Dalene M, Jakobsson K, Rannug A, Skarping G, Hagmar L (1996) MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation. 4,4'-Diphenylmethane diisocyanate is not soluble in water. American Industrial Hygiene Association journal, 43:8997. 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. Information on the peer review of this CICAD is presented in Appendix 2. Hannover, Fraunhofer Institute for Toxicology and Aerosol Research (Report No. anate. Once absorbed, it appears to be predominantly conjugated to protein. NIOSH (1994a) Letter from NIOSH to Jim Walter Resources, Inc. with a study report. Detection limits of HPLC for MDI and PMDI, which vary depending on the sampling methodology, can be below 0.01 mg/m3. A similar, smaller difference was seen with non-Hodgkins lymphoma. V 92.102). IPCS (1993) International Chemical Safety Card Methylene bisphenyl isocyanate (MDI). En un estudio de toxicidad/carcinogenicidad por inhalacin crnica de dos aos, las ratas expuestas a un aerosol de PMDI en concentraciones de 0, 0,19, 0,98, y 6,03 mg/m3 mostraron cambios en el aparato respiratorio. Une tude sur un tang a montr que laccumulation du MDI le long de la chane alimentaire aquatique est extrmement peu probable, comme on peut sy attendre du fait de sa trs faible solubilit et de sa forte ractivit en solution aqueuse. WHO Library Cataloguing-in-Publication Data, Diphenylmethane diisocyanate (MDI). Rhone-Poulenc Chimie (1977) Biological action of TDI and MDI in water. The published studies have a number of limitations (e.g., short duration of exposure, concomitant exposure to other substances), which result in low power to detect cancer occurrence in target organs of interest. The Ontario Ministry of Labour, Canada, assessed the cause of multiple respiratory complaints among workers at a plant that manufactures automotive instrument panels using polyurethane (Liss et al., 1996). In contrast, the respiration rate was decreased in a dose-dependent manner in mice exposed to MDI aerosol concentrations between 10.2 and 58.5 mg/m3 (Weyel & Schaffer, 1985). Fetal body weights were comparable in all groups, and no external treatment-related abnormalities were observed in the fetuses. TDI and MDI can be released into the air, water, and soil at places where they are made or used. Woellner RC, Hall S, Greaves I, Schoenwetter WF (1997) Epidemic of asthma in a wood products plant using methylene diphenyl diisocyanate. https://doi.org/10.1007/s10965-022-02929-3, DOI: https://doi.org/10.1007/s10965-022-02929-3. A casereference study within the cohort was made to assess more thoroughly the association between exposure to TDI and MDI and risk of cancer (Hagmar et al., 1993b). Shimizu H, Suzuki Y, Takemura N, Goto S, Matsushita H (1985) The results of microbial mutation test for forty-three industrial chemicals. Le MDI polymris (PMDI), qui est la forme technique et commerciale principale de ce compos est en fait un mlange contenant 25 80 % de 4,4-MDI monomre et des oligomres 3-6 cycles plus quelques isomres comme lisomre 2,2. Under such heterogeneous conditions, the disappearance of PMDI shows zero-order kinetics. The Committee accepts opinions based on scientific aspects of the provisional OEL until the next annual general meeting. (1998) evaluated whether MDI-specific IgG or IgE could be sensitive biological markers of disease or of MDI exposure. El diisocianato de difenilmetano (MDI) es el nombre genrico de un producto utilizado en la industria. The total annual global production of MDI and PMDI was about 1.2 million tonnes in 1991, 1.5 million tonnes in 1993, 1.78 million tonnes in 1994, and 1.95 million tonnes in 1996. These isocyanate solutions have a range of different advantages . `"v7.=:@[pxBD O5 Average mass 250.252 Da. Female Wistar rats (80 per exposure group) were exposed (whole body) to MDI in aerosol at 0.23, 0.70, or 2.05 mg/m3 (MMAD about 1 m) for 17 h per day, 5 days per week, for up to 24 months. Polym Sci Ser A 48(4):382387, Nagy T et al (2015) New insight into the kinetics of diisocyanate-alcohol reactions by high-performance liquid chromatography and mass spectrometry. El MDI polimrico (PMDI), forma tcnico/comercial primaria del MDI, es en realidad una mezcla que contiene un 25%-80% de 4,4-MDI monomrico, as como oligmeros con 3-6 anillos y otros ismeros secundarios, como el ismero 2,2. The tack can be fine-tuned by adjusting the amount of soy flour added. Two different reaction mechanisms for this transformation are possible, namely "phosgenations first" and "step-wise phosgenations". Cross-reactivity to toluene diisocyanate (TDI) and other isocyanates was demonstrated. Polymeric MDI. In one high-dose