4,4'-Diphenylmethane diisocyanate (MDI) is a colorless to pale yellow liquid at room temperature, and a key ingredient in the production of polyurethane foams, coatings, sealants, and elastomers. It is synthesized by reacting aniline with formaldehyde to produce diphenylmethane, which is then reacted with phosgene to produce MDI. MDI is a highly reactive compound that can cause severe skin and eye irritation, and respiratory problems. It is classified as a potential human carcinogen by the International Agency for Research on Cancer (IARC). Despite its toxicity, MDI is widely used in various industries due to its excellent properties, including its high reactivity, flexibility, and durability. It is a subject of ongoing research to develop safer and more sustainable alternatives to MDI for polyurethane production.'
4,4'-diphenylmethane diisocyanate: used as a hardening agent incorporated in polyurethanes [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
diphenylmethane-4,4'-diisocyanate : A diisocyanate consisting of diphenylmethane with two isocyanate groups at the 4- and 4'-positions. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]
| ID Source | ID |
|---|---|
| PubMed CID | 7570 |
| CHEMBL ID | 1488467 |
| CHEBI ID | 53218 |
| SCHEMBL ID | 19943 |
| MeSH ID | M0047889 |
| Synonym |
|---|
| LS-14365 |
| 1,1'-methylenebis(4-isocyanatobenzene) |
| 26447-40-5 |
| inchi=1/c15h10n2o2/c18-10-16-14-5-1-12(2-6-14)9-13-3-7-15(8-4-13)17-11-19/h1-8h,9h |
| diphenylmethan-4,4'-diisocyanat |
| methylenebis(4,4'-phenyl isocyanate) |
| methylenebis(4-isocyanatobenzene) |
| nsc-9596 |
| diphenylmethane diisocyanate |
| bis(p-isocyanatophenyl)methane |
| methylenebis(p-phenyl isocyanate) |
| methylenedi(p-phenylene isocyanate) |
| bis(4-isocyanatophenyl)methane |
| methylenebis(4-phenyl isocyanate) |
| bis(1,4-isocyanatophenyl)methane |
| 4,4'-methylenebis(phenyl isocyanate) |
| 4,4'-diisocyanate de diphenylmethane |
| di-(4-isocyanatophenyl)methane |
| 4,4'-methylenedi-p-phenylene diisocyanate |
| diphenylmethane 4,4'-diisocyanate |
| methylenebis(4-phenylene isocyanate) |
| isocyanic acid, ester with diphenylmethane |
| methylbisphenyl isocyanate |
| wln: ocnr d1r dnco |
| difenil-metan-diisocianato |
| p,p'-methylenebis(phenyl isocyanate) |
| 4,4'-methylenedi(phenyl diisocyanate) |
| 4,4'-diisocyanatodiphenylmethane |
| isocyanic acid, methylenedi-p-phenylene ester |
| nci-c50668 |
| hylene m 50 |
| hylene m-50 |
| benzene,1'-methylenebis[4-isocyanato- |
| methylenedi(p-phenylene diisocyanate) |
| 4,4'-diphenylmethane diisocyanate |
| p,p'-diphenylmethane diisocyanate |
| difenylmethaan-diisocyanaat |
| methylene bisphenyl isocyanate |
| nsc9596 |
| diphenylmethane p,p'-diisocyanate |
| isonate 125 mf |
| methylenedi(p-phenyl isocyanate) |
| isonate 125m |
| mdi , |
| nacconate 300 |
| 4,4'-methylenedi(phenylene isocyanate) |
| caradate 30 |
| MDR , |
| 101-68-8 |
| desmodur 44 |
| methylenebis(p-phenylene isocyanate) |
| benzene, 1,1'-methylenebis[4-isocyanato- |
| diphenylmethane-4,4'-diisocyanate |
| 4,4'-methylenebis(phenylisocyanate) |
| methylenebis(phenyl isocyanate) |
| 4,4'-methylene diphenyl diisocyanate |
| NCGC00091061-01 |
| rubinate 44 |
| 4,4'-methylenediphenyl isocyanate |
| einecs 202-966-0 |
| nsc 9596 |
| 4,4'-methylenediphenyl diisocyanate |
| methylene di-p-phenylene isocyanate |
| bis(para-isocyanatophenyl)methane |
| methylenebis(para-phenyl isocyanate) |
| methylenebis(phenylisocyanate) |
| ai3-15256 |
| hsdb 2630 |
| benzene, 1,1'-methylenebis(4-isocyanato- |
| methylenebis(phenylisocyanate) [diisocyanates] |
| brn 0797662 |
| hylene m50 |
| para,para'-diphenylmethane diisocyanate |
| difenylmethaan-dissocyanaat [dutch] |
| 4,4'-methylenediphenylene diisocyanate |
| diphenylmethyl diisocyanate |
| isonate |
