. l[Ipb*GY+g1hYNIN c/-"a7BYE93R;( `PyQ2/xeI )PxrZT@ChaAT Rjt !@@e*9s)g JTc:PPk US EPA (1994) Methods for derivation of inhalation reference concentrations and applications of inhalation dosimetry. Base-catalysed reactions of isocyanates with alcohols should be carried out in inert solvents. Carcinogenesis, 17(5):10691073. Commercial uses of uncured MDI products in locations where the general population could be exposed. Where spillage is to soil or water, MDI has a transient existence due to its reaction with the water to produce predominantly insoluble polyureas. On day 21 of pregnancy, the female rats were sacrificed and a caesarean section was performed. Compared with the controls, the foundry workers had more respiratory symptoms and a significantly lower mean FEV1 and forced expiratory flow from 25% to 75% of the FVC (FEF2575, or mid-expiratory flow rate of the FVC). Out of 5541 new cases reported between 1989 and 1991, 28% were occupational asthma. Los efectos finales en la salud ms preocupantes son el asma de origen ocupacional, la neumonitis por hipersensibilidad y las enfermedades inflamatorias de las vas respiratorias superiores mediante la inhalacin de MDI polimrico o monomrico. The LC50 in this study was estimated to be 490 mg/m3. The by far most important reaction, however, is step-growth polymerization of a diisocyanate with a polyol compound such as a polyester or polyether polyol which leads to the formation of urethane bonds. In: Mohr U, ed. Alveolar cell hyperplasia, considered preneoplastic, exhibited a concentrationresponse trend, with the incidence reaching significance in the high-exposure group. Another way to dispose of waste MDI is to react the material with a neutralization solution. Day BW, Basalyga DM, Kramarik JA, Karol MH (1997) Formation, solvolysis and transcarbamoylation reactions of bis(S-glutathionyl) adducts of 2,4- and 2,6-diisocyanatotoluene. Shimizu H, Suzuki Y, Takemura N, Goto S, Matsushita H (1985) The results of microbial mutation test for forty-three industrial chemicals. Amagasaki, Sumitomo Bayer Urethane Co. (unpublished report). Bernstein DI, Korbee L, Stauder T, Bernstein JA, Scinto J, Herd ZL, Bernstein IL (1993) Clinical aspects of allergic disease. If you are an author contributing to an RSC publication, you do not need to request permission Il se forme galement de la MDA mais sa concentration est toujours faible. Prepared by TNO, Zeist, for International Isocyanate Institute (unpublished; III Report No. Ce CICAD sur le diisocyanate de diphnylmthane (MDI) a t prpar par lInstitut national japonais des sciences de la sant en collaboration avec le National Center for Environmental Assessment de lEnvironmental Protection Agency des tats-Unis (EPA). A NIOSH (1994a) report noted skin irritation attributed to MDI. Un estudio de exposicin por inhalacin con MDI radiomarcado indica que alguna forma o parte del MDI se distribuye por todo el organismo, sobre todo en los pulmones, los msculos, los riones y el aparato digestivo. To request permission to reproduce material from this article, please go to the Journal of the National Cancer Institute, 72:471476. Mol Catal 504:111485, Krl P (2007) Synthesis methods, chemical structures and phase structures of linear polyurethanes Properties and applications of linear polyurethanes in polyurethane elastomers, copolymers and ionomers. 0 Los datos obtenidos en animales proporcionan indicios claros de sensibilizacin cutnea y respiratoria debida al MDI. Spirometry showed a partly reversible obstructive dysfunction, and a skin-prick test was positive for MDIHSA. Partial substitution of polymeric methylene diphenyl diisocyanate resin with soy flour increases the cold tack of the resin to the level achieved by urea formaldehyde resin. 