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SECTION 1. CHEMICAL IDENTIFICATION

CHEMINFO Record Number: 136
CCOHS Chemical Name: Toluene-2,6-diisocyanate

Synonyms:
Di-isocyanate de toluylene
2,6-Diisocyanato-1-methylbenzene
2,6-Diisocyanatotoluene
Isocyanic acid, 2-methyl-m-phenylene ester
2-Methyl-m-phenylene isocyanate
2,6-TDI
2,6-Toluene diisocyanate
Toluene diisocyanate
Toluylene-2,6-diisocyanate
Tolylene-2,6-diisocyanate

CAS Registry Number: 91-08-7
UN/NA Number(s): 2078
RTECS Number(s): CZ6310000
EU EINECS/ELINCS Number: 202-039-0
Chemical Family: Isocyanic acid ester / isocyanate / aromatic isocyanate / diisocyanate / aromatic diisocyanate
Molecular Formula: C9-H6-N2-O2
Structural Formula: CH3-C6H3-(N=C=O)2

SECTION 2. DESCRIPTION

Appearance and Odour:
Clear, colourless or pale yellow liquid with a characteristic pungent odour.(24)

Odour Threshold:
0.05 (detection).(5) Also reported as 2.10 ppm (24)

Warning Properties:
NOT RELIABLE - Odour threshold is above the TLV. Irritation of the eyes and nose at concentrations above the TLV.

Composition/Purity:
Mainly available as a mixture with 2,4-TDI and to a lesser extent as pure 2,6-TDI. This record contains information for pure 2,6-TDI, where possible. CHEMINFO records are available for the mixtures of 80% 2,4-TDI:20% 2,6-TDI (record 134) and 65% 2,4-TDI:35% 2,6-TDI (record 135), as well as pure 2,4- TDI (record 83).

Uses and Occurrences:
Mixtures of 2,4- and 2,6-TDI are largely used to manufacture flexible polyurethane foams (used mainly in the furniture and bedding industry) and rigid polyurethane foams (used primarily as insulation). Smaller amounts are used to make elastomers, coatings such as polyurethane paints, varnishes and wire enamels, adhesives and sealants.(1,2)


SECTION 3. HAZARDS IDENTIFICATION

EMERGENCY OVERVIEW:
Clear, colourless or pale yellow liquid with a characteristic pungent odour. Can probably burn if strongly heated. Can decompose at high temperatures forming toxic gases, such as nitrogen oxides and hydrogen cyanide. May polymerize if heated. Reacts vigorously with water above 50 deg C. Closed containers may develop pressure and rupture on prolonged exposure to heat or if contaminated with water. VERY TOXIC. Irritating to eyes, skin and respiratory tract. May cause lung injury--effects may be delayed. RESPIRATORY SENSITIZER. May cause severe allergic respiratory reaction. SKIN SENSITIZER. May cause severe skin reaction. SUSPECT CANCER HAZARD - may cause cancer.



POTENTIAL HEALTH EFFECTS

Effects of Short-Term (Acute) Exposure

Inhalation:
Toluene-2,6-diisocyanate (2,6-TDI) can cause irritation at vapour levels of 0.05 ppm and above.(5,17) Symptoms include eye and nose irritation, sore or burning throat, runny nose, shortness of breath, wheezing and laryngitis. Coughing with chest pain or tightness may also occur, frequently at night. These symptoms may occur during exposure or may be delayed for several hours.(9)
High exposures could cause inflammation of the lung tissue (chemical pneumonitis), chemical bronchitis with severe asthma-like wheezing, severe coughing spasms and accumulation of fluid in the lungs (pulmonary edema), which could prove fatal.(6,9) Symptoms of pulmonary edema may not appear until several hours after exposure and are aggravated by physical exertion.
Effects such as euphoria, muscle incoordination and loss of consciousness have been reported after a single severe exposure to TDI. Headache, difficulty in concentration, poor memory and confusion may persist for up to 4 years.(18)
Some people may become sensitized to 2,6-TDI--see Effects of Long-term (Chronic) Exposure.

