Report on Carcinogens, Twelfth Edition (2011)

National Toxicology Program, Department of Health and Human Services

Toluene Diisocyanates

CAS No. 26471-62-5

Reasonably anticipated to be a human carcinogen

First listed in the Fourth Annual Report on Carcinogens (1985)

Also known as TDI; 1,3-diisocyanatomethyl benzene; isocyanic 

acid, methyl-m-phenylene ester; or tolylene diisocyanate

Isomers also known as toluene-2,4-diisocyanate and toluene-2,6-

diisocyanate

CH3

N

CH3

N N

C

O

C

O

C

N

O

C

O

2,4-Toluene diisocyanate 2,6-Toluene diisocyanate

CAS No. 584-84-9 CAS No. 91-08-7

Carcinogenicity

Toluene diisocyanates are reasonably anticipated to be human carcinogens based on sufficient evidence of carcinogenicity from studies in experimental animals. 

Cancer Studies in Experimental Animals

Oral exposure to toluene diisocyanates caused tumors at several different tissue sites in rats and mice. Administration of commercialgrade toluene diisocyanate (analyzed as 85% 2,4 isomer and 15% 2,6 

isomer) by stomach tube caused liver tumors (hepatocellular adenoma) in female rats and mice, benign mammary-gland tumors 

(fibroadenoma) in female rats, and benign tumors of the pancreas 

(acinar-cell adenoma) in male rats. It also increased the combined 

incidences of benign and malignant tumors of subcutaneous tissue 

(fibroma and fibrosarcoma) in male rats and of the blood vessels 

(hemangioma and hemangiosarcoma) in female mice (NTP 1986).

Cancer Studies in Humans

No epidemiological studies were identified that evaluated the relationship between human cancer and exposure specifically to toluene 

diisocyanates.

Properties

Toluene diisocyanates exist at room temperature as a clear, colorless to pale-yellow liquid with a pungent odor. They decompose in 

water, but are very soluble in acetone and benzene, and are miscible with ether, diglycol monomethyl ether, carbon tetrachloride, 

chlorobenzene, kerosene, and olive oil. They are combustible when 

exposed to heat or flame and darken when exposed to sunlight (IARC 

1999, HSDB 2009). 2,4-Toluene diisocyanate is available as a commercial product with purity of at least 99.5%, but most commonly as 

an 80:20 mixture of 2,4-toluene diisocyanate and 2,6-toluene diisocyanate (IARC 1986). Physical and chemical properties of toluene diisocyanates are listed in the following table.

Property

Toluene 

diisocyanates 

mixed

2,4-Toluene 

diisocyanate

2,6-Toluene 

diisocyanate

Molecular weighta 174.2 174.2 174.2

Specific gravity at

25°Ca (g/mL) 1.22 or 0.01 1.22 or 0.01 1.22 or 0.01

Melting pointa 11°C to 14°C (FP) 19.5°C to 21.5°C 18.3°C

Boiling pointa 251°C 251°C 129°C to 133°C

at 18 mm Hg

Log Kow

b 3.74 3.74 3.74

Water solubility

at 25°Cb 0.0376 g/L 0.0376 g/L decomposes

Vapor pressurea 2.30 × 10–2

mm Hg at 25°C

8.0 × 10–3

mm Hg at 20°C

2.1 × 10–2

mm Hg at 25°C

Vapor density

relative to airc 6 6 6

Sources: aHSDB 2009, bChemIDplus 2009, cAkron 2009. FP = freezing point.

Use

Toluene diisocyanates are used primarily to manufacture flexible 

polyurethane foams for use in furniture, bedding, and automotive 

and airline seats. Other, smaller uses are for polyurethane elastomers (for automobile bumper covers, industrial rollers, sport soles 

and boots, and mechanical goods) and coatings (for automotive refinishing, wood finishes, and high-performance anti-corrosion coatings) 

(ICIS 2009). Toluene diisocyanate–based rigid polyurethane foam is 

used in household refrigerators and for residential sheathing or commercial roofing in board or laminate form (IARC 1986). “Pour-inplace” or “spray-in” rigid foam is used as insulation for truck trailers, 

railroad freight cars, and cargo containers. Polyurethane-modified 

alkyds contain approximately 6% to 7% isocyanate, mostly toluene 

diisocyanates, and are used as coating materials, such as floor finishes, wood finishes, and paints. Moisture-curing coatings are used 

as wood and concrete sealants and floor finishes. Aircraft, truck, and 

passenger-car coatings often are composed of toluene diisocyanate 

prepolymer systems. Castable urethane elastomers are used in applications requiring strength, flexibility, and shock absorption, and are 

resistant to oil, solvents, and ultraviolet radiation. They are used in 

adhesive and sealant compounds and in automobile parts, shoe soles, 

rollerskate wheels, pond liners, and blood bags. They are also used in 

oil fields and mines. Certain elastomer products are produced from 

the pure 2,4 isomer rather than the 80:20 mixture.

