Isocyanic acid, methylenedi-p-phenylene ester

RTECS #

NQ9350000

CAS #

101-68-8
See: NMAM or OSHA Methods

Updated

March 2019

Molecular Weight

250.27

Molecular Formula

C₁₅H₁₀N₂O₂

Synonyms

1,1'-Methylenebis(4-isocyanatobenzene)
4,4'-Diisocyanatodiphenylmethane
4,4'-Diphenylmethane diisocyanate
4,4'-Methylenebis(phenyl isocyanate)
4,4'-Methylenediphenyl diisocyanate
4,4'-Methylenediphenyl isocyanate
4,4'-Methylenediphenylene isocyanate
4-4'-Diisocyanate de diphenylmethane (French)
Benzene, 1,1'-methylenebis(4-isocyanato- (9CI)
Bis(1,4-isocyanatophenyl)methane
Bis(4-isocyanatophenyl)methane
Bis(p-isocyanatophenyl)methane
Caradate 30
Desmodur 44
Difenil-metan-diisocianato (Italian)
Difenylmethaan-dissocyanaat (Dutch)
Diphenyl methane diisocyanate
Diphenylmethan-4,4'-diisocyanat (German)
Diphenylmethane 4,4'-diisocyanate
Diphenylmethane diisocyanate (ACGIH:OSHA)
Hylene M50
Isonate
Isonate 125 MF
Isonate 125M
MDI
MDI (OSHA)
Methylene bisphenyl isocyanate
Methylene bisphenyl isocyanate (ACGIH:OSHA)
Methylenebis(4-isocyanatobenzene)
Methylenebis(4-phenyl isocyanate)
Methylenebis(4-phenylene isocyanate)
Methylenebis(p-phenyl isocyanate)
Methylenebis(p-phenylene isocyanate)
Methylenediphenyl diisocyanate
Methylenedi-p-phenylene diisocyanate
Methylenedi-p-phenylene isocyanate
Nacconate 300
NCI-C50668
p,p'-Diphenylmethane diisocyanate
p,p'-Methylenebis(phenyl isocyanate)
Rubinate 44

Skin and Eye Irritation and References

Route/Organism	Dose	Effect	Reference
eye /rabbit	100 mg	moderate	NTIS** OTS0516728
skin /rabbit	500 mg/24H		EJTXAZ 9,41,1976

Mutation Data and Reference

System Test	Route/Organism/Tissue	Dose	Reference
Cytogenetic Analysis	lymphocyte/human	540 mg/L	TOLED5 36,37,1987
Cytogenetic Analysis	lymphocyte/human	0.64 mg/plate	CRTXB2 31,737,2001
DNA adduct	inhalation/rat	0.002 mg/L/17H/1Y	CRTXB2 31,737,2001
DNA adduct	inhalation/rat	2 mg/m³/52W- intermittent	CRNGDP 17,1069,1996
DNA Damage	inhalation/human	20 ppb/15M-continuous	TOLED5 60,131,1992
micronucleus test	inhalation/rat	7.1 mg/m³/3H	TOSCF2 58,102,2000
mutation in microorganisms	/Salmonella typhimurium	0.02 mg/plate (+enzymatic activation step)	CRTXB2 31,737,2001
mutation in microorganisms	/Salmonella typhimurium	50 µg/plate (-enzymatic activation step)	SWEHDO 6,221,1980
sister chromatid exchange	lymphocyte/human	2170 mg/L	TOLED5 36,37,1987

Reproductive Effects Data and References

Route/Organism	Dose	Effect	Reference
inhalation/rat	9 mg/m³/6H (6-15D pregnant)	Reproductive: Other effects on female Reproductive: Specific developmental abnormalities: Musculoskeletal system	NTIS** OTS0572542

