99 mole%; 99.94 mole%; nanograde [REF-207, p.129]

MANUFACTURERS: 
  . Amerada Hess Corp, Hq, 1185 Ave of the Americas, New York, NY 10036, (212) 997-8500; Subsidiary: Hess Oil Virgin Islands Corp; Production site: St Croix, Virgin Islands 00850 [QR] [REF-208, p.475]
  . American Petrofina Inc, Hq, PO Box 2159, Dallas, TX 75221, (214) 750-2400; Subsidiary: Fina Oil and Chemical Co; Production site: Port Arthur, TX 77640 [QR] [REF-208, p.475]
  . Amoco Corp, Hq, 200 E Randolph Dr, Chicago, IL 60601, (312) 856-6111; Subsidiary: Amoco Oil Co, 200 E Randolph Dr, Chicago, IL 60601, (312) 856-5111; Production site: Texas City, TX 77590 [QR] [REF-208, p.475]
  . Aristech Chemical Corporation, Hq, 600 Grant St, Pittsburgh, PA 15230-0250, (412) 433-2747; Production site: 400 State Street, Clairton, PA 15025 [QR] [REF-208, p.475]
  . Arochem International Inc, Hq, 300 Stamford Place, Stamford, CT 06902, (203) 357-8448; Production site: Penuelas, PR 00700 [QR]  [REF-208, p.475]
  . Ashland Oil, Inc, Hq, 1401 Winchester Avenue, Ashland, KY 41101, (606) 329-3333; Ashland Chemical Company, Division, PO Box 2219, Columbus, OH 43216; Petrochemicals Division; Production site: Leach Station, Catlettsburg, KY 41129 [QR] [REF-208, p.475]
  . Atlantic Richfield Co, Hq, Arco Towers, Atlantic Richfield Plaza, Los Angeles, CA 90071, (213) 486-3511; Lyondell Petrochemical Co, division, One Houston Center, 1221 McKinney, Suite 1600, PO Box 3646, Houston, TX 77253-3646; Production sites: Channelview, TX 77530; Houston, TX 77001 [QR] [REF-208, p.475]
  . BP America, Inc, Hq, 200 Public Sq, Cleveland, OH 44114-2375, (216) 586-4141; Subsidiary: BP Chemicals America, Inc; Production site: Lima, OH 45802; Sohio Oil Company; Production site: Alliance, LA 70037 [QR] [REF-208, p.475]
  . Champlin Refining & Chemicals Inc, Hq, PO Box 160066, Irving, TX 75016-0066, (214) 402-7000; Production site: Corpus Christi, TX 78469 [QR] [REF-208, p.475]
  . Chevron Corp, Hq, 225 Bush St, San Francisco, CA 94104, (415) 894-7700; Subsidiary: Chevron Chemical Co, Aromatics and Derivatives Division, PO Box 3766, Houston, TX 77253; Production sites: Philadelphia, PA 19101; Port Arthur, TX 77640 [QR] [REF-208, p.475]
  . Citgo Petroleum Corp, Hq, 6130 S Yale St, Tulsa, OK 74136, (918) 495-4000; Production site: Lake Charles, LA 70601 [QR] [REF-208, p.475]
  . The Coastal Corp, Hq, 9 Greenway Plaza, Houston, TX 77046, (713) 877-1400; Subsidiaries: Coastal Eagle Point Oil Co (address same as Hq), (713) 877-6553; Production site: Westville, NJ 08093; Coastal Refining and Marketing, Inc (address same as Hq); Production site: Corpus Christi, TX 78403 [QR] [REF-208, p.476]
  . Crown Central Petroleum Corp, Hq, One N Charles, The Blaustein Building, Baltimore, MD 21203, (301) 539-7400; Chemical Division, 4747 Bellaire Boulevard, Bellaire, TX 77401; Production site: Pasadena, TX 77501 [QR] [REF-208, p.476]
  . Dow Chemical USA, Hq, 2020 Dow Center, Midland, MI 48674, (517) 636-1000; Production sites: Freeport, TX 77541; Plaquemine, LA 70764 [QR] [REF-208, p.476]
  . Exxon Corp, Hq, 1251 Ave of the Americas, New York, NY 10020, (212) 333-1000; Exxon Chemical Co, division, Exxon Chemical Americas, PO Box 3272, Houston, TX 77001; Production sites: Baton Rouge, LA 70821; Bayton, TX 77520 [QR] [REF-208, p.476]
  . Hoechst Celanese Corp, Hq, Route 202-206 N, Somerville, NJ 08876, (201) 231-2000; Engineering Plastics Group, 1 Main St, Chatham, NJ 07928; Production site: Bayport, TX 77062 [QR] [REF-208, p.476]
  . Kerr-McGee Corp, Hq, Kerr-McGee Center, PO Box 25861, Oklahoma City, OK 73125, (405) 270-1313; Subsidiary: Kerr-McGee Refining Corp; Southwestern Refining Co, Inc; Production site: Corpus Christi, TX 78469 [QR] [REF-208, p.476]
  . Koch Industries, Inc, Hq, PO Box 2256, Wichita, KS 67201, (316) 832-5500; Subsidiary: Koch Refining Co, PO Box 2256, Wichita, KS 67201, (316) 832-5259; Production site: Corpus Christi, TX 78403 [QR] [REF-208, p.476]
  . Mobil Corp, Mobil Oil Corp, Hq, 150 East 42nd St, New York, NY 10017, (212) 883-4242; Mobil Chemical Company, division, 100 First Stamford Place, PO Box 10070, Stamford, CT 06904-2070; Petrochemicals Division, World Towers One, 15600 JF Kennedy Boulevard, Houston, TX 77032-2343; Production site: Beaumont, TX 77704; US Marketing and Refining Division; Production site: Chalmette, LA 70043 [QR] [REF-208, p.476]
  . Occidental Petroleum Corporation, Hq, 10889 Wilshire Blvd, Suite 1500, Los Angeles, CA 90024, (213) 879-1700; Subsidiary: Cain Chemical Inc, 5 Greenway Plaza, Suite 2500, Houston, TX 77227-7702, (713) 623-2246; Petrochemical Division; Production sites: Chocolate Bayou, TX 77511; Corpus Christi, TX 78410-0940 [QR] [REF-208, p.476]
  . Phillips Petroleum Company, Hq, Phillips Building, Bartlesville, OK 74004, (918) 661-6600; Subsidiaries: Phillips 66 Company; Chemicals Division; Specialty Chemicals, 352 Adams Building, Bartlesville, OK 74004, (918) 661-7066; Production site: Sweeny, TX 77480; Phillips Puerto Rico Core Inc, 15th Floor, Banco Popular Center, Hato, PR 00936; Production site: Guayama, PR 00654 [QR] [REF-208, p.476]
  . Salomon Inc, Hq, 1221 Ave of the Americas, New York, NY 10036, (212) 764-3700; Phibro Energy, Inc, 600 Steamboat Rd, Greenwich, CT 06830; Hill Petroleum; Hill Chemical Co, PO Box 5038, Houston, TX 77262; Production site: Houston, TX 77012 [QR] [REF-208, p.476]
  . Shell Oil Company, Hq, One Shell Plaza, PO Box 2463, Houston, TX 77252-2463, (713) 241-6161; Shell Chemical Company, division (address same as Hq); Production sites: Deer Park, TX 77536 (Houston Plant); Odessa, TX 79760; Wood River, IL 62095 [QR] [REF-208, p.476]
  . Sun Company, Inc, Hq, 100 Matsonford Road, Radner, PA 19087, (215) 293-6000; Subsidiary: Sun Refining and Marketing Company, 1801 Market Street, Philadelphia, PA 19103, (215) 977-3000; Production sites: Marcus Hook, PA 19061; Toledo, OH 43693; Tulsa, OK 74102 [QR] [REF-208, p.476]
  . Texaco Inc, Hq, 2000 Westchester Ave, White Plains, NY 10650, (914) 253-4000; Subsidiary: Texaco Chemical Co, 4800 Fournace Pl, PO Box 430, Bellaire, TX 77401, (713) 666-8000; Production sites: Delaware City, DE 19706; El Dorado, KS 67042; Port Arthur, TX 77640 [QR] [REF-208, p.476]
  . Unocal Corp, Hq, 1201 W Fifth St, PO Box 7600, Los Angeles, CA 90051, (213) 977-7600; Subsidiary: Union Oil Co of California, Union Oil Center, 1201 W 5th St, Los Angeles, CA 90017, (213) 977-7600; Oil & Gas Division; Production sites: Beaumont, TX 77704 (Refinery); Chicago, IL 60690 [QR] [REF-208, p.477]
  . USX Corporation, Hq, 600 Grant Street, Pittsburgh, PA 15219-4776, (412) 433-1121; Subsidiary: Marathon Oil Co; Marathon Petroleum Company, subsidiary, 539 South Main Street, Findlay, OH 45840, (419) 422-2121; Production site: Texas City, TX 77592-1191 [QR] [REF-208, p.477]

