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SUBSTANCE IDENTIFICATION

HSDB Chemical Name 2,4-TOLUENE DIISOCYANATE
HSDB Number 874
Last Revision Date 2005/08/23
Last Review Date Reviewed by SRP on 9/15/2001
CAS Registry Number 584-84-9

Synonyms
AI3-15101; BENZENE, 2,4-DIISOCYANATO-1-METHYL-; CRESORCINOL DIISOCYANATE [REF-1, p.3193]; DESMODUR T80; DI-ISOCYANATE DE TOLUYLENE (FRENCH); DI-ISO-CYANATOLUENE; 2,4-DIISOCYANATO-1-METHYLBENZENE; 2,4-DIISOCYANATOTOLUENE; DIISOCYANAT-TOLUOL (GERMAN); HYLENE T; HYLENE TCPA [REF-1, p.3193]; HYLENE TLC; HYLENE TM [REF-1, p.3193]; HYLENE TM-65 [REF-1, p.3193]; HYLENE TRF [REF-1, p.3193]; ISOCYANIC ACID, METHYLPHENYLENE ESTER [REF-1, p.3193]; ISOCYANIC ACID, 4-METHYL-M-PHENYLENE ESTER; 4-Methyl-meta-phenylene diisocyanate [REF-2, p.V39 287]; 4-METHYL-PHENYLENE DIISOCYANATE; 4-METHYL-M-PHENYLENE ISOCYANATE; 4-METHYL-PHENYLENE ISOCYANATE; MONDUR TD; MONDUR TD-80; MONDUR TDS; NACCONATE 100 [REF-1, p.3193]; NCI-C50533; NIAX TDI [REF-1, p.3193]; NIAX TDI-P [REF-1, p.3193]; RUBINATE TDI 80/20 [REF-1, p.3193]; 2,4-TDI; TDI-80 [REF-1, p.3193]; TOLUEEN-DIISOCYANAAT (DUTCH); TOLUEN-DISOCIANATO (ITALIAN); META-TOLUENE DIISOCYANATE [REF-3, p.II-414]; TOLUENE-2,4-DIISOCYANATE; TOLUENE, 2,4-DIISOCYANATO- [REF-4, p.1026]; TOLUILENODWUIZOCYJANIAN (POLISH); TOLUYLENE-2,4-DIISOCYANATE; TOLYENE-2,4-DIISOCYANATE; TOLYLENE DIISOCYANATE [REF-3, p.II-414]; m-Tolylene diisocyanate [REF-5, p.527]; TOLYLENE-2,4-DIISOCYANATE; TULUYLENDIISOCYANAT (GERMAN)

Molecular Formula C9-H6-N2-O2

Shipping Number/Name
UN 2078; Toluene diisocyanate IMO 6.1; Toluene diisocyanate

STCC Number/Name
49 215 75; Toluene diisocyanate

DESCRIPTION AND WARNING PROPERTIES

Color/Form
A WATER-WHITE LIQ WHICH TURNS STRAW-COLORED ON STANDING [REF-18, p.1161] Clear to light yellow liq or crystals [REF-19, p.970] Colorless to pale yellow, solid or liquid (above 71 deg F). [REF-20, p.312]

Odor
Sharp, pungent [REF-7, p.1626]

Odor Threshold
The odor threshold is 0.4 ppm in about half of the subjects. [REF-30, p.3165] 0.4-2.14 ppm /Purity not specified/ [REF-9] Air: 0.17 ul/l; odor safety class E; E= Less than 10% of attentive persons can detect the TLV. [REF-31] Odor recognition in air: 2.10 ppm (purity) [REF-32, p.158] Odor low= 3.2 mg/cu m; High= 17.12 mg/cu m [REF-33]

Skin, Eye, And Respiratory Irritations
AS A VAPOR ... /TOLUENE DIISOCYANATE/ IS A POWERFUL IRRITANT TO EYES, SKIN, RESPIRATORY TRACT. /TOLUENE DIISOCYANATE/ [REF-3, p.II-414] A severe skin and eye irritant. Capable of producing severe dermatitis and bronchial spasm. [REF-1, p.3194]

SAFETY HAZARDS AND PROTECTION

DOT Emergency Guidelines
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Fire or Explosion: Combustible material: may burn but does not ignite readily. Substance will react with water (some violently) releasing flammable, toxic or corrosive gases and runoff. When heated, vapors may form explosive mixtures with air: indoors, outdoors and sewers explosion hazards. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapors may travel to source of ignition and flash back. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated or if contaminated with water. /Toluene diisocyanate/ [QR] [REF-25]
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Health: TOXIC; inhalation, ingestion or contact (skin, eyes) with vapors, dusts or substance may cause severe injury, burns or death. Contact with molten substance may cause severe burns to skin and eyes. Reaction with water or moist air will release toxic, corrosive or flammable gases. Reaction with water may generate much heat which will increase the concentration of fumes in the air. Fire will produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution. /Toluene diisocyanate/ [QR] [REF-25]
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Public Safety: CALL Emergency Response Telephone Number ... . As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate enclosed areas. /Toluene diisocyanate/ [QR] [REF-25]
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Wear chemical protective clothing that is specifically recommended by the manufacturer. It may provide little or no thermal protection. Structural firefighters' protective clothing provides limited protection in fire situations ONLY; it is not effective in spill situations where direct contact with the substance is possible. /Toluene diisocyanate/ [QR] [REF-25]
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Evacuation: ... Fire: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. /Toluene diisocyanate/ [QR] [REF-25]
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ Fire: Note: Most foams will react with the material and release corrosive/toxic gases. Small fires: CO2, dry chemical, dry sand, alcohol-resistant foam. Large fires: Water spray, fog or alcohol-resistant foam. ... Move containers from fire area if you can do it without risk. Use water spray or fog; do not use straight streams. Fire involving tanks or car/trailer loads: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. 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 tanks engulfed in fire. /Toluene diisocyanate/ [QR] [REF-25]
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ 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 damaged containers or spilled material unless wearing appropriate protective clothing. Stop leak if you can do it without risk. A vapor suppressing foam may be used to reduce vapors. ... DO NOT GET WATER on spilled substance or inside containers. Use water spray to reduce vapors or divert vapor cloud drift. Avoid allowing water runoff to contact spilled material. Prevent entry into waterways, sewers, basements or confined areas. Small spills: Cover with DRY earth, DRY sand, or other non-combustible material followed with plastic sheet to minimize spreading or contact with rain. Use clean non-sparking tools to collect material and place it into loosely covered plastic containers for later disposal. /Toluene diisocyanate/ [QR] [REF-25]
  • /GUIDE 156: SUBSTANCES - TOXIC AND/OR CORROSIVE (COMBUSTIBLE/WATER-SENSITIVE)/ First Aid: Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. 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. For minor skin contact, avoid spreading material on unaffected skin. 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. /Toluene diisocyanate/ [QR] [REF-25]


FIRE AND REACTIVITY

Fire Potential
  • ... Combustible when exposed to heat or flame ... [REF-2, p.V39 288]

Flash Point
132 DEG C (270 DEG F) (OPEN CUP) [REF-26, p.1501]

Autoignition Temperature
620 deg C [REF-19, p.970]

Fire Fighting Procedures
  • FIREFIGHTERS MUST BE PROTECTED AGAINST DIISOCYANATE VAPORS & NITROGEN DIOXIDE BY COMPLETE PROTECTIVE EQUIPMENT (..., RUBBER GLOVES, ETC). /DIISOCYANATES/ [REF-27, p.103]
  • Water or foam may cause frothing. [REF-9]
  • Where there is a fire involving isocyanates, carbon dioxide or powder extinguishers must be employed. Firemen must be equipped with self-contained breathing apparatus. /Isocyanates/ [REF-18, p.1162]
  • If material on fire or involved in fire: Do not extinguish fire unless flow can be stopped. Use water in flooding quantities as fog. Solid streams of water may be ineffective. Cool all affected containers with flooding quantities of water. Apply water from as far a distance as possible. Use "alcohol" foam, dry chemical, or carbon dioxide. Use water spray to knock-down vapors. /Toluene diisocyanate/ [REF-28, p.1058]

Toxic Combustion Products
  • Irritating vapors are generated when heated. [REF-9]
  • Toxic oxides of nitrogen are produced during combustion of this material. /Toluene diisocyanate/ [REF-28, p.1058]

Explosive Limits and Potential
  • When involved in fires, may cause rupture of containers and explosion hazard by evolving a large quantity of vapors. [REF-5, p.528]
  • Explosive in the form of vapor when exposed to heat or flame. [REF-1, p.3194]

Reactivities and Incompatibilities
  • Strong oxidizers, water, acids, bases, and amines (may cause foam and spatter); alcohols [Note: Reacts slowly with water to form carbon dioxide and polyureas]. [REF-20, p.312]
  • Liquid is heavier than water and reacts with water, forming carbon dioxide. [REF-23, p.49-88]
  • 0.9-9.5 vol % in air. Reacts violently with amines, alcohols, bases and warm water, causing explosion hazards. [REF-19, p.970]
  • Reacts readily with cmpd containing active hydrogens, such as water, acids and alc; contact with bases, such as caustic soda and tertiary amines, may cause uncontrollable polymerization and rapid evolution of heat; high temp can cause formation of dimer. [REF-2, p.V39 288]
  • Polythene containers holding the diisocyanate may harden and burst in prolonged storage, because of slow absorption of water vapor through the wall leading to urea deposition from hydrolysis and generation of pressure of liberated carbon dioxide. [REF-29, p.776]
  • It can react with aniline. The heat of this reaction may be sufficient to ignite surrounding combustibles and the material itself. /Toluene diisocyanate/ [REF-28, p.1058]

Decomposition
  • WHEN HEATED TO DECOMPOSITION, IT EMITS HIGHLY TOXIC FUMES OF /NITROGEN OXIDES/. [REF-1, p.3194]

Polymerization
  • Polymerization: Slow, not hazardous, above 113 deg F; Liquid-water interfacial tension: (est) 45 dynes/cm= 0.045 N/m at 25 deg C [REF-9]
  • The diisocyanate may undergo exothermic polymerization in contact with bases or more than traces of acyl chlorides, sometimes used as stabilizers. [REF-29, p.776]


PROTECTIVE EQUIPMENT AND CONTROLS

Protective Equipment and Clothing
  • Organic vapor canister; goggles or face shield; rubber gloves, boots and apron. [REF-9]
  • ... Provide the workers with protective clothing, gloves and goggles. Respiratory protection may be provided by masks incorporating a prefilter, but the best form of protection in work carried on in a high concn of isocyanates is air-supplied breathing apparatus. /Isocyanates/ [REF-18, p.1162]
  • PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq detergent /should be available./ ... Safety pipettes should be used for all pipetting. ... In animal laboratory, personnel should ... wear protective suits (preferably disposable, one-piece & close-fitting at ankles & wrists), gloves, hair covering & overshoes. ... In chemical laboratory, gloves & gowns should always be worn ... however, gloves should not be assumed to provide full protection. Carefully fitted masks or respirators may be necessary when working with particulates or gases, & disposable plastic aprons might provide addnl protection. ... Gowns ... /should be/ of distinctive color, this is a reminder that they are not to be worn outside the laboratory. /Chemical Carcinogens/ [REF-34, p.8]
  • Wear appropriate personal protective clothing to prevent skin contact. [REF-20, p.313]
  • Wear appropriate eye protection to prevent eye contact. [REF-20, p.313]
  • 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. [REF-20, p.313]
  • Facilities for quickly drenching the body should be provided within the immediate work area for emergency use where there is a possibility of exposure. [REF-20, p.313]
  • 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 a full facepiece and is operated in a pressure-demand or other positive pressure mode. Any supplied-air respirator that has a full facepiece 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. [REF-20, p.313]
  • Recommendations for respirator selection. Condition: Escape from suddenly occurring respiratory hazards: Respirator Class(es): Any air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or back-mounted organic vapor canister. Any appropriate escape-type, self-contained breathing apparatus. [REF-20, p.313]

Other Preventative Measures
  • APPROPRIATE PROTECTIVE MEASURES FOR WORKERS WITH ... /TOLUENE DIISOCYANATE/ PRESENT A MAJOR DIFFICULTY, SINCE CONCENTRATIONS OF THE CHEMICAL AS LOW AS 0.01 PPM ARE APPARENTLY TOO HIGH FOR SAFETY. /TOLUENE DIISOCYANATE/ [REF-35, p.226]
  • Because pulmonary effects can be produced in man at very low levels in air, toluene diisocyanate should be used only in areas with adequate general and local ventilation ... . /Toluene diisocyanate/ [REF-30, p.3164]
  • Contact lenses should not be worn when working with this chemical. [REF-20, p.313]
  • 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.
  • The sanitary facilities at the disposal of the workers must incl showers. /Isocyanates/ [REF-18, p.1162]
  • 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-34, 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 a reminder that they should not be worn outside of lab. /Chemical Carcinogens/ [REF-34, 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-34, 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-34, 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 a 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-34, 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 a 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-34, 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. ... Methods ... should ... where possible, be simple & sensitive. /Chemical Carcinogens/ [REF-34, 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-34, 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. ... A 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-34, p.11]
  • SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. Quality assurance to ascertain the completeness of the cleaning procedures should be implemented before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at end of shift, but should remain at employee's place of work for cleaning.
  • The worker should immediately wash the skin when it becomes contaminated. [REF-20, p.313]
  • The worker should wash daily at the end of each work shift. [REF-20, p.313]
  • Work clothing that becomes wet or significantly contaminated should be removed and replaced. [REF-20, p.313]
  • Workers whose clothing may have become contaminated should change into uncontaminated clothing before leaving the work premises. [REF-20, p.313]
  • If material not on fire and not involved in fire: Keep sparks, flames, and other sources of ignition away. Keep material out of water sources and sewers. Build dikes to contain flow as necessary. Attempt to stop leak if without undue personnel hazard. Use water spray to knock-down vapors. /Toluene diisocyanate/ [REF-28, p.1058]
  • Personnel protection: Avoid breathing vapors. Keep upwind. ... Avoid bodily contact with the material. Do not handle broken packages unless wearing appropriate personnel protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. /Toluene diisocyanate/ [REF-28, p.1058]
  • Evacuation: If material leaking (not on fire), consider evacuation from downwind area based on amount of material spilled, location and weather conditions. /Toluene diisocyanate/ [REF-28, p.1058]


STORAGE, CLEANUP AND DISPOSAL

Stability/Shelf Life
  • DARKENS ON EXPOSURE TO SUNLIGHT [REF-26, p.1501]