animal, a bronchioloalveolar adenoma was observed. British journal of industrial medicine, 50:10031007. The extent to which MDI, in either monomeric or polymeric form, disperses in air beyond the point of release and exposes general populations is not known. Jaf, L., Al-Moameri, H. & Ghosh, T. Simulation approach for characterizing the isocyanates reactivity in polyurethane gel reactions. Les points daboutissement toxicologiques les plus proccupants sont lasthme dorigine professionnelle, les pneumopathies dhypersensibilit et les affections inflammatoires des voies respiratoires suprieures conscutives linhalation de MDI ou de PMDI. American journal of industrial medicine, 33:471477. Washington, DC, US Government Printing Office, February 1984, p. 5521-1. Tse KS, Johnson A, Chan H, Chan-Yeung C (1985) A study of serum antibody activity in workers with occupational exposure to diphenylmethane diisocyanate. Since the first study found high mortality, probably due to the use of very young animals, another 13-week study was conducted at actual mean concentrations of 0.35, 1.4, and 7.2 mg/m3 (Reuzel et al., 1994a). The polyureas formed from MDI appear to be stable to chemical attack, as would be expected from its insolubility and the stability of ureas. volume29, Articlenumber:92 (2022) This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organization, or the World Health Organization. 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. 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). Haemoglobin adducts of these metabolites were also detected. Gahlmann R (1993) A critical review for the International Isocyanate Institute. Under normal circumstances, exposure is likely only from releases to the atmosphere. No. No short-term study on monomeric MDI and no data from oral or dermal routes were available. The heterogeneous hydrolysis reactions were carried out in glass reaction tubes under nitrogen with initial polyurea loadings of 2 g/L in deionized water or buffer solution. We expect that these results lay a firm foundation for the experimental study of substituted isocyanates and their relationship to the energetic pathways of related systems. The mean number of MDI exposure years was 8.6, 1.1, and 0 years for group I, group II, and group III, respectively. Carcinogenesis, 16(3): 573582. The specific humoral immune response can be IgE as well as IgG mediated, but many patients with sensitization to isocyanates have no demonstrative serum antibodies against the isocyanates. D16. Basal cell hyperplasia in the olfactory epithelium was elevated significantly in males only at the mid and high concentrations. Animal data provide clear evidence of skin and respiratory sensitization due to MDI. No treatment-related findings in dams and fetuses occurred at 1 and 4 mg/m3. They underwent inhalation challenges using the MDI resin for progressively increasing periods of time on separate days. Worker exposures are already subject to protective controls in occupational settings. To investigate the immunopathogenesis of diisocyanate-caused asthma, diisocyanate-exposed workers were evaluated for in vitro production of antigen-specific mononuclear cell-derived histamine releasing factor (HRF). Some isocyanates react with water to form amines and liberate carbon dioxide. This CICAD was approved as an international assessment at a meeting of the Final Review Board, held in Stockholm, Sweden, on 2528 May 1999. The challenge solution induced ear swelling of delayed onset, with its peak at 24 h. Passive transfer of the MDI-induced contact sensitivity was achieved by injecting lymphocytes from the lymph nodes of MDI-sensitized mice into the caudal vein of syngeneic mice, and the effector cells were found to be T-cells. Aquatic invertebrates showed no immobilization after a 24-h exposure to nominal concentrations of up to 1000 mg MDI/litre (Rhone-Poulanc Chimie, 1977; Caspers et al., 1986). 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. The purpose of the IOMC is to promote coordination of the policies and activities pursued by the Participating Organizations, jointly or separately, to achieve the sound management of chemicals in relation to human health and the environment. Musk et al. Such disorders were still observed, but no more frequently than in the group at concentrations below 0.05 mg/m3. Identified uses : . Appelman LM, de Jong AWJ, Keller J (1986) Additional studies into the presence of MDA in samples of test atmospheres containing polymeric MDI aerosol. LRLB['5ZXkz6d@68 |!\!