OTHER MANUFACTURING INFORMATION: 
  . Benzene is a component of gasoline; European concn 5-16%, USA concn 0.3-2.0% averaging 0.8%. [REF-16, p.21]
  . An aromatic fraction containing benzene was known in the 18th century as a product of the distillation of coal. Benzene, or bicarburet of hydrogen as it was called, was first isolated in 1825 by Faraday, who obtained if from a liq condensed by compressing oil gas. In 1833 Mitscherlich obtained bicarburet of hydrogen by distilling benzoic acid with lime & suggested the name benzin ... . Liebig objected & proposed the name benzole. In 1843 benzene was found by AW Hoffman in light oil derived from coal tar. The commercial recovery of benzene from this source was developed & described by Mansfield in 1849. ... Discovery of benzene in coal gas after 1876 initiated the recovery of coal gas light oil as a source. ... Although petroleum was known to contain benzene, recovery ... was not undertaken on a commercial scale until about 1941. [REF-206, p.V3(78) 744]
  . PURIFICATION BY WASHING WITH WATER: BRITISH PATENT 863,711 (1961 TO SCHLOVEN-CHEMIE AND KOPPERS GMBH), CHEM ABSTR 55: 16971F (1961). LAB PREPN BY DIAZOTIZATION OF ANILINE, FOLLOWED BY REDUCTION OF THE DIAZOTIZATION SALT IN SODIUM HYDROXIDE SOLN USING STANNOUS CHLORIDE: GATTERMANN-WIELAND, PRAXIS DES ORGANISCHEN CHEMIKERS (DE GRUYTER, BERLIN, 40TH ED: 247 (1961)). [REF-3, p.151]
  . The pure compound is now called benzene, the name approved by the IUPAC & adopted by the MCA & the ASTM. The term benzol is used to describe commercial products that are largely benzene, & is rarely seen in the USA but is still found in British publications. Benzene ... should not be confused with the product benzin or benzine ... . [REF-206, p.V3(78) 744]
  . The Comission of European Communities ... prohibit the use of benzene in products intended for use as toys (eg, children's balloons). [REF-2, p.V29 98]
  . ... Benzene has been banned as ingredient in products intended for use in the home. [REF-53, p.III-398]
  . The 16th highest-volume chemical produced in USA (1985) [REF-207, p.129]

MAJOR USES: 
  . MFR MEDICINAL CHEM, DYES, ORG CMPD, ARTIFICIAL LEATHER, LINOLEUM, OIL CLOTH, VARNISHES, LACQUERS; SOLVENT FOR WAXES, RESINS, OILS /USE AS SOLVENT IS NOW DISCOURAGED/ [REF-3, p.151]
  . Used for printing & lithography, paint, rubber, dry cleaning, adhesives & coatings, detergents [REF-16, p.20]
  . Extraction and rectification; preparation and use of inks in the graphic arts industries; as a thinner for paints; as a degreasing agent [REF-209, p.96]
  . [SRI] CHEM INT FOR ETHYLBENZENE, CUMENE, CYCLOHEXANE, NITROBENZENE, MALEIC ANHYDRIDE, CHLOROBENZENES, DETERGENT ALKYLATE, ANTHRAQUINONE, BENZENE HEXACHLORIDE, BENZENE SULFONIC ACID, BIPHENYL, HYDROQUINONE, & RESORCINOL 
  . /Benzol for/ pesticidal uses /has been/ cancelled. /It/ was in use alone or in formulations for screwworm control on animals. /It was/ an ingredient of some early grain fumigants [REF-210, p.C-35]
  . In the tire industry (McMichael et al, 1975), & in shoe factories (Aksoy et al, 1974), benzene is used extensively. [REF-29, p.1638]
  . Used primarily as a raw material in the synthesis of styrene (polystyrene plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon), aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents), chlorobenzenes, and other products used in the production of drugs, dyes, insecticides, and plastics. [REF-211]
  . MEDICATION (VET): [QR]

CONSUMPTION PATTERNS:
    Consumption by chemical industry in USA, 1977: 1.4 billion gallons annually. [REF-212, p.296]
    [SRI] CHEM INT FOR ETHYLBENZENE, 49.1%; CHEM INT FOR CUMENE, 18.4%; CHEM INT FOR  CYCLOHEXANE, 15.1%; CHEM INT FOR NITROBENZENE, 4.5%; CHEM INT FOR MALEIC  ANHYDRIDE, 2.8%; CHEM INT FOR CHLOROBENZENES, 2.5%; CHEM INT FOR DETERGENT  ALKYLATE, 2.4%; EXPORTS, 2.7%; OTHER USES, 2.5% (1981 NON-GASOLINE USES) 
    Demand: (1980) 1,586 Million Gal; /Projected demand for/ (1984): 1,708 Million Gal [REF-213]
    BENZENE RANKED 17TH IN 1981 & 1982 IN THE TOP 50 CHEMICAL PRODUCTION: BILLIONS OF LB: 7.87 (1982), 9.61 (1981). [REF-214]
    Ethylbenzene/styrene, 52%; cumene/phenol, 22%; clyclohexane, 15%; nitrobenzene/aniline, 4.5%; detergent alkylate, 2.5%; chlorobenzenes, maleic anhydride and other, 3%; exports, 1% (1984) [REF-215]
    USA benzene demand /is projected to/ climb /from/ 3.8% in 1987, to 5.7 million tons, and reach 6 million tons in 1990 (1987 and 1990) [REF-216]
    In future, coal will increasingly replace petroleum & natural gas as a source of hydrocarbons both for fuel & petrochemicals. Processes such as USA Steel Corporation's Clean Coke process, which yields 38% coke & 20% chemical by-products compared to 73% coke & 2% chemical by-products in conventional coking technology, should soon be used commercially. New coking, liquefaction, & gasification processes for coal are all potential sources of benzene. [REF-206, p.V3(78) 756]
    CHEMICAL PROFILE: Benzene. Ethylbenzene/styrene, 55%; cumene/phenol, 21%; cyclohexane, 14%; nitrobenzene/aniline, 5%; detergent alkylate, 3%; chlorobenzenes, exports and others, 2%. [REF-217]
    CHEMICAL PROFILE: Benzene. Demand: 1986: 1,603 million gal; 1987: 1,667 million gal; 1991 /projected/: 1,790 million gal. (Includes imports; 155 million gal were imported in 1986.) [REF-217]