Storage Conditions
  • IF STORED IN TANKS, IT SHOULD BE BLANKETED WITH INERT GAS SUCH AS NITROGEN OR WITH DRY AIR. SEPARATE FROM OXIDIZING MATERIALS. [REF-23, p.49-88]
  • Storage temp: 75-100 deg F [REF-9]
  • Protect containers against physical damage. Store in a cool, dry, well- ventilated location, away from all possible ignition sources. Outdoors, detached or isolated storage is preferred. If stored in tanks, it should be blanketed with an inert gas such as nitrogen or with dry air. Care should be taken to prevent contact between isocyanates and strong alkali, which cause uncontrollable polymerization. [REF-5, p.528]
  • PRECAUTIONS FOR "CARCINOGENS": Storage site should be as close as practical 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-34, p.13]
  • Storage in polyethylene containers is hazardous due to absorption of water through the plastic. [REF-1, p.3194]

Cleanup Methods
  • MONO- AND/OR DIISOCYANATES ARE REMOVED FROM GASES, WITHOUT FORMATION OF INSOL UREAS, BY HYDROLYSIS WITH DIL AQ ALKALIES OR MINERAL ACIDS IN THE PRESENCE OF ACTIVE CHARCOAL AND/OR AL2O3. /DIISOCYANATES/ [REF-39]
  • EFFECT OF WATER VAPOR ON ATMOSPHERIC TOLUENE DIISOCYANATE (TDI) WAS DETERMINED QUANTITATIVELY. AT 24 DEG C & ATMOSPHERIC PRESSURE MAX REDUCTION OF 50% WAS OBTAINED FOR INITIAL CONCN OF 0.4 & 0.034 PPM. THE DATA SUGGEST THAT INCR HUMIDITY WOULD BE ONLY MARGINALLY USEFUL AS A CONTROL METHOD. THEY DO, HOWEVER, EMPHASIZE THE NEED FOR SENSITIVE ANALYTICAL PROCEDURES TO MEASURE BOTH TOLUENE DIISOCYANATE AND THE TOLUENE DIISOCYANATE UREA AROUND THE TLV. /TOLUENE DIISOCYANATE/ [REF-40]
  • Spillage: Neutralize with special mixt (50% water, 45% alc, 5% concn ammonia water), collect leaking liq in sealable containers (extra personal protection: self-contained breathing apparatus). [REF-19, p.970]
  • PRECAUTIONS FOR "CARCINOGENS": A high-efficiency particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes or animal rooms ... Filter housing that is designed so that used filters can be transferred into plastic bag without contaminating maintenance staff is avail commercially. Filters should be placed in plastic bags immediately after removal ... The plastic bag should be sealed immediately ... The sealed bag should be labelled properly ... Waste liquids ... should be placed or collected in proper containers for disposal. The lid should be secured & the bottles properly labelled. Once filled, bottles should be placed in plastic bag, so that outer surface ... is not contaminated ... The plastic bag should also be sealed & labelled. ... Broken glassware ... should be decontaminated by solvent extraction, by chemical destruction, or in specially designed incinerators. /Chemical Carcinogens/ [REF-34, p.15]

Disposal Methods
  • Generators of waste (equal to or greater than 100 kg/mo) containing this contaminant, EPA hazardous waste number U223, must conform with USEPA regulations in storage, transportation, treatment and disposal of waste. [REF-41]
  • Concentrated wastes from distillation equipment are preferably burnt in special waste incinerators. This also holds for complex and concentrated wastes, which cannot be regenerated by distillation. Because of the high reactivity of TDI /toluene diisocyanate/ waste waters contain only reaction products from the reaction with water. These can be biodegraded by treatment with activated sludge. Recommendable methods: Incineration, alkaline hydrolysis, discharge to sewer. Not recommendable: Landfill. Peer-review: Avoid contact or inhalation, add TDI to excess dilute alkali, and discharge to sewer. TDI can react explosively with moisture. (Peer-review conclusions of an IRPTC expert consultation (May 1985)) [REF-42, p.101]
  • Toluene diisocyanate is a waste chemical stream constituent which may be subjected to ultimate disposal by controlled incineration. Controlled incineration: Oxides of nitrogen are removed from the effluent gas by scrubbers and/or thermal devices. /Toluene diisocyanate/ [REF-43, p.2-10]
  • A potential candidate for rotary kiln incineration at a temperature range of 820 to 1,600 deg C and residence times of seconds for liquids and gases, and hours for solids. A potential candidate for liquid injection incineration at a temperature range of 650 to 1,600 deg C and a residence time of 0.1 to 2 seconds. A potential candidate for fluidized bed incineration at a temperature range of 450 to 980 deg C and residence times of seconds for liquids and gases, and longer for solids. [REF-43, p.3-16]
  • This compound should be susceptible to removal from waste water by air stripping. [REF-44, p.3-5, 3-11,12]
  • 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-34, p.14]
  • PRECAUTIONS FOR "CARCINOGENS": ... Incineration may be only feasible method for disposal of contaminated laboratory waste from biological expt. However, not all incinerators are suitable for this purpose. The most efficient type ... is probably the gas-fired type, in which a first-stage combustion with a less than stoichiometric air:fuel ratio is followed by a second stage with excess air. Some ... are designed to accept ... aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb soln onto suitable combustible material, such as sawdust. Alternatively, chem destruction may be used, esp when small quantities ... are to be destroyed in laboratory. /Chemical Carcinogens/ [REF-34, 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-34, p.15]
  • PRECAUTIONS FOR "CARCINOGENS": ... Small quantities of ... some carcinogens can be destroyed using chem reactions ... but no general rules can be given. ... As a 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 saturated soln of potassium permanganate in acetone, which appears to be a 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-34, 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-34, p.17]


HEALTH HAZARDS AND TOXIC EFFECTS

Human Toxicity Values
TCLo Human inhalation 0.5 ppm [REF-5, p.528]

Non-Human Toxicity Values
LC50 Rabbit inhalation 11 ppm, 4 hr/day, 14 days [REF-93, p.1108]
LC50 Rat inhalation 14 ppm/4 hr [REF-5, p.528]
LC50 Mouse inhalation 10 ppm/4 hr [REF-5, p.528]
LC50 Guinea pig inhalation 13 ppm/4 hr [REF-5, p.528]
LD50 Rat oral 5800 mg/kg [REF-1, p.3194]

Human Toxicity Excerpts
IT CAUSES SKIN IRRITATION, ALLERGIC ECZEMA. ... [REF-53, p.1364]

AS A VAPOR TOLUENE DIISOCYANATE IS A POWERFUL IRRITANT TO ... RESPIRATORY TRACT. INDUSTRIAL EXPOSURES TO SURPRISINGLY LOW CONCN HAVE PRODUCED RESPIRATORY SYMPTOMS: A SENSATION OF CONSTRICTION OF CHEST, COUGH & DYSPNEA. SIMILARITY TO ASTHMATIC ATTACK WITH SEVERE BRONCHOSPASM HAS BEEN MENTIONED ... X-RAYS WERE UNIFORMLY NEGATIVE. EOSINOPHILIA WAS NOTED. REMOVAL FROM EXPOSURE HAS RESULTED IN SEQUELAE-FREE RECOVERY, BUT ON RE-EXPOSURE THERE MAY BE INCREASED SENSITIVITY. /TOLUENE DIISOCYANATE/ [REF-3, p.II-414]

EXPOSURE TO LEVELS AS LOW AS 0.014 MG/CU M (0.002 PPM) CAN RESULT IN CHRONIC LOSS OF PULMONARY FUNCTION. A MORE ACUTE, ASTHMATIC TYPE OF BRONCHITIS IS NOT UNCOMMON ... FRANK ASTHMA MAY OCCUR. [REF-21, p.V19 311]

ACCIDENTAL SPLASH ... IN EYES OF WORKMEN HAS CAUSED KERATITIS & CONJUNCTIVITIS. ONE CASE ... DESCRIBES "UNUSUAL AMT OF PHOTOPHOBIA & BLEPHAROSPASM" ... SECOND CASE ... DESCRIBED ... INVOLVED SEVERE IRIDOCYCLITIS & SECONDARY GLAUCOMA. /TOLUENE DIISOCYANATE/ [REF-54, p.929]

... Toluene diisocyanate is an irritant causing inflammation & occasional sensitization of skin, lacrimation, smarting, burning, & pricking sensation in the eyes; abdominal distress, nausea, & vomiting. ... Exposure to high concn may lead to chemical bronchitis with severe bronchospasm, chemical pneumonitis, pulmonary edema, headache, & insomnia. ... Repeated exposure at lower concn may produce a chronic-like syndrome in many people. Symptoms may incl coughing, wheezing, tightness, or congestion in the chest & shortness of breath. ... /Toluene diisocyanate/ [REF-55, p.1582]

Acute & chronic decr of ventilatory capacity measured as forced expiratory volume one second, with or without overt symptoms of resp difficulty. ... [REF-55, p.1586]

Resp health of 277 toluene diisocyanate workers was studied prospectively. Peak and 8-hr TWA concn were determined in over 200 samples. Smoking had a significant effect on spirometric tests and lung volumes. After adjustment for smoking, the 74 men in the high toluene diisocyanate exposure group had significantly larger declines in forced expiratory vol than the 149 men in the low exposure category. /Toluene diisocyanate/ [REF-56]

A STUDY OF WORKERS ENGAGED IN MFR OF TOLYLENE DIISOCYANATE WAS CARRIED OUT OVER 9 YR. IT WAS FOUND THAT FORCED EXPIRATORY VOL OF AFFECTED MEN WAS ON AVG 267 ML LOWER THAN PREDICTED FIGURES FROM A CONTROL GROUP, & THE FORCED VITAL CAPACITY WAS 269 ML LOWER. [REF-57]

MEN COMPLAINED OF NEUROLOGICAL SYMPTOMS AFTER SINGLE EXPOSURE TO TDI. EFFECTS WERE EUPHORIA, ATAXIA, & LOSS OF CONSCIOUSNESS; HEADACHE, DIFFICULTY IN CONCENTRATION, POOR MEMORY & CONFUSION IN 3 WK. 4 YR LATER PERSONALITY CHANGES, IRRITABILITY, OR DEPRESSION WAS STILL NOTED. [REF-58]

FIREMEN EXPOSED TO FUMES OF TOLUENE DIISOCYANATE EXPERIENCED SYMPTOMS DURING & AFTER FIRE. SYMPTOMS WERE MAINLY GI, RESP, OR NEUROLOGICAL. GI SYMPTOMS SUBSIDED WITHIN 2 DAYS OF ONSET, SOME MEN SUSTAINED LONG-TERM RESP TRACT DAMAGE. /TOLUENE DIISOCYANATE/ [REF-59]

AFTER OCCUPATIONAL EXPOSURE, 112 PLANT WORKERS WERE TESTED BY INHALATION CHALLENGE WITH 0.005 PPM TO 0.02 PPM TOLUENE DIISOCYANATE. NO TOLUENE DIISOCYANATE INDUCED IMMUNOLOGIC CHANGES WERE NOTED WITH THE EXCEPTION OF 3 INDIVIDUALS WHO DEMONSTRATED SMALL POSITIVE WHEAL-&-ERYTHEMA REACTIONS. AIRWAYS OBSTRUCTION WAS ALSO NOTED. /TOLUENE DIISOCYANATE/ [REF-60]

The biconcave shape of normal human erythrocytes was altered into cup-shaped cells by toluene diisocyanate. The extent of toluene diisocyanate induced shape change of erythrocytes was concn-dependent. The resultant modified red cells had a decr ability to pass through a microporous membrane and also an incr resistance to hemolysis. Isolated membranes obtained from toluene diisocyanate treated cells showed incr crosslinking of membrane proteins and phospholipids. /Toluene diisocyanate/ [REF-61]

In 37 polyurethane workers with isocyanate asthma, exam carried out 40 mo after exposure had ceased showed that asthmatic symptoms had disappeared in 32 workers but that chronic bronchitis had developed in six. The progressive impairment of ventilatory function was evaluated by measuring the decr in forced vital capacity and forced expiratory vol after exposure had ceased. Mean annual decr of 86.3 and 67.7 ml, respectively, were observed. Toluene diisocyanate induces chronic and irreversible lung damage even after exposure is discontinued, and impairment of forced vital capacity is greater than that of forced expiratory volume. /Toluene diisocyanate/ [REF-62]

Radioallergosorbent testing was used to look for the presence of specific IgE antibody against a para-tolyl-monoisocyanate human serum albumin conjugate in sera from five groups of subjects. The first three groups consisted of individuals exposed to toluene diisocyanate who had been shown by bronchial provocation testing with levels of toluene diisocyanate below the threshold limit value of 0.02 ppm to have immediate asthmatic reactions, late asthmatic reactions or no resp changes at all. The two control groups consisted of atopic and non-atopic individuals who had no resp symptoms and no known exposure to toluene diisocyanate. Although radioallergosorbent showed high counts/min in some of the sera from patient with proven toluene diisocyanate induced resp disease, these levels were not significantly different from controls and appeared to reflect the presence in these sera of high levels of total IgE (greater than 100 u/ml). There is no evidence from this study for the presence of specific IgE antibody against a para-tolyl monoisocyanate human serum albumin conjugate in patients with toluene diisocyanate induced resp disease. /Toluene diisocyanate/ [REF-63]

20 CASES OF OCCUPATIONAL /SKIN CONDITIONS/ CAUSED BY ISOCYANATES ESP TOLUENE DIISOCYANATE ARE REPORTED. FINDINGS GIVE SOME EVIDENCE FOR CROSS-SENSITIZATION BETWEEN CHEMICALLY RELATED CMPD. /TOLUENE DIISOCYANATE/ [REF-64]

AN IMMUNOLOGIC TEST PROCEDURE WAS USED ON WORKERS IN A TOLUENE 2,4-DIISOCYANATE PLANT. IMMUNOLOGIC CHANGES PRODUCING TOLERANCE TO TDI EXPOSURE ALSO RESULTED IN NEGATIVE RESPONSE TO ANTIGEN CHALLENGE TESTS. SOME INDIVIDUALS EXPOSED TO TDI MAY HAVE PROTECTIVE ANTIBODIES BUT STILL EXPERIENCE BRONCHOCONSTRICTION. [REF-65]