39). ocyanate. V84.313/220758). US EPA (1998) Toxicological review of methylene diphenyl diisocyanate (MDI). Wuppeltal, Bayer AG, Institute for Toxicology. A standard outline has been developed to encourage consistency in form. Dangerous pressure can build up if container is sealed. The content of monomeric MDI generally is between 45% and 65% on a w/w basis (Mobay, 1983). In a 2-year chronic inhalation toxicity/carcinogenicity study, rats that were exposed to PMDI aerosol at concentrations of 0, 0.19, 0.98, or 6.03 mg/m3 showed changes in the respiratory tract. Biodegradation in water and sediment: simulation tests; Biodegradation in soil; . MDI was used at the manufacturing plants during only the last 2 years of the study period. Herbold B (1980a) [MDI Salmonella/microsome test for investigation of point mutation activity.] Diphenylmethane diisocyanate (MDI) is the generic name of a product used in industrial settings. Carcinogenesis, 16(10):25832587. When rats were exposed to PMDI aerosol (in which more than 99% of particles were smaller than 5 m) for 4 h at concentrations of 384, 418, 500, or 523 mg/m3, animals sat quietly with closed eyes during exposure, and their breathing became laboured and nostrils dilated, especially in the highest concentration group (Appelman & de Jong, 1982). There were no statistically significant differences in the total 5-year decrement in FEV1 among exposed workers versus FEV1 values in unexposed workers. Lyon, International Agency for Research on Cancer, pp. RSC Adv 5(22):1717117178, Ghoreishi R, Zhao Y, Suppes GJ (2014) Reaction modeling of urethane polyols using fraction primary secondary and hindered-secondary hydroxyl content. Comme il ne subsiste que peu de temps dans leau, sa solubilit dans ce solvant est purement thorique. CAS Toluene diisocyanate (TDI) and methylenediphenyl diisocyanate (MDI) are highly reactive materials used on a large scale in the production of polyurethanes. DOI: 10.1039/D1CP03302F. Research Triangle Park, NC, US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Toxicology Program (Technical Report No. Chem. Some isocyanates react with water to form amines and liberate carbon dioxide. It was found that the tentative associations, derived from the previous cohort study, between exposure to isocyanates and excess risk for non-Hodgkins lymphomas and rectal cancer were not supported. Concise International Chemical Assessment Documents (CICADs) are the latest in a family of publications from the International Programme on Chemical Safety (IPCS) a cooperative programme of the World Health Organization (WHO), the International Labour Organization (ILO), and the United Nations Environment Programme (UNEP). 4,4'-Methylenediphenylene diisocyanate. (1982), Gee & Morgan (1985), and Sulotto et al. Environ. 414, mated female Wistar rats (8 per group) were exposed to PMDI by inhalation (whole body) at exposure levels of 0, 2, 8, or 12 mg/m3 for 6 h per day from day 6 up to and including day 15 of pregnancy (Waalkens-Berendsen & Arts, 1992). Zeiger E (1987) Salmonella mutagenicity test: III. The value considered most appropriate as a basis for development of a tolerable concentration (TC) in air is the lower 95% confidence limit on the BMC at the 10% risk level (BMC10) using the Reuzel et al. [1] More specifically, it is an aliphatic diisocyanate. For CH 3 NCO + OH, H abstraction by OH at the methyl group is the main reaction channel according to our calculations and predicted to be four orders of magnitude faster than OH addition at the NCO group. The most commonly used DIs include 4,4-methylene diphenyl diisocyanate (MDI, CAS 101-68-8), toluene diisocyanate (TDI, mainly used as a mixture of 2,4-TDI and 2,6-TDI isomers CAS 26471-62-5), hexamethylene diisocyanate (HDI, CAS 822-06-0) and isophorone diisocyanate (IPDI, CAS 4098-71-9). They are based on selected national or regional evaluation documents or on existing EHCs. International archives of occupational and environmental health, 61(8):495501. Una vez recogida de manera adecuada la forma aerosol mediante interceptadores, burbujas o filtros, el MDI y el PMDI se analizan mediante cromatografa lquida de alto rendimiento. 