U.S. PRODUCTION:
    (1967) 9.6X10+8 gal (data reported by tar distillers are not included) [REF-218, p.10]
    [SRI] (1977) 4.80X10+12 G 
    (1980) 1.5X10+9 gal (data reported by tar distillers are not included) [REF-218, p.10]
    (1981) 4.3X10+11 GRAMS [REF-219]
    (1981) 1.3X10+9 gal (all grades produced from light-oil distillates of tar and tar crudes) [REF-218, p.9]
    [SRI] (1982) 3.55X10+12 G 
    (1985) 3.74X10+9 g (98-100% pure from petroleum and natural gas) [REF-220, p.19]
    (1985) 5.16X10+8 g (90-97.9% pure from petroleum and natural gas) [REF-220, p.19]
    (1986) 4.39X10+11 g [REF-216]
    (1986) 1.39X10+9 gal [REF-221]
    (1987) 1.59X10+9 gal (est) [REF-221]
    Benzene ranks 16th in production volume for chemicals produced in the USA, with approx 9.9 billion lb being produced in 1984, 9.1 billion lb in 1983, and 7.8 billion lb in 1982. [REF-222]
    (1990) 12.45 billion lb [REF-223]
    (1991) 11.49 billion lb [REF-224]
    (1992) 11.27 billion lb [REF-225]
    (1993) 12.32 billion lb [REF-225]

U.S. IMPORTS:
    [SRI] (1978) 2.26X10+11 G 
    (1979) 1.6 billion kg [REF-226, p.28]
    [SRI] (1983) 4.93X10+11 G 
    (1985) 4.96X10+11 g [REF-227, p.1-546]
    (1986) 4.72X10+11 g [REF-216]
    (1986) 1.56X10+8 lb [REF-228, p.1-492]
    Imports in 1987 were estimated to total 175 million gallons. [REF-229, p.96]

U.S. EXPORTS:
    [SRI] (1978) 1.52X10+11 G 
    [SRI] (1983) 3.66X10+10 G 
    (1979) 1.3 million lb [REF-226, p.28]
    (1985) 3.77X10+10 g [REF-230, p.2-69]
    Exports were thought to be less than 10 million gallons. [REF-231, p.11]

                 *** CHEMICAL AND PHYSICAL PROPERTIES ***

MOLECULAR WEIGHT             : 78.11 [REF-3, p.151]
MELTING POINT                : 5.5 DEG C [REF-75, p.V7 203]
BOILING POINT                : 80.1 DEG C [REF-3, p.151]
DENSITY/SPECIFIC GRAVITY     : 0.8787 AT 15 DEG C/4 DEG C [REF-3, p.151]
VAPOR DENSITY                : 2.7 (AIR= 1) [REF-8, p.1222]
VAPOR PRESSURE               : 100 MM HG AT 26.1 DEG C [REF-13, p.361]
OCTANOL/WATER PARTITION COEFFICIENT:
                               log Kow= 2.13 [REF-232]
CRITICAL TEMPERATURE AND PRESSURE:
                               288.9 deg C; 48.6 atm [REF-4, p.F-65]
RELATIVE EVAPORATION RATE    : 2.8 (ether= 1) [REF-233, p.34]
VISCOSITY                    : 0.6468 mPa's @ 20 C [REF-234, p.4]
SURFACE TENSION              : 28.9 DYNES/CM (0.0289 NEWTONS/M AT 20 DEG C) [REF-9]
HEAT OF COMBUSTION           : -9698 cal/g (17,460 Btu/lb, or -406.0X10+5 J/kg) [REF-9]
HEAT OF VAPORIZATION         : Latent heat of vaporization: 94.1 cal/g (169 Btu/lb, or 3.94X10+5 J/kg) [REF-9]

SOLUBILITIES: 
  . 0.180 g/100 g of water at 25 deg C [REF-206, p.V3(78) 746]
  . MISCIBLE WITH ALCOHOL, CHLOROFORM, ETHER, CARBON DISULFIDE, ACETONE, OILS, CARBON TETRACHLORIDE, & GLACIAL ACETIC ACID [REF-3, p.151]

SPECTRAL PROPERTIES: 
  . MAX ABSORPTION (ALCOHOL): 243 NM (LOG E= 2.2), 249 NM (LOG E= 2.3), 256 NM (LOG E= 2.4), 261 NM (LOG E= 2.2); SADTLER REF NUMBER: 6402 (IR, PRISM), 1765 (UV) [REF-4, p.C-146]
  . INDEX OF REFRACTION: 1.50108 AT 20 DEG C/D [REF-3, p.151]
  . UV: 198 (Sadtler Research Laboratories Spectral Collection) [REF-235, p.V1 154]
  . MASS: 102 (Atlas of Mass Spectral Data, John Wiley & Sons, New York) [REF-235, p.V1 154]
  . IR: 136 (Sadtler Research Laboratories IR Grating Collection) [REF-235, p.V1 154]
  . NMR: 3429 (Sadtler Research Laboratories Spectral Collection) [REF-235, p.V1 154]
  . Intense mass spectral peaks: 78 m/z [REF-236, p.73]

OTHER CHEMICAL/PHYSICAL: 
  . Conversion factors: 1 ppm= 3.242 mg/cu m at 20 C [REF-85, p.113]
  . SPECIFIC DISPERSION 189.6; DENSITY OF SATURATED VAPOR-AIR MIXT AT 760 MM HG (AIR= 1) IS 1.22 AT 26 DEG C; PERCENT IN SATURATED IN AIR AT 760 MM HG IS 13.15 AT 26 DEG C [REF-8, p.1222]
  . Blood/air partition coefficient is 7.8 [REF-237, p.49]
  . Sublimes -30 to 5 deg C [REF-4, p.C-664]
  . Heat of fusion 30.45 cal/g; 127.40 J/g; 9,951 J/mol [REF-4, p.C-668]
  . Heat capacity: 135.6 (liquid), 81.6 (gas) J/mol deg K at 1 atm (to convert to calories/mol-K multiply by 0.2390057) [REF-4, p.D-174]
  . Vapors burn with smoky flame [REF-113, p.116]
  . Very useful compilations of the thermodynamic properties of benzene are given by Rossini & co-workers, Selected Values of Physical and Thermodynamic Properties of Hydrocarbons and Related Compounds, Amer Petrol Res Proj 44, Carnegie Press, Pittsburgh, PA (1953); and in American Petroleum Insititute Project 44, data sheets, API Data Distribution Office, A&M; Press, College Station, Texas [REF-206, p.V3(78) 745]
  . A comprehensive collection of general properties of benzene, thermodynamic & transport properties, & benzene in binary multicomponent systems is contained in Hancock & co-workers, Benzene and Its Industrial Derivatives, John Wiley & Sons, Inc, New York, 1975 pp.97-117 [REF-206, p.V3(78) 745]

                           *** REFERENCES *** 

SPECIAL REPORTS:

  . DHHS/NTP; Sixth Annual Report on Carcinogens (1991)
  . DHHS/NTP; Toxicology & Carcinogenesis Studies of Benzene in F344/N Rats and B6C3F1 Mice (Gavage Studies) Technical Report Series No. 289 (1986) NIH Publication No. 86-2545
  . DHHS/ATSDR; Toxicological Profile for Benzene (Update) TP-92/03 (1993)
  . WHO; Environmental Health Criteria 150: Benzene (1993)
  . DHHS/NTP; Seventh Annual Report on Carcinogens (1994)
  . U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) for Benzene (71-43-2) Toxicological Review in Adobe PDF. Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of October 16, 1998.