/'8[~xRoUpxeOe"Ar^%Kosb.?nNUi PMDI is the form produced commercially from aniline and formaldehyde using hydrochloric acid as catalyst. A further potential breakdown product of MDI in water is an oligourea. Further purification entails fractionation of the MDI isomer mixture. 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. Share sensitive information only on official, secure websites. ), de fibres (spandex) et de semelles de chaussures. Based on the marginal increase in lung to body weight ratios, it was concluded that 2.2 mg PMDI/m3, which was the lowest dose level examined, was a NOAEL. Mancuso G, Reggiani M, Berdondini RM (1996) Occupational dermatitis in shoemakers. Guinea-pigs exposed to monomeric MDI aerosol at concentrations between 0.6 and 350 mg/m3 (no other details available) for 3 h showed a decrease in respiration rate and an increase in tidal volume at lower concentrations, whereas a concentration-dependent increase in respiration rate was seen above 10.4 mg/m3 (Thorne et al., 1986). It has a CASRN of 9016-87-9. Analyst, 122:275278. MDI, like the other isocyanates, is an allergen and sensitizer. Humoral as well as cellular immunity may be involved in the pathogenesis of hypersensitivity due to isocyanates. CICADs join the Environmental Health Criteria documents (EHCs) as authoritative documents on the risk assessment of chemicals. The other one reacted only to MDI. Hydrogenated MDI ( H12MDI or 4,4-diisocyanato dicyclohexylmethane) is an organic compound in the class known as isocyanates. 4,4'-Methylenediphenyl diisocyanate (MDI) 101-68-8 30-70 SECTION 4: FIRST AID MEASURES EYE: H319 Causes serious eye irritation. MDI is not stable in DMSO, there being many products generated within minutes (Herbold, 1990a,b; Gahlmann, 1993). In a subchronic study by Reuzel et al. Based on EPAs screening-level review of hazard and exposure information, including information indicating uncured MDI and its related polyisocyanates are used in a range of consumer and commercial products as well as in products intended only for an industrial market, EPA intends to: Previous Actions:Read about the ongoing federal partnership activities for safer use of spray polyurethane foam containing MDI and related compounds. Such . Molecular understanding of the 4,4-MDA formation can provide strategy to prevent from side reactions. Accidental release measures Monomeric 4,4-MDI is a white to pale yellow solid at room temperature, with a molecular weight of 250.26. Chemical Name: Diphenylmethane Diisocyanate (MDI) CAS-No. On day 21 of pregnancy, the female rats were sacrificed and a caesarean section was performed. 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). Slight erythema observed initially at all dose levels did not last after 7 days. Although there were many limitations, such as involvement of confounding factors in mixed exposures and lack of knowledge of actual exposure concentrations, it was concluded that significant impairment of lung spirometry values was observed in the collective exposed to PMDI concentrations up to 0.87 mg/m3. Journal of occupational medicine, 24(10):746750. The method comprises the following steps of: adding the MDI and an organic solvent into a reaction kettle, raising the temperature, dissolving the MDI, stirring uniformly, adding dehydrated polyol, and reacting for 1 to 6 hours at the temperature of between 40 . 19570, 27.9.1990). Selon toutes les tudes disponibles, on trouve de la MDA libre ou actyle en milieu fortement hydrolytique. Leverkusen, Bayer AG. such a reaction was observed only upon challenge with an irritating . Mobile parts of the macrobenthos (e.g., Gastropoda) remained unaffected. Several publications indicate that complex immunological reactions are involved in the process of sensitization to MDI (Pezzini et al., 1984; Tse et al., 1985; Liss et al., 1988; Cartier et al., 1989). IARC (1999) 4,4-Methylenediphenyl diisocyanate and polymeric 4,4-methylenediphenyl diisocyanate. (1990). Vandenplas O, Malo JL, Dugas M, Cartier A, Desjardins A, Levesque J, Shaughnessy MA, Grammer LC (1993) Hypersensitivity pneumonitis-like reaction among workers exposed to diphenylmethane diisocyanate (MDI). Appelman LM, de Jong AWJ (1982) Acute inhalation toxicity study of polymeric MDI in rats. tRlt RF shC Nakata M (1983) Test report on fish toxicity of polymethylene polyphenyl polyisocyanate: internal communication. . (1994). Animal inhalation studies have shown that PMDI exposure (see section 8.4.2 for details of particle size distribution) results in significant deposition both in the nasal region and in the alveolar region of the lungs (Reuzel et al., 1994a,b). Despite these data, the small sample size, possible selection bias for workers involved in litigation, possible confounding factors, lack