3. Cincinnati, OH, US Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health (Report No. Representatives of nongovernmental organizations may be invited to observe the proceedings of the Final Review Board. On dispose depuis peu dune nouvelle mthode pour dterminer la composition des mlanges complexes aroports disocyanates et de composs apparents qui prennent naissance au cours de la dcomposition thermique du polyurthane. The health end-points of most concern are occupationally induced asthma, hypersensitivity pneumonitis, and inflammatory upper respiratory tract diseases through inhalation of polymeric or monomeric MDI. EFFECTS ON OTHER ORGANISMS IN THE LABORATORY AND FIELD, 11.1.1 Hazard identification and doseresponse assessment, 11.1.2 Criteria for setting tolerable intakes or guidance values for MDI, 12. The highest concentration resulted in 25% mortality (15/60 animals, only during the first 7 weeks), growth retardation, severe respiratory distress, degeneration of nasal tissues, and focal inflammatory changes in the lungs. HETA 91-0386-2427, May). (n`f5-[Z>$*OnR4 #@2 t<9cl0HUT7B5@(21<88{4@1 V;.qnh1/::SV-vr#9. Most of the macrobenthos populations regained densities equivalent to the control populations after 2 months of exposure, with the exception of Bivalvia (because of their long generation times). 31R0354/93046, 39.09.1994). Littorin M, Truedsson L, Welinder H, Skarping G, Martensson U, Sjoeholm AG (1994) Acute respiratory disorder, rhinoconjunctivitis and fever associated with the pyrolysis of polyurethane derived from diphenylmethane diisocyanate. Ce CICAD a t approuv en tant quvaluation internationale lors dune runion du Comit dvaluation finale qui sest tenue Stockholm (Sude) du 25 au 28 mai 1999. Sepai O, Henschler D, Sabbioni G (1995b) Albumin adducts, hemoglobin adducts and urinary metabolites in workers exposed to 4,4-methylenediphenyl diisocyanate. Anlogamente, en un pequeo nmero de pruebas realizadas con organismos terrestres no se observaron efectos en las condiciones de la prueba. Le PMDI sert la confection de mousses rigides ou souples, de liants pour sable de moulage et disolants thermiques. Sepai O, Schuetze D, Heinrich U, Hoymann HG, Henschler D, Sabbioni G (1995a) Hemoglobin adducts and urine metabolites of 4,4-methylenediamine after 4,4-methylenediphenyl diisocyanate exposure of rats. La informacin sobre la exposicin ocupacional es limitada; en diferentes industrias se ha notificado que no son frecuentes las exposiciones medias ponderadas por el tiempo de ocho horas superiores a 50 g/m3. At the time of assessment, four of the five patients remained symptomatic despite having had no contact with MDI for periods ranging from 5 to 9 months. [8], The positions of the isocyanate groups influences their reactivity. Blom & Oldersma (1994) observed no effects on cell multiplication of the freshwater alga Scenedesmus subspicatus after a 3-day exposure to a nominal concentration of 1640 mg PMDI/litre. water, the rate of reaction is very slow at temperatures below 122F (50C). The two major competing reaction mechanisms during pMDI curing with: (a) water, where an aromatic amine (after the release of CO 2 ) reacts with isocyanate to form urea, biuret, and polyurea; and . What material of storage tank can be suitable of storing methylene diphenyl diisocyanate? The investigators did not find an association (using standardized mortality ratios or SMRs) between exposure to diisocyanates and cancer. Monomeric 4,4-MDI is a white to pale yellow solid at room temperature, with a molecular weight of 250. (1994b) for PMDI, there was no apparent effect of monomeric MDI on nasal tissues at any exposure level. Under normal circumstances, exposure of the general public to MDI is likely only from releases to the atmosphere. Eighteen employees of a single wood products plant using heated MDI in the manufacture of a synthetic wood product with lower respiratory tract symptoms were later confirmed to have occupational asthma after examination of the relationship between onset of symptoms, smoking behaviour, prior experience, and family history of respiratory disorder (Woellner et al., 1997). . PMDI is a dark reddish brown viscous liquid with an indefinite melting point around 0 C and a vapour pressure of <1 mPa at 20 C (DFG, 1997). Il ny a pas eu dtudes consacres aux effets du MDI ou du PMDI sur les paramtres gnsiques. 