Skin Contact:
Liquid TDI produces marked inflammation.(6) Prolonged or further contact can cause severe inflammation, redness, rash, swelling, blistering and burns.(1) Isocyanates, in general, can cause skin discolouration (staining) and hardening of the skin after repeated exposures. Skin contact is not expected to result in the absorption of harmful amounts.(17) Skin sensitization may occur in some individuals, but it is not common.(6)

Eye Contact:
Liquid TDI can cause watering of the eyes, severe irritation and possible clouding of the cornea. Human volunteers exposed to vapour concentrations above 0.05 ppm developed irritation which was more severe at 0.08-0.1 ppm.(5) Exposure to high TDI vapour concentrations can lead to formation of solid particles in the eye fluid which can cause mechanical irritation hours after exposure.(19)

Ingestion:
There have been no reports of people ingesting 2,6-TDI and ingestion is unlikely to occur in the workplace. Animal studies indicate that TDI has low toxicity by ingestion. Ingestion could cause irritation of the mouth, throat and digestive tract.

Effects of Long-Term (Chronic) Exposure

Respiratory Sensitization:
Respiratory sensitization has developed in people working with TDI.(8,9) Sensitization is usually caused by a very large exposure, or by multiple exposures.(9) However, symptoms of sensitization have occurred in some workers exposed frequently to low levels (0.0003 to 0.03 ppm).(18)
Although varying periods of exposure (1 day to years) may elapse before sensitization occurs, it develops more often during the first few months of exposure. Sensitized individuals react to very low levels of TDI (below 0.001 ppm) that have no effect on unsensitized people.(8) At first, the symptoms may appear to be a cold or mild hay fever. However, severe asthmatic symptoms can develop and include wheezing, chest tightness, shortness of breath, difficulty breathing and/or coughing. Fever, chills, general feelings of discomfort, headache, and fatigue can also occur. Symptoms may occur immediately upon exposure (within an hour), several hours after exposure or both, and/or at night.(8,9,18,20) Typically, the asthma improves with removal from exposure (e.g. weekends or vacations) and returns, in some cases, in the form of an "acute attack", on renewed exposure.(18)
Animal studies indicate that respiratory sensitivity to TDI may result from skin, as well as inhalation exposures.(9)
Sensitized people who continue to work with TDI may develop symptoms sooner after each exposure. The number and severity of symptoms may increase. Death has occurred in sensitized individuals accidently exposed to relatively low concentrations of TDI.(18)
Following removal from exposure, some sensitized workers may continue to show a slow decline in lung function and have persistent respiratory problems such as asthmatic symptoms, chronic bronchitis and hypersensitivity to TDI for months or years.(8,9,21) Others recover completely within months if they have no further isocyanate exposure.(9,21) Several studies have shown that long-term exposure to TDI at levels as low as 0.0015-0.0035 ppm may cause impaired lung function, such as diminished respiratory capacity.(9,18)
TDI may also cause hypersensitivity pneumonitis, another allergic lung disease, which is characterized by symptoms such as shortness of breath, fever, malaise, non-productive cough, and chills.(9,18) Cross-sensitization between different isocyanates may occur. People sensitized to TDI have shown sensitization to methylene bisphenyl isocyanate (MDI) and hexamethylene-1,6-diisocyanate (HDI), where no previous exposure to MDI or HDI was known.(4,18) Exposure to isocyanates is likely to cause aggravation to individuals with existing respiratory disease, such as chronic bronchitis, and emphysema.(4)

Skin Sensitization:
Repeated skin contact with TDI has caused skin sensitization in humans, although the condition is not common.(3,4) Once a person is sensitized, contact with even a small amount of TDI can cause outbreaks of dermatitis with symptoms such as redness, rash, itching and swelling. This can spread from the hands or arms to the face and body. Some people who inhaled TDI developed extensive skin rashes that lasted 1 to 1.5 weeks. There was no direct skin contact with the liquid.(20)

Carcinogenicity:

The risk of cancer associated with exposure to isocyanates has been examined in 4 human population studies. No strong association or consistent pattern has been observed. The International Agency for Research on Cancer (IARC) has determined 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.(35)

The International Agency for Research on Cancer (IARC) has concluded that this chemical is possibly carcinogenic to humans (Group 2B).

