4,4 -Methylenediphenyl diisocyanate

Embryotoxicity study of monomeric 4,4 -methylenediphenyl diisocyanate (MDI) aerosol after inhalation exposure in Wistar rats. Fundam Applied Toxicol 32 96-101, 1996... 

Polymethylene polyphenyl isocyanate (see also 4,4 -Methylenediphenyl diisocyanate)... 

Maki-Paakkanen, J. Norppa, H. (1987) Chromosome aberrations and sister-chromatid exchanges induced by technical grade toluene diisocyanate and methylenediphenyl diisocyanate in cultured human lymphocytes. Toxicol. Lett., 36, 37-4.3... 

The principal material of commerce is not pure 4,4 -methylenediphenyl diisocyanate but is a mixture containing 4,4 -mcthylcnediphenyl diisocyanate, other methylenedi-phenyl diisocyanate isomers, and low oligomers of the general structure shown above. 

This dark amber mixture is commonly called polymeric, or generic, or non-isomer-specific methylenediphenyl diisocyanate. Its composition is variable but typically is in the range of 40-50% 4,4 -methylcncdiphcnyl diisocyanate, 2.5. 0% 2,4 -mcthylenediphenyl diisocyanate, 0.1-0 2% 2,2 -mcthylcncdiphcnyl diisocyanate, and the remainder (50-60%) higher homologues (Woods, 1990 European Union, 1999). 

The world production of methylenediphenyl diisocyanate all types included was 1200 thousand tonnes in 1991. In the European Union, approximately 790 thousand tonnes were manufactured in 1996, compared with 540 thousand tormes in 1991 and 267 thousand tonnes in 1980 215 thousand toimes were processed in 1980 (European Union, 1999). 

Some data on levels of occupational exposure to 4,4 -methylenediphenyl diisocyanate have been presented in a previous I ARC Monograph (lARC, 1979). 

Methylenediphenyl diisocyanate can be released to the environment in waste stream emissions from sites of industrial manufacture and use. Toxic Release Inventory reports to the United States Environmental Protection Agency before at least the mid-1990s were subject to serious overestimation of the releases to the environment, because of errors in the way that the figures were calculated by industry. Within the European Union, total emissions from production sites in 1996 were about 43 kg and emissions from processing plants in the same year were about 7100 kg (European Union, 1999). 

No international guideline for 4,4 -methylenediphenyl diisocyanate in drinking-water has been established (WHO, 1993). 

No data were available to the Working Group with regard to preparations of monomeric 4,4 -methylenediphenyl diisocyanate alone. The following is a study of a preparation containing both monomeric and polymeric 4,4 -methylenediphenyl diisocyanate. 

Following topical administration of [ 4C]4,4 -methylenediphenyl diisocyanate in acetone to female Wistar rats, 20% of the administered dose was eliminated in the faeces within 24 h, while less than 1% appeared in the urine (Vock Lutz, 1997). 

Isocyanate-induced asthma and hypersensitivity pneumonitis in humans have been reviewed (Baur, 1995 Bernstein, 1996). A case of fatal asthma of a 4,4 -mcthylcncdiphcnyl diisocyanate-scnsitized subject has been described (Carino et al., 1997). Exposure to 4,4 -methylenediphcnyl diisocyanate is a frequent cause of occupational asthma (Liss et al., 1988 Vogelmcicr et al., 1991 Bernstein et al., 1993) but may also induce hypersensitivity pneumonitis (Malo Zeiss, 1982 Vandenplas et al., 1993) and inflammatory upper respiratory tract diseases (Liss et al., 1988 Littorin et al., 1994). Most patients with 4,4 -methylenediphcnyl diisocyanate-induced asthma have elevated levels of IgG-class antibodies towards 4,4 -methylenediphenyl diisocyanate-albumin conjugates in the plasma, while IgE-class antibodies are rare (Liss et al., 1988). 

A second study reported that technical-grade 4,4 -methylenediphenyl diisocyanate (containing 25% 4,4 -methylenediphenyl triisocyanate and 30% unspecified higher molecular weight compounds) increased the frequency of sister chromatid exchanges and chromosomal aberrations in hmnan lymphocytes in the presence or absence of exogenous metabolic activation. 

Results from an inhalation study showed that a low level (5-10 adducts/10 nucleotides) of arylamine-derived DNA adducts was formed in the olfactory epithelium of female Wistar rats exposed to an average atmospheric concentration of 0.7-2.0 mg/m 4,4 -methylenediphenyl diisocyanate for 17 h per day on five days per week for one year. Adducts were not detected in DNA from lung, liver, bladder, kidney, respiratory epithelium or peripheral blood lymphocytes of exposed animals (Vock et al., 1996). 

Methylenediphenyl diisocyanate is used for the production of polyurethane coatings and elastomers. 

Polymeric 4,4 -methylenediphenyl diisocyanate containing 44.8-50.2% monomeric 4,4 -mcthylcncdiphcnyl diisocyanate was tested for carcinogenicity by inhalation in rats. An increased incidence of lung tumours was observed. 

The major urinary metabolites of 4,4 -methylenediphenyl diisocyanate are 4,4 -methy-... 

Methylenediphenyl diisocyanate forms low-level DNA adducts in vivo and... 

European Union (1999) Ministry of Social Affairs, Public Health and the Environment, Belgian Federal Department of the Environment (Rapporteur), 1999. Methylenediphenyl Diisocyanate Risk Assessment, Draft of 5.02.99... 

Vock, E.H., Hoymann, H.-G, Heinrich, U. Lutz, W.K. (1996) zp-Postlabeling of a DNAadduct derived from 4,4 -methylenedianiline, in the olfactory epithelium of rats exposed by inhalation to 4,4 -methylenediphenyl diisocyanate. Carcinogenesis, 17, 1069-1073... 

METHYLENEDIOXY-6-PROPYLBENZYL-n-BUTYL DIETHYLENEGLYCOL ETHER see PIX250 4,4 -METHYLENEDIPHENYL DIISOCYANATE see MJP400... 

Methylenediphenyl diisocyanate (MDI) is used to produce polyurethane foams. 

METHYLENEDIPHENYL DIISOCYANATE (101-68-8) Combustible solid (flash point 385°F/196°C). Violent reaction with acids, bases, alcohols, amines. Incompatible with ammonia, amides, glycols, caprolactam. Unstable above 100°F/38°C. Attacks some plastics, rubber, and coatings. Reacts slowly with water. 

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