2, 4-Toluene diisocyanate exposure

Manetz, T.C., Pettit, D.A. and Meade, B.J., The determination of draining lymph node cell cytokine mRNA levels in BALB/c mice following dermal sodium lauryl sulfate, di-nitrofluorobenzene, and toluene diisocyanate exposure. Toxicol. Appl. Pharm., 171, 174, 2001. 

By analogy to toluene diisocyanate, exposure of humans to sufficient concentrations is expected to cause irritation of the eyes, nose, and throat a choking sensation and a productive cough of paroxysmal type with retrosternal soreness and chest pain. ... 

Huang J, Wang XP, Chen BM, et al. 1991a. Immunological effects of toluene diisocyanate exposure on painters. Arch Environ Contam Toxicol 21(4) 607-611. 

Kazuyuki 0, Higashi T, Nakadate T, et al. 1992. Fom year follow-up of effects toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing worker. Int Arch Occup Environ Health 63 565-569. 

Omae, K., Nakadate, T., Higashi, T., Nakaza, M., Aizawa, Y. Sakurai, H. (1992a) Four-year follow-up of effects of toluene diisocyanate exposure on the respiratoiy system in polyurethane foam manufacturing workers I. Study design and results of the first cross-sectional observation. Int. Arch, occup. environ. Health, 63, 559-564... 

Certain LMW agents will cause OA via a poorly defined mechanism. Only about 20% of workers with OA to toluene diisocyanate (TDI) have IgE detectable to TDI indicating that IgE antibody may be more an indicator of exposure rather than a mediator of the disease [10], Similar data exist for workers with asthma caused by plicatic acid from western red cedar [11], The inability to detect IgE antibody in the majority of these workers may be based in technical issues such as the nature of the chemical-protein... 

Karol, M.H., Concentration-dependent immunologic response to toluene diisocyanate (TDI) following inhalation exposure. Toxicol. Appl. Pharmacol., 68, 229, 1983. 

National Institute For Occupational Safety and Health Criteria for a Recommended Standard. . . Occupational Exposure to Toluene Diisocyanate. DHEW (NIOSH Pub No (HSM) 73-11022. Washington, DC, US Government Printing Office, 1973... 

Exposure to MOCA was believed to be the cause of urinary frequency and mild hematuria in two of six exposed workers however, a variety of other materials including toluene diisocyanate, polyester resins, polyether resins, and isocyanate-containing resins also were present. ... 

Chester E, Martinez-Catinchi EL, Schwartz HI, et al Patterns of airway reactivity to asthma produced by exposure to toluene diisocyanate. Chest 75 229, 1979... 

ParkH-S, Nahm D-H Prognostic factors for toluene diisocyanate-induced occupational asthma after removal from exposure. Clin Exp A//cr 27(10) 1145-ff 50, 1997... 

Luo CJ, Nelson KG, Fishbein A Persistent reactive airway dysfunction s)mdrome after exposure to toluene diisocyanate. Br J Ind Mci 47 239-241, 1990... 

Marczynski B, Czuppon AB, Marek W, et al Indication of DNA stand breaks in human white blood cells after in vitro exposure to toluene diisocyanate. Toxicol Ind Health 8 157-169, 1992... 

Maitre A, Berode M, Perdix A, et al Biological monitoring of occupational exposure to toluene diisocyanate. Int Arch Occup Environ Health 65 97-100, 1993... 

The NIOSH-recommended limit for occupational exposure is 0.035 milligrams per cubic meter (.035 mg/m ), which is the same as 5 parts per billion (ppb). There is no established OSHA permissible exposure limit (PEL) for HDI at this time however, a similar substance, toluene diisocyanate (TDI), has a PEL of 5 parts per billion (ppb). The American Conference of Governmental Industrial Hygienists (ACGDT) places the limit for HDI inhalation exposure at 5 ppb. 

Hagmar L, Stromberg U, Welinder H, et al. 1993. Incidence of cancer and exposure to toluene diisocyanate and methylene diphenyldiisocyanate a cohort based case-referent study in the polyurethane foam manufacturing industry. Br J Ind Med 50(11) 1003-1007. 

Luckenbach M, Kielar R. 1980. Toxic corneal epithelial edema from exposure to high atmospheric concentration of toluene diisocyanates. Am J Ophthalmol 90(5) 682-686. 