The American Conference of Governmental Industrial Hygienists (ACGIH) has designated this chemical as not classifiable as a human carcinogen (A4).

ACGIH has published a Notice of Intended Change proposing that the carcinogenicity designation be changed to A3 (animal carcinogen).

The US National Toxicology Program (NTP) has listed this chemical as reasonably anticipated to be a human carcinogen.

Teratogenicity and Embryotoxicity:
No human or animal information is available.

Reproductive Toxicity:
No human or animal information is available.

Mutagenicity:
It is not possible to conclude that 2,6-TDI is mutagenic. There is no human information available. Negative results have been obtained in rats and mice exposed to toluene diisocyanate (80% 2,4-TDI: 20% 2,6-TDI mixture). 2,6-TDI was mutagenic in a number of short-term tests.(12,15,16,35)

Toxicologically Synergistic Materials:
No information was located.

Potential for Accumulation:
2,6-TDI probably does not accumulate. It can enter the body by inhalation or by ingestion. In oral studies on rats, most 2,6-TDI was polymerized in the stomach and excreted in the feces. Approximately 10% was recovered in the urine within 24 hours. The main urinary metabolite was 2,6-bis(acetylamino)toluene, which suggests that 2,6-TDI is metabolized to 2,6-diaminotoluene (2,6-TDA).(13) In a human inhalation study, 2,6-TDA was found in the plasma and the urine. Absorption through the lungs and elimination in the urine is rapid. About 80% of the 2,6-TDA was excreted in the urine within 4 to 6 hours. Only traces were being excreted after 24 hours. The total amount of 2,6-TDA eliminated after 24 hours was 17 to 23% of the inhaled dose.(23)

Health Comments:
Many reports do not specify which isomer of TDI (2,4- or 2,6-TDI) was used or its purity. In many studies, commercial-grade TDI (80% 2,4- and 20% 2,6-TDI) was used. Also, certain sampling/analysis methods may be inaccurate for 2,6-TDI and may underestimate exposure to total TDI.


SECTION 4. FIRST AID MEASURES

Inhalation:
Take proper precautions to ensure your own safety before attempting rescue, (e.g. wear appropriate protective equipment, use the "buddy" system). Remove source of contamination or move victim to fresh air. If breathing is difficult, oxygen may be beneficial if administered by trained personnel, preferably on a doctor's advice. DO NOT allow victim to move about unnecessarily. Symptoms of pulmonary edema can be delayed up to 48 hour after exposure. Immediately transport victim to an emergency care facility.

Skin Contact:
Avoid direct contact. Wear chemical protective gloves and respiratory protection if necessary. Remove contaminated clothing, shoes and leather goods (e.g. watchbands, belts) and place in covered container. Quickly and gently blot or brush away excess chemical. Wash gently and thoroughly with water and non-abrasive soap for 20 minutes or until the chemical is removed. Obtain medical attention immediately. Discard contaminated clothing, shoes and leather goods.

Eye Contact:
Avoid direct contact. Wear chemical protective gloves, if necessary. Quickly and gently blot or brush away excess chemical. Immediately flush the contaminated eye(s) with lukewarm, gently flowing water for 20 minutes, or until the chemical is removed while holding the eyelid(s) open. Take care not to rinse contaminated water into the unaffected eye or onto the face. Obtain medical attention immediately.

Ingestion:
NEVER give anything by mouth if victim is rapidly losing consciousness, is unconscious or is convulsing. Have victim rinse mouth thoroughly with water. DO NOT INDUCE VOMITING. Have victim drink 240 to 300 mL (8 to 10 oz.) of water to dilute material in stomach. If vomiting occurs naturally, rinse mouth and repeat administration of water. Obtain medical attention immediately.