of pertinent matched control, lack of objective exposure data, and lack of knowledge on mechanism preclude the credibility of the findings. Sa tension de vapeur est infrieure 1 mPa 20 C. American journal of industrial medicine, 31:5663. The same negative result was seen in the liver, bladder, kidney, respiratory epithelium, and peripheral lymphocytes. If moisture is present in the mixture (Figure 4), then the isocyanate will react with this water to form an unstable carbamic acid which then decomposes to form urea and carbon dioxide gas thus resulting in foaming. Although limited in various ways, a cohort study and a retrospective study showed no significant association with cancer morbidity. Weisburger EK, Murthy ASK, Lilja HS, Lamb JC (1984) Neoplastic response of F344 rats and B6C3F1 mice to the polymer and dyestuff intermediates, 4,4-methylenebis(N,N-dimethyl)benzenamine, 4,4-oxydianiline, and 4,4-methylenedianiline. Twenty-three per cent of the radioactivity administered was found in the carcass; however, less than 1% of the radioactivity was recovered from the major organs. Typical polyols used are polyethylene adipate (a polyester) and poly(tetramethylene ether) glycol (a polyether). Our results indicate that an additional RNCO molecule might catalyze imidic acid formation but have less influence on the efficiency of carbamate formation. Se busc la bibliografa hasta noviembre de 1998 mediante MEDLINE, para localizar cualquier informacin nueva pertinente a la evaluacin. In the case of diisocyanates, the reactivity of the isocyanate (N=C=O, or NCO) functional group toward water and biological (macro)molecules and the resulting reaction products are key. These procedures are designed to take advantage of the expertise that exists around the world expertise that is required to produce the high-quality evaluations of toxicological, exposure, and other data that are necessary for assessing risks to human health and/or the environment. Methylene diphenyl diisocyanate (MDI) is an aromatic diisocyanate. E-mail: (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. Sin embargo, los resultados de las pruebas acuticas carecen de valor, debido a que el MDI es prcticamente insoluble en agua. You must check the information on the packaging and safety data sheet, supplied by . There is clear evidence of skin sensitization due to MDI. Brochhagen FK, Keller J (1983) Accident involving a road tanker carrying tolulene diisocyanate (TDI) countermeasures and experience. The overall objectives of the IPCS are to establish the scientific basis for assessment of the risk to human health and the environment from exposure to chemicals, through international peer review processes, as a prerequisite for the promotion of chemical safety, and to provide technical assistance in strengthening national capacities for the sound management of chemicals. Pour ce qui est de lexposition par la voie respiratoire, on ne dispose que dtudes limites sur le rat. @B96@@T `$0xG& BI\Aq4XJ4g!`,ZB3IP%h1$l t42'c|q"D>WG3% *(N"&$$0A *M The investigators discussed the possibility that there may be selection bias, because the study group did not include any subject with symptoms suggesting hypersensitivity to isocyanate; those who were experiencing adverse effects may have been included in the small numbers of subjects who had left and been lost to follow-up. ISBN 92 4 153027 8 (NLM Classification: QV 280) Base-catalysed reactions of isocyanates with alcohols should be carried out in inert solvents. These groups react with compounds that have an active hydrogen, such as water, alcohols, and amines. El MDI no mostr toxicidad para los peces, los invertebrados acuticos, las algas o los microorganismos en ninguna de las condiciones de prueba de exposicin aguda o prolongada. l[Ipb*GY+g1hYNIN c/-"a7BYE93R;( `PyQ2/xeI )PxrZT@ChaAT Rjt !@@e*9s)g JTc:PPk Based on a marginal increase in lung to body weight ratio at higher doses, it was concluded that 2.2 mg/m3, which was the lowest dose level examined, was a no-observed-adverse-effect level (NOAEL). MDI reacts with water to produce MDA. While every effort is made to ensure that CICADs represent the current status of knowledge, new information is being developed constantly. Olfactory epithelial degeneration was elevated significantly at the high concentration in both sexes. In the German study evaluating lung decrement, significant reversible adverse effects on lung function were observed in persons exposed to MDI concentrations above 0.2 mg/m3. Andersen M, Bineru ML, Kiel P, Larsen H, Maxild J (1980) Mutagenic action of isocyanates used in the production of polyurethanes. However, because of the known