The sera of 20 blood donors, 70 factory workers, and 1 casualty patient were assayed for IgE which bound to a p-tolyl-isocyanate human serum albumin conjugate. 3 factory workers had abnormally high assay values in assoc with active toluene diisocyanate disease, as indicated by asthma or measurement showing chronic airway obstruction. One factory worker had an exceptionally high assay value without clinical evidence of toluene diisocyanate disease. Hapten inhibition studies indicated possible heterogeneity of the IgE detected by the assay. Clinical histories suggest that toluene diisocyanate disease can incl susceptibility to asthma triggered by events other than toluene diisocyanate exposure. /Toluene diisocyanate/ [REF-66]

The outcome of the resp symptoms, pulmonary function tests and bronchial hyper-responsiveness was studied in 47 workers with resp disease due to toluene diisocyanate (27 asthmatic and 20 non-asthmatic subjects) after about 2 yr from the first exam. The data suggest that stopping occupational exposure to toluene diisocyanate frequently did not produce an improvement of the toluene diisocyanate bronchial asthma, and persistence of the exposure causes a more rapid decline in the resp function. /Toluene diisocyanate/ [REF-67]

The report of a 5 yr follow-up study of 107 workers in a polyurethane manufacturing plant using forced expiratory vol measurements and questionnaires on resp symptoms and smoking habits is presented. Toluene diisocyanate exposure levels were monitored. Mean forced expiratory vol was higher than that predicted for healthy subjects and the 5 yr change in forced expiratory vol did not exceed that expected from aging. No acute changes in forced expiratory vol was observed on a Monday either before or after a 2 wk vacation and no ventilatory function improvement was observed during vacation. Low-level isocyanate exposure (time-weighted avg concn around 0.001 ppm) was not assoc with chronic resp symptoms or effects on ventilatory capacity. /Toluene diisocyanate/ [REF-68]

... Patients with toluene diisocyanate induced asthma continue to be symptomatic for month and even yr after cessation of toluene diisocyanate exposure. ... It is thought that toluene diisocyanate may cause the airways to become hyperreactive to many agents such as smoke and other air pollutants. ... Some individuals susceptible to toluene diisocyanate induced asthma develop cross-reactivity to other diisocyanate. ... /Toluene diisocyanate/ [REF-69, p.305]

A 47 yr old nonsmoking spray painter had an adenocarcinoma of the lung. He had been exposed to toluene diisocyanate and 4,4'-methylenediphenyl diisocyanate for 15 yr and had a 10 yr history of lung disease thought to be caused by exposure to isocyanates. /Isocyanates/ [REF-2, p.V39 311]

FOUR PATIENTS EXPOSED TO ISOCYANATE VAPOR DEVELOPED DYSPNEA ASSOC WITH RESTRICTION & REDUCED GAS TRANSFER AS WELL AS AIRWAYS OBSTRUCTION. IT IS SUGGESTED THAT PATIENTS EXPOSED TO ISOCYANATES MAY OCCASIONALLY DEVELOP A HYPERSENSITIVITY PNEUMONITIS RATHER THAN THE MORE USUAL ASTHMATIC SYNDROME. /ISOCYANATE/ [REF-70]

SOME WORKERS BECOME EXCEEDINGLY SENSITIVE TO TOLUENE DIISOCYANATE VAPORS & RESPOND DRAMATICALLY TO MINUTE AMT OF THIS MATERIAL IN THE AIR. /TOLUENE DIISOCYANATE/ [REF-13, p.336]

Highly reactive low molecular weight cmpd such as toluene diisocyanate, used in a variety of chem processes, paints and plastics, are replacing the more classical protein antigens as the most commonly implicated agents in occupational asthma. /Toluene diisocyanate/ [REF-71]

ORGANIC ISOCYANATES ARE PARTICULARLY POISONOUS WHEN BREATHED. FURTHERMORE THE TOXICITY VARIES ACCORDING TO PHYSICAL & CHEMICAL NATURE OF ISOCYANATE. AMONG MOST POISONOUS ... ARE TOLUENE 2,4- & 2,6-DIISOCYANATES. [REF-27, p.100]

Toluene diisocyanate may produce a true hemorrhagic syndrome affecting the bone marrow and producing primarily thrombocyte series suppression. /Toluene diisocyanate/ [REF-18, p.303]

A case of building-related health complaints among 14 full-time employees and 1 part-time employee was investigated with respect to the relationship among frequency of symptoms (involving eyes, nose, sinuses, throat, lung, skeletomuscular system, and central nervous system) and antibodies to human serum albumin conjugates of toluene diisocyanate. Antibody testing was done by the ELISA procedure. Employees noted the presence or absence of symptoms by filling in questionnaires. Anti-toluene diisocyanate isotypes were found in 12 of 14 full-time employees and were nondetectable in one part-time employee. Antibody titers were positively but not significantly correlated with % of total symptoms as follows: toluene diisocyanate-IgG (r= 0.48), toluene diisocyanate-IgG (r= 0.55). Anti-toluene diisocyanate human serum albumin IgE titers were neg in 7 subjects and pos in 5. Anti-toluene diisocyanate human serum albumin-IgG antibodies were detected in all employees tested. /Toluene diisocyanate/ [REF-72]

A 41 yr old automobile paint sprayer showed the clinical features of hypersensitivity pneumonitis 1 wk after he had begun to work with paint material containing toluene diisocyanate. His symptoms (non-productive cough, dyspnea on exertion, and intermittent fever) began 6 to 8 hr after exposure to toluene diisocyanate and spontaneously disappeared by the next morning. He had diffuse, fine reticulonodular shadows on a chest roentgenogram and a restrictive impairment of pulmonary function. Immunoglobulin G antibody to toluene diisocyanate human serum albumin was present in bronchoalveolar lavage fluid and sera; IgA antibody was present only in bronchoalveolar lavage fluid. Also, the patient had sensitized bronchoalveolar lymphocytes to toluene diisocyanate human serum albumin. The histologic findings from a bronchial biopsy, showed an acute exudative reaction; the presence of alveolar edema and lymphocytic infiltrates in alveolar and bronchiolar walls, which suggested hypersensitivity pneumonitis. Bronchoalveolar lavage, which was repeated on four separate occasions showed lymphocytosis and a predominance of suppressor cytotoxic T cells. Findings from serial determination of humoral antibodies showed no changes consistent with the results of clinical and laboratory studies. In contrast, blastogenic responses of bronchoalveolar lymphocytes to toluene diisocyanate markedly decr, and the patient showed clinical improvement despite continued exposure to toluene diisocyanate. /Toluene diisocyanate/ [REF-73]

Symptoms: Conjunctivitis, corneal opacities, irritative to skin, blistering; nausea, vomiting, jaundice, anemia. May be irritative to throat causing asthmatic attack in low concentration; may cause pulmonary edema in high concentration; chronic liver diseases. [REF-5, p.528]

Strong mucous membrane irritation causes eye, pulmonary, and gastrointestinal tract symptoms. These compounds are potent pulmonary sensitizers which cause bronchospasm, even in patients without prior airway hyperreactivity. Diisocyanate compounds act either as inducers of nonspecific bronchial hyperreactivity or as direct pharmacologic agonists. Isocyanates apparently have the potential to sensitize certain segments of the population. Elevated humoral antibodies (ie, specific IgE antibodies to the p-tolyl determinant but not the diisocyanate conjugate) were detected in sensitized workers, but cell-mediated immunity also may produce hypersensitivity reactions. In the absence of renewed exposure, radioallergosorbent titers may not distinguish sensitive from nonsensitized workers. At high doses, toluene diisocyanate may act directly on bronchial mucosa by interfering with cholinergic and adrenergic mechanisms. /Isocyanates/ [REF-47, p.881]

Clinical signs of isocyanate exposure involved mucosal irritation of the respiratory and gastrointestinal tracts. Conjunctival irritation, skin inflammation (erythema, pain, vesiculation), and gastrointestinal disturbances (nausea, vomiting, abdominal pain) occur soon after exposure. Pulmonary symptoms include cough, burning, substernal pain, dyspnea, choking sensation, sputum production, and hoarseness. Prominent bronchospasm (eg, wheezing, rhonchi, dyspnea, cough) may be present. Neurologic symptoms include headache, insomnia, euphoria, ataxia, anxiety neurosis, depression, and paranoia which may persist for several weeks. Persistent memory deficits, personality changes, irritability, and depression have been reported after severe exposures to toluene diisocyanate. Lacrimation, photophobia, profuse lid edema, and superficial corneal abrasions were the most common ophthalmologic effects at Bhopal. No case of blindness or irreversible ocular damage was noted on follow-up examination. /Isocyanates/ [REF-47, p.881]

Neurological symptoms were reported in 23 firemen heavily exposed to toluene diisocyanate during a polyurethane manufacturing plant fire. Symptom included euphoria, ataxia, and loss of consciousness with long lasting mild subjective symptoms of personality change, irritability, depression, and memory difficulties. /Toluene diisocyanate/ [REF-74, p.34]

Ten sensitized subjects, previously shown to develop a dual or late asthmatic reaction after inhaling toluene diisocyanate were examined. In each subject, forced expiratory volume in one second was measured and venous blood was taken before, and 30 minutes and eight, 24, 48, and 72 hours after exposure to toluene diisocyanate (0.005-0.05 ppm for 10-30 minutes). Filtered air was used as a control. Differential leukocyte counts were determined and phenotypic analysis was performed by immunofluorescene on mononuclear cells using monoclonal antibodies (anti-CD3, anti-CD4, anti-CD8, and anti-HLA-DR). Five subjects developed a dual asthmatic reaction and five had a late reaction. Percentage of CD8 positive lymphocytes increased significantly eight hours after exposure to toluene diisocyanate (from 27 plus or minus 3 (SEM) % to 42.1 plus or minus 5%) in the subjects with an isolated late reaction. A delayed significant further increase in suppressor/cytotoxic T lymphocytes was seen in seven of the 10 subject 48 hours after active exposure (from 27 plus or minus 2% to 22 plus or minus 4.8%), irrespective of the type of asthmatic reaction developed after exposure to toluene diisocyanate. Eosinophil percentage increased from 2.5% plus or minus 1.0 to 6.4 plus or minus 1.2 24 hours after exposure to toluene diisocyante and the increase was sustained for up to 48 hours (4.7 plus or minus 1.1). No significant variations of forced expiratory volume in one second or cell percentages were seen in the controls. In conclusion, the events triggered by exposure to toluene diisocyante in sensitised subjects included changes in lung function and systemic effects which lasted longer than bronchoconstriction and concerned suppressor/cytotoxic lumphocytes and eosinophils. These results suggest that toluene diisocyanate induced late asthmatic reactions may be associated with an immunological response to toluene diisocyanate or to its products. /Toluene diisocyanate/ [REF-75]

A 46 year old man who had worked in a paint processing plant for over 29 years was admitted to the hospital with complaints of nocturnal dyspnea and dry cough. A chest X-ray film showed diffuse granular shadows in bilateral lungs. Pulmonary function tests revealed reduction of diffusing capacity and restrictive impairments. Hypersensitivity pneumonities due to isocyanates was speculated from his occupational history and clinical course. Positive skin tests against TDT-HSA and MDI-HSA, precipitating antibody against TDI-HSA, and negative lymphocyte stimulating tests of peripheral blood and bronchoalveolar lavage fluid were also noticed. Environmental provocation test was positive. Histological findings of transbronchial lung biopsy specimens showed diffuse alveolitis and Masson body, but no granulomas. According to these results, the patient was diagnosed as hypersensitivity pneumonitis due to toluene diisocyanate. Type III allergy of Gell-Coomhbs seems to participate in this case. The granulomatous lesion is seen less frequently in isocyanate-related hypersensitivity pneumonitis than in hypersensitivity pneumonitis induced by organic dusts, which suggest the difference in immunological and histological reactions between both types of hypersensitivity pneumonitis. [REF-76]

Several studies on the prognosis of isocyanate induced asthma show that a significant proportion of patients continue to experience asthmatic symptoms and nonspecific bronchial hyperresponsiveness after cessation of work, and that further exposure to isocyanates in sensitized subjects leads almost invariably to persistence of respiratory symptoms and of bronchial hyperresponsiveness and the deterioration of airway function. Specific bronchial reactivity to isocyanates may change after cessation of work; however, some subjects continue to be sensitive to toluene diisocyanate several months after cessation of work. The determination of an unfavorable prognosis for asthma seem to be the same as those for other types of occupational asthma due to low molecular weight compounds (ie red cedar asthma); long duration of exposure before the onset of asthma, long duration of symptoms before diagnosis, airway obstruction, and dual airway response after specific challenge tests. Also, single acute exposure to high levels of TDI in the workplace (spills) can result in persistent nonspecific bronchial hyperresponsiveness. Potential mechanisms of persistence of symptoms and of nonspecific bronchial hyperresponsiveness may be chronic inflammation, bronchial smooth muscle alteration, autonomic nervous system disregulation. /Toluene diisocyanate/ [REF-77]

Toluene diisocyanate (TDI) sensitivity accompanied by nonspecific bronchial hyperresponsiveness occurs in approximately 5% of occupationally exposed workers. We report the case of a 32 yr old worker followed longitudinally after removal from isocyanate exposure. Toluene diisocyanate reactivity was lost 11 mo after removal from exposure and nonspecific bronchial hyperresponsiveness resolved after 17 mo. Bronchial reactivity to radishes (Raphanus sativus), which developed concurrently with toluene diisocyanate reactivity, was lost 2 yr later. Immunopharmacologic results show that the worker's initial decreased ability of lymphocytes to produce cyclic AMP returned to near normal after 2 yr. IgE antibodies to a human serum albumin tolyl monoisocyanate conjugate were still present at this time. /Toluene diisocyanate/ [REF-78]

Sera of 6 workers with conclusive evidence for IgE-mediated sensitization to isocyanates were used for evaluation of immunologic cross-reactivities among 8 different isocyanate-protein conjugates. In all cases radioallergosorbent test and/or skin-test investigations revealed the presence of IgE antibodies reacting specifically with human serum albumin conjugated with those isocyanates to which workers were exposed as well as with other isocyanates with which they were not in contact. By the radioallergosorbent test inhibition technique, moderate to strong mutual cross-reactivities between all tested isocyanate-human serum albumin conjugates, even between aromatics and aliphatics, were demonstrated in tests with 5 sera. One serum contained IgE antibodies that were almost completely specific to toluene diisocyanate-human serum albumin with this serum only weak cross-reactivities with other isocyanate conjugates were demonstrated. /Isocyanates/ [REF-79]

Toluene diisocyanates are potent respiratory irritants and sensitizers, even at low airborne concentrations. Chronic bronchitis, chronic restrictive pulmonary disease and hypersensitivity pneumonitis have also been described among toluene diisocyanate exposed people. /Toluene diisocyanates/ [REF-45, p.V71 871]