Production

Toluene diisocyanates have been produced commercially since the 

late 1930s (IARC 1986). In 1993, the production capacity for toluene 

diisocyanates in North America was estimated at more than 1 billion 

pounds (IARC 1999). In 2009, the United States had one producer 

of each isomer of toluene diisocyanate (2,4 and 2,6), three producers 

of the mixed isomer product (SRI 2009), one supplier of mixed toluene diisocyanates, three suppliers of 2,6-toluene diisocyanate, and 

fourteen suppliers of 2,4-toluene diisocyanate (ChemSources 2009). 

Reports filed under the U.S. Environmental Protection Agency’s Toxic Substances Control Act Inventory Update Rule indicated 

that U.S. production plus imports of an 80:20 mixture of 2,4- and 

2,6-toluene diisocyanate totaled 100 million to 500 million pounds 

in 1986, 500 million to 1 billion pounds from 1990 to 2002, and over 

1 billion pounds in 2006 (EPA 2004, EPA 2009). The reported quantities of 2,4-toluene diisocyanate were 100 million to 500 million 

pounds in 1986 and 1990, falling to between 1 million and 10 million pounds from 1994 to 2002. Reported quantities of 2,6-toluene 

diisocyanate were 50 million to 100 million pounds in 1986 and 10 

million to 50 million pounds in 1990; no inventory update reports 

for 2,6-toluene diisocyanate have been filed since 1990 (EPA 2004).

Table of Contents: http://ntp.niehs.nih.gov/go/roc12

Page 414
Report on Carcinogens, Twelfth Edition (2011)

National Toxicology Program, Department of Health and Human Services

U.S. imports of mixed isomers of toluene diisocyanate were 

984,000 kg (2.1 million pounds) in 1989, reaching a low of 1,000 kg 

(2,200 lb) in 1996 and a peak of 15 million kilograms (32 million 

pounds) in 2006; 2008 imports were 500,000 kg (1.1 million pounds) 

(USITC 2009). U.S. imports of unmixed isomers were 426,000  kg 

(939,000 lb) in 1989, reaching a low of 9,000 kg (19,800 lb) in 1998 

and a peak of 1.3 million kilograms (2.8 million pounds) in 2004; 2008 

imports were 130,000 kg (286,000 lb) in 2008. U.S. exports of mixed 

isomers of toluene diisocyanate were 62 million kilograms (125 million pounds) in 1989, rising to a high of 277 million kilograms (609 

million pounds) in 2003; they have since trended lower. U.S. exports 

of unmixed isomers of toluene diisocyanate peaked in 1994 at 46 million kilograms (101 million pounds), falling to a low of 3.9 million 

kilograms (8.6 million pounds) in 2008.

Exposure

The primary routes of potential human exposure to toluene diisocyanates are inhalation and dermal contact. Exposure to toluene diisocyanates is primarily occupational; however, several commercially 

available household products may pose a risk of exposure to toluene 

diisocyanates to the general population if used indiscriminately. For 

example, consumers may be exposed to toluene diisocyanates volatilized from polyurethane varnishes during the application of such 

coatings (IPCS 1987). A model developed to predict the background 

concentration of toluene diisocyanate in Western Europe estimated 

that if annual toluene diisocyanate usage were 100,000 tons, the background air concentration would be approximately 0.0001 μg/m3

 (Tury

et al. 2003).

According to EPA’s Toxics Release Inventory, environmental releases of mixed toluene diisocyanates were highest in 2001 and 2004, 

at over 125,000 lb; 45,642 lb was released in 2003. The same trend held 

for the individual isomers; however, releases were lowest in 1995 for 

2,4-toluene diisocyanate and in 2002 for 2,6-toluene diisocyanate. In 

2006, releases of toluene diisocyanates (mixed isomers), 2,4-toluene 

diisocyanate, and 2,6-toluene diisocyanate from 139 facilities totaled 

73,778 lb (TRI 2009). 

Because of the high volatility of toluene diisocyanates, exposure 

can occur in all phases of its manufacture and use (IPCS 1987). Toluene diisocyanate occurs in the work environment, primarily in air, 

during its commercial production, handling, and processing and 

during the production of polyurethane foam and coated fabrics. 

However, manual handlers of uncured polyurethane foam were significantly more likely to have detectable urinary adducts of toluene 

diisocyanates than non-handlers working in areas with similar air 

concentrations of toluene diisocyanate (Austin 2007). The National 

Occupational Exposure Survey (conducted from 1981 to 1983) estimated that nearly 40,000 workers potentially were exposed to toluene diisocyanates (NIOSH 1990). Workers potentially exposed to 

toluene diisocyanates include adhesive workers, insulation workers, 

diisocyanate-resin workers, lacquer workers, organic-chemical synthesizers, paint sprayers, polyurethane makers, rubber workers, ship 

builders, textile processors, and wire-coating workers (IPCS 1987). 