| methylenedi-p-phenylene diisocyanate |
| difenil-metan-diisocianato [italian] |
| ccris 2303 |
| para,para'-methylenebis(phenyl isocyanate) |
| 4-4'-diisocyanate de diphenylmethane [french] |
| methylene diphenyl diisocyanate |
| methylenedi-para-phenylene diisocyanate |
| 4,4'-methylenediphenylene isocyanate |
| diphenylmethan-4,4'-diisocyanat [german] |
| methylenebis(para-phenylene isocyanate) |
| diphenyl methane diisocyanate |
| 4,4'-diphenylmethanediisocyante |
| methylenediphenyl diisocyanate, 4,4'- |
| 4,4'-methylenebis(phenyl isocyanate), 98% |
| NCGC00091061-02 |
| methylenediphenyl diisocyanate |
| non-isomeric-specific mdi |
| crude mdi |
| generic mdi |
| 4,4'-,2,4'-,2,2'-diisocyanatodiphenylmethane |
| pmdi |
| einecs 247-714-0 |
| isocyanic acid, methylenediphenylene ester |
| 4-4'-diisocyanate de diphenylmethane |
| 4,4'-methylenedi(phenyl isocyanate) |
| methylenebisphenyl diisocyanate |
| CHEBI:53218 , |
| D0897 |
| methylenediphenyl 4,4'-diisocyanate |
| 1-isocyanato-4-[(4-isocyanatophenyl)methyl]benzene |
| AKOS000119302 |
| NCGC00091061-03 |
| C19453 |
| dsstox_gsid_47473 |
| cas-9016-87-9 |
| NCGC00256765-01 |
| dsstox_rid_82371 |
| dsstox_cid_4196 |
| tox21_302585 |
| dtxsid7025180 , |
| cas-101-68-8 |
| dtxcid704196 |
| NCGC00257822-01 |
| tox21_200268 |
| 25686-28-6 |
| methylenedi-p-phenyl diisocyanate |
| ccris 8160 |
| 6152asv70i , |
| unii-6152asv70i |
| pure mdi |
| ec 202-966-0 |
| diphenylmethane-4,4'-diisocyanate [un2489] [keep away from food] |
| b0lo6bbs8c , |
| unii-b0lo6bbs8c |
| difenylmethaan-dissocyanaat |
| 4-13-00-00396 (beilstein handbook reference) |
| FT-0625273 |
| FT-0617061 |
| EPITOPE ID:113240 |
| 65916-89-4 |
| CHEMBL1488467 |
| SCHEMBL19943 |
| methylene diphenyl diisocyanate [inci] |
| methylene bisphenyl diisocyanate [hsdb] |
| 4,4'-methylenediphenyldiisocyanate |
| methylenediphenyldiisocyanate, 4,4'- |
| 4,4'-diphenylmethanediisocyanate |
| 4,4'-mdi |
| 4,4'diisocyanatodiphenylmethane |
| 4,4'- diphenylmethane diisocyanate |
| 4,4'diphenylmethane diisocyanate |
| p,p'-methylenebis[phenyl isocyanate] |
| diphenylmethylene diisocyanate |
| isocyanic acid, diphenylmethylene ester |
| methylenebis[4-phenylene isocyanate] |
| un 2489 |
| methylenebis[p-phenyl isocyanate] |
| methylenebis[4-isocyanatobenzene] |
| 1-isocyanato-4-(4-isocyanatobenzyl)benzene # |
| diphenylmethane 4,4-diisocyanate |
| methylenebis[4-phenyl isocyanate] |
| methylenebisphenylene diisocyanate |
| 4,4'-methylenebis[phenyl isocyanate] |
| nocconate 300 |
| methylenebis[p-phenylene isocyanate] |
| W-108905 |
| mfcd00036131 |
| 4,4'-mdi, analytical standard |
| diphenylmethan-4,4'-diisocyanate |
| Q417646 |
| 1,1'-methylenebis [4-isocyanoto benzene] |
| EN300-19009 |
| 4,4/'-diphenylmethane diisocyanate |
| Excerpt | Reference | Relevance |
|---|---|---|
| " The combination of autoclave sterilization and a PU produced from a larger-molecular-weight polyol is recommended to minimize the production of potentially toxic compounds." | ( The relative safety of gamma-ray, autoclave, and ethylene oxide gas sterilization of thermosetting polyurethane. Shintani, H, ) | 0.13 |
| " There have been no previous studies on the potential prenatal toxic effects of this compound." | ( Embryotoxicity study of monomeric 4,4'-methylenediphenyl diisocyanate (MDI) aerosol after inhalation exposure in Wistar rats. Buschmann, J; Fuhst, R; Heinrich, U; Koch, W, 1996) | 0.29 |
| Excerpt | Relevance | Reference |
|---|---|---|
| " The dose-response relationships for hemoglobin adducts and urine metabolites were non-linear over this dose range." | ( Hemoglobin adducts and urine metabolites of 4,4'-methylenedianiline after 4,4'-methylenediphenyl diisocyanate exposure of rats. Heinrich, U; Henschler, D; Hoymann, HG; Sabbioni, G; Schütze, D; Sepai, O, 1995) | 0.29 |