207. Prepared by BASF, Ludwigshafen, for US Environmental Protection Agency (unpublished; Project No. US EPA Integrated Risk Information System: Methylene Diphenyl Diisocyanate (monomeric MDI) and polymeric MDI (PMDI) (CASRN 101-68-8, . Before acceptance for publication as CICADs by IPCS, these documents undergo extensive peer review by internationally selected experts to ensure their completeness, accuracy in the way in which the original data are represented, and the validity of the conclusions drawn. Ces travaux donnent penser que la MDA plasmatique acido-hydrolysable pourrait constituer un biomarqueur intressant dune exposition de longue dure au MDI. Thorne PS, Hillebrand JA, Karol MH (1986) Pulmonary irritation and hypersensitivity in guinea pigs exposed to 4,4-diphenylmethane diisocyanate (MDI) aerosol. volume29, Articlenumber:92 (2022) 11272). 207 and a terrestrial plant growth test conducted according to OECD Guideline No. TDI is used to make flexible polyurethane foam for furniture, bedding, carpet underlay and other products. The non-neoplastic information in this study suggests a NOAEL of 0.19 mg/m3 and a lowest-observed-adverse-effect level (LOAEL) of 0.98 mg/m3. Macromolecules 29(9):31983202, Nagy L et al (2017) Kinetics of Uncatalyzed Reactions of 2,4- and 4,4-Diphenylmethane-Diisocyanate with Primary and Secondary Alcohols. The blood and urine samples were analysed for the presence of adducts and metabolites using gas chromatographymass spectrometry methods. J.K., Murthy, A.S. and Lilja, H.: Carcinogenesis studies of 4,4'methylenedianiline dihydrochloride given in drinking water to F344/N rats and B6C3F1 mice. The question of whether MDI vapour or aerosol can hydrolyse in humid air to yield MDA was assessed in a long-term study (Appelman et al., 1986) and a study of chipboard production (Giersig, 1989). NTP (1986) Toxicology and carcinogenesis studies of commercial grade 2,4(80%)- and 2,6(20%)-toluene diisocyanate in F344/N rats and B6C3F1 mice (gavage studies). Olfactory epithelial degeneration was elevated significantly at the high concentration in both sexes. MDI may come into contact with soil after accidental spillage during transportation or storage. . What is claimed is: 1. Authors are required to take reviewers comments into account and revise their draft, if necessary. Thorne PS, Hillebrand JA, Lewis DR, Karol MH (1987) Contact sensitivity by diisocyanates; potencies and cross-reactivities. You do not have JavaScript enabled. All possible structures of the isomers and their dimers were optimized . In a second experiment using topical administration, 32P-postlabelling analysis did not reveal isocyanateDNA adducts in the skin (Vock & Lutz, 1997). 4,4-Diphenylmethane diisocyanate; Methylene bis . N.O.S. All major producers of MDI are members of the International Isocyanate Institute, whose aim is the promotion of the safe handling of MDI and TDI in the workplace, community and environment. J Am Chem Soc 81(18):48384842, Barblat A, Caraculacu AA, Iurea V (1978) The influence of the structure of aromatic diisocyanates on the preparation and the properties of polyurethanes. Le compos est ensuite limin avec ses mtabolites, 57 et 13 % de la radioactivit tant respectivement rcuprs dans les matires fcales et les urines au bout de 4 jours. Center for Computational Quantum Chemistry, University of Georgia, 140 Cedar Street, Athens, Georgia, USA La Ficha internacional de seguridad qumica (ICSC 0298) para el MDI, preparada por el Programa Internacional de Seguridad de las Sustancias Qumicas (IPCS, 1993), tambin se reproduce en el presente documento. Lecture, University of Bielefeld, Bielefeld, June (unpublished report). please go to the Copyright Clearance Center request page. . MDI is primarily used to make rigid polyurethane foams used as insulation for homes. Levels were continuously monitored and never exceeded 50 g/m3. 