PRIOR HISTORY OF ACCIDENTS:

  . /On June 30, 1992/ a derailed tank car fell 135 feet from a trestle cracking open and spilling most of its 26,200 gallons of benzene solution into the Nemadji River in Wisconsin. /This accident/ resulted in a 10 hr evacuation of more than 50,000 people. About 25 persons went to hospitals in Superior, WI and Duluth, MN complaining of dizziness, headaches, and burning eyes and skin, after a noxious gas cloud enveloped low-lying areas. The vapor was dispersed later that day by wind and rain. [REF-238]

REFERENCES:

  REF- 1:  NIOSH; Criteria Document: Benzene  (1974) DHEW Pub No 74-137
  REF- 2:  IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).  (1982)
  REF- 3:  The Merck Index. 10th ed. Rahway, New Jersey: Merck Co., Inc., 1983. 
  REF- 4:  Weast, R.C. (ed.) Handbook of Chemistry and Physics, 68th ed. Boca Raton, Florida: CRC Press Inc., 1987-1988. 
  REF- 5:  NIOSH. «NIOSH Pocket Guide» to Chemical Hazards. DHHS (NIOSH) Publication No. 94-116. Washington, D.C.: U.S. Government Printing Office, June 1994. 
  REF- 6:  National Fire Protection Association. Fire Protection Guide on Hazardous Materials. 9th ed. Boston, MA: National Fire Protection Association, 1986. 
  REF- 7:  USEPA; Supplement to Development Doc: Haz Subset Regs Sect 311, FWPCA, (1975) EPA 440/9-75-009
  REF- 8:  Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963. 
  REF- 9:  U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5.
  REF- 10:  USEPA; Health Advisories for 25 Organics: Benzene (1987) PB 87-235578
  REF- 11:  Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982. 
  REF- 12:  U.S. Department of Transportation. 1996 North American Emergency Response Guidebook. A Guidebook for First Responders During the Initial Phase of aHazardous Materials/Dangerous Goods Incident. U.S. Department of Transportation (U.S. DOT) Research and Special Programs Administration, Office of HazardousMaterials Initiatives and Training (DHM-50), Washington, D.C. (1996). 
  REF- 13:  Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984. 
  REF- 14:  Environment Canada; Tech Info for Problem Spills: Benzene (Draft) (1981)
  REF- 15:  Bretherick, L. Handbook of Reactive Chemical Hazards. 3rd ed. Boston, MA: Butterworths, 1985. 
  REF- 16:  NIOSH; Criteria Document: Benzene (1974) DHEW Pub No 74-137
  REF- 17:  NIOSH; Criteria Document: Benzene (1974) DHEW Pub. No. 74-137
  REF- 18:  Dreisbach, R.H. Handbook of Poisoning. 12th ed. Norwalk, CT: Appleton and Lange, 1987. 
  REF- 19:  Montesano, R., H. Bartsch, E.Boyland, G. Della Porta, L. Fishbein, R. A. Griesemer, A.B. Swan, L. Tomatis, and W. Davis (eds.). Handling Chemical Carcinogens in the Laboratory:Problems of Safety. IARC Scientific Publications No. 33. Lyon, France: International Agency for Research on Cancer, 1979. 
  REF- 20:  ACGIH; Guidelines Select of Chem Protect Clothing Volume #1 Field Guide (1983)
  REF- 21:  NIOSH. Pocket Guide to Chemical Hazards. 2nd Printing. DHHS (NIOSH) Publ. No. 85-114. Washington, D.C.: U.S. Dept. of Health and Human Services, NIOSH/Supt.of Documents, GPO, February 1987. 
  REF- 22:  USEPA; Methods to Treat, Control and Monitor Spilled Hazardous Materials, EPA-670/2-75-042 (1975) EPA 670/2-75-042
  REF- 23:  USEPA; Intermedia Priority Pollutant Guidance Documents (July, 1982)
  REF- 24:  United Nations. Treatment and Disposal Methods for Waste Chemicals (IRPTC File). Data Profile Series No. 5. Geneva, Switzerland: United Nations Environmental Programme, Dec. 1985. 
  REF- 25:  USEPA; Management of Hazardous Waste Leachate, EPA Contract No. 68-03-2766 (1982)
  REF- 26:  USEPA; Engineering Handbook for Hazardous Waste Incineration (1981) EPA 68-03-3025
  REF- 27:  Patterson JW; Industrial Wastewater Treatment Technolgy 2nd Edition (1985)
  REF- 28:  KOCSIS JJ ET AL; SCIENCE 160: 427 (1968)
  REF- 29:  Gilman, A.G., L.S.Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 7th ed. New York: Macmillan Publishing Co., Inc., 1985. 
  REF- 30:  Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986. 
  REF- 31:  Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975. 
  REF- 32:  Thienes, C., and T.J. Haley. Clinical Toxicology. 5th ed. Philadelphia: Lea and Febiger, 1972. 
  REF- 33:  GERNER-SMIDT P, FRIEDRICH U; MUTAT RES 58 (2-3): 313-6 (1978)
  REF- 34:  MNATSAKANOV ST, POGOSYAN AS; BIOL ZH ARM 26 (12): 38-43 (1973)
  REF- 35:  SNYDER R ET AL; LIFE SCIENCES 21 (12): 1709-22 (1977)
  REF- 36:  VIGLIANI EC, FORNI A; ENVIRON RES 11 (1): 122-7 (1976)
  REF- 37:  Morimoto K; Japan J Ind Health 8: 23-5 (1976)
  REF- 38:  European Chemical Industry, Ecology and Toxicology Center (1984)
  REF- 39:  Vigliani EC; Ann NY Acad Sci 271: 143 (1976)
  REF- 40:  Pagnotto LD et al; Am Ind Hyg Assoc J 40: 137 (1979)
  REF- 41:  Funes-Cravioto F et al; Lancet p. 322 (1977) as cited in USEPA; Ambient Water Quality Criteria for Benzene (1980) EPA 440/5-80-018
  REF- 42:  Vigliani EC, Forni A; J Occup Med 11 p.148 (1969) as cited in USEPA; Ambient Water Quality Criteria for Benzene (1980) EPA 440/5-80-018
  REF- 43:  USEPA; Ambient Water Quality Criteria for Benzene (1980) EPA 440/5-80-018
  REF- 44:  Infante PF et al; Lancet p. 322 (1977) as cited in USEPA; Ambient Water Quality Criteria: Benzene (1980) EPA 440/5-80-018
  REF- 45:  Savilahti M; Arch Gewerbpathol Gewerbhyg 15: 147-57 (1956)
  REF- 46:  Ott MG et al; Arch Environ Health 33: 3-10 (1978)
  REF- 47:  Towsent et al; J Occup Med 20: 543-8 (1978)
  REF- 48:  Waldbott GL; Health Eff of Envir Poll (1973)
  REF- 49:  MORIMOTO K; CANCER RES 43 (3): 1330-4 (1983)
  REF- 50:  DECOUFLE P ET AL; ENVIRON RES 30 (1): 16-25 (1983)
  REF- 51:  CHIRCU V ET AL; REV ROUM MED INTERNE 19 (4): 373-8 (1981)
  REF- 52:  Mehlman MA, ed; Adv Mod Environ Toxicol Vol IV: Carcinogenicity and Toxicity of Benzene (1983)