First Aid Comments:
Provide general supportive measures (comfort, warmth, rest). Consult a doctor and/or the nearest Poison Control Centre for all exposures except minor instances of inhalation or skin ontact. Some recommendations in the above sections may be considered medical acts in some jurisdictions. These recommendations should be reviewed with a doctor and appropriate delegation of authority obtained, as required. All first aid procedures should be periodically reviewed by a doctor familiar with the material and its condition of use in the workplace.



SECTION 5. FIRE FIGHTING MEASURES

Flash Point:
Greater than 110 deg C (230 deg F) (closed cup) (25)

Lower Flammable (Explosive) Limit (LFL/LEL):
Not available

Upper Flammable (Explosive) Limit (UFL/UEL):
Not available

Autoignition (Ignition) Temperature:
Not available

Sensitivity to Mechanical Impact:
Not available. Probably not sensitive. Stable material.

Sensitivity to Static Charge:
Not available. Probably not sensitive since 2,6-TDI has a high flash point.

Combustion and Thermal Decomposition Products:
Cyanides, nitrogen oxides

Fire Hazard Summary:
This material can probably burn if strongly heated. During a fire, irritating/toxic nitrogen oxides and hygrogen cyanide may be generated. May react vigorously with water at high temperatures. Closed containers may rupture violently when heated.

Extinguishing Media:
Water spray, carbon dioxide, foam, dry chemical powder (17)

Fire Fighting Instructions:
Evacuate area and fight fire from a safe distance or a protected location. Approach fire from upwind to avoid hazardous vapours and toxic decomposition products.
Water or water-based foam, if used in very large quantities, may be effective for fighting fires involving 2,6-toluene diisocyanate (2,6-TDI). However, care must be taken since the reaction between water or water-based foam and hot TDI can be vigorous.(17) Some dry chemical powders may produce foam when used.
Isolate materials not yet involved in the fire and protect personnel. Move containers from fire area if this can be done without risk. Water spray or fog can be used to absorb heat and protect exposed material of structures. Keep fire-exposed tanks or containers cool by spraying with water to minimize the risk of rupture. If a leak or spill has not ignited, use water spray to disperse the vapours and to protect personnel attempting to stop a leak.
After the fire has been extinguished, the area should not be considered safe until a thorough inspection for residual isocyanate has been carried out by properly protected personnel.
2,6-TDI and its decomposition products, for example hydrogen cyanide and nitrogen oxides, are extremely hazardous to health. Do not enter any fire area without specialized protective equipment suitable for the occasion. Firefighter's normal protective clothing (Bunker Gear) will not provide adequate protection. A full-body encapsulating chemical resistant suit with positive pressure self-contained breathing apparatus (MSHA/NIOSH approved or equivalent) may be necessary.



NATIONAL FIRE PROTECTION ASSOCIATION (NFPA) HAZARD IDENTIFICATION

NFPA - Comments:
NFPA has no listing for this chemical in Codes 49 or 325.


SECTION 9. PHYSICAL AND CHEMICAL PROPERTIES

Molecular Weight: 174.16

Conversion Factor:
1 ppm = 7.11 mg/m3; 1 mg/m3 = 0.14 ppm (calculated)

Physical State: Liquid
Melting Point: 7.2 deg C (45 deg F) (freezing point) (2)
Boiling Point: 129-133 deg C (264-271 deg F) at 18 mm Hg (1,2,25)
Relative Density (Specific Gravity): 1.225 at 20 deg C (water = 1) (25)
Solubility in Water: Insoluble. Reacts with water.
Solubility in Other Liquids: Soluble in aromatic hydrocarbons, nitrobenzene, acetone, ethers, esters, halogenated hydrocarbons.
Coefficient of Oil/Water Distribution (Partition Coefficient): Not applicable. Reacts with water.
pH Value: Not applicable. Reacts with water.
Vapour Density: 6.0 (air = 1)
Vapour Pressure: Approx. 0.002 kPa (approx 0.016 mm Hg) at 20 deg C
Saturation Vapour Concentration: Approx. 21 ppm at 20 deg C (calculated)
Evaporation Rate: Not available
Critical Temperature: Not available

SECTION 10. STABILITY AND REACTIVITY

Stability:
Moderately stable. May darken on exposure to sunlight.