Acute Toxicity Data and References

Route/Organism	Dose	Effect	Reference
In Vitro/Human, lung	Inhibitor Concentration Low: 7.575 µg/well/24H	In Vitro Toxicity Studies: Other assays	TIVIEQ 27,1151,2013
inhalation/human	lowest published toxic concentration: 130 ppb/30M	Immunological Including Allergic: Increased immune response Nutritional and Gross Metabolic: Body temperature increase	AIHAAP 27,121,1966
inhalation/rat	lethal concentration (50 percent kill): 178 mg/m³		AIHAAP 43,89,1982
inhalation/rat	lowest published toxic concentration: 8 mg/m³/6H	Lung, Thorax, or Respiration: Changes in lung weight Lung, Thorax, or Respiration: Other changes	ARTODN 74,257,2000
inhalation/rat	lowest published toxic concentration: 20 mg/m³/6H	Lung, Thorax, or Respiration: Other changes Biochemical: Metabolism (intermediary): Lipids including transport	ARTODN 74,257,2000
inhalation/rat	lowest published toxic concentration: 2.4 mg/m³/6H	Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi Lung, Thorax, or Respiration: Other changes Biochemical: Metabolism (intermediary): Other proteins	ARTODN 74,257,2000
inhalation/rat	lowest published toxic concentration: 0.7 mg/m³/6H	Behavioral: Muscle contraction or spasticity Eye: Change in extra- ocular muscles Eye: Other eye effects	ARTODN 74,257,2000
inhalation/rat	lowest published toxic concentration: 10 mg/m³/6H	Lung, Thorax, or Respiration: Other changes Biochemical: Metabolism (intermediary): Other proteins	JJATDK 22,371,2002
inhalation/rat	lowest published toxic concentration: 30 mg/m³/6H	Lung, Thorax, or Respiration: Other changes Lung, Thorax, or Respiration: Changes in lung weight Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects	JJATDK 22,371,2002
inhalation/rat	Lowest published lethal concentration: 2240 mg/m³/1H		ARTODN 78,243,2004
oral/mouse	lethal dose (50 percent kill): 2200 mg/kg		85GMAT -,63,1982
oral/rat	lethal dose (50 percent kill): 9200 mg/kg	Behavioral: Somnolence (general depressed activity) Behavioral: Ataxia Nutritional and Gross Metabolic: Body temperature decrease	NTIS** OTS0516728

Other Multiple Dose Data and References

Route/Organism	Dose	Effect	Reference
inhalation/guinea pig	lowest published toxic concentration: 2 mg/m³/3H/5D- intermittent	Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi Lung, Thorax, or Respiration: Changes in lung weight	NTIS** OTS0538162
inhalation/mouse	lowest published toxic concentration: 10.7 mg/m³/5D- intermittent	Blood: Other changes	MUREAV 723,1,2011
inhalation/rat	lowest published toxic concentration: 3 mg/m³/18H/90D- intermittent	Olfaction: Other olfaction effects Lung, Thorax, or Respiration: Other changes Blood: Other changes	NTIS** OTS0534539
inhalation/rat	lowest published toxic concentration: 110 mg/m³/3W- intermittent	Lung, Thorax, or Respiration: Other changes Lung, Thorax, or Respiration: Changes in lung weight	TOXID9 1,102,2001
inhalation/rat	lowest published toxic concentration: 110 mg/m³/1H/3W- intermittent	Olfaction: Other olfaction effects Lung, Thorax, or Respiration: Respiratory depression Lung, Thorax, or Respiration: Changes in lung weight	ARTODN 75,234,2001
inhalation/rat	lowest published toxic concentration: 6 mg/m³/6H/2Y- intermittent	Lung, Thorax, or Respiration: Other changes Lung, Thorax, or Respiration: Tumors	CRTXB2 31,737,2001
inhalation/rat	lowest published toxic concentration: 10 mg/m³/6H/4W- intermittent	Lung, Thorax, or Respiration: Other changes Lung, Thorax, or Respiration: Changes in lung weight Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects	JJATDK 22,371,2002
inhalation/rat	lowest published toxic concentration: 30 mg/m³/5D- intermittent	Immunological Including Allergic: Hypersensitivity delayed (multiple organ involvement)	TOXID9 72,230,2003
skin/mouse	lowest published toxic dose: 220 mg/kg/12D- intermittent	Skin: After topical application: Cutaneous sensitization (experimental) Biochemical: Metabolism (intermediary): Other proteins Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation	TXCYAC 207,487,2005
skin/mouse	lowest published toxic dose: 280 mg/kg/14D- intermittent	Immunological Including Allergic: Increase in humoral response	TOSCF2 94,108,2006
skin/