  REF- 53:  Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984. 
  REF- 54:  Askoy M; Brit J Haematol 66 (2): 209-11 (1987)
  REF- 55:  Askoy M et al; Brit J Indust Med 44 (11): 785-7 (1987)
  REF- 56:  Austin H et al; Am J Epidemiol 127 (3): 419-39 (1988)
  REF- 57:  Brandt L; Med Oncol Tumor Pharmacother 4 (3/4): 199-205 (1987)
  REF- 58:  deJong G et al; Mutat Res 204 (3): 451-64 (1988)
  REF- 59:  Flandrin G, Collado S; Brit J Haematol 67 (1): 119-20 (1987)
  REF- 60:  Ng JP et al; Brit J Haematol 67 (1): 116 (1987)
  REF- 61:  Inove O et al; Internat Arch Occupat Environ Health 60 (1): 15-20 (1988)
  REF- 62:  Jin C et al; Br J Ind Med 44 (2): 124-8 (1987)
  REF- 63:  Sandler DP, Collman GW; Amer J Epidemcol 126 (6): 1017-32 (1987)
  REF- 64:  Schwartz E; Amer J Indust Med 12 (1): 91-9 (1987)
  REF- 65:  Sokolov VV, Frasch VN; J Hyg Epidemiol Microbiol Immunol 31 (2): 135-43 (1987)
  REF- 66:  Souza V, Puig M; Mutat Res 189 (3): 357-62 (1987)
  REF- 67:  Wong O; Brit J Indust Med 44 (6): 382-95 (1987)
  REF- 68:  Wong O; Brit J Indust Med 44 (6): 365-81 (1987)
  REF- 69:  Yin S et al; Indust Health 25 (3): 113-30 (1987)
  REF- 70:  Yin SN et al; Br J Ind Med 44 (3): 192-5 (1987)
  REF- 71:  SORSA M ET AL; TERATOG CARCINOG MUTAGEN 2 (2): 137-50 (1982)
  REF- 72:  Brandt L; Med Oncol Tumor Pharmacother 2 (1): 7-10 (1985)
  REF- 73:  Wallace L et al; Arch Environ Health 42 (5): 272-9 (1987)
  REF- 74:  National Research Council. Drinking Water & Health Volume 1. Washington, DC: National Academy Press, 1977. 
  REF- 75:  IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).  (1974)
  REF- 76:  American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH:American Conference of Governmental Industrial Hygienists, 1986. 
  REF- 77:  GREEN JD ET AL; TOXICOL APPL PHARMACOL 46 (1): 9-18 (1978)
  REF- 78:  Dobrokhotov VB; Gig Sanit 37: 36 (1972)
  REF- 79:  Siou G et al; Mutat Res 90: 273-8 (1981)
  REF- 80:  Schmidt W; Mutat Res 31: 9-15 (1975)
  REF- 81:  Gofmekler VA; Hyg Sanit 33: 327 (1968)
  REF- 82:  USEPA; Ambient Water Quality Criteria: Benzene (1980) EPA 440/5-80-018
  REF- 83:  Ward JM et al; Arch Environ Health 30 (22): (1975) as cited in USEPA; Ambient Water Quality Criteria: Benzene (1980) EPA 440/5-80-018
  REF- 84:  CANTELMO A ET AL; PHYSIOL MECH MAR POLLUT TOXIC (PROC SYMP POLLUT MAR ORG): 349-89 (1982)
  REF- 85:  Verschueren, K. Handbook of Environmental Data of Organic Chemicals. 2nd ed. New York, NY: Van Nostrand Reinhold Co., 1983. 
  REF- 86:  Keller KA, Snyder CA; Toxicology 42: 171-81 (1986)
  REF- 87:  USEPA; ECAO Atlas Document: Benzene IV-11 (1980)
  REF- 88:  Crebelli R et al; Mutagenesis 2 (3): 235-8 (1987)
  REF- 89:  Cronkite BP; Blood Cells 12 (1): 129-37 (1986)
  REF- 90:  Kalf GF; CRC Crit Rev Toxicol 18 (2): 141-59 (1987)
  REF- 91:  King AG et al; Mol Pharmacol 32 (6): 807-12 (1987)
  REF- 92:  Lewis JG et al; Toxicol Appl Pharmacol 92 (2): 246-54 (1988)
  REF- 93:  Li GL et al; J Toxicol Environ Health 19 (4): 581-9 (1986)
  REF- 94:  Maronpot RR; Environ Health Perspect 73: 125-30 (1987)
  REF- 95:  Moszczynski P, Lisiewicz J; Med Pr 36 (5): 316-24 (1985)
  REF- 96:  Siddiqui SM et al; Toxicol 48 (3): 245-51 (1988)
  REF- 97:  Suleiman SA; Arch Toxicol 59 (6): 402-7 (1987)
  REF- 98:  Toxicology & Carcinogenesis Studies of Benzene in F344/N Rats and B6C3F1 Mice (Gavage Studies). Technical Report Series No. 289 (1986) NIH Publication No. 86-2545 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
  REF- 99:  IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer,1972-PRESENT. (Multivolume work).  (1987)
  REF- 100:  American Conference of Governmental Industrial Hygienists. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents and BiologicalExposure Indices (BEIs) for 1995-1996. Cincinnati, OH: ACGIH, 1995. 
  REF- 101:  U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) for Benzene (71-43-2) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of October 16, 1998
  REF- 102:  Toxicology & Carcinogenesis Studies of Benzene in F344/N Rats and B6C3F1 Mice (Gavage Studies). Technical Report Series No. 289 (1986) NIH Publication No. 86-2545 U.S. Department of Health and Human Services, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 Abstract available at http://ntp-server.niehs.nih.gov/htdocs/pub.html
  REF- 103:  Bio Dynamics Inc.; An Inhalation Female Fertility Study With Benzene in Rats, Final Report. (1980), EPA Document No. FYI-AX-0481-0110, Fiche No. 0110-0 
  REF- 104:  Hazelton Laboratories America, Inc.; Inhalation Teratology Study in Rats, Benzene, Final Report. (1982), EPA Document No. FYI-AX-0482-0127, Fiche No. 0127-0 
  REF- 105:  Bio/dynamics Inc.; A Dominant-Lethal Inhalation Study with Benzene in Rats, Final Report, (1980), EPA Document No. FYI-AX-0481-0110, Fiche No. OTS0000110-0 
  REF- 106:  Hazleton Laboratories America Inc.; Subchronic Inhalation Study in Mice and Rats, Final Report, (1983), EPA Document No. FYI-AX-0783-0203, Fiche No. OTS0000203-1 
  REF- 107:  Brookhaven National Laboratory; Evaluation of Micronuclei Frequency in the Peripheral Blood of Male and Female CD-1 Mice Exposed Chemically to Benzene for 90 Days, Final Report, (1985), EPA Document No. FYI-AX-1085-0393, Fiche No. OTS0000393-1 
  REF- 108:  Bio/dynamics Inc.; Determination of Time to Steady State Level in Blood During Inhalation Exposure of Benzene to Rats and Mice, (1980), EPA Document No. FYI-AX-0281-0104, Fiche No. OTS0000104-0 
  REF- 109:  Bio/dynamics Inc.; Determination of Benzene, Phenol, Catechol and Hydroquinone in the Blood of Rats and Mice After Inhalation Exposure to Benzene at Various Concentrations, (1980), EPA Document No. FYI-AX-0281-0104, Fiche No. OTS0000104-0 