Persson P, Dalene M, Skarping G, et al. 1993. Biological monitoring of occupational exposure to toluene diisocyanate measmement of toluenediamine in hydrolysed urine and plasma by gas chromatography-mass spectrometry. Br J Ind Med 50(12) 1111-1118. 

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. 

According to the 1981-83 National Occupational Exposure Survey (NOES, 1997), approximately 40 000 workers in the United States were potentially exposed to toluene diisocyanates (see General Remarks). Occupational exposures to toluene diisocyanates may occur during their production and in the production of polyurethane foams, elastomers, coatings, adhesives and finishes. Exposure may also occur in the use of some polyurethane products. Data on occupational exposure levels have been presented in a previous monograph (lARC, 1986). More recent exposure levels have been reported in connection with epidemiological (Section 2) and toxicological (Section 4) studies. 

The American Conference of Governmental Industrial Hygienists (ACGIH) (1997) has recommended 0.036 mg/m as the 8-h time-weighted average threshold limit value for occupational exposures to 2,4-toluene diisocyanate in workplace air. Similar values have been used as standards or guidelines for 2,4- or 2,6-toluene diisocyanates in several countries. In some other countries, values ranging from 0.04 to 0.14 mg/m for mixed isomers have been used (International Labour Office, 1991). 

In the Montreal case-control study carried out by Siemiatycki (1991) (see monograph on dichloromethane in this volume), the investigators estimated the associations between 293 workplace substances and several types of cancer. Isocyanates were one of the substances, and it was stated that the most common form in this study was toluene diisocyanates. The main occupations to which isocyanate exposure was attributed in this study were motor vehicle refinishers, motor vehicle mechanics and foundry workers. Only 0.8% of the study subjects had ever been exposed to isocyanates. For most types of cancer examined (oesophagus, stomach, colon, rectum, pancreas, prostate, bladder, kidney, skin melanoma, lymphoma), there was no indication of an excess risk due to isocyanates. For lung cancer, in the population subgroup of French Canadians (the majority ethnic group in this region), based on 10 cases exposed at any level, the odds ratio was 2.2 (90% CI, 0.9-5.3). [The interpretation of the null results has to take into account the small numbers and presumably low exposure levels. Workers had multiple exposures.]... 

A follow-up study (Pisati et al., 1993) of patients with toluene diisocyanate-induced asthma suggested that a short period of exposure and a short duration of symptoms before diagnosis, followed by complete cessation of exposure, are likely to lead to improvement of the symptoms and lung function. A decrease only of the exposure led to deterioration of lung function, and long exposure and duration of symptoms were unfavourable prognostically. 

No deterioration of lung function, but an increased frequency of respiratory symptoms were observed in a follow-up study among non-sensitized workers with a mean exposure to toluene diisocyanates of 3 ppb [21.3 J,g/m (Omae et al., 1992a). This study also suggested that among workers with a mean exposure of 8 ppb [57 pg/m ], peak exposures to 30 ppb [213 pg/ni ] and above were associated with a loss of ventilatory function among employees not sensitized to toluene diisocyanates (Omae et al., 1992b). 

Inhalation exposure to toluene diisocyanates is irritating to the eyes and respiratory tract, and induced chronic rhinitis, interstitial pneumonia and catarrhal bronchitis after long-term exposure. Respiratory sensitization to toluene diisocyanate developed in guinea-pigs after inhalation but also after dermal exposure (lARC, 1986). 

Toluene diisocyanates induced respiratory epithelial inflammation, metaplasia and necrosis in mice at the lowest concentration tested (0.71 mg/m ) after the shortest exposure period studied (6 h 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 (Zissu, 1995)... 

Inhalation exposure of guinea-pigs to toluene diisocyanates (3 h per day on five consecutive days) led to sensitization (antibody formation, pulmonary reactiveness to toluene diisocyanate-albumin conjugate), at exposure levels > 0.14 mg/m (Huang et al., 1993). 

Toluene diisocyanates are industrial chemicals produced in large volumes. Exposure... 

Lind, P, Dalene, M., Sharping, G. Hagmar, L. (1996) Toxicokinetics of 2,4- and 2,6-toluene-diamine in hydrolysed urine and plasma after occupational exposure to 2,4- and 2,6-toluene diisocyanate. Occup. environ. Med., 53, 94-99... 

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