| " At this stage, the ponds were isolated from one another and MDI was added at a dosage of 1 g/liter on top of the sediment of treated part of the first pond, 10 g/liter to the second pond, and 0 g/liter to the third pond (untreated control)." | ( Fate and biological effects of polymeric MDI (4,4'-diphenylmethane diisocyanate and homologs) in small artificial ponds. Heimbach, F; Jaeger, K; Sporenberg, W, 1996) | 0.55 |
| " With all other chemicals, the dose-response curves for DNA fragmentation and viability were mirror images." | ( Investigation of the induction of DNA double-strand breaks by methylenediphenyl-4-4'-diisocyanate in cultured human lung epithelial cells. Gahlmann, R; Lutz, WK; Vamvakas, S; Vock, EH, 1998) | 0.3 |
| " Basal ACH dose-response curves, measured twice in intervals of 1 h using tracheal preparations of 11 guinea pigs previously not exposed to IC, were reproducible." | ( Subchronic exposure to diisocyanates increases guinea pig tracheal smooth muscle responses to acetylcholine. Baur, X; Marczynski, B; Marek, W; Mensing, T; Potthast, J, 1999) | 0.3 |
| " Histopathological findings were then combined with this information to give an overall dose-response curve for both studies as a whole." | ( Chronic pulmonary effects of respirable methylene diphenyl diisocyanate (MDI) aerosol in rats: combination of findings from two bioassays. Ernst, H; Feron, VJ; Gamer, A; Hoffmann, HD; Kittel, B; Koch, W; Kuper, CF; Mallett, AK; Muhle, H; Rittinghausen, S, 2001) | 0.31 |
| " Additional groups were dosed by gavage and intraperitoneal injection." | ( Analysis of biomarkers in rats and dogs exposed to polymeric methylenediphenyl diisocyanate (pMDI) and its glutathione adduct. Brown, WE; Hext, P; Leibold, E; Leng, G; Pauluhn, J, 2006) | 0.33 |
| " Two types of dose-response relationships are addressed with the following focus: (1) does sensitization dose and surface area influence the subsequent elicitation response and (2) is the elicitation response more dependent on previous elicitation doses or more on skin sensitizing dose? These two aims are investigated in two elaborated experiments, using inflammatory (bronchoalveolar lavage, BAL) and physiologic (Penh) endpoints to characterize asthma-like responses in rats." | ( Brown Norway rat asthma model of diphenylmethane-4,4'-diisocyanate (MDI): analysis of the elicitation dose-response relationship. Pauluhn, J, 2008) | 0.35 |
| Role | Description |
|---|---|
| hapten | Any substance capable of eliciting an immune response only when attached to a large carrier such as a protein. Examples include dinitrophenols; oligosaccharides; peptides; and heavy metals. |
| allergen | A chemical compound, or part thereof, which causes the onset of an allergic reaction by interacting with any of the molecular pathways involved in an allergy. |
| [role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Class | Description |
|---|---|
| diisocyanate | An isocyanate compound containing two isocyanate functional groups. Manufactured for reaction with polyols in the production of polyurethanes. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Chain A, Cruzipain | Trypanosoma cruzi | Potency | 15.8489 | 0.0020 | 14.6779 | 39.8107 | AID1476 |
| hypoxia-inducible factor 1 alpha subunit | Homo sapiens (human) | Potency | 42.8894 | 3.1890 | 29.8841 | 59.4836 | AID1224846 |
| GLI family zinc finger 3 | Homo sapiens (human) | Potency | 32.0337 | 0.0007 | 14.5928 | 83.7951 | AID1259369; AID1259392 |
| AR protein | Homo sapiens (human) | Potency | 44.6684 | 0.0002 | 21.2231 | 8,912.5098 | AID588516 |
| thyroid stimulating hormone receptor | Homo sapiens (human) | Potency | 15.8489 | 0.0013 | 18.0743 | 39.8107 | AID926; AID938 |