Hazardous Polymerization:
2,6-TDI may undergo uncontrollable polymerization upon contact with water or other materials which react with 2,6-TDI. It may also polymerize if heated above 177 deg C or above 45 deg C for prolonged periods. The resulting heat and pressure build-up could rupture closed containers.(2,26)

Incompatibility - Materials to Avoid:

NOTE: Chemical reactions that could result in a hazardous situation (e.g. generation of flammable or toxic chemicals, fire or detonation) are listed here. Many of these reactions can be done safely if specific control measures (e.g. cooling of the reaction) are in place. Although not intended to be complete, an overview of important reactions involving common chemicals is provided to assist in the development of safe work practices.


WATER - Reacts slowly, forming carbon dioxide and non-toxic, insoluble polyureas which could rupture closed containers. Above 50 deg C, the reaction may become progressively more vigorous.(17,26)
ALCOHOLS, ACIDS, BASES, AMINES - May react vigorously with the generation of heat.(17)
AMIDES, PHENOLS, MERCAPTANS, URETHANES, UREAS AND SURFACE ACTIVE MATERIALS (surfactants, non-ionic detergents) - May react vigorously or violently with generation of heat.(26)
METAL COMPOUNDS (e.g. organotin catalysts) - May polymerize with generation of heat and pressure.(26)

Hazardous Decomposition Products:
2,6-Diaminotoluene (formed by the reaction of 2,6-TDI with water) (1)

Conditions to Avoid:
Moisture, heat

Corrosivity to Metals:
Not generally corrosive towards metals.(17)

Stability and Reactivity Comments:
Isocyanates are very reactive compounds and are especially highly reactive toward a large number of compounds with active hydrogens, particularly at high temperatures and in the presence of catalysts, such as acids, bases, tertiary amines and organotin compounds.(26) See reference 26 for some of the reactions of isocyanates. May attack and make brittle many plastic (for example polyethylene, polypropylene and polyurethane) and rubber materials in a short time.(17)


SECTION 11. TOXICOLOGICAL INFORMATION

No standard animal toxicity values are available for pure toluene-2,6-diisocyanate (2,6-TDI).

LC50 (mouse): 9.7 ppm (4-hour exposure) (unspecified TDI composition) (36)
LC50 (rabbit): 11 ppm (4-hour exposure) (unspecified TDI composition) (36)
LC50 (guinea pig): 12.7 ppm (4-hour exposure) (unspecified TDI composition) (36)
LC50 (rat): 13.9 ppm (4-hour exposure) (unspecified TDI composition) (36)

LD50 (oral, rat): 7500 mg/kg (unspecified TDI composition) (2, unconfirmed)

LD50 (dermal, rabbit): 10,000 mg/kg (unspecified TDI composition) (1, unconfirmed)

Eye Irritation:

Application of a drop of 2,6-TDI caused immediate pain, tearing and swelling of the lids in rabbits. Mild corneal damage occurred.(3)

Skin Irritation:

No studies are available on the effects of pure 2,6-TDI. Pure 2,4-TDI and the 80:20 mixture have caused moderate to severe skin irritation in rabbits, including moderate to marked redness, swelling and leathery skin. Prolonged contact skin can cause redness, swelling, blistering and burns.(1,4)

Effects of Short-Term (Acute) Exposure:

