Toluene diisocyanate carcinogenicity

The lARC has determined that there is inadequate evidence for the carcinogenicity of toluene diisocyanates in humans and sufficient evidence in experimental animals. ... 

Dieter MP, Boorman GA, Jameson GW, 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. Toxicol Ind Health 6 599-621, 1990... 

We have already been introduced to polyurethane chemistry in Chapter 10, Section 2, where we used toluene diisocyanate (TDI) reacting with a diol to give a polyurethane. Polyurethanes derived from MDI are more rigid than those from TDI. New applications for these rigid foams are in home insulation and exterior autobody parts. The intermediate MDA is now on the Reasonably Anticipated to Be Human Carcinogens list and the effect of this action on the market for MDI remains to be seen. The TLV-TWA values for MDA and MDI are some of the lowest of the chemicals we have discussed, being 0.1 and 0.005 ppm respectively. 

Important commercial isocyanates include the diisocyanate monomers toluene diisocyanate (TDI), methylene diphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI), and MDI-, TDI-, and HDI-based isocyanates (e.g., prepolymers and polyisocyanates). World-wide production volume is estimated at over 12 billion lb. Isocyanates (diisocyanates, polyisocyanates, and prepolymers) all cause similar health effects, most commonly asthma [32]. Isocyanates are reported to be the leading attributable cause of work-related asthma [16]. Isocyanates are potent sensitizers that can trigger a severe and potentially fatal asthma attack in sensitized persons at very low isocyanate exposure levels [16]. Toluene diisocyanate is reasonably anticipated to be a human carcinogen by National Toxicology Program. 

There is inadequate evidence for the carcinogenicity of toluene diisocyanates in humans. 

Toluene diisocyanates are possibly carcinogenic to humans (Group 211). 

Adducts to hemoglobin are perhaps the most useful means of biological monitoring by adduct formation. Hemoglobin is, of course, present in blood, which is the most accurate type of sample for biological monitoring. Adducts to blood plasma albumin are also useful monitors and have been applied to the determination of exposure to toluene diisocyanate, benzo(a)pyrene, styrene, styrene oxide, and aflatoxin Bj. The DNA adduct of styrene oxide has been measured to indicate exposure to carcinogenic styrene oxide.12... 

Experimental studies have shown that dermal application of toluene diisocyanate can elicit pulmonary sensitization. International Agency for Research on Cancer lists toluene diisocyanate as an animal carcinogen (from studies using gavage administration). 

Bolognesi C, Baur X, Marczynski B, et al. (2002) Carcinogenic risk of toluene diisocyanate and 4,4 -methylenedi-phenyl diisocyanate Epidemiological and experimental evidence. Critical Reviews in Toxicology 31 737-772. 

Toluene diisocyanates Possible carcinogen Raw material polyurethane 26 h — ... 

Because of its high toxicity, carcinogenicity, and ability to cause sensitization, toluene diisocyanate should be handled using the "basic prudent practices" of Chapter 5.C, supplemented by the additional precautions for work with compounds of high toxicity (Chapter 5.D). In particular, work with TDI should be conducted in a fume hood to prevent exposure by inhalation, and splash goggles and impermeable gloves should be worn at all times to prevent eye and skin contact. 

HC f lithium hydride, methyUsocyanate, toluene diisocyanate, 2,4,6-trinitrotoluene (TNT), tri-o-cresylphosphate, vinyl chloride... 

Toluene-2,4-diisocyanate is a highly toxic compound by inhalation, a skin and eye irritant, and a carcinogenic substance. Exposure to its vapors can cause tracheobronchitis, pulmonary edema, hemorrhage, and death. The target organs are the respiratory system and skin. The toxic effects were also noted in the liver, kidney, and gastrointestinal tract. 

Toluene-2,4-diisocyanate caused tumor in the liver and pancreas in test animals. There is snfficient evidence of its carcinogenicity in animals. Its cancer-causing activity in humans has not been established. 

---