interaction of DMSO with MDI to yield MDA and possibly other reaction products, these positive results should not be construed as meaningful for human health risk assessment. However, this is the only source of environmental information and extensive review available at present to the Final Review Board. The abundance of some zooplankton species (Cladocera) was clearly reduced in the high-dosed pond 28 weeks after application. In these studies, the test substance was initially dissolved in acetone, which was then mixed with sand. It can therefore be expected that, in aqueous environments, the rate of reaction with water (50 M) would always by far exceed that with other OH-bearing molecules (mM). EPA is concerned about potential health effects that may result from exposures to the consumer or self-employed worker while using products containing uncured (unreacted) MDI and its related polyisocyanates (e.g., spray-applied foam sealants, adhesives, and coatings) or incidental exposures to the general population while such products are used in or around buildings including homes or schools. Hiasa Y, Kitahori Y, Enoki N, Konishi N, Shimoyama T (1984) 4,4-diaminodiphenylmethane: promoting effect on the development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl)nitrosamine. The BMC10 is first converted to a human equivalent concentration (HEC) by application of the Regional Dose Deposited Ratio (RDDR) calculated using a computer program provided in US EPA (1994). Dangerous pressure can build up if container is sealed. IARC (1986) 4,4-Methylenedianiline and its dihydrochloride. DNA radioactivity in the liver was at the limit of detection. British journal of industrial medicine, 50:537543. TDI had been used in all the plants and MDI in all but one, so it was impossible to evaluate their individual effects. 4,4'-Diphenylmethane diisocyanate may be toxic by ingestion, inhalation, or skin absorption. La production annuelle totale de MDI et de PMDI a t denviron 1,2 millions de tonnes en 1991, de 1,5 millions en 1993, de 1,78 millions en 1994 et de 1,95 millions de tonnes en 1996. 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. In Japan, 0.200.27 million tonnes were produced in 19921996 (Chemical Daily, 1997). Methylene diphenyl diisocyanate, toluene diisocyanate, and Diethylene glycol were utilized for getting the kinetic parameters. 47 0 obj <>stream 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). Schuetze D, Sepai O, Lewalter J, Miksche L, Henschler D, Sabbioni G (1995) Biomonitoring of workers exposed to 4,4-methylenediamine and 4,4-methylenediphenyl diisocyanate. High exposures involving MDI in ambient environments are expected to be rare. (1994) and Heimbach et al. 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. 9341, 1.8.1980) (in German). J Chem Educ 95(9):15541561, Chen Z et al (2017) Kinetics of waterisocyanate reaction in N N-dimethylformamide. In the case of TDI-polyurea, concentrations of free 2,4- and 2,6-toluenediamine in water were measured after hydrolysis at 120, 140, and 160 degrees C. Sensitization to MDI is probably the cause of asthma in these workers. However, monomeric MDI is soluble in octane, benzene, and kerosene (Chemical Society of Japan, 1989). Le dpouillement bibliographique a t poursuivi jusqu novembre 1998 laide du systme MEDLINE, la recherche de toute information nouvelle susceptible dtre utile lvaluation. About 10% of the radioactivity was retained at the site of application. 86-2507). 39). Methylene di-p-phenyl diisocyanate,flakes; 4,4'-Diphenylmethane Diisocyanate; PMDI. PMDI used in experiments is complex and composed of 56 major constituents having 24 aromatic rings. TDI and MDI are extremely reactive chemicals and do not stay in the environment long. * ccq@uga.edu 4,4'-MDI can be obtained by purifying the diphenylmethane diisocyanate mixture. Because of the relatively low number of workers (25) exposed to MDI (less than 0.04 mg/m3), the short study duration, confounding from prior exposure to TDI (0.05 mg/m3) and possibly to amine catalyst, and the uncertainty in the actual duration of MDI exposure, this study offers limited assurance that MDI is without effect on pulmonary function. Liss GM, Tarlo SM, Banks DE (1996) Evidence for occupational asthma among compensation claimants at a polyurethane utilizing facility. Effects on lung function were assessed by DFG (1997) based on the results of nine studies namely, Cavelier et al. BASF is moving forward with the final phase of the expansion project for the methylene diphenyl diisocyanate (MDI) plant at its Verbund site in Geismar, Louisiana.

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