  REF- 110:  Bio/dynamics Inc.; Part II: Determination of Material Balance in Rats, (1980), EPA Document No. FYI-AX-0281-0104, Fiche No. OTS0000104-0 
  REF- 111:  Oak Ridge National Laboratory; Toxicokinetics of Percutaneous Penetration of Petroleum Products, Draft Final Report, (no date), EPA Document No. FYI-AX-0685-0356, Fiche No. OTS0000356-1 
  REF- 112:  Bio/dynamics Inc.; Part I: Determination of Benzene Uptake by the Lungs in Rats and Mice, Under Conditions of Prolonged Exposure, (no date), EPA Document No. FYI-AX-0281-0104, Fiche No. OTS0000104-0 
  REF- 113:  International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983. 
  REF- 114:  Casarett, L.J., and J. Doull. Toxicology: The Basic Science of Poisons. New York: MacMillan Publishing Co., 1975. 
  REF- 115:  SNYDER R ET AL; RES COMMUN CHEM PATHOL PHARMACOL 20 (1): 191-4 (1978)
  REF- 116:  Andrews LS et al; Biochem Pharmacol 26: 293 (1977)
  REF- 117:  USEPA; ECAO Atlas Document: Benzene IV-1 (1980)
  REF- 118:  Rickert DE et al; Toxicol Appl Pharmacol 49: 417-23 (1979)
  REF- 119:  Goodman LS, Gilmann A; The Pharm Basis of Therapeutics (1970)
  REF- 120:  Blank IH, McAuliffe DJ; J Investigat Dermatol 85: 522-6 (1985)
  REF- 121:  Goodwin, B.L. Handbook of Intermediary Metabolism of Aromatic Compounds. New York: Wiley, 1976. 
  REF- 122:  Jerina D, Daly JW; Science 185: 573 (1974) as cited in USEPA; Ambient Water Quality Criteria: Benzene (1980) EPA 440/5-80-018
  REF- 123:  Snyder R et al; Adv Exp Biol 136A: 245-56 (1982)
  REF- 124:  Longacre SL et al; Adv Exp Med Biol 136A: 307-17 (1982)
  REF- 125:  Snyder R et al; Adv Mod Environ Toxicol 4: 123-36 (1983)
  REF- 126:  Gadel K et al; Xenobiotica 15: 211-20 (1985)
  REF- 127:  Nakajima T et al; Biochemical Pharmacol 36 (17): 2799-804 (1987)
  REF- 128:  Snyder R et al; Arch Toxicol 60 (1-3): 61-4 (1987)
  REF- 129:  Rickert DE et al; Toxicol Appl Pharmacol 49: 417 (1979) as cited in USEPA; Ambient Water Quality Criteria: Benzene (1980) EPA 440/5-80-018
  REF- 130:  LUTZ WK, SCHLATTER C; CHEM BIOL INTERACT 18 (2): 241-6 (1977)
  REF- 131:  SNYDER R ET AL; BIOLOGICAL REACTIVE INTERMEDIATES II, PART A, PLENUM PUBLISHING CORP 245 (1982)
  REF- 132:  LEE EW ET AL; ENVIRON HEALTH PERSPECTIVE 39: 29-37 (1981)
  REF- 133:  JOHANSSON I, INGELMAN-SUNDBERG M; J BIO CHEM 258 (12): 7311-6 (1983)
  REF- 134:  Kalf GF et al; Chem-Biol Interact 42 (3): 353-70 (1982)
  REF- 135:  Harper BL, Legator MS; Mutat Res 179 (1): 23-31 (1987)
  REF- 136:  Kocsis JJ et al; Science 160: 427 (1968)
  REF- 137:  INGELMAN-SUNDBERG M ET AL; DEV BIOCHEM 23 (ISS CYTOCHROME P450, BIOCHEM BIOPHYS ENVIRON IMPLIC): 19-26 (1982)
  REF- 138:  USEPA; ECAO Atlas Document: Benzene IV-12 (1980)
  REF- 139:  (1) Haider K et al; Arch Microbiol 96: 183-200 (1974) (2) Jury WA et al; J Environ Qual 13: 573-9 (1984)
  REF- 140:  (1) Mackay D, Yeun ATK; Environ Sci Technol 17: 211-7 (1983) (2) Vaishnav DD, Babeu L; Bull Environ Contam Toxicol 39: 237-44 (1987) (3) Wakeman SG et al; Bull Environ Contam Toxicol 31: 582-4 (1983)
  REF- 141:  (1) Wakeham SG et al; Bull Environ Contam Toxicol 31: 582-4 (1983) (2) Hustert K et al; Chemosphere 10: 995-8 (1981)
  REF- 142:  (1) Kato T et al; Yokohama Kokuritsu Diagaku Kankyo Kagaku Kenkyu Senta Kiyo 6: 11-20 (1980) (2) Korte F, Klein W; Ecotox Environ Saftey 6: 311-27 (1982) (3) Eisenreich SJ et al; Environ Sci Technol 15: 30-8 (1981)
  REF- 143:  (1) Vaishnav DD, Babeu L; J Great Lakes Res 12: 184-91 (1986) (2) Vaishnav DD, Babeu L; Bull Environ Contam Toxicol 39: 237-44 (1987) (3) Lee RF, Ryan C; Microbial Degradation of Pollutants in Marine Environments. pp. 443-50 USEPA-600/9-72-012 (1979) (4) Haider K et al; Arch Microbiol 96: 183-200 (1974) (5) Wakeman SG et al; Bull Environ Contam Toxicol 31: 582-4 (1983)
  REF- 144:  (1) Barker Jf et al; Ground Water Monit Rev 7: 64-72 (1987) (2) Delfino JJ, Miles CJ; Soil Crop Sci Soc FL Proc 44: 9-14 (1985) (3) Smith RV, Rosazza SP; Arch Biochem Biophys 161: 551-8 (1974) (4) Gibson DT et al; Biochem 7: 2653-62 (1968)
  REF- 145:  (1) Davis EM et al; Water Res 15: 1125-7 (1981) (2) Stover EL, Kincannon DF; J Water Pollut Control Fed 55: 97-109 (1983) (3) Setzkorn EA, Huddleston RL; J Amer Oil Chem Soc 42: 1081-4 (1965) (4) Tabak HH et al; J Water Pollut Control Fed 53: 1503-18 (1981) (5) Feiler HD et al; Proc Natl Conf Munic Sludge Manag 8th, pp. 72-81 (1979)
  REF- 146:  (1) Noyes WA et al; J Chem Phys 44: 2100-6 (1966) (2) Silverstein RM, Bassler GC; p. 166 in: Spectrometric Identification of Organic Compounds 2nd ed. (1968) (3) Howard PH, Durkin PR; Sources of Contamination, ambient levels, and fate of benzene in the environment. pp. 65 USEPA-560/5-75-005 (1974) (4) Hustert K et al; Chemosphere 10: 995-8 (1981) (5) Perry RA et al; J Phys Chem 81: 296-304 (1977)
  REF- 147:  (1) Farley FF; Inter Conf on Photochemical Oxidant Pollution and Its Control. pp. 713-27 USEPA-600/3-77-001B (1977) (2) Yanagihara S et al; Proc Int Clean Air Cong 4th, pp. 472-7 (1977) (3) Korte F, Klein W; Ecotox Environ Saftey 6: 311-27 (1982) (4) Nojima K et al; Chemosphere 4: 77-82 (1975) (5) Hoshino M et al; Kokuritsu Kogai Kekyusho Kenkyu Hokoku 5: 43-59 (1978) (6) Kopczynski SL; Int J Air Water Pollut 8: 107-20 (1964) (7) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. NY: McGraw-Hill pp. 7-4 (1982)
  REF- 148:  (1) Ogata M, Miyake Y; Water Res 12: 1041-4 (1978) (2) Korn S et al; Fish Bull Natl Marine Fish Ser 75: 633-6 (1977) (3) Ogata M et al; Bull Environ Contam Toxicol 33: 561-7 (1984) (4) Hansch C, Leo AJ; Medchem Project Issue No. 26 Claremont, CA: Pomona College (1985) (5) Lyman WJ et al; Handbook of Chem Property Estimation Methods NY: McGraw-Hill p. 5-5 (1982)