Inhalation:
In general, TDI is corrosive and can cause respiratory irritation at approximately 0.1 to 0.5 ppm.(1,5) Inhalation of non-lethal concentrations by mice, rats, rabbits and guinea pigs has caused severe respiratory effects such as bronchitis, bronchopneumonia, emphysema and bleeding of the lungs (pulmonary hemorrhage).(6) All rats died following three or five 6-hour exposures to 10 ppm 2,6-TDI, while 4 of 5 rats died after two 6-hour exposures to 10 ppm.(5) 2,6-TDI was severely irritating. Moderate pulmonary edema and severe, acute emphysema were observed.(5) 2,6-TDI is a sensory irritant of the upper respiratory tract which inhibits respiration. Mice were exposed to 0.37 to 7.6 mg/m3 (0.005 to 1.1 ppm) 2,6-TDI vapour for 3 hours. The RD50 value (the concentration required to reduce the respiratory rate by 50%) was 1.8 mg/m3 (0.26 ppm). This compares with 1.4 mg/m3 (0.20 ppm), the RD50 for 2,4-TDI. No pulmonary irritation was observed.(7)

Ingestion:
TDI has been reported to cause gastrointestinal effects and effects on the liver and kidneys.(1,4) Following administration of large doses (1500 mg/kg) of TDI (80:20 mixture) to rats 10 times over 2 weeks, 3/6 rats died. Weight loss and damage to the liver, stomach and kidneys were observed.(1)

Effects of Long-Term (Chronic) Exposure:

Inhalation:
Rats, guinea pigs and rabbits exposed to 0.1 ppm TDI (unspecified composition) for 5 days/week for up to 58 exposures or for 38 consecutive days developed lung inflammation. Lung damage generally increased in severity for several days after exposure ended.(6,8) No effects on other organs were observed. No lung changes were seen in rats and rabbits exposed to 0.01 ppm once a week for 38 weeks.(8) Guinea pigs that inhaled 0.02 ppm TDI for 70 days had no respiratory problems.(9,10)

Skin Sensitization:
Skin sensitization has been produced by direct application of pure 2,4-TDI to the skin.(11) Skin sensitization have also been produced by inhalation exposure.(10)

Respiratory Sensitization:
Concentration dependent respiratory sensitization has been produced in animals by pure 2,4-TDI, as well as by the 80% 2,4- and 20% 2,6-TDI mixture.(9,10) Respiratory sensitization has been produced by direct application of pure 2,4-TDI to the skin.(11)

Carcinogenicity:
No animal information is available for pure 2,6-TDI. No tumours were observed in male and female rats and mice that inhaled 0.05 and 0.15 ppm of the 80% 2,4-TDI:20% 2,6-TDI mixture for approximately 2 years.(12,13) However, tumours did develop at a number of sites after male and female rats and female mice were given large daily oral doses (30 to 240 mg/kg) of 80:20 TDI for 105 or 106 weeks. No tumours were observed in male mice.(12,13) See the CHEMINFO review of toluene diisocyanate (80:20 mixture) for further details. The International Agency for Research on Cancer (IARC) has determined there is sufficient evidence for the carcinogenicity of toluene diisocyanate to experimental animals.(2,14,35)

Mutagenicity:
Negative results have been reported in studies using live animals exposed to the 80% 2,4-TDI:20% 2,6-TDI mixture.(35)
2,6-TDI induced sister chromatid exchanges and chromosomal aberrations in cultured Chinese hamster ovary (CHO) cells without metabolic activation. Negative results were obtained with activation.(15) In another assay, 2,6-TDI was mutagenic in the L5178Y mouse lymphoma cell forward mutation assay, both with and without metabolic activation.(16) 2,6-TDI gave positive results in 2 strains of Salmonella typhimurium (TA98 and TA100) with metabolic activation and negative results in 2 other strains (TA1536 and TA1537), both with and without activation.(12)