10491058 (IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol. Base-catalysed reactions of isocyanates with alcohols should be carried out in inert solvents. Harith Al-Moameri. Smaller numbers of animals were assessed at various time points for lung function and for examination of bronchioalveolar lavage (BAL) fluid for cell counts and protein and enzyme determinations. A hypersensitivity pneumonitis type of reaction has also been reported. The highest exposure category comprised jobs in which either the 8-h time-weighted average exposure (to isocyanates) during 19781986 was greater than 0.04 mg/m3 or excursions above 0.1 mg/m3 occurred on most days. Liss GM, Bernstein DI, Moller DR, Gallagher JS, Stephenson RL, Bernstein IL (1988) Pulmonary and immunologocal evaluation of foundry workers exposed to methylene diisocyanate (MDI). A total of 24 substituted RNCO + H2O reactions were studied. In an unpublished pharmacokinetic study (Istin, 1977), nose-only exposure of male Sprague-Dawley rats to an aerosol (particle sizes less than 5 m) of radiolabelled (in the methylene group) monomeric MDI for 15 min resulted in the distribution of radioactivity, predominantly to the lungs and a variety of extrarespiratory sites (principally muscle, liver, kidneys, and the digestive tract), after 96 h when the animals were sacrificed. Pezzini A, Riviera A, Paggiaro P, Spiazzi A, Gerosa F, Filieri M, Toma G, Tridente G (1984) Specific IgE antibodies in twenty-eight workers with diisocyanate-induced bronchial asthma. No desquamation or fissuring was noted with the compound. Liquid chromatography with ultraviolet detection of monomeric and polymeric isocyanates as their dibutylamine derivatives. PMDI, the primary technical/commercial form of MDI, is actually a mixture that contains 2580% monomeric 4,4-MDI as well as oligomers containing 36 rings and other minor isomers, such as the 2,2-isomer. Des tudes portant sur des ouvriers ont permis de mettre en vidence de la mthylnedianiline sous diverses formes dans leur sang et leurs urines : MDA libre, MDA actyle et adduits MDA-hmoglobine et MDA-albumine. IARC (1999) 4,4-Methylenediphenyl diisocyanate and polymeric 4,4-methylenediphenyl diisocyanate. In one high-dose animal, a bronchioloalveolar adenoma was observed. TDI had been used in all the plants and MDI in all but one, so it was impossible to evaluate their individual effects. Cross-reactivity to toluene diisocyanate (TDI) and other isocyanates was demonstrated. PMDI is a dark reddish brown liquid with an indefinite melting point around 0 C and a vapour pressure of <1 mPa at 20 C. The observed or likely fates of MDI in air, water, and soil have been described by Brochhagen & Keller (1983) and Gilbert (1988). (1995b) reported the formation of adducts of MDA and acetylated MDA with haemoglobin or albumin in the blood of workers exposed to MDI, as described in section 6.2. Sepai et al. Cartier A, Grammer L, Malo JL, Lagier F, Ghezzo H, Harris K, Patterson R (1989) Specific serum antibodies against isocyanates: association with occupational asthma. Toxicologist, 6:15. The para-isocyanate moieties were found to be more reactive compared to the ortho-isocyanate moieties. Wash with plenty of soap and water. Cincinnati, OH, US Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health (Report No. El PMDI se utiliza para fabricar espuma rgida y flexible, aglutinantes de arena y resina de fundicin y aislantes trmicos. A health study of the 78 workers in an iron and steel foundry in Vancouver, Canada, was carried out, and the results were compared with those found in 372 railway repair yard workers (Johnson et al., 1985). @B96@@T `$0xG& BI\Aq4XJ4g!`,ZB3IP%h1$l t42'c|q"D>WG3% *(N"&$$0A *M van der Hoeven N, Roza P, Henzen L (1992a) Determination of the effect of TDI, TDA, MDI, and MDA on the emergence and growth of the plant species Avena sativa and Lactuca sativa according to OECD Guideline No.