Methylene diisocyanate , toxicity

Monochlorobenzene and 1,2-dichlorobenzene are both colorless, flammable hquids with a sweet, penetrating odor. These are soluble in benzene and alcohols, but are insoluble in water. The vapors are heavier than air and may travel a considerable distance from the source of evaporation. Ignition and flashback to the source may lead to a fire, releasing in toxic and corrosive gases. Monochlorobenzene is a process solvent for methylene diisocyanate, the latter being used as a solvent in adhesives, polishes, waxes, pharmaceutical products, and natural rubber. 

PU are compounds formed by reacting the polyol component with an isocyanate compound, typically toluene diisocyanate (TDI) methylene diisocyanate (MDI) or hexamethylene diisocyanate. Polyols are relatively non-toxic (i.e., polyether type polyols are found to be safe, because they are low in oral toxicity with almost no irritation effect to the eyes and skin), however, isocyanates are highly toxic and the product can have a significant toxicity if remnants of isocyanate are in it, which manifests itself mainly as a respiratory (as well as a dermal) hazard. Exposure to the vapour of isocyanates directly may cause irritation for the eyes, respiratory tract and skin. Such an irritation may be too severe to produce bronchitis and pulmonary oedema. As health hazards of isocyanates are considered, one immediately remembers one of the worst industrial disasters of the 20th century, that occurred in Bhopal, India, because of the toxic cloud of methyl isocyanate was released accidentally from the Union Carbide pesticide factory in December 1984. An estimated 3,000 people died immediately with a final of some 20,000, most suffocating from the cloud s toxic chemicals, and some 50,000 were injured, most were residents living near the plant. 

Nonyellowing urethane sealants can be made using aliphatic or cycloaliphatic polyisocyanates or with compounds where the NCO group is removed from the benzene ring by at least one methylene group. These include hexa-methylene diisocyanate (most frequently as its less toxic biuret with water), methylcyclohexyl diisocyanate, dimer acid diisocyanate, and xylene diisocyanate. Since these materials are considerably more expensive than TDI, usage is limited. 

CAUTION The handling of isocyanates should be done with great care because of their known toxicity hazard. The hazards and chemistry of methyl isocyanate have recently been reported. Toluene diisocyanate (TDI), methylene diisocyanate (MDI), and methyl isocyanate (MIC) are flammable, very reactive, and have in common low maximum allowable concentrations for employee exposure by the Occupational Safety and Health Administration (OSHA). 

Biodegradable poly(phosphoester-urethanes) containing bisglycophosphite as the chain extender were synthesized. Methylene bis-4-phenyl isocyanate (MDI) and toluene diisocyanate (TDI) were initially used as diisocyanates. Since there was a concern that the degradation products could be toxic, the ethyl 2,6-diisocyanatohexanoate (LDI) was synthesized and replaced the MDI (or TDI). The hydrolytic stability and solubility of these polymers were tested. Preliminary release studies of 5-fluorouracil from MDI based poly(phosphoester-urethane) and methotrexate from LDI based poly(phosphoester-urethane) are also reported. 

Reuzel PGJ, Arts JHE, Lomax LG, et al Chronic inhalation toxicity and carcinogenicity studies of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats. Fundam Appl Toxicol 22 195-210, 1994... 

Reuzel, P.G.J., Arts, J.H.E., Lomax, L.G, Kuijpers, M.H.K., Kuper. C.F., Gembardt, C., Feron, V.J. Loser, E. (1994) Chronic inhalation toxicity and carcinogenicity study of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats. Fundam. appl. Toxicol., 22, 195-210... 

Processes are under development to manufacture methylene diphenyl diisocyanate (MDI) without using toxic and corrosive phosgene. The proposed process schemes usually consist of three steps alkoxycarbonylation of nitrobenzene or aniline with CO and an alcohol to alkyl plienylcarbamate, condensation of the carbamate, and then thermal decomposition of the resulting urethane to MDI. For example, the condensation of methyl N—phcnylcarbamate (MPC), and IICHO into methylene diphenyl diurethane (MDU) is carried out in the presence of an acid catalyst. 

Isoouanates. Various isocyanates are employed in the polymer industry. These compounds are powerful irritants and they are highly toxic. Of particular interest are methylene-di-paraphenylene isocyanate (MDI) and toluene-2,4-diisocyanate (TDI). Various alkyl isocyanates (e.g., methyl, ethyl, propyl, butyl, and cyclohexyl) derivatives may also be of current interest with respect to potential occupational health hazards. Simultaneous analysis of MDI and TDI by HPLC has been accomplished by a modification of the method of Dunlap et al. (28). Air samples are collected in impingers containing p-nitrobenzyl-n-... 

The primary product is aniline (eq. (8)), which then undergoes addition of carbonyl selenide, Se=C=0, in the presence of a strong base [17]. The resulting urethane can further be converted into the methylene diurethane, which is then cracked to the diisocyanate MDI 2, a key industrial intermediate for the production of polyurethane foams and elastomers (cf. Section 3.3.5). It was probably for toxicity reasons that completion of a technical plant at one of the Arco sites [18] was hampered. 

Precaution Combustible moderate fire risk incompat. with strong oxidizers, halogen gases, halogenated compds., 2,4,6-trichloro-1,3,5-triazine vigorous reactions possible polymerizes violently on contact with methylene bisphenyl diisocyanate Hazardous Decomp. Prods. On decomp., emits toxic fumes of NOx... 

Toxicity. While many new materials are added to the adhesive chemist s arsenal, some are being removed as well. Compounds which cause health and environmental concern include ethylenimine, methylene-fcw(o-chloroan-iline) (MOCA), hexamethylene diisocyanate, formaldehyde. Some systems are no longer in use in others, modifications have been made. Thus radiation-curing technology is replacing some types of multifunctional acrylate monomers with alkoxylated compounds, because the latter are less irritating and less toxic. An example is trimethylolpropane triethoxy triacrylate. 

The alveolar proteinosis caused by heavy exposure to silica ( acute silico-proteinosis ) and possibly by other agents (Blanc 1992) would qualify for this entity. Similarly, some instances of exogenous lipoid pneumonitis seem to correspond well to the concept of subacute toxic pneumonitis. The pulmonary haemorrhagic syndrome associated with exposure to trimellitic anhydride and, possibly, to methylene diphenyl diisocyanate is also a potential form of toxic response but, in this instance, the role of specific immunological mechanisms is likely. 

---