Fifty seven polyurethane foam manufacturing workers & 24 reference workers were followed for 4 yr to clarify the effects on pulmonary function of working in polyurethane foam factories with exposure to toluene diisocyanate. No significant differences in the average annual losses of pulmonary function for 4 yr were observed among the 28 polyurethane foam workers whose toluene diisocyanate exposure levels were very low (mean = 0.1 ppb, group L), the remaining 29 polyurethane foam workers with mean toluene diisocyanate exposure of 5.7 ppb (group H), & the reference workers. However, 15 polyurethane foam workers in group H who had experienced peak exposure excursions to 30 ppb or above with a mean concn of 8.2 ppb showed significantly larger average annual losses in % maximal mid-expiratory flow, forced expiratory volume in 1 sec ratio to vital capacity, & forced expiratory flow at 25% of forced vital capacity than expected, & significantly larger average annual losses in some obstructive pulmonary function indices than those of the 14 remaining polyurethane foam workers in group H whose peak exposure excursion levels were 3-14 ppb with a mean time-weighted average of 1.7 ppb, group L, & the reference workers. These findings suggest that the peak exposure excursion level of toluene diisocyanate might be important in inducing obstructive pulmonary function changes in the polyurethane foam workers rather than the TWA exposure levels, though further comparative studies of the AAL in those who are exposed to different peak exposure excursion levels but the same mean exposure levels are necessary. From the standpoint of prevention, the proposition that peak exposure excursion levels exceeding 20 ppb should be avoided is reasonable. [REF-80]

EXPOSURE TO TOLUENE 2,4-DIISOCYANATE RESULTED IN DECR OF CO-DIFFUSION CONSTANT, WHICH GAVE RISE TO DIFFUSE INTERSTITIAL PULMONARY FIBROSIS. THESE EFFECTS WERE OBSERVED IN WORKERS IN FOAM MFR FOR AUTOMOBILE SEATS. [REF-81]

Guinea pigs were exposed to 29 ppb of toluene diisocyanate (97.8% 2,4- and 2.2% 2,6-) vapors 5 hr/day for 20 consecutive days. Animals were killed 20 hr after the last exposure, and tracheal smooth muscle relaxation and contraction responses to agonists were determined. There was no difference in beta-adrenergic responsiveness between the exposed animals and controls. Significant differences in carbachol-produced contractability were observed. The dose-effect curve from carbachol-stimulated strips was shifted upward and to the left for toluene diisocyanate exposed animals. The maximal smooth muscle tension was also greater in toluene diisocyanate exposed animals. The observed incr in maximal tension and the shift of the dose-effect curve for toluene diisocyanate exposed animals suggest a direct effect of toluene diisocyanate on tracheal smooth muscle. [REF-82]

Non-Human Toxicity Excerpts
WHEN INGESTED, SOLUTIONS ARE IRRITATING TO THE GASTROINTESTINAL TRACT. [REF-3, p.II-414]

TEST APPLICATION OF DROP OF META- AND PARA-TOLUENEDIISOCYANATES ON RABBIT EYE CAUSED IMMEDIATE PAIN, LACRIMATION, SWELLING OF LIDS, & CONJUNCTIVAL REACTION. /MIXT OF 2,4- & 2,6 ISOMERS/ [REF-54, p.929]

Lesions occurring in the resp tract of mice after exposure to 10 sensory irritants, at a concn which elicited a resp rate decr of 50%, were compared with respect to type and severity. The RD50 of 2,4-toluene diisocyanate was 0.4 ppm. After exposure of mice for 6 hr/day for 5 days, the resp tract was examined for histopathological changes. All irritants produced lesions in the nasal cavity with a distinct anterior-posterior severity gradient. [REF-83]

Allergic dermatitis was developed in mice by sensitization to toluene diisocyanate following which the mice were exposed to toluene diisocyanate vapor to see if a delayed type allergy plays a role in lung disorders caused by toluene diisocyanate. At a concn of 0.6 ppm, inhaled for 2 hr, allergic dermatitis did develop, but without noticeable pathological change in the resp organs. /Toluene diisocyanate/ [REF-84]

Young adult guinea pigs received 2 open, epicutaneous induction applications (25 ul) of 8, 20 or 40% toluene diisocyanate in n-butyl ether on 2 separate areas. Five days later, animals were challenged with 0.0, 0.025, 0.05, 0.1, 0.2 and 0.4% TDI (25 ul/concn site). All challenge applications except the 0.0% soln elicited a positive response in 75-100% of the animals, and the severity of the skin reactions was dependent on the concn of the challenge and induction application. In another study using lower doses, animals received a total induction application (25 ul/each of 2 sites) of either 4 or 8% toluene diisocyanate. Toluene diisocyanate did not elicit a sensitization response at challenge concn up to 0.012% (total application of 3 ug) when a 4% induction application was used, while a challenge concn of 0.025% (total application of 6.25 ug) elicited a sensitization response in 63% of the animals. At the 8% induction application (total application of 4000 ug), all challenges, except the 0.0% indicated sensitization, and the intensities of the skin reactions were correlated with the challenge concn and the induction application. /Toluene diisocyanate/ [REF-85]

Two strains of guinea pigs were parenterally immunized with well-characterized diisocyanate-protein conjugates. Hapten-specific IgE antibodies were detected in the sera of English short-hair strain guinea pigs immunized with toluene diisocyanate-human serum albumin when the serum was analyzed by the 168 hr passive cutaneous anaphylaxis technique followed by iv challenge with a conjugate coupled to an unrelated carrier protein, transferrin. IgG1 antibodies and precipitating antibodies were demonstrated in Hartley strain guinea pigs immunized with the toluene diisocyanate-human serum albumin conjugate. It became apparent that immune responses of guinea pigs immunized with protein conjugates of bifunctional isocyanates were heterogeneous and involved multiple specificities for hapten, carrier protein, and new antigenic determinants. It was postulated that the complex nature of the immune response generated by diisocyanate cmpd in the guinea pig may also serve as an appropriate model of isocyanate-induced human sensitivity reactions, which are known to involve diverse immunologic and nonimmunologic mechanisms. /Toluene diisocyanate/ [REF-86]

Groups of 50 male and 50 female B6C3F1 mice, 12 wk of age, were admin 120 or 240 mg/kg body wt (males) or 120 mg/kg body wt (females) commercial-grade (86% 2,4 isomer; 14% 2,6 isomer) toluene diisocyanate in corn oil by gavage on five days per wk for 105 wk. The concn of toluene diisocyanate ... was equivalent to 36 or 72 mg/ml and 18 or 36 mg/ml. Groups of 50 male and 50 female mice received corn oil only and served as vehicle controls. ... No treatment-related tumor was seen in male mice. The survival rate in females was: 34/50 (68%) control, 43/50 (86%) low-dose and 33/50 (66%) high-dose animals. In females, hemangiomas (in the spleen and subcutaneous tissues) and hemangiosarcomas (in the liver, ovaries and peritoneum) occurred in 0/50 (0%) control, 1/50 (2%) low-dose and 5/50 (10%) high-dose animals, giving a statistically significant positive trend (p= 0.01, Cochran-Armitage trend test). The incidence of hepatocellular adenomas was also significantly incr in females: 2/50 (4%) control, 3/50 (6%) low-dose and 12/50 (24%) high-dose animals (p= 0.001, Cochran-Armitage trend test). [REF-2, p.V39 302]

Groups of 50 male and 50 female Fischer 344/N rats, 11 wk old, were admin 30 or 60 mg/kg body wt (males) or 60 or 120 mg/kg body wt (females) commercial-grade toluene diisocyanate (86% 2,4 isomer; 14% 2,6 isomer) in corn oil by gavage on five days per wk for 106 wk. The concn of toluene diisocyanate was 9 or 18 mg/ml and 18 or 36 mg/ml. Groups of 50 male and 50 female rats received corn oil only and served as vehicle controls. ... A treatment-related incr in the incidence of subcutaneous fibromas and fibrosarcomas individually and combined was observed in males. The incidence of fibrosarcomas was 0/50 control, 3/50 low-dose and 3/50 high-dose animals; the combined incidence was 3/50 (6%) control, 6/50 (12%) low-dose and 12/50 (24%) high-dose animals. ... The overall rate of mammary fibroadenomas in female rats was: 15/50 (30%) controls, 21/50 (42%)low-dose and 18/50 (36%) high-dose. ... The terminal tumor rate for mammary fibroadenomas was: 13/36 (36%) controls, 15/19 (79%) low-dose and 4/6 (67%) high-dose animals. The dose-related incidence of pancreatic acinar-cell adenomas in males ... was significantly incr in the high-dose compared to controls (p= 0.034). In females, pancreatic islet-cell adenomas were found at terminal sacrifice in 0/36 controls, 3/19 low-dose and 2/6 high-dose animals (p is less than or equal to 0.01, tests for incidental tumors comparing each dose group to controls). One islet-cell carcinoma was observed in one low-dose female. A dose-related increase in the incidence of neoplastic nodules in the liver of female rats was also noted. [REF-2, p.V39 303]

Groups of 120 male and 120 female CD-1 mice, three to four weeks old, were exposed to 0, 0.05 or 0.15 ppm (0, 0.36 or 1.07 mg/cu m) production-grade toluene diisocyanate (approx 80% 2,4 isomer & 20% 2,6 isomer) in an inhalation chamber for 6 hr/day on 5 days/wk for 104 wk. There was a significant reduction in body weight in the high-dose group (sex not stated) and a significant increase in mortality in both high- and low-dose females by the termination of the study. No such effect was seen in males. Neither the types of tumors observed nor their incidences were dose-related, and both corresponded to those seen in historical controls for this strain of mice. However, dose-related pathological changes were observed in the nasal cavity (chronic or necrotic rhinitis), together with changes in the lower respiratory tract (interstitial pneumonia, catarrhal bronchitis) in both groups. [REF-2, p.V39 303]

Groups of 126 male and 126 female Sprague-Dawley CD rats, six to nine weeks old, were exposed to 0, 0.05 or 0.15 ppm (0, 0.36 or 1.07 mg/cu m) production-grade toluene diisocyanate (approx 80% 2,4 isomer and 20% 2,6 isomer) in an inhalation chamber for 6 hr/day on 5 days/wk for 108 wk or 110 wk. A significant reduction in weight gain was observed during the first 12 wk of the study among the high-dose animals of each sex, but body-weight gain was similar in all groups thereafter. No significant difference in mortality between treated and control groups of either sex was reported. Tumor incidences and types were reported to be similar in control and treated groups. [REF-2, p.V39 304]

Single or repeated exposure to concn of 2,4-toluene diisocyanate ranging from 0.05-14 mg/cu m (0.007-2 ppm) for periods of up to 3 hr resulted in reductions in respiratory rate in Swiss mice. The concn of toluene diisocyanate that caused a 50% decrease in the respiratory rate in mice was reported to be 3 mg/cu m (0.39 ppm); pulmonary injury was characterized principally by squamous metaplasia of the respiratory epithelium. [REF-2, p.V39 306]

2,4-Toluene diisocyanate, tested at up to 2500 ug/plate, was not mutagenic to Salmonella typhimurium TA1535, TA1538, TA98 or TA100 in the presence of a metabolic system from the liver of Aroclor-induced rats. [REF-2, p.V39 307]

Twenty-seven chemicals (including toluene 2,4-diisocyanate) previously tested in rodent carcinogenicity assays were tested for induction of chromosomal aberrations and sister chromatid exchanges in Chinese hamster ovary cells as part of a larger analysis of the correlation between results of in vitro genetic toxicity assays and carcinogenicity bioassays. Chemicals were tested up to toxic doses with and without exogenous metabolic activation. Toluene 2,4-diisocyanate at 300-1000 ug/ml did not induce chromosomal aberrations either with or without S9. Results from sister chromatid exchange assays were equivocal because, although no evidence for induction of sister chromatid exchanges was seen in tests conducted with S9, 2 of 3 trials performed in the absence of S9 and with delayed harvest showed a significant elevation in the incidence of sister chromatid exchanges. In one trial, doses of 300-500 ug/ml resulted in a slight but significant rise in the number of sister chromatid exchanges per cell, but this response did not increase with dose; in the other, a significant dose related increase in the frequency of sister chromatid exchanges was observed within a range of 250-400 ug/ml. [REF-87]

Groups of guinea pigs were exposed, via inhalation, to toluene diisocyanate concentrations ranging from 0.12 to 10 ppm. Exposure was for 3 hr/day on 5 consecutive days. Beginning on day 22, animals were evaluated for toluene diisocyanate specific antibodies, skin sensitivity, and pulmonary sensitivity to toluene diisocyanate. No antibodies were detected in animals exposed to 0.12 ppm toluene diisocyanate, whereas 55% of animals exposed to 0.36 ppm toluene diisocyanate or greater displayed toluene diisocyanate specific antibodies in their sera. Exposure to higher toluene diisocyanate concentrations resulted in both a greater percentage of animals producing antibodies and higher antibody titers. Pulmonary sensitivity, assessed by bronchial provocation challenge with toluene diisocyanate protein antigen, was not detected in animals exposed to 0.12 ppm toluene diisocyanate but was present in guinea pigs exposed to toluene diisocyanate concentrations of 0.36 ppm or greater. However, exposure concentrations higher than 2 ppm were pneumotoxic and resulted in few pulmonary hyprsensitivity reactions. Exposure of animals to 0.02 ppm toluene diisocyanate for 15 weeks did not result in either dermal sensitivity, pulmonary sensitivity, or production oftoluene diisocyanate specific antibody. The exposure protocol, as well as the exposure concentration, was important for establishment of sensitivity. Recognition of the concentration-response relationship governing immune reaction to inhaled toluene diisocyanate should permit establishment of safe airborne exposure levels for industrial workers to prevent sensitization. /Toluene diisocyanate/ [REF-88]

Groups of male and female rats and mice were exposed to 0.05 and 0.15 ppm of toluene-diisocyanate by inhalation for 6 hr/day, 5 days/week for approx 2 years. Type and incidence of tumors and the number of tumor-bearing animals of either species did not indicate any carcinogenic effect. Hematology, biochemistry, urinalysis, and cytogenicity did not reveal any untoward effect. Increased mortality (females only), reduced weight gain and signs of irritation in the upper and lower respiratory tract resulted from exposure to toluene diisocyante in the mouse study with the highest incidence in the 0.15 ppm exposure level. Male and female rats of the 0.15 ppm group gained less weight during the first 12 weeks of the study. Histopathological examination in the rat study has not been completed, but no effect in the respiratory tract or in any other tissue has yet been seen. /Toluene diisocyanate/ [REF-89]