| progesterone receptor | Homo sapiens (human) | Potency | 60.0753 | 0.0004 | 17.9460 | 75.1148 | AID1346795 |
| glucocorticoid receptor [Homo sapiens] | Homo sapiens (human) | Potency | 44.1719 | 0.0002 | 14.3764 | 60.0339 | AID588533; AID720692 |
| estrogen-related nuclear receptor alpha | Homo sapiens (human) | Potency | 37.9049 | 0.0015 | 30.6073 | 15,848.9004 | AID1224849 |
| pregnane X nuclear receptor | Homo sapiens (human) | Potency | 37.9049 | 0.0054 | 28.0263 | 1,258.9301 | AID1346982 |
| estrogen nuclear receptor alpha | Homo sapiens (human) | Potency | 60.5829 | 0.0002 | 29.3054 | 16,493.5996 | AID743075 |
| peroxisome proliferator activated receptor gamma | Homo sapiens (human) | Potency | 44.6684 | 0.0010 | 19.4141 | 70.9645 | AID588536 |
| vitamin D (1,25- dihydroxyvitamin D3) receptor | Homo sapiens (human) | Potency | 24.3016 | 0.0237 | 23.2282 | 63.5986 | AID588543; AID743223 |
| cytochrome P450, family 19, subfamily A, polypeptide 1, isoform CRA_a | Homo sapiens (human) | Potency | 33.7828 | 0.0017 | 23.8393 | 78.1014 | AID743083 |
| activating transcription factor 6 | Homo sapiens (human) | Potency | 21.6504 | 0.1434 | 27.6121 | 59.8106 | AID1159516; AID1159519 |
| nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105), isoform CRA_a | Homo sapiens (human) | Potency | 42.8894 | 19.7391 | 45.9784 | 64.9432 | AID1159509 |
| Histone H2A.x | Cricetulus griseus (Chinese hamster) | Potency | 80.9706 | 0.0391 | 47.5451 | 146.8240 | AID1224845 |
| potassium voltage-gated channel subfamily H member 2 isoform d | Homo sapiens (human) | Potency | 79.4328 | 0.0178 | 9.6374 | 44.6684 | AID588834 |
| heat shock protein beta-1 | Homo sapiens (human) | Potency | 53.9946 | 0.0420 | 27.3789 | 61.6448 | AID743210 |
| nuclear factor NF-kappa-B p105 subunit isoform 1 | Homo sapiens (human) | Potency | 31.6228 | 4.4668 | 24.8329 | 44.6684 | AID651749 |
| cytochrome P450 3A4 isoform 1 | Homo sapiens (human) | Potency | 12.5893 | 0.0316 | 10.2792 | 39.8107 | AID884; AID885 |
| Gamma-aminobutyric acid receptor subunit pi | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Cellular tumor antigen p53 | Homo sapiens (human) | Potency | 60.0753 | 0.0023 | 19.5956 | 74.0614 | AID651631 |
| Gamma-aminobutyric acid receptor subunit beta-1 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit delta | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit gamma-2 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit alpha-5 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit alpha-3 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit gamma-1 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit alpha-2 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit alpha-4 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit gamma-3 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit alpha-6 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit alpha-1 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit beta-3 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit beta-2 | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| GABA theta subunit | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| Gamma-aminobutyric acid receptor subunit epsilon | Rattus norvegicus (Norway rat) | Potency | 12.5893 | 1.0000 | 12.2248 | 31.6228 | AID885 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 61 (20.27) | 18.7374 |
| 1990's | 70 (23.26) | 18.2507 |
| 2000's | 90 (29.90) | 29.6817 |
| 2010's | 68 (22.59) | 24.3611 |
| 2020's | 12 (3.99) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (34.42) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 1 (0.32%) | 5.53% |
| Reviews | 18 (5.71%) | 6.00% |
| Case Studies | 59 (18.73%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 237 (75.24%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||