4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

doi:10.1002/3527600418.mb10168stae4515

Cited by 3 publications

(4 citation statements)

References 113 publications

(121 reference statements)

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“…The carcinogenicity detected in a chronic oral gavage studies of TDI with mice and rats exhibited a pattern of tumor sites and incidences that could be explained by the release of TDA, and the relevance for human exposure was questioned (Dieter et al, 1990, 1991; Doe, 1991; Sielken et al, 2012). The difficulty in assessing the genotoxic potential of MDI and TDI, and the relevance of released MDA and TDA is addressed in literature (Bolognesi et al, 2001; Prueitt et al, 2013) and in expert panel reviews (ATSDR, 2018; MAK Commission, 2003, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…The primary acute and chronic effects of air exposure to MDI and TDI at the workplace are respiratory inflammation, respiratory sensitization, and lung function decrement; for dermal exposure, skin irritation and skin sensitization are the observable adverse effects (ATSDR, 2018; MAK Commission, 2003, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…For both MDI studies, lung tumors occurred towards the end of the studies at respiratory irritating concentrations (Feron et al, 2001). The German MAK Commission classified MDI as MAK-Cat.4 9 carcinogen and allocated an occupational exposure limit of 50 μg/m³ (MAK Commission, 2008). In these chronic rat inhalation studies, the NOAEC for tumor formation was 1.07 mg/m 3 for TDI (Löser, 1983) and 0.2 mg/m 3 for MDI; the LOAEC for MDI was 1.0 mg/m 3 (Feron et al, 2001; Hoymann et al, 1995; Reuzel et al, 1994a).…”

Section: Resultsmentioning

confidence: 99%

“…The different grades of MDI and TDI exhibit similar chemical reactivity. Both substances are known to be capable of causing lung decrement and sensitization in overexposed workers as relevant adverse effects (ATSDR, 2018; MAK Commission, 2003, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Absorption, distribution, metabolism, and excretion of methylene diphenyl diisocyanate and toluene diisocyanate: Many similarities and few differences

Schupp

Plehiers²

2022

Toxicol Ind Health

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Methylene diphenyl diisocyanate (MDI) and toluene diisocyanate (TDI) are high production volume chemicals used for the manufacture of polyurethanes. For both substances, the most relevant adverse health effects after overexposure in the workplace are isocyanate-induced asthma, lung function decrement and, to a much lesser extent, skin effects. Over the last two decades many articles have addressed the reactivity of MDI and TDI in biological media and the associated biochemistry, which increased the understanding of their biochemical and physiological behavior. In this review, these new insights with respect to similarities and differences concerning the adsorption, distribution, metabolism, and excretion (ADME) of these two diisocyanates and the implications on their toxicities are summarized. Both TDI and MDI show very similar behavior in reactivity to biological macromolecules, distribution, metabolism, and excretion. Evidence suggests that the isocyanate (NCO) group is scavenged at the portal-of-entry and is not systemically available in unbound reactive form. This explains the lack of other than portal-of-entry toxicity observed in repeated-dose inhalation tests.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Absorption, distribution, metabolism, and excretion of methylene diphenyl diisocyanate and toluene diisocyanate: Many similarities and few differences

Schupp

Plehiers²

2022

Toxicol Ind Health

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Hexamethylene diisocyanate, 2,4‐toluene diisocyanate, 2,6‐toluene diisocyanate, isophorone diisocyanate and 4,4′‐methylene diphenyl diisocyanate – Determination of hexamethylenediamine, 2,4‐toluenediamine, 2,6‐toluenediamine, isophoronediamine and 4,4′‐methylenedianiline in urine using gas chromatography‐mass spectrometry [Biomonitoring Methods, 2017]

Cocker

Jones

Leng³

et al. 2017

The MAK‐Collection for Occupational Health and Safety

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The working group “Analyses in Biological Materials” of the Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area verified the present biomonitoring method. The described method allows the simultaneous determination of the metabolites of hexamethylene diisocyanate ( HDI ), 2,4‐toluene diisocyanate and 2,6‐toluene diisocyanate ( TDI ), isophorone diisocyanate ( IPDI ) and methylene diphenyl diisocyanate (MDI) in human urine. After acid hydrolysis the released amines, hexamethylenediamine ( HDA ), 2,4‐toluenediamine, and 2,6‐toluenediamine ( TDA ), isophorone diamine ( IPDA ) and 4,4′‐methylenedianiline ( 4,4 ′ ‐MDA ) are extracted from urine, derivatised using heptafluorobutyric anhydride and quantified by NCI‐GC‐MS. The method was extensively validated and the reliability data were confirmed by independent laboratories, which have established and cross‐checked the whole procedure.

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A validated liquid chromatography/tandem mass spectrometry method for 4,4′‐methylenedianiline quantitation in human urine as a measure of 4,4′‐methylene diphenyl diisocyanate exposure

Lépine

Sleno

Lesage

et al. 2019

Rapid Comm Mass Spectrometry

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Rationale 4,4′‐Methylene diphenyl diisocyanate (MDI) is a highly reactive isocyanate used in the production of polyurethanes. Workers exposed to these products may develop sensitization to the diisocyanate compounds, leading to occupational asthma. Quantifying MDI levels is necessary to ensure workplace safety. MDI is metabolized by acetylation and/or conjugation to macromolecules for excretion into urine. All metabolites can be chemically hydrolyzed to form the free diamine 4,4′‐methylenedianiline (MDA) as a urinary biomarker of MDI exposure. Current methods involve long sample preparation, or have been designed using costly automation. There is therefore a need to develop a new practical method for assessing exposure to MDI. Methods Urine samples were acidified and heated to form MDA, followed by neutralization and liquid–liquid extraction. Extracts were separated by reversed‐phase chromatography on a HSS T3 column followed by analysis on a triple quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode. Results 13C15N‐MDA was selected as the internal standard (IS) of choice following an investigation of internal standard stability. The hydrolysis efficiency, forming free MDA from conjugated metabolites in vivo, was evaluated using 4,4′‐methylenebis(acetanilide) spiked into urine and complete hydrolysis occurred after 1 h. A dynamic range of 5 to 500 nM was achieved, and was useful for monitoring MDI exposure considering the biological guidance value (BGV) of 10 μg/L (~50 nM) proposed by the German Research Foundation (DFG). The limit of detection (LOD) and limit of quantification (LOQ) of the method were 0.8 and 2.7 nM, respectively. The intra‐day and inter‐day precisions were 4.33% and 4.27%, respectively. Finally, the method was tested with inter‐laboratory samples from the German External Quality Assessment Scheme (G‐EQUAS) program and the results submitted were all within the allowable tolerance range. Conclusions A practical and validated method for the analysis of small‐ to medium‐sized batches of samples has been developed for the biological monitoring of MDI exposure in human urine.

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4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

Abstract: The article contains sections titled: Toxic Effects and Mode of Action Mechanism of Action Toxicokinetics and Metabolism Absorption, distribution, elimination Metabolism Binding to macromolecules/biological monitoring Effects in Humans Single … Show more

Cited by 3 publications

References 113 publications

Absorption, distribution, metabolism, and excretion of methylene diphenyl diisocyanate and toluene diisocyanate: Many similarities and few differences

Absorption, distribution, metabolism, and excretion of methylene diphenyl diisocyanate and toluene diisocyanate: Many similarities and few differences

A validated liquid chromatography/tandem mass spectrometry method for 4,4′‐methylenedianiline quantitation in human urine as a measure of 4,4′‐methylene diphenyl diisocyanate exposure

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