  REF- 149:  (1) Chiou CT et al; Environ Sci Technol 17: 227-31 (1983) (2) Piet GJ, Morra CF; pp. 31-42 in Artifical Groundwater Recharge L Huisman, Tl Olsthorn eds Marshfield MA; Pitman Pub (1983) (3) Green WJ et al; J Water Pollut Control Fed 53: 1347-54 (1981) (4) Sabljic A; J Agric Food Chem 32: 243-6 (1984) (5) Hansch C, Leo AJ; Medchem Project Issue No. 26 Claremont, CA: Pomona College (1985) (6) Lyman WJ et al; Handbook of Chem Property Estimation Methods NY: McGraw-Hill p. 4-9 (1982) (7) Swann RL et al; Res Rev 85: 17-28 (1983) (8) Kenaga EE; Ecotox Environ Safety 4: 26-38 (1980)
  REF- 150:  (1) Wakeham SG et al; Environ Sci Technol 17: 611-7 (1983) (2) Jury WA et al; J Environ Qual 13: 573-9 (1984) (3) Mackay D, Yeun ATK; Environ Sci Technol 17: 211-7 (1983)
  REF- 151:  (1) Hine J, Mookerjee PK; J Org Chem 40: 292-8 (1975) (2) Lyman WJ et al; Handbook of Chem Property Estimation Methods NY: McGraw-Hill pp. 15-9 to 15-31 (1982) (3) Riddick JA et al; Organic Solvents: Physical Properties and Methods of Purification. Techniques of Chemistry 4th ed. Wiley-Interscience pp. 1325 (1986)
  REF- 152:  (1) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99-106 (1982) (2) Graedel TE; Chemical Cmpds in the Atmos, New York, NY: Academic Press (1978)
  REF- 153:  DHHS/NTP; Fourth Annual Report On Carcinogens (1985) NTP 85-002
  REF- 154:  (1) Brass HJ et al; Drinking Water Qual Enhancement Source Prot pp. 393-416 (1977) (2) Coleman WE et al; Analysis and Identification of Organic Substances in Water. L Keith ed, Ann Arbor MI: Ann Arbor Press Chapt 21, pp. 305-27 (1976) (3) Burmaster DE; Environ 24: 6-13,33-6 (1982) (4) NAS; Drinking Water and Health, Vol 3 (1980) (5) Cotruvo JA; Sci Total Environ 47: 7-26 (1985) (6) Krill RM, Sonzogni WC; J Am Water Works Assoc 78: 70-5 (1986)
  REF- 155:  (1) Tester DJ, Harker RJ; Water Pollut Control 80: 614-31 (1981)
  REF- 156:  (1) Ewing BB et al; Monitoring to Detect Previously Unrecognized Pollutants in Surface Waters. 75 pp. USEPA-560/6-77-015 (1977) (2) Konasewich D et al; Great Lake Water Qual Board (1978) (3) Kraybill HF; NY Acad Sci Annals 298: 80-9 (1977) (4) Staples CA et al; Environ Toxicol Chem 4: 131-42 (1985)
  REF- 157:  (1) Sauer TC Jr; Org Geochem 3: 91-101 (1981)
  REF- 158:  (1) Kato T et al; Yokohama Kokuritsu Daigaku Kankyo Kagaku Kenkyu Senta Kiyo 6: 11-20 (1980) (2) IARC; Monograph. Some Industrial Chemicals and Dyestuffs. 29: 99-106 (1982)
  REF- 159:  (1) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99-106 (1982) (2) SRI; Human Exposure to Atmospheric Benzene, Menlo Park, CA: SRI, Center for Resource and Environmental (1977) (3) Fentiman AF et al; Environmental Monitoring Benzene pp. 105-10 (PB-295641) (1979) (4) Plumb H Jr; Ground Water Monit Rev 7: 94-100 (1987) (5) Staples CA et al; Environ Toxicol Chem 4: 131-42 (1985)
  REF- 160:  (1) US EPA; Treatability Manual. p. I.9.1-1 to I.9.1-5 USEPA-600/2-82-001A (1981)
  REF- 161:  (1) IARC; Monograph. Some Industrial Chemicals and Dyestuffs 29: 99-106 (1982) (2) Whelan JK et al; Geochim Cosmochim Acta 44: 1767-85 (1980) (3) Staples CA et al; Environ Toxicol Chem 4: 131-42 (1985)
  REF- 162:  (1) Brodzinsky R, Singh HB; Volatile Organic Chemicals In The Atmosphere: An Assessment Of Available Data 198 pp. SRI Inter 68-02-3452 (1982) (2) Cavanagh LA et al; Environ Sci Technol 3: 251-7 (1969) (3) IARC; monograph. Some Industrial Chemicals and Dyestuffs 29: 99-106 (1982) (4) Singh HB et al; Atmos Environ 19: 1911-9 (1985) (5) Nutmagul W, Cronn DR; J Atmos Chem 2: 415-33 (1985) (6) Greenberg JP, Zimmerman PR; Am Chem Soc Div Environ Chem 192nd Natl Mtg 26: 10-3 (1986)
  REF- 163:  (1) Brodzinsky R, Singh HB; Volatile Organic Chemicals In The Atmosphere: An Assessment Of Available Data 198 pp. SRI Inter 68-02-3452 (1982) (2) Pilar S, Graydon WF; Environ Sci Technol 7: 628-712 (1973) (3) Singh WB et al; Atmos Environ 15: 601-20 (1981) (4) Bozzelli JW, Kebbekus BB; Analysis Of Selected Volatile Organic Substances In Ambient Air. Newark, NJ: NJ Inst Technol 80 pp. (1979) (5) IARC; monograph. Some Industrial Chemicals and Dyestuffs 29: 99-106 (1982)
  REF- 164:  (1) Brodzinsky R, Singh HB; Volatile Organic Chemicals In The Atmosphere: An Assessment Of Available Data 198 pp. SRI Inter 68-02-3452 (1982) (2) Tsani-Bazaca E et al; Environ Technol Lett 2: 303-16 (1981) (3) IARC; monograph. Some Industrial Chemicals and Dyestuffs 29: 99-106 (1982)
  REF- 165:  USEPA; June-September, 6-9 AM, Ambient Air Benzene Concentrations In 39 U.S. Cities, 1984-1986 (1987)
  REF- 166:  (1) USEPA; Ambient Water Quality Criteria: Benzene  EPA-440/5-80-018 (1980)
  REF- 167:  (1) Graedel TC; Chem Cmpds Atmos New York NY: Academic Press (1978) (2) Whelan JK et al; Nature 299: 50-2 (1982)
  REF- 168:  (1) Ferrario JB et al; Bull Environ Contam Toxicol 34: 246-55 (1985)
  REF- 169:  (1) Pellizzari ED et al; Environ Sci Technol 16: 781-5 (1982)
  REF- 170:  (1) IARC; Monograph, Some Industrial Chem and Dyestuffs 29: 99-106 (1982) (2) Graedel TE; Chem Compounds in the Atmos, New York, NY Academic Press (1978)
  REF- 171:  (1) Stanford Research Institute; Human Exposure to Atmospheric Benzene. Center for Resource and Environmental Studies Report No. 30, p 3, Menlo Park, CA: SRI (1977)
  REF- 172:  (1) NIOSH; The National Occupational Exposure Survey (NOES) (1983) (2) NIOSH; The National Occupational Hazard Survey (NOHS) (1974)
  REF- 173:  (1) Brodzinsky R, Singh HB; Volatile Organic Chemicals In The Atmosphere: An Assessment Of Available Fata 198 pp. SRI Inter 68-02-3452 (1982) (2) IARC; monograph. Some Industrial Chemicals and Dyestuffs 29: 99-106 (1982) (3) Brass HJ et al; Drinking Water Qual Enhancement Source Prot pp 393-416 (1977)