Toluene diisocyanate, a polymerizing agent used in production of plastics, can cause airway disease in some exposed individuals. Using guinea pigs as a model, the response of the airways and the type II cells of the peripheral lung was monitored morphologically and morphometrically after exposure to toluene diisocyanate vapors at 30 ppb, 260 ppb, and 3100 ppb. The two low doses of toluene diisocyanate caused little change in airways epithelium. There was not gross inflammatory cell infiltrate, however, surface infoldings and intracellular ciliated cysts increased in numbers. Animals exposed to 3100 ppb toluene diisocyanate 4 hr/day for 5 days, sustained considerable damage to the epithelium, and stratified nonkeratinizing cells lined the airways until ine week after exposure. Polymorphonuclear leukocytes were present in the early period after exposure. Increased numbers of eosinophils were present between one and two weeks following exposure. Mitoses in the epithelium were common during recovery. In the peripheral lung, though a modest subjective increase in the number of type II cells was seen after 3100 ppb toluene diisocyanate, the volume density of type II cells, and organellar components (lamellar bodies, mitochondria, cisternal bodies) did not change significantly after any exposure level of toluene diisocyanate. /Toluene diisocyanate/ [REF-90]

A number of industrial chemicals induce hypersensitivity responses in employees. 2,4-Toluene diisocynate (TDI) can cause pulmonary sensitization and allergic skin reactions. Since many commercial materials contain TDI, a study was designed to determine the concentration dependent elicitation of dermal sensitization in guinea pigs treated with TDI. Young adult guinea pigs received 2 open, epicutaneous induction applications (25 ul) of 8, 20 or 40% TDI in n-butyl ether on 2 separate areas. Five days later, animals were challenged with 0.0, 0.025, 0.05, 0.1, 0.2 and 0.4% TDI (25 ul per concentration site). All challange applications except the 0.0% solution elicited a positive response in 75-100% of the animals, and the severity of the skin reactions was dependent on the concentrations of the challenge and induction application. In another study using lower doses, animals received a total induction application (25 ul per each of 2 sites) of either 4 or 8% TDI and were challenged with 0.0, 0.006, 0.012, 0.025, 0.05 and 0.1% of TDI (25 ul per site). TDI did not elicit a sensitization response at challenge concentrations up to 0.012% (total application of 3 ug) when a 4% induction application was used, while a challenge concentration of 0.025% (total application of 6.25 ug) elicited a sensitization response in 63% of the animals. At the 8% induction application (total application of 4000 ug), all challenges, except the 0.0% indicated sensitization, and the intensities of the skin reactions were correlated with the challenge concentrations and the induction application. TDI produced sensitization at dilute induction concentrations and the severity of the dermal response was correlated with the concentration used at induction and challenge. No observed effect levels were determined below which the challenge concentration did not elicit a dermal hypersensitivity reaction. When 4% TDI was applied at induction, no observed effect was seen with a dermal challenge application of 3 ug whereas an effect was seen with 6.25 ug (in 35 ul) when n-butyl ether was the solvent. [REF-85]

Guinea pigs were exposed by head only inhalation for 5 hr to concentrations of approximately 1 ppm of toluene diisocyanate and 14 days later pinnal application of toluene diisocyanate on 3 consecutive days was followed by a dermal application of toluene diisocyanate after a further 7 days. The degree of contact sensitivity, measured 24 hr later, showed that prior inhalation inhibited the skin reaction to toluene diisocyanate but it did not change the skin reaction to chloro-dinitrobenzene in guinea pigs sensitized and challenged similarly with chloro-dinitrobenzene. The inhibition lasted up to 9 weeks. However, it did not occur in guinea pigs after intranasal instillation (instead of inhalation) and only occurred after oral dosage with toluene diisocyanate when the dose was relatively high. Treatment with cyclophosphamide before toluene diisocyanate inhalation reversed the inhibition of contact sensitivity, suggesting an involvement of suppressor cells. /Toluene diisocyanate/ [REF-91]

Acetylcholinesterase activity was measured in bronchial tissue homogenate and blood from rats subjected to single and repeated 4 hr daily inhalation exposure to toluene diisocyanate or control atmospheres. A single 4 hr exposure to toluene diisocyanate in the concentration range of 0.7-4.3 ppm did not decrease AChE activity in bronchial tissue but a 4 hr exposure to 0.6 ppm toluene diisocyanate, or greater, for two consecutive days did reduce this activity (19% to 33% of the controls). Increasing the level of exposure to toluene diisocyanate for two consecutive days from 0.6 to 4.0 ppm and extending the length of exposure to 1.2 ppm toluene diisocyanate from 2 to 4, 9 or 14 days produced no further decrease in bronchial ACHE activity. Throughout these experiments, blood AChE activity remained unchanged. In rats exposed to 0.3 or 1 ppm toluene diisocyanate for 3 weeks, staining of the bronchial smooth muscle for AChE was reduced (36% of the controls) after exposure to 1 ppm toluene diisocyanate. These results support, for the first time, in vivo and localized anti-AChE activity by TDI. /Toluene diisocyanate/ [REF-92]

Toluene diisocyanates induced respiratory epithelial inflammation, metaplasia and necrosis in mice at the lowest concentration tested (0.71 mg/cu m) after the shortest exposure period studied (6 hr per day for four days). The reaction became more severe when the exposure period was extended to 9 or 14 days. No effects were observed in the olfactory epithelium, trachea or lungs. /Toluene diisocyanates/ [REF-45, p.V71 872]

In vitro tracheal hyperreactivity to carbachol was induced in mice by cutaneous application of toluene diisocyanates (isomeric composition not indicated), followed by nasal toluene diisocyanate challenge; this was not accompanied by an elevation of toluene diisocyanate specific IgE. The reaction could be transferred to naive recipient mice by transfusion of lymphoid cells from sensitized mice. /Toluene diisocyanates/ [REF-45, p.V71 872]

Inhalation exposure of guinea pigs to toluene diisocyanates (3 hr per day on five consecutive days) led to sensitization (antibody formation, pulmonary reactiveness to toluene diisocyanate albumin conjugate), at exposure levels > or = to 0.14 mg/cu m. /Toluene diisocyanates/ [REF-45, p.V71 872]

When guinea pigs were sensitized to toluene diisocyanates by daily instillations for one week on the nasal mucosa and further exposed nasally once a week for four weeks, pulmonary alveolitis, characterized by infiltration of mononuclear cells and eosinophils, was observed. Vasculitis was not found, and fibrosis was negligible, but small nonnecrotizing granulomas, containing epithelioid histiocytes, multinucleated giant cells, lymphocytes and eosinophils were also observed. The histological picture was thus reminiscent of the hypersensitivity pneumonitis described in humans after exposure to toluene diisocyanates. /Toluene diisocyanates/ [REF-45, p.V71 872]

Evidence for Carcinogenicity
Evaluation: There is inadequate evidence for the carcinogenicity of toluene diisocyanates in humans. There is sufficient evidence for the carcinogenicity of toluene diisocyanates in experimental animals. Overall evaluation: Toluene diisocyanates are possibly carcinogenic to humans (Group 2B). /Toluene diisocyanates/ [QR] [REF-45, p.V71 876]

A4: Not classifiable as a human carcinogen. [QR] [REF-46, p.56]

TSCA Test Submissions
The mutagenicity of toluene 2,4-diisocyanate was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537 and TA1538 (Ames Test), both in the presence and absence of metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity determinations, toluene 2,4-diisocyanate, diluted in acetone, was tested at concentrations up to 300 ug/plate with metabolic activation and up to 8 ug/plate without metabolic activation using the plate incorporation technique. Toluene 2,4-diisocyanate did not cause a positive response in any tester strain with or without metabolic activation. [UR] [REF-94]


EMERGENCY TREATMENT

Antidote and Emergency Treatment
Irrigate eyes with running water for at least 15 min, and call for medical treatment of ophthalmologist. Wash contaminated areas of body with soap and water. [REF-5, p.528]

Noncardiogenic pulmonary edema and bronchospasm are the most immediate serious clinical consequences of isocyanate exposure. Markedly symptomatic patients should receive oxygen, ventilatory support, and an intravenous line. Treatment for asthma includes inhaled sympathomimetics (salbutamol, metaproterenol), intravenous theophylline, parenteral sympathomimetics (epinephrine, terbutaline), and steroids. Copiously irrigate contaminated skin and eyes with saline. Few medical data are available to guide gut decontamination. Activated charcoal (1 g/kg) and a cathartic (sorbitol, magnesium citrate) may be useful for ingestions. Most treatment is symptomatic. Mydriatics, systemic analgesics, and topical antibiotics (Sulamyd) may be used for corneal abrasions. There is no effective therapy for sensitized workers, and these people should be moved to a work site devoid of exposure to isocyanates. /Isocyanates/ [REF-47, p.881]

Copiously irrigate contaminated skin and eyes with saline. Few medical data are available to guide gut decontamination. Activated charcoal (1 g/kg) and a cathartic (sorbitol, magnesium citrate) may be useful for ingestions. /Isocyanates/ [REF-47, p.881]

Most treatment is symptomatic. Mydriatics, systemic analgesics, and topical antibiotics (Sulamyd) may be used for corneal abrasions. There is no effective therapy for sensitized workers, and these people should be moved to a work site devoid of exposure to isocyanates. /Isocyanates/ [REF-47, p.881]

Any employee who begins to experience shortness of breath during a shift should be removed from work immediately and should not return to work until pulmonary function tests have returned to base line. As is the case with asthma of any type, pulmonary function recovery may lag behind symptom recovery and take up to eight weeks to return to normal. If sensitized, the individual should not return to work in a toluene diisocyanate area or work with any other isocyanate. [REF-48, p.1020]

Medical Surveillance
COMPLETE BIOLOGIC MONITORING, INCL PULMONARY FUNCTION & IMMUNOLOGIC STUDIES, HAS BEEN PERFORMED CONCURRENTLY WITH COMPREHENSIVE ENVIRONMENTAL MONITORING PROGRAM IN A PLANT MANUFACTURING TOLUENE 2,4-DIISOCYANATE. [REF-49]

/Protect from exposure/ those individuals with diseases of blood and liver. Physical exam of exposed personnel annually, incl blood count and liver functions. [REF-5, p.528]

A SCREENING PROGRAM WAS UNDERTAKEN AT A RESEARCH & DEVELOPMENT FACILITY OF A LARGE TOLUENE DIISOCYANATE MANUFACTURING CORPORATION. THE PURPOSE WAS TO DETERMINE THE OCCURRENCE OF ANTIBODIES TO TOLUENE DIISOCYANATE IN SELECTED WORKER POPULATIONS. NO TOLYL-REACTIVE IMMUNOGLOBULIN-E ANTIBODIES WERE DETECTED IN SERA WHEN WORKERS WERE EXPOSED ONLY TO AMBIENT TOLUENE DIISOCYANATE CONCN. WORKERS HAD ACUTE EXPOSURES TO TOLUENE DIISOCYANATE AS A RESULT OF SPILLS OR SPLASHES. ANTIBODY RESPONSES DEVELOPED IN 3 OF 4 INDIVIDUALS WHOSE ACUTE EXPOSURES WERE ACCOMPANIED BY IMMEDIATE RESPIRATORY SYMPTOMATOLOGY & A DECREASED FORCED EXPIRATORY VOLUME. AN ANTIBODY RESPONSE DEVELOPED IN 1 OF 9 WORKERS & IMMEDIATE RESPIRATORY SYMPTOMS, BUT NO SPIROMETRIC CHANGES UPON ACUTE TDI EXPOSURE. ROUTINE SEROLOGIC SCREENING OF WORKERS FOR TOLYL-REACTIVE ANTIBODIES MAY BE OF VALUE IN CONFIRMING SUSPECTED ISOCYANATE EXPOSURE & IN PROVIDING AN EARLY WARNING OF DEVELOPING TDI HYPERSENSITIVITY. /TOLUENE DIISOCYANATE/ [REF-50]

MEDICAL EVALUATIONS OF 15 WORKERS WERE MADE TO DETERMINE THE HEALTH EFFECTS OF EXPOSURE TO TOLUENE DIISOCYANATE PHOSGENE & TOLUENE DIISOCYANATE. THE FOLLOWING STEPS WERE RECOMMENDED: THE ENTIRE FACTORY POPULATION SHOULD BE SURVEYED PERIODICALLY FOR SYMPTOMS OF LOWER RESPIRATORY TRACT DISEASES & LUNG FUNCTION ABNORMALITIES THAT MAY BE CAUSED BY CHEMICAL EXPOSURE; TOLUENE DIISOCYANATE EXPOSURE SHOULD BE ENDED FOR SENSITIZED WORKERS OR FOR THOSE WITH EXCESSIVE DECLINE IN LUNG FUNCTION. /TOLUENE DIISOCYANATE/ [REF-51]

PRECAUTIONS FOR "CARCINOGENS": Whenever medical surveillance is indicated, in particular when exposure to a carcinogen has occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or other/ tests that might become useful or mandatory. /Chemical Carcinogens/ [REF-34, p.23]

The assessment of toluene diisocyanate exposure can be accomplished through measurement of the isomer-specific metabolites, 2,4-toluene diamine and 2,6-toluene diamine. This test may be useful for identification of exposures from both inhalation and dermal absorption. However, collection of urine samples must be obtained shortly after exposure, since later samples correlated poorly with exposure. Serum or Plasma Reference Ranges: Normal - not established; Exposed - not established; Toxic - not established. Urine Reference Ranges: Normal - none detected; Exposed - exposure to air level of 40 ug/cu m (current TLV) gave a 6 to 8 hour urine level of 8.6 ug/l (average); Toxic - not established. [REF-52, p.1157]

Respiratory Symptoms Questionnaires: Questionnaires published by the American Thoracic Society (ATS) and the British Medical Research Council have proven useful for identifying people with chronic bronchitis. Certain pulmonary function tests such as the FEV1 ... have been found to be better predictors of chronic airflow obstruction. [REF-52, p.1158]

Chest Radiography: Chest radiographs are widely used to assess pulmonary disease. They are useful for detecting early lung cancer in asymptomatic people, and especially for detecting peripheral tumors such as adenocarcinomas. However, even though OSHA mandates this test for exposure to some toxicants such as asbestos, experts' views on the risk-to-benefit ratio in detection of pulmonary disease conflict, so routine annual chest x-rays are not recommended for all people. [REF-52, p.1158]