Worker exposure to toluene diisocyanates is most likely to occur during sample collection, residue removal, spill clean-up, and equipment 

maintenance; employees are required to use air-line respirators during these operations. The highest exposure levels have occurred during the spray application of polyurethane foam. The construction 

industry uses polyurethane formulations in thermal insulation, adhesives, lacquers, and paints. In most cases, the foam is applied through 

air-spraying in confined spaces; exposure to concentrations above 

safe limits are a particular concern for the sprayers and their helpers. In the United States, a typical modern housing unit of 1,800 ft2

floor space, including furniture, carpet underlay, and bedding, contains 306 lb of flexible polyurethane foam. The transportation industry 

uses approximately 21% of flexible polyurethane foam for automobile seating and padding, resulting in the use of 24 to 31 lb of polyurethane per automobile (IARC 1986). 

Studies summarized by the International Agency for Research 

on Cancer (IARC 1986, 1999) reported workplace air concentrations of toluene diisocyanates ranging from less than 1 to more than 

1,000 μg/m3

; the current Occupational Safety and Health Administration ceiling concentration is 0.02 ppm (~140 μg/m3

). Workplace air 

concentrations measured in 2005 close to the mixer in a polyurethane 

factory were up to 12.1 μg/m3

 for 2,4-toluene diisocyanate, 8.1 μg/m3

for 2,6-toluene diisocyanate, and 20.2 μg/m3

 for total toluene diisocyanates (Tinnerberg and Mattsson 2008). Analysis of the isomeric 

composition of atmospheric toluene diisocyanates in a plant producing polyurethane foam found a higher concentration of the 2,6 

isomer than of the 2,4 isomer, particularly at the finishing end of the 

production process. Median air concentrations of 2,4-toluene diisocyanate were 5.0 μg/m3

 for initial mixing and 2.3 μg/m3 for finishing. The respective median concentrations for the 2,6 isomer were 

6.4 and 7.8 μg/m3

, with a maximum exceeding 450 μg/m3 at the finishing end. These findings were attributed to enhanced emission of 

the less chemically active 2,6 isomer from the cured foam bats and 

retention of the 2,4 isomer as a polymer. Aniline and the 2,4 and 2,6 

isomers of toluene diisocyanate were detected under controlled experimental conditions in the thermodegradation fumes of polyurethane varnish used in the insulation of copper wire. Consistent with 

these findings, the compounds were also detected in the workplace 

atmosphere during the industrial production of polyurethane-coated 

wire (IARC 1986, 1999).

Since 2001, exposure has been confirmed by measuring toluene diisocyanate adducts in the plasma and urine of exposed workers. Toluenediamine, a metabolite of toluene diisocyanate, has been measured 

in the plasma at levels up to 27.2 ng/mL for 2,4-toluenediamine and 

62.1 ng/mL for 2,6-toluenediamine (Tinnerberg and Mattsson 2008). 

Swedish workers manufacturing polyurethane products excreted 53.2 

to 259.6 nmol of toluenediamine per gram of creatinine (Bolognesi

et al. 2001). Concentrations of toluene diisocyanate in urine of occupationally exposed workers ranged from 0 to 76 μg/L for the 2,4 

isomer and from 0 to 31 μg/L for the 2,6 isomer. 

Regulations

Coast Guard, Department of Homeland Security

Minimum requirements have been established for the safe transport of toluene diisocyanate on ships 

and barges.

Department of Transportation (DOT)

Toluene diisocyanate is considered a hazardous material, and special requirements have been set for 

marking, labeling, and transporting this material.

Environmental Protection Agency (EPA)

Clean Air Act

National Emissions Standards for Hazardous Air Pollutants: 2,4-Toluene diisocyanate is listed as a 

hazardous air pollutant.

New Source Performance Standards: Manufacture of diisocyanates is subject to certain provisions for the 

control of volatile organic compound emissions.

Prevention of Accidental Release: Threshold quantity (TQ) = 10,000 lb.

Comprehensive Environmental Response, Compensation, and Liability Act

Reportable quantity (RQ) = 100 lb.

Emergency Planning and Community Right-To-Know Act

Toxics Release Inventory: 2,4-Toluene diisocyanate is subject to reporting requirements.

Resource Conservation and Recovery Act

Listed Hazardous Waste: Waste codes for which the listing is based wholly or partly on the presence of 

toluene diisocyanates = U223, K027.

Listed as a hazardous constituent of waste.
Report on Carcinogens, Twelfth Edition (2011)

National Toxicology Program, Department of Health and Human Services

Occupational Safety and Health Administration (OSHA)

While this section accurately identifies OSHA’s legally enforceable PELs for this substance in 2010, 

specific PELs may not reflect the more current studies and may not adequately protect workers.

Ceiling concentration = 0.02 ppm (0.14 mg/m3) for toluene-2,4-diisocyanate.

Guidelines

National Institute for Occupational Safety and Health (NIOSH)

Immediately dangerous to life and health (IDLH) limit = 2.5 ppm for toluene-2,4-diisocyanate.

Toluene-2,4-diisocyanate is listed as a potential occupational carcinogen.

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