  REF- 174:  (1) Pellizzari ED et al; Environ Sci Technol 16: 781-5 (1982) (2) IARC; Monograph. Some Industrial Chemicals and Dyestuffs. 29: 99-106 (1982) (3) Antoine SR et al; Bull Environ Contam Toxicol 36: 364-71 (1986) (4) Stanley JS; Broad Scan Analysis of the FY82 National Human Adipose Tissue Survey Specimens Vol. I Executive Summary p. 5 USEPA-560/5-86-035 (1986)
  REF- 175:  40 CFR 180.1001(d) (7/1/87)
  REF- 176:  29 CFR 1910.1028(c) (7/1/98)
  REF- 177:  29 CFR 1910.1000 (7/1/98)
  REF- 178:  NIOSH/CDC. NIOSH Recommendations for Occupational Safety and Health Standards Sept. 1986. (Supplement to Morbidity and Mortality Weekly Report 35 No. 15, Sept. 26, 1986) 
  REF- 179:  American Conference of Governmental Industrial Hygienists. Threshold Limit Values (TLVs) for Chemical Substances and Physical Agents Biological Exposure Indices for 1998. Cincinnati, OH: ACGIH, 1998. 
  REF- 180:  40 CFR 61.110 (7/1/87)
  REF- 181:  40 CFR 60.489 (7/1/87)
  REF- 182:  40 CFR 61.01 (7/1/87)
  REF- 183:  40 CFR 61.240 (7/1/87)
  REF- 184:  USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93)
  REF- 185:  40 CFR 401.15 (7/1/87)
  REF- 186:  40 CFR 116.4 (7/1/87)
  REF- 187:  49 CFR 171.2 (7/1/96)
  REF- 188:  IATA. Dangerous Goods Regulations. 38th ed. Montreal, Canada and Geneva, Switzerland: International Air Transport Association, Dangerous Goods Board, January, 1997. 
  REF- 189:  IMDG; International Maritime Dangerous Goods Code; International Maritime Organization (1988)
  REF- 190:  53 FR 13382 (4/22/88)
  REF- 191:  40 CFR 261.31 (7/1/87)
  REF- 192:  52 FR 25942 (7/9/87)
  REF- 193:  21 CFR 175.105 (4/1/88)
  REF- 194:  U.S. Department of Health, Education Welfare, Public Health Service. Center for Disease Control, National Institute for Occupational Safety Health. NIOSH Manual ofAnalytical Methods. 2nd ed. Volumes 1-7. Washington, DC: U.S. Government Printing Office, 1977-present.  S311
  REF- 195:  U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSHManual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984. 
  REF- 196:  PELLIZZARI ED; ENVIRON SCI TECHNOL 16 (11): 781-5 (1982)
  REF- 197:  STRAY H; J CHROMATOGR 248 (1): 155-9 (1982)
  REF- 198:  KOZLOSKI RP, SAWHNEY BL; BULL ENVIRON CONTAM TOXICOL 29 (1): 1-6 (1982)
  REF- 199:  USEPA: Test Methods for Evaluating Solid Waste SW-846 (1986)
  REF- 200:  USEPA; Test Methods for Evaluating Solid Waste SW-846 (1986)
  REF- 201:  40 CFR 136.1 (7/1/87)
  REF- 202:  40 CFR 136 (7/1/87)
  REF- 203:  Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975. 
  REF- 204:  Tietz, N.W. (ed.). Clinical Guide to Laboratory Tests. Philadelphia, PA: W.B. Saunders Co., 1983. 
  REF- 205:  Gad-el Karim et al; Xerobiotic 15: 211-20 (1985)
  REF- 206:  Kirk-Othmer Encyclopedia of Chemical Technology. 3rd ed., Volumes 1-26. New York, NY: John Wiley and Sons, 1978-1984. 
  REF- 207:  Sax, N.I. and R.J. Lewis, Sr. (eds.). Hawley's Condensed Chemical Dictionary. 11th ed. New York: Van Nostrand Reinhold Co., 1987. 
  REF- 208:  SRI. 1989 Directory of Chemical Producers - United States of America. Menlo Park, CA: SRI International, 1989. 
  REF- 209:  Fishbein L; Potential Indust Carcins & Mutagens (1977) USEPA 560/ 5-77-005
  REF- 210:  Farm Chemicals Handbook 87. Willoughby, Ohio: Meister Publishing Co., 1987. 
  REF- 211:  NTP; Toxicology and Carcinogenesis Studies of Benzene p.24 Report# 289 (1986) NIH Pub# 86-2545
  REF- 212:  Fishbein L; Pot Ind Carcin & Muta (1977) EPA 560/5-77-005
  REF- 213:  Kavaler. Chem Market Reporter (1981)
  REF- 214:  CHEMICAL & ENGINEERING NEWS; MAY 2: 11 (1983)
  REF- 215:  CHEMICAL PROFILE: Benzene, (1984)
  REF- 216:  CHEM WEEK 140 (14): 14 (1987)
  REF- 217:  Kavaler AR; Chemical Marketing Reporter 231 (24): 49 (1987)
  REF- 218:  United States International Trade Commission. Synthetic Organic Chemicals-- United States Production and Sales, 1981. USITC Publications 1291 Washington, DC: United States InternationalTrade Commission, 1981. 
  REF- 219:  United States International Trade Commission. Synthetic Organic Chemicals-- United States Production and Sales, 1981. USITC Publications 1291 Washington, DC: United States InternationalTrade Commission, 1981.
  REF- 220:  USITC. SYN ORG CHEM-U.S. PROD/SALES 1985
  REF- 221:  USITC. SYN ORG CHEM-U.S. PROD/SALES. PRELIMINARY 1987
  REF- 222:  Chemical & Engineering News p.11-20 (5/6/85) as cited in Toxicology and Carcinogenesis Studies of Benzene p.24 Report# 289 (1986) NIH Pub# 86-2545
  REF- 223:  Chem & Engineering News 70 (15): 17 (4/13/92)
  REF- 224:  Chem & Engineering News 71 (15): 11 (4/12/93)
  REF- 225:  Chem & Engineering News 72 (15): 13 (4/11/94)
  REF- 226:  DHHS/NTP; Third Annual Report On Carcinogens (1983) NTP 82-330
  REF- 227:  BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1985 
  REF- 228:  BUREAU OF THE CENSUS. US IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1986
  REF- 229:  Chemical & Engineering News p.11 (2/9/87) as cited in DHHS/ATSDR; Toxicological Profile for Benzene (Draft) (Dec/1987)
  REF- 230:  BUREAU OF THE CENSUS. U.S. EXPORTS, SCHEDULE E, 1985
  REF- 231:  Chemical & Engineering News (2/9/87)
  REF- 232:  Hansch C, Leo AJ; Medchem Project Issue No.26 Claremont, CA: Pomona College (1985)
  REF- 233:  AAI, Alliance of American Insurers, Handbook of Organic Industrial Solvents (1980) as cited in DHHS/ATSDR; Toxicological Profile for Benzene (Draft) (Dec/1987)
  REF- 234:  Cheremisinoff PN; Benzene - Basic and Hazardous Props (1979) as cited in Environment Canada; Tech Info for Problem Spills: Benzene (Draft) (1981)
  REF- 235:  Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985. 
  REF- 236:  Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, FederalRepublic of Germany. 1985. 
  REF- 237:  Sato A, Nakajima T; Toxicol Appl Pharmacol 48 (1979)
  REF- 238:  C&E; News 70 (27): 5 (1992)

                          ***  END OF RECORD  ***