Pulmonary Function Tests: The tests that have been found to be practical for population monitoring include: Spirometry and expiratory flow volume curves; Determination of lung volumes; Diffusing capacity for carbon monoxide; Single breath nitrogen washout; Inhalation challenge tests; Serial measurements of peak expiratory flow; Exercise testing; Spirometry, for the measurement of FVC(forced vital capacity) and FEV1 (forced expiratory volume in 1 second), has been found to be the most reproducible and least variable test of pulmonary function. [REF-52, p.1158]

METABOLISM AND PHARMACOLOGY

Populations at Special Risk
IN VIEW OF POTENTIALLY HAZARDOUS LEVELS OF TOLUENE DIISOCYANATE IN COMMERCIALLY AVAIL AEROSOLS, ... PATIENT WITH ALLERGIC DIATHESES & OBSTRUCTIVE LUNG DISEASE CAUTIONED AGAINST THEIR USE. [REF-95]

Individuals once sensitized are vulnerable to serious health consequences. [REF-23, p.49-88]

Individuals with diseases of the blood or liver /may be at an increased risk from exposure to this chemical/. [REF-5, p.528]

Absorption, Distribution, and Excretion
Toluene diisocyanate may be absorbed into the body by inhalation, ingestion and through the skin. /Toluene diisocyanate/ [REF-19, p.970]

The use of radioactively labeled isocyanate has made it possible to follow the initial uptake of the compound into the bloodstream independent of the final fate of the isocyanate. This study shows that the rate of uptake into the blood is linear during exposure to concentrations ranging from 0.00005 to 0.146 ppm and that the uptake continues to increase slightly postexposure. It also demonstrates that the radioactivity clears from the bloodstream to a level corresponding to approximately a 100 nM concentration of tolyl group after 72 hr and persists at a nanomolar level even 2 weeks following the exposure. This is similar to the response previously reported by this group for radioactively labeled methyl isocyanate. The initial ratre of (14)C uptake is also a linear function of the concentration of toluene diisocyanate when expressed either as concentration (ppm) or as concentration multiplied by duration of exposure (ppm/hr). This is discussed in comparison with the toxic responses as a function of both ppm and ppm/hr. Finally the inclusion of the data on methyl isocyanate indicates that the uptake into arterial blood is a function of exposure concentration, independent of isocyanate structure. /Toluene diisocyanate/ [REF-96]

... The route dependent metabolism of (14)C toluene 2,4-diisocyanate and (14)C toluene 2,4 diamine in Fischer 344 rats. Forty-eight hours after an oral dose of 60 mg (14)C toluene 2,4 diisocyanate/kg bw, 81%, 8% and 4% of the radioactivity was found in the feces, urine and tissue/carcass/gastrointestinal tract contents, respectively. Markedly different results were obtained following inhalation exposure of rats to 2 ppm (14.2 mg/cu m) (14)C toluene 2,4 diisocyanate for 2 hr. Forty eight hours after exposure, 47%, 15% and 34% of the recovered radioactivity was in the feces, urine and tissue/carcass/gastrointestinal tract contents, respectively. [REF-45, p.V71 871]

In comparative studies, (14)C toluene 2,4-diamine, the hydrolysis product of (14)C toluene 2,4-diisocyanate, was administered to rats at doses of 3 mg/kg bw (orally or intravenously) and 60 mg/kg bw orally. After 48 hr, the distribution of radioactivity was similar in all cases (urine, 64 72%; feces, 20 31%; and tissue/carcass/gastrointestinal tract, 2 5%). Comparison of the toluene 2,4-diisocyanate inhalation group with the oral toluene 2,4-diisocyanate and toluene 2,4-diamine treatment groups indicated that a larger percentage of the inhaled radioactivity was in the tissues/carcass and that excretion of radioactivity into the urine was slower following toluene 2,4-diisocyanate inhalation. [REF-45, p.V71 871]

Following inhalation or oral exposure to (14)C toluene 2,4-diisocyanate, about 90% and 65% of the quantitated urinary metabolites were acid labile conjugates. In contrast, only 16 39% of the urinary metabolites were conjugated following oral administration of (14)C toluene 2,4-diamine. [REF-45, p.V71 871]

Inhalation exposure to toluene 2,4-diisocyanate results primarily in the formation of acid labile conjugates, with little or no toluene 2,4-diamine being formed. This suggests that the disposition of inhaled toluene 2,4-diisocyanate is quite different from that of orally administered toluene 2,4-diisocyanate or of intravenously or orally administered toluene 2,4-diamine. [REF-45, p.V71 871]

The toxicokinetics of 2,4- and 2,6-toluenediisocyanates in 11 chronically exposed workers at two flexible foam polyurethane production plants have been reported. The toluene diisocyanate, concentrations in air varied between 0.4 and 4 ug/cu m in one plant and in the other between 10 and 120 ug/cu m. In one of the plants, the plasma 2,4-toluene diamine levels were 0.4-1 ug/mL before a 4-5 week holiday and 0.2-0.5 ug/mL afterwards. The corresponding plasma levels of 2,6-toluene diamine were 2-6 and 0.5-2 ug/mL, respectively. In the other plant, the plasma 2,4 toluene diamine concentrations were 2-23 ng/mL before the holiday and 0.5-6 ng/mL afterwards and those of 2,6-toluene diamine were 7-24 ng/mL before and 3-6 ng/mL afterwards. The plasma concentrations of 2,4-toluene diamine were, 2-24 ng/mL before a 12 day holiday, and 1-14 ng/mL afterwards. The corresponding values for plasma 2,6-toluene diamine were 12-29 and 8-17 ng/mL, respectively The urinary elimination rates for 2,4-toluene diamine before the, holiday were 0.04-0.54 and 0.02-0.18 ug/hr afterwards. The corresponding values for 2,6-toluene diamine were 0.18-0.76 ug/hr before and 0.09-0.27 ug/hr after the holiday. The half life in urine ranged from 5.8 to 11 days for 2,4 and 2.6 toluene diamines. The differences in exposure were reflected by the plasma toluene diamine concentrations. The mean half life in plasma was 21 (range, 14-34) days for 2,4-toluene diamine and 21 (16-26) days for 2,6-toluene diamine, The study showed that the half life in plasma of chronically exposed workers for 2,4- and 2,6-toluene diamine was twice as long as for volunteers with short term exposure. An indication of a two phase elimination pattern in urine was found. The first phase was related to the more recent exposure and the second, much slower one was probably related to release of toluene diamines in urine from toluene diisocyanate adducts in the body. [REF-45, p.V71 870]

Two men were exposed to toluene diisocyanate atmospheres at three different air concn (ca 25, 50 & 70 ug/cu m). The toluene diisocyanate atmospheres were generated by a gas-phase permeation method, & the exposures were performed in an 8-cu m stainless-steel test chamber. The effective exposure period was 4 hr. The isomeric composition of the air in the test chamber was 30% 2,4-toluene diisocyanate and 70% 2,6-toluene diisocyanate. The concn of toluene diisocyanate in air of the test chamber was determined by an HPLC method using the 9-(N-methyl-amino-methyl)-anthracene reagent & by a continuous-monitoring filter-tape instrument. Following the hydrolysis of plasma & urine, the related amines, 2,4-toluenediamine & 2,6-toluenediamine, were determined as pentafluoropropionic anhydride derivatives by capillary gas chromatography using selected ion monitoring in the electron impact mode. In plasma, 2,4- & 2,6-toluenediamine showed a rapid-phase elimination half-time of ca 2-5 hr, & that for the slow phase was greater than 6 days. A connection was observed between concn of 2,4- and 2,6-toluene diisocyanate in air & the levels of 2,4- & 2,6-toluenediamine in plasma. The cumulated amount of 2,4-toluenediamine excreted in the urine over 24 hr was ca 15%-19% of the estimated inhaled dose of 2,4-toluene diisocyanate, & that of 2,6-toluenediamine was ca 17%-23% of the inhaled dose of 2,6-toluene diisocyanate. A connection was found between the cumulated (24 hr) urinary excretion of 2,4- & 2,6-toluenediamine & the air concn of 2,4- & 2,6-toluene diisocyanate in the test chamber. [REF-97]

Metabolism/Metabolites
In man, tolylene-2,4-diisocyanate is metab into 2,4-diaminotoluene. ... [REF-98, p.212]

The major metabolites of toluene diisocyanates in both animals and humans are toluene diamines and their acetylated products. /Toluene diisocyanates/ [REF-45, p.V71 870]

Inhalation exposure to toluene 2,4-diisocyanate results primarily in the formation of acid labile conjugates, with little or no toluene 2,4-diamine being formed. [REF-45, p.V71 871]

Biological Half/Life
The half life in urine ranged from 5.8 to 11 days for 2,4 and 2.6 toluene diamines. The differences in exposure were reflected by the plasma toluene diamine concentrations. The mean half life in plasma was 21 (range, 14-34) days for 2,4-toluene diamine and 21 (16-26) days for 2,6-toluene diamine, The study showed that the half life in plasma of chronically exposed workers for 2,4- and 2,6-toluene diamine was twice as long as for volunteers with short term exposure. [REF-45, p.V71 870]

Mechanism of Action
Exposure of workers to isocyanates may result in irritation and/or sensitization of the resp tract. An immunologic mechanism for sensitization has been presented. This investigation explored whether, as a possible mechanism for the irritation reaction, the toxic resp effect of isocyanates might be due to their ability to inhibit cholinesterase. Molar ratios of 50:1 or greater were required for 50% inhibition of purified human serum cholinesterase by 2,4-toluene diisocyanate. When whole human plasma was the source of cholinesterase, the molar concn of 2,4-toluene diisocyanate needed to effect 50% enzyme inhibition suggested affinity labeling by this reagent. [REF-99]

... The sensitizing agent /such as toluene diisocyanate/ acts in vivo to haptenate self-proteins, and this haptenated self-protein serves as the stimulus for generation of the allergic immune response. [REF-100, p.265]

It ... has been reported that toluene diisocyanate forms antigenic complexes with proteins, transforms lymphocytes in sensitized individuals, induces skin-sensitizing antibodies in animals, and induces specific antibody formation. [REF-101, p.798]

Toluene diisocyanate (TDI) has ... been found to suppress the incr of intracellular cyclic adenosine monophosphate (cAMP) by the beta-agonist isoproterenol in peripheral blood lymphocytes indicative of a pharmacologic mechanism of action. Research data suggest that isocyanates may cause nonspecific inhibition of a variety of membrane receptors & enzyme systems. Both immunologic & nonimmunologic mechanisms appear to be involved. Although much research has been directed toward the mechanism of isocyanate-induced disease, the complete pathophysiology remains unknown. /Toluene diisocyanate/ [REF-102, p.947]

Interactions
2,4-Toluene diisocyanate exerted a nonspecific inhibitory effect on the beta-adrenergic adenylate cyclase system of frog erythrocyte membrane preparation stimulated by the beta-agonist isoproterenol in vitro. This inhibition was dose-dependent, ie, incr concn of toluene diisocyanate (TDI) produced progressively greater inhibition. The similarity in response between toluene diisocyanate and the isocyanates 1,6-diisocyanatohexane & diphenylmethane 4,4'-diisocyanate suggests that the isocyanate group plays a critical role in inhibiting the responsiveness of this system to beta-agonists. [REF-103]

ENVIRONMENTAL FATE AND EXPOSURE POTENTIAL

Environmental Fate/Exposure Summary
2,4-Toluene diisocyanate's production and use in the manufacture of polyurethane foam products and coatings, in sprays, insulation materials, and polyurethane foam coated fabrics may result in its release to the environment through various waste streams. Commercial toluene diisocyanate (TDI) typically contains 80% of 2,4-toluene diisocyanate. If released to air, a vapor pressure of 8X10-3 mm Hg at 25 deg C indicates 2,4-toluene diisocyanate will exist solely as a vapor in the ambient atmosphere. Vapor-phase 2,4-toluene diisocyanate will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 1.7 days. Atmospheric degradation may also occur through contact with clouds, fog or rain. If released to water or moist soil, 2,4-toluene diisocyanate is not expected to leach or adsorb to solids due to its rapid degradation reaction with water. 2,4-Toluene diisocyanate is not expected to volatilize from dry soil surfaces based upon its vapor pressure. If spilled on wet land, TDI is rapidly degraded. If released into water, a crust forms around the liquid TDI and <0.5% of the original material remains after 35 days. Low concentrations of TDI hydrolyze in the aqueous environment in approximately a day. Occupational exposure to 2,4-toluene diisocyanate occurs through inhalation of vapors and aerosols and through dermal contact with this compound and other compounds containing 2,4-toluene diisocyanate. The general population may be exposed to 2,4-toluene diisocyanate through the use of commercially available urethane adhesives containing this compound. (SRC)

Environmental Fate
  • TERRESTRIAL FATE: 2,4-Toluene diisocyanate reacts readily with compounds containing active hydrogens, such as water, acids, and alcohols(1); therefore, leaching will not occur(SRC). 2,4-Toluene diisocyanate is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 8X10-3 mm Hg(2). In a simulated spill, 5 kg of TDI in a container was covered with 50 kg of sand and 5 kg of water at ambient temperatures and samples taken from the top and bottom of the sand pile(3). After 24 hr, 5.5% of the TDI remained unreacted and after 8 days 3.5% remained(5). The reaction product was largely polyureas(3). Ten days after a spill of 13 tons of toluene diisocyanate (TDI) (2,4- plus 2,6-isomers) onto a swampy, wet forest soil, TDI and toluenediamines were found in the soil(2,3). The TDI solidified and the area was covered with sand. The soil concn of TDI and toluenediamine combined declined from the parts per thousand to parts per million range between 10 days and 12 weeks after the spill(3). One year later, neither TDI nor toluenediamine could be found in soil samples(4). After 6 years, only TDI-derived polyureas were found at the site in soil samples at depths to 100 cm(4). [REF-106]
  • AQUATIC FATE: 2,4-Toluene diisocyanate reacts readily with compounds containing active hydrogens, such as water, acids, and alcohols(1); therefore, adsorption to suspended solids and sediment will not occur(SRC). When low concns of toluene diisocycnate (TDI) are released into model river or seaway systems, it is hydrolyzed within a day(2). An experiment was performed to simulate a spill into running water by pouring 0.5 liter of TDI into 20 liters of slowly overflowing water(3). Barely detectable amounts of toluenediamine were present in the overflow samples. As in the stagnant water simulation, a crust formed that contained <0.5% of the original TDI after 35 days(3). [REF-107]
  • ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 2,4-toluene diisocyanate, which has a vapor pressure of 8X10-3 mm Hg at 25 deg C(2), is expected to exist solely as a vapor in the ambient atmosphere. Vapor-phase 2,4-toluene diisocyanate is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 1.7 days(SRC), calculated from its rate constant of 6.3X10-12 cu cm/molecule-sec at 25 deg C(SRC) determined using a structure estimation method(3). Atmospheric degradation may also occur through contact with clouds, fog or rain. [REF-108]