SECTION 16. OTHER INFORMATION

Selected Bibliography:
(1) Daugherty, M.L. Toluene diisocyanate (TDI). Chemical hazard information profile: draft report. United States Environmental Protection Agency, July, 1984.
(2) IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans : some chemicals used in plastics and elastomers. Vol. 39. IARC, 1986. p. 287-323
(3) Grant, W.M., et al Toxicology of the eye. 4th edition. Charles C. Thomas, 1993. p. 1439-1440
(4) Woolrich, P.F. Toxicology, industrial hygiene and medical control of TDI, MDI and PMPPI. American Industrial Hygiene Association Journal. Vol. 43, no. 2 (February, 1982). p. 89-97
(5) Henschler, D., et al. The toxicology of the toluene diisocyanates. Archiv fur Toxicologie. Vol. 19 (1962). p. 364-387. (English translation: NIOSHTIC Control Number 00102123)
(6) Criteria for a recommended standard: occupational exposure to toluene diisocyanate. National Institute for Occupational Safety and Health, 1973
(7) Weyel, D.A., et al. Sensory irritation, pulmonary irritation, and acute lethality of a polymeric isocyanate and sensory irritation of 2,6-toluene diisocyanate. Toxicology and Applied Pharmacology. Vol. 64 (1982). P. 423-430
(8) Toluene-2,4-diisocyanate. In: Documentation of the threshold limit values and biological exposure induces. 5th ed. ACGIH, 1986. p. 580-585
(9) Karol, M.H. Respiratory effects of inhaled isocyanates. Critical Reviews in Toxicology. Vol. 16, issue 4 (1986). p. 349-379
(10) Karol, M.H. Concentration-dependent immunologic response to toluene diisocyanate (TDI) following inhalation exposure. Toxicology and Applied Pharmacology. Vol. 68, no. 2 (April, 1983). p. 229-241
(11) Karol, M.H., et al. Dermal contact with toluene diisocyanate (TDI) produces respiratory tract hypersensitivity in guinea pigs. Toxicology and Applied Pharmacology. Vol. 58, no. 2 (April, 1981). p. 221-230
(12) NTP technical report on the toxicology and carcinogenesis studies of commercial grade 2,4 (80%)- and 2,6 (20%)- toluene diisocyanate (Cas no. 26471-62-5) in F344/N rats and B6C3F1 mice (gavage studies). (NTP TR 251). U.S. Department of Health and Human Services, 1986
(13) Dieter, M.P., et al. The carcinogenic activity of commercial grade toluene diisocyanate in rats and mice in relation to the metabolism of the 2,4- and 2,6-TDI isomers. Toxicology and Industrial Health. Vol. 6, no. 6 (December, 1990). p. 599-621
(14) IARC Monographs on the evaluation of carcinogenic risks to humans : overall evaluations of carcinogenicity : an updating of IARC Monographs volumes 1 to 42. Supplement 7. IARC, 1987. p. 46, 72
(15) Gulati, D.K., et al. Chromosome aberration and sister chromatid exchange tests in Chinese hamster ovary cells in vitro. III: Results with 27 chemicals. Environmental and Molecular Mutagenesis. Vol.13, no. 2 (1989). p. 133-193
(16) McGregor, D.B., et al. Responses of the L5178Y mouse lymphoma cell forward mutation assay. V: 27 coded chemicals. Environmental and Molecular Mutagenesis. Vol. 17, no. 3 (1991). p. 196-219
(17) Recommendations for the handling of toluene diisocyanate (TDI). International Isocyanate Institute, Inc. Edition: January 1976. Revised: November 1980
(18) Musk, A.W., et al. Isocyanates and respiratory disease: current status. American Journal of Industrial Medicine. Vol. 13 (1988). p. 331-349
(19) Precautions for the proper usage of polyurethanes, polyisocyanurates and related material (technical bulletin 107). 2nd edition. Kalamazoo, MI : The Upjohn Company, 1980
(20) Karol, M.H., et al. Longitudinal study of tolyl-reactive IgE antibodies in workers hypersensitive to TDI. Journal of Occupational Medicine. Vol. 21, no. 5 (May, 1979). p. 354-358
(21) Mapp, C.E., et al. Persistent asthma due to isocyanates: a follow-up study of subjects with occupational asthma due to toluene diisocyanate (TDI). American Review of Respiratory Diseases. Vol. 137 (1988). p. 1326-1329