Biodegradation
  • Various process wastewaters from a petrochemical complex were subjected to biodegradability tests(1). Biodegradation tests on 2,4-toluene diisocyanate revealed 15% COD removal and 23% TOC removal of applied concentration. [REF-109]

Abiotic Degradation
  • The rate constant for the vapor-phase reaction of 2,4-toluene diisocyanate with photochemically-produced hydroxyl radicals has been estimated as 6.3X10-12 cu cm/molecule-sec at 25 deg C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.7 days at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). 2,4-Toluene diisocyanate reacts readily with compounds containing active hydrogens, such as water, acids, and alcohols(2). Contact with bases may cause uncontrollable polymerization with rapid evolution of heat(2). Hydrolysis of one of the isocyanate groups to the amine will be followed by rapid reaction of the amine with an isocyanate group on another molecule leading to dimers, oligomers, and polymers unless the solution is very dilute(2). In one experiment the hydrolysis product yield was 20% diamine and 80% polyurea(3). When 50 ppm of toluene diisocyanate was added to a model river and seawater systems, the concn was 0.1 ppm or less at the end of 1 day(4). [REF-110]
  • Gas phase loss of TDI was originally thought to be due to reaction of TDI with water vapor(1). One early work showed that the percent disappearance of TDI in air depended almost solely on the water vapor concentration, increasing 3.2% per unit increase in absolute humidity (g water/kg dry air), so that at 15 g water/kg dry air, a 50% reduction in TDI was obtained(1). These reductions were obtained after 8 sec and did not differ appreciably after 75 sec(1). The reaction product of 2,4-toluene diisocyanate vapor with limited quantities of moisture was reported to be 3,3'-diisocyanto-4,4'-dimethylcarbanilide(3). Other work contradicted these earlier findings and a program was instituted to study the gas-phase reactions between TDI and water using a room sized environmental chamber(2). They found that over a relative humidity range of 7-70%, the loss rate of TDI was independent of humidity and no toluenediamine or TDI-urea products could be detected(2). In addition deposition onto the chamber walls was an important removal process(2). Subsequent experiments were performed in the environmental chamber to assess the importance of photolysis, reaction with free radicals, and adsorption onto particulate matter as atmospheric removal processes(3). The loss rate of TDI in irradiated clean air was first order with a half-life of 3.3 hr(3). By using a free radical scavenger, it was shown that free-radicals and not photolysis was responsible for the removal. The half-life is consistent with the reaction with photochemically generated hydroxyl radicals(3). The addition of an urban surrogate hydrocarbon mixture (polluted urban air) or ammonium sulfate particulate matter, a major component of atmospheric aerosols, did not significantly alter removal rates(3). Because the concentration of hydroxyl radicals generally increases in polluted air, shorter half-lives are expected(SRC). [REF-111]
  • Ten days after a spill of 13 tons of toluene diisocyanate (TDI) onto swampy, wet forest soil, TDI and toluenediamines were found in the soil(1,2). The TDI solidified and the area was covered with sand. The soil concn of TDI and toluenediamine combined declined from the parts per thousand to parts per million range between 10 days and 12 wk after the spill(2). No TDI was detected in a connecting brook 10 days after the spill(3). After 6 years, only TDI-derived polyureas were found at the site(2). In a simulated spill, 5 kg of TDI in a container was covered with 50 kg of sand and 5 kg of water at ambient temperatures and samples taken from the top and bottom of the sand pile. After 24 hr, 5.5% of the TDI remained unreacted and after 8 days 3.5% remained(3). The reaction product was largely polyureas(3). [REF-112]

Bioconcentration
  • 2,4-Toluene diisocyanate hydrolyzes rapidly in aqueous solution(1); therefore, bioconcentration will not be environmentally important(SRC). [REF-113]

Soil Adsorption/Mobility
  • 2,4-Toluene diisocyanate hydrolyzes rapidly in aqueous solution(1); therefore, leaching and adsorption to sediment will not be environmentally important(SRC). [REF-113]

Volatilization from Water/Soil
  • 2,4-Toluene diisocyanate hydrolyzes rapidly in aqueous solution(1); therefore, volatilization from water will not be environmentally important(SRC). 2,4-Toluene diisocyanate is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 8X10-3 mm Hg(2). [REF-114]


SOURCES AND CONCENTRATIONS

Natural Occurring Sources
  • 2,4-Toluene diisocyanate is not known to occur as a natural product(1). [REF-104]

Artificial Sources
  • 2,4-Toluene diisocyanate's production and use in the preparation of polyurethane foams, elastomers and coatings, as a cross-linking agent for nylon-6, and as a hardener in polyurethane adhesives and finishes(1) may result in its release to the environment through various waste streams(SRC). [REF-105]

Effluents Concentrations
  • Toluene diisocyanate (TDI), no isomer specified, has been reported in waste water from furniture manufacturing in the concn range of 0.1-4.1 ppm(1). Stack exhaust from a polyurethane foam production plant were reported to contain 100-17,700 ug/cu m of TDI (no isomer specified)(1). [REF-113]

Other Environmental Concentrations
  • Commercial toluene diisocyanate typically contains 80% 2,4-toluene diisocyanate(1). TDI monomer has been found in a urethane foam fabric coating in concn of <200 mg/kg(2). [REF-115]


HUMAN ENVIRONMENTAL EXPOSURE

Probable Routes Of Human Exposure
  • VARNISHERS WHO PRESENTED OR COMPLAINED OF SYMPTOMS OF BRONCHIAL ASTHMA OR PERSISTENT ASTHMATIC BRONCHITIS FOLLOWING THE USE OF POLYURETHANIC LACQUERS CONTAINING ISOCYANATES WERE EXAM. SOME VARNISHERS PRESENTED CHRONIC BRONCHITIS AS AN IRRITATIVE ACTION OF ISOCYANATES. /ISOCYANATES/ [REF-116]
  • Pulmonary function tests were done and compared to current and past potential exposure levels of toluene diisocyanate (TDI) for 57 TDI manufacturing workers and 89 workers not exposed to TDI or other known respiratory hazards. The avg TDI plant experience at Texas Operations of Dow Chemical USA was 4.1 + or - 2.8 yr. Routine industrial hygiene measurements have shown TDI exposure below a time weighted avg of 0.005 ppm and a short term exposure of 0.02 ppm. Ranking was made of department and job classification by level of potential exposure to TDI (none, n= 10; moderate, n= 14; and high, n= 33). TDI exposure, whether classified as current, highest career level, cumulative or cumulative highest to date, was not associated with a decline of forced expiratory volume. [REF-117]
  • NIOSH (NOES Survey 1981-1983) has statistically estimated that 10,291 workers (545 of these are female) are potentially exposed to 2,4-toluene diisocyanate in the US(1). Occupational exposure to 2,4-toluene diisocyanate may occur through inhalation and dermal contact with this compound at workplaces where 2,4-toluene diisocyanate is produced or used(SRC). The general population may be exposed to 2,4-toluene diisocyanate through the use of commercially available urethane adhesives containing this compound(SRC). [REF-118]
  • Concentration ranges of worker exposure to 2,4-toluene diisocyanate in a polyurethane foam plant were 5-11 ug/cu m in gases and not detected to 187 ug/cu m in aerosols(1). Mean concn ranges of toluene diisocyanate (TDI) reported in ambient workplace air were 0.7-710 ug/cu m in TDI production, not detected-1490 ug/cu m during polyurethane foam production, 70-140 mg/cu m during elastomers production, 13-1050 ug/cu m during polyurethane foam use, 10-710 ug/cu m during polyurethane spray paint use, and <1-740 ug/cu m during the production of polyurethane-coated wire(2). Mean concn in personal samples ranged from not detected-540 ug/cu m during polyurethane foam production and 2-1220 ug/cu m during polyurethane spray foam use(2). Additionally, mean concn of TDI released from insulation in ship's hold was reported to be 120-150 ug/cu m and that released from coated fabric in a workplace 2-10 ug/cu m(2). During the outdoor application of TDI foam to a 40 ft diameter storage tanks, the mean atmospheric TDI concn downwind from the spray gun was 0.3 ppm at 8 ft, 0.02 ppm at 40 ft, and 0.002 ppm at 150 ft(3). TDI was not detected more than 8 ft upwind of the spray gun(3). Air sample concns taken within 2 ft of the foam surface immediately after spraying had ceased was found to be 0.03 ppm(3). Mean TDI concns near the pumping equipment during material transfer was 0.02 ppm(3). [REF-119]
  • Airborne toluene diisocyanate in two plants producing flexible polyurethane foam for use in matresses, carpet pads, and air filters by a continuous slab process were determined(1). In this process the starting materials are mixed internally in a foaming nozzle and is poured onto moving kraft paper at which time the material foams and heats up (mixing end). The foam slab is then carried into a ventilated curing tunnel during which time the unreacted toluene diisocyanate and other material is driven off due to the high internal temperature (finishing end). The paper liner is subsequently stripped off and the slab cut into pieces. Concentration medians for 2,4-toluene diisocyanate were 0.70 and 0.33 ppb for the mixing and finishing ends, respectively(1). Only an insignificant number of samples exceeded the 20 ppb ceiling recommended by the ACGIH(1). In a similar Finish study, toluene diisocyanate vapor concentrations ranged from 25-80 ug/cu m for pouring, 14-44 ug/cu m for paper stripping, and 1-8 ug/cu m for cutting(2). Personal monitors measured 9-34 ug/cu m and 5-30 ug/cu m of the 2,4-isomer for pouring and paper stripping, respectively(2). While 2,4-toluene diisocyanate constitutes 80% of toluene diisocyanate, and 2,6-toluene diisocyanate 20%, the 2,4-isomer is more reactive so that the concentration of the 2,6-isomer is higher in workplace air(2). The percentage of 2,4-toluene diisocyanate to total toluene diisocyanate measured with the personal monitors ranged from 29 to 69%(2). [REF-120]


STANDARDS AND REGULATIONS

Immediately Dangerous to Life or Health (IDLH)
  • NIOSH considers toluene-2,4-diisocyanate to be a potential occupational carcinogen. [REF-20, p.312]

OSHA Standards
  • Permissible Exposure Limit: Table Z-1 Ceiling value: 0.02 ppm (0.14 mg/cu m). [REF-121]
  • Vacated 1989 OSHA PEL TWA 0.005 ppm (0.04 mg/cu m); STEL 0.02 ppm (0.15 mg/cu m) is still enforced in some states. [REF-20, p.372]

Niosh Recommendations
  • NIOSH considers toluene-2,4-diisocyanate to be a potential occupational carcinogen. [REF-20, p.312]
  • NIOSH usually recommends that occupational exposures to carcinogens be limited to the lowest feasible concentration. [REF-20, p.312]

Threshold Limit Values
  • 8 hr Time Weighted Avg (TWA): 0.005 ppm; 15 min Short Term Exposure Limit (STEL): 0.02 ppm, sensitizer [QR] [REF-46, p.56]
  • A4: Not classifiable as a human carcinogen. [REF-46, p.56]

Other Occupational Permissible Levels
  • Other recommendations: Federal Republic of Germany (1992) 0.01 ppm, short-term limit 0.02 ppm, 5 min, 8 times/shift, sensitizer; Sweden (1990) 0.005 ppm, 5-min ceiling limit 0.01 ppm, sensitizer; United Kingdom (1991) 0.02 mg/cu m as -NCO, 10-min STEL 0.07 mg/cu m as-NCO, maximum exposure limits. [REF-55, p.1588]

Atmospheric Standards
  • This action promulgates standards of performance for equipment leaks of Volatile Organic Compounds (VOC) in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). 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. Toluene 2,4-diisocyanate is produced, as an intermediate or a final product, by process units covered under this subpart. [REF-122]
  • Listed as a hazardous air pollutant (HAP) generally known or suspected to cause serious health problems. The Clean Air Act, as amended in 1990, directs EPA to set standards requiring major sources to sharply reduce routine emissions of toxic pollutants. EPA is required to establish and phase in specific performance based standards for all air emission sources that emit one or more of the listed pollutants. 2,4-Toluene diisocyanate is included on this list. [REF-123]

Transport Methods and Regulations
  • No person may /transport,/ offer or accept a 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-36]
  • 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 a manual of industry carrier regulations to be followed by all IATA Member airlines when transporting hazardous materials. [QR] [REF-37, p.263]
  • The International Maritime Dangerous Goods Code lays down basic principles for transporting hazardous chemicals. Detailed recommendations for individual substances and a number of recommendations for good practice are included in the classes dealing with such substances. A 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-38, p.101]

CERCLA Reportable Quantities
  • Persons in charge of vessels or facilities are required to notify the National Response Center (NRC) immediately, when there is a release of this designated hazardous substance, in an amount equal to or greater than its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is (800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The rule for determining when notification is required is stated in 40 CFR 302.4 (section IV. D.3.b). [REF-124]
  • Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Toluene 2,4-diisocyanate is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 lbs. [REF-125]

FDA Requirements
  • Toluene 2,4-diisocyanate is an indirect food additive for use only as a component of adhesives. [REF-126]


MONITORING AND ANALYSIS METHODS

Sampling Procedures
  • A passive dosimeter for monitoring occupational exposure to both 2,6- and 2,4-toluene diisocyanate (TDI) was developed. The device is constructed from a 37 mm aerosol cassette. The collection medium used in the dosimeter is 0.5% sulfuric acid. Membranes of both the permeation and diffusion types were evaluated for use in the dosimeter. Microporous teflon diffusion membranes exhibited superior performance in terms of surface effects (mass transfer coefficient <0.006 ug/ppb/hr) and residual TDI (not detected) and were chosen for use. Collected TDI is determined as toluenediamine by either colorimetry using a modification of the Marcali technique or fluorometry using fluorescamine reagent. The manufacturer claims an accuracy of + or - 15%. A significant dependence on wind speed was minimized by use of a second microporous membrane as a wind screen. The mass transfer rate of TDI was found to be approximately 0.0152 ug/ppb/hr and was equivalent for the 2,4- and 2,6- isomers of TDI. [REF-127]
  • NIOSH Method 2535. Analyte: Toluene-2,4-diisocyanate. Matrix: Air. Sampler: Tube with reagent coated glass wool (N-((4-nitrophenyl) methyl)-propylamine on glass wool). Flow Rate: 0.2 to 1 l/min: Sample Size: 10 liter. Shipment: Protect from light. Sample Stability: At least 14 days at 25 deg C. [REF-128]
  • NIOSH Method 5521. Analyte: 2,4-Toluene diisocyanate. Matrix: Air. Sampler: Impinger (solution of 1-(2-methoxyphenyl)-piperazine in toluene). Flow Rate: 1 l/min: Sample Size: 100 liters. Shipment: Ship in screw-cap vial refrigerated @ 4 deg C or lower. Sample Stability: May be unstable. [REF-128]