(22) Report on Carcinogens. 11th ed. US Department of Health and Human Services, Public Health Service, National Toxicology Program
(23) Brorson, T., et al. Biological monitoring of isocyanates and related amines. IV. 2,4- and 2,6-toluenediamine in hydrolysed plasma and urine after test-chamber exposure of humans to 2,4- and 2,6-toluene diisocyanate. International Archives of Occupational and Environmental Health. Vol. 63 (1991). p. 253-259
(24) HSDB record for 2,6-toluene diisocyanate. Date of last update: 9404
(25) The Sigma-Aldrich Library of Chemical Safety Data. Edition II. Vol. 2. Sigma-Aldrich Corporation, 1988. p. 3376C
(26) Kirk-Othmer encyclopedia of chemical technology. 3rd. edition. Vol. 13. John Wiley and Sons, 1981. p. 789-818
(27) A laboratory study of impinger efficiencies and a comparison of the Marcali method, MDH25 and paper tape monitors for the measurement of 2,4- and 2,6-toluene diisocyanate. London, England : Health and Safety Executive Research Laboratory Services Division, 1985
(28) Rando, R.J., et al. Modified Marcali method for the determination of total toluene diisocyanate in air. American Industrial Hygiene Association Journal. Vol. 46, no. 4 (1985). p. 206-210
(29) Booth, K.S., et al. State-of-the-art monitoring and analysis for airborne isocyanates. In: Polyurethane-marketing & technology-partners in progress : Proceedings of the SPI 28th annual technical/marketing conference. Society of the Plastics Industry, 1984. p. 10-16
(30) Forsberg, K., et al. Quick selection guide to chemical protective clothing. 4th ed. Van Nostrand Reinhold, 2002
(31) NIOSH pocket guide to chemical hazards. NIOSH, June 1994. p. 312-313
(32) European Communities (EC). Commission Directive 2004/73/EC. Apr. 29, 2004
(33) Key-Schwartz, R.J. Analytical problems encountered with NIOSH method 5521 for total isocyanates. AIHA Journal. Vol. 56 (1995). p. 474-479
(34) Streicher, R.P., et al. Investigation of the ability of MDHS method 25 to determine urethane-bound isocyanate groups. AIHA Journal. Vol. 56 (1995). p. 437-442
(35) International Agency for Research on Cancer (IARC). IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 71, parts 1, 2 and 3. Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide. IARC, 1999
(36) Duncan et al. Toluene diisocyanate inhalation toxicity pathology and mortality. American Industrial Hygiene Association Journal. Vol. 23 (1962) p. 447-456
(37) Occupational Safety and Health Administration (OSHA). Diisocyanates. In: OSHA Analytical Methods Manual. Revision Date: Oct. 31, 2001. Available at: <www.osha-slc.gov/dts/sltc/methods/toc.html>
(38) National Institute for Occupational Safety and Health (NIOSH). Isocyanates, Monomeric. In: NIOSH Manual of Analytical Methods (NMAM(R)). 4th ed. Edited by M.E. Cassinelli, et al. DHHS (NIOSH) Publication 94-113. Aug. 1994. Available at: <www.cdc.gov/niosh/nmam/nmammenu.html>

Information on chemicals reviewed in the CHEMINFO database is drawn from a number of publicly available sources. A list of general references used to compile CHEMINFO records is available in the database Help.


Review/Preparation Date: 1996-03-06

Revision Indicators:
WHMIS (proposed class) 1997-07-01
US transport 1998-03-01
TLV comments 1999-03-01
Mutagenicity 1999-12-01
Toxicological info 1999-12-01
EU Risk 2000-05-01
EU Safety 2000-05-01
TDG 2002-05-29
PEL transitional comments 2003-11-21
PEL-TWA transitional 2003-11-21
PEL final comments 2003-11-21
Resistance of materials for PPE 2004-04-02
TLV proposed changes 2004-06-08
EU comments 2005-01-26
EU classification 2005-01-26
Passive Sampling Devices 2005-02-28
Bibliography 2005-02-28
TLV-TWA 2006-03-15
TLV-STEL 2006-03-15
TLV definitions 2006-03-15
TLV proposed changes 2006-03-15
WHMIS detailed classification 2006-03-16
Carcinogenicity 2006-03-16



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