Analytic Laboratory Methods
  • LIQ CHROMATOGRAPHY HAS BEEN USED TO SEPARATE TOLUENE DIISOCYANATE ISOMERS AS UREA DERIVATIVES FROM PREPD MIXT ... WITH DETECTION BY UV SPECTROSCOPY. LIMIT OF DETECTION WAS 1.2 NG OF 2,4- OR 2,6-ISOMER. GAS CHROMATOGRAPHY WITH ELECTRON CAPTURE DETECTION HAS BEEN USED TO DETERMINE 2,4-TOLUENE DIISOCYANATE IN ... AIR, WITH LOWER LIMIT OF DETECTION OF 0.035 MG/CU M (0.005 PPM). [REF-21, p.V19 309]
  • 2,4-TDI IS DETERMINED IN AIR BY HYDROLYSIS IN HYDROCHLORIC ACID-ACETIC ACID TO THE DIAMINE, WHICH IS DIAZOTIZED, COUPLED WITH N-1-NAPHTHYLETHYLENEDIAMINE, AND DETERMINED SPECTROPHOTOMETRICALLY AT 550 NM. THE RANGE OF STANDARDS USED IS 0.007-0.140 PPM IN A 20-L SAMPLE. [REF-129]
  • GAS CHROMATOGRAPHIC METHOD IS DESCRIBED FOR THE ANALYTICAL DETERMINATION OF FREE MONOMERIC TDI IN POLYURETHANE PAINTS. [REF-130]
  • SIMULTANEOUS DETERMINATION OF 2,4- AND 2,6-DIISOCYANATOTOLUENE AND 3,3'-DICHLORO-4,4'-DIAMINODIPHENYLMETHANE IN AIR WAS DETERMINED BY GAS-LIQUID CHROMATOGRAPHY. [REF-131]
  • NIOSH Method 2535. Analyte: Toluene-2,4-diisocyanate. Matrix: Air. Procedure: High performance liquid chromatography, ultra violet detection. For 2,4-toluene diisocyanate this method has an estimated detection limit of 0.1 ug/sample. The precision/RSD is 0.067 and the recovery is 2 ml methanol, ultrasonic bath 3 min. Applicability: The working range is 0.1004 to 0.35 ppm (0.03 to 2.5 mg/cu m) for a 10-liter air sample. Interferences: The reagent is slightly unstable in the dark at 25 deg C. Tailing during high performance liquid chromatography, a result of reagent deterioration, may raise detection limit. [REF-128]
  • NIOSH Method 5521. Analyte: 2,4-Toluene diisocyanate. Matrix: Air. Procedure: High performance liquid chromatography, electrochemical and ultra violet detection. For 2,4-toluene diisocyanate this method has an estimated detection limit of 0.1 ug diisocyanate/sample. The precision/RSD is not determined. Applicability: The working range is from 5 ug/cu m 2,4-toluene diisocyanate to more than 1 mg/cu m for 100 liter air samples. Interferences: Any substance which elutes with the ureas and absorbs ultraviolet light or is electroactive will interfere with the analysis. [REF-128]
  • NIOSH Method 5522. Isocyanates. Analyte: tryptamine derivatives of isocynates. HPLC, fluorescence detector/electrochemical detector. Range: 0.3 to 14.0 ug/sample. Detection limit: 0.1 ug/sample. [REF-128]
  • NIOSH Method 5516. 2,4- and 2,6-Toluene Diisocyanate (in the presence of isocyanates). HPLC, UV detection. Air. [REF-128]
  • EPA Method 8250. Packed Column Gas Chromatography/Mass Spectrometry Technique for the determination of semivolatile organic compounds in extracts prepared from all types of solid waste matrices, soil, and groundwater. This method is applicable to quantify most neutral, acidic, and basic organic compounds that are soluble in methylene chloride and capable of being eluted with derivatization as sharp peaks from a gas chromatographic packed column. No results were given for detection limit. Precision and method accuracy were found to be directly related to the concentration of the analyte and essentially independent of the sample matrix. [REF-132]


MANUFACTURING AND USE INFORMATION

Methods of Manufacturing
  • NITRATION OF TOLUENE, FOLLOWED BY REDUCTION TO DIAMINE, REACTION WITH PHOSGENE, PURIFICATION, AND RECOVERY OF COPRODUCT HYDROGEN CHLORIDE. [REF-6]
  • Usually prepared from toluene-2,4-diamine and phosgene. [REF-7, p.1626]

Impurities
  • THE 2,6 ISOMER IS AN IMPURITY [REF-8, p.1030]

Formulations/Preparations
  • Grades or Purity: Commercial distilled, 99% total diisocyanate. The following isomer ratios are shipped: a) 100% 2,4-; b) 80% 2,4-; 20% 2,6- (most common); c) 65% 2,4-; 35% 2,6-. [REF-9]

Manufacturers
  • BASF Corporation, Hq, 3000 Continental Dr. - North, Mount Oilve, NJ 07828-1234, (973) 426-2600, Polymers Division, Urethanes; Production site: Geismar, LA 70734 /2,4/2,6-Toluene diisocyanate (mixed)/ [REF-10, p.691]
  • Bayer Corp., Hq, 100 Bayer Rd., Pittsburgh, PA 15219-2502, (412) 777-2000, Polyurethane Division; Production sites: Baytown, TX 77521; New Martinsville, WV 26155 /2,4/2,6-Toluene diisocyanate (mixed)/ [REF-10, p.691]
  • Dow Chemical, USA, Hq, 2030 Dow Center, Midland, MI 48674, (517) 636-1000; Production site: Freeport, TX 77541 /2,4/2,6-Toluene diisocyanate (mixed)/ [REF-10, p.691]
  • Huntsman ICI Chemicals LLC, 500 Huntsman Way, Salt Lake City, UT 84108, (801) 584-5700; Production site: Geismar, LA 70734 /2,4/2,6-Toluene diisocyanate (mixed)/ [REF-10, p.691]
  • Lyondell Chemical Company, 1221 McKinney St., Suite 700, Houston, TX 77010, (713) 652-7200; Production site: Lake Charles, LA 70602 /2,4/2,6-Toluene diisocyanate (mixed)/ [REF-10, p.691]

Other Manufacturing Information
  • Method of purification: distillation to remove hydrogen chloride. [REF-11, p.1113]
  • Commercial toluene diisocyanate (TDI) typically contains 80% of 2,4-toluene diisocyanate. [REF-12]
  • ... MANY /SPANDEX FORMULATIONS/ ARE BASED ON ... 2,4-TOLUENE DIISOCYANATE. ... [REF-13, p.347]

Major Uses
  • CHEMICAL INTERMEDIATE
  • In the preparation of polyurethane foams, elastomers and coatings, as a cross-linking agent for nylon-6, and as a hardener in polyurethane adhesives and finishes. /2,4/2,6-Toluene diisocyanate (mixed)/ [REF-14, p.V71 PT 2]

Consumption Patterns
56% FOR FLEXIBLE AND SEMIFLEXIBLE POLYURETHANE FOAMS; 29% EXPORTED; 7% FOR RIGID POLYURETHANE FOAMS; 4% FOR URETHANE SURFACE COATINGS; 3% FOR POLYURETHANE ELASTOMERS; 1% FOR MISC APPLCNS INCLUDING SPANDEX FIBERS, ADHESIVES, SEALANTS (1970)

U.S. Production
(1972) 1.90X10+11 GRAMS
(1975) 2.17X10+11 GRAMS
(1984) 2.41X10+11 G (EST FOR 2,4 ISOMER) /BASED ON VALUE FOR 80:20 MIXTURE 2,4-2,6 TDI/ [REF-15, p.25]

U.S. Imports
(1972) NEGLIGIBLE
(1975) NEGLIGIBLE
(1983) 2.00X10+7 G /FOR 2,4-TDI DIMER/ [REF-16, p.29]
(1983) 8.94X10+8 G /FOR TDI(UNMIXED)/ [REF-16, p.29]
(1983) 2.00X10+9 G /FOR 2,4 (AND 2,6) TDI/ [REF-17, p.29]

U.S. Exports
(1972) 2.82X10+10 GRAMS
(1975) 5.13X10+10 GRAMS

CHEMICAL AND PHYSICAL PROPERTIES

Molecular Weight 174.16 [REF-7, p.1626]
Melting Point 19.5-21.5 deg C [REF-7, p.1626]
Boiling Point 251 deg C @ 760 mm Hg [REF-7, p.1626]
Density/Specific Gravity 1.2244 @ 20 deg C/4 deg C [REF-7, p.1626]
Vapor Density 6.0 (Air= 1) [REF-23, p.325M-87]
Vapor Pressure 8.0X10-3 mm Hg @ 20 deg C [REF-24, p.697]
Surface Tension 25 dynes/cm= 0.025 N/m at 25 deg C (est) [REF-9]
Heat of Combustion -10300 Btu/lb= -5720 cal/g= -239x10+5 J/kg (est) [REF-9]

Solubilities
  • Miscible with alcohol (decomposition). Miscible with ether, acetone, benzene, carbon tetrachloride, chlorobenzene, diglycol monomethyl ether, kerosene, olive oil; sol in ethyl acetate. [REF-7, p.1626]

Spectral Properties
  • Index of refraction: 1.5654 @ 25 deg C/D [REF-21, p.V19 304]
  • MASS: 815 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63) [REF-22, p.V2 365]

Other Chemical/Physical Properties
  • Reacts with water with evolution of carbon dioxide. [REF-7, p.1626]
  • Concn alkaline cmpd such as sodium hydroxide or tert-amines may cause run-away polymerization. [REF-7, p.1626]
  • Saturated liquid density: 75.879 lb/cu ft; liquid heat capacity: 0.398 Btu/lb-F; liquid thermal conductivity: 1.179 Btu-inch/hr-sq ft-F; liquid viscosity: 3.769 Centipoise (all at 85 deg F) [REF-9]
  • Saturated vapor pressure: 0.004 lb/sq in; saturated vapor density: 0.00011 lb/cu ft (all at 130 deg F) [REF-9]


REFERENCES

Special Reports
  • Rietz B; Dan Kemi 64 (4): 112-3 (1983). This is a review of methods for determination of isocyanates in air.
  • Burge PS; Clin Exp Dermatol 6 (3): 235-41 (1981). This article discusses the causes of occupational asthma and dermatitis.
  • Bernstein IL; J Allergy Clin Immunol 70 (1): 24-31 (1982). This article reviews isocyanate-induced pulmonary diseases.
  • TSCA CHIPs present a preliminary assessment of toluene 2,4-diisocyanate's potential for injury to human health & the environment (available at EPA's TSCA Assistance Office: (202) 554-1404
  • Dharmarajan V et al; Am Ind Hyg Assoc J 47 (7): 393-8 (1986). Two brands of air-purifying organic vapor cartridges ... and a disposable respirator ... were evaluated for protection against toluene diisocyanate vapors. ...
  • NIOSH; Current Intelligence Bulletin 53. Toluene Diisocyanate (TDI) and Toluenediamine (TDA): Evidence of Carcinogenicity. (1989)
  • Woolrich PF; Am Ind Hyg Assoc J 43 (2): 89-97 (1982). Article contains information regarding physiologic effects, toxicity, industrial hygiene and medical control of those isocyanates generally associated with polyurethanes.
  • Industrial Accident Prevention Association; Isocyanates p.1-2 (1986). Chemical identity; potential exposure; exposure limits; properties; health effects; industrial hygiene practices and control; personal protective equipment; fire, explosions, dangerous combinations; storage, spillage, disposal, transport.
  • NIOSH Current Intelligence Bulletin 53: Toluene diisocyanate and Toluenediamine; MMWR 40 (11): 189 (1991).
  • U.S. Department of Health & Human Services/National Toxicology Program; Tenth Report on Carcinogens. National Institutes of Environmental Health Sciences. The Report on Carcinogens is an informational scientific and public health document that identifies and discusses substances (including agents, mixtures, or exposure circumstances) that may pose a carcinogenic hazard to human health. Toluene Diisocyanate (26471-62-5) was first listed in the Fourth Annual Report on Carcinogens (1985) as reasonably anticipated to be a human carcinogen. /Toluene Diisocyanate/

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  • REF - 119: (1) Lesage J et al; Amer Ind Hyg Assoc J 53: 146-53 (1992) (2) IARC; Monograph on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Some Chemicals used in Plastics and Elastomers 39: 287-323 (1985) (3) Peterson JE et al; Amer Ind Hyg Assoc J 23: 345-52 (1962)
  • REF - 120: (1) Rando RJ et al; Am Ind Hyg Assoc J 45: 199-203 (1984) (2) Rosenberg C, Savolainen H; J Chromatography 367: 385-92 (1986)
  • REF - 121: 29 CFR 1910.1000 (7/1/2000)
  • REF - 122: 40 CFR 60.489 (7/1/2000)
  • REF - 123: Clean Air Act as amended in 1990, Sect. 112 (b) (1) Public Law 101-549 Nov. 15, 1990
  • REF - 124: 40 CFR 302.4 (7/1/2000)
  • REF - 125: 40 CFR 355 (7/1/2000)
  • REF - 126: 21 CFR 175.105 (4/1/2000)
  • REF - 127: Rando RJ et al; Am Ind Hyg Assoc J 50 (1): 1-7 (1989)
  • REF - 128: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods. 4th ed. Methods A-Z & Supplements. Washington, DC: U.S. Government Printing Office, Aug 1994.
  • REF - 129: DIMITRIADES B; HEALTH LAB SCI 12 (3): 278-82 (1975)
  • REF - 130: SCRIMA M, SALVADORI P; LAV UM 28 (2): 48-59 (1976)
  • REF - 131: EBELL ET AL; ANN OCCUP HYG 23 (2): 185 (1980)
  • REF - 132: USEPA; Test Methods for Evaluating Solid Waste SW-846 (1986)


END OF RECORD

HSDB® is provided quarterly by US National Library of Medicine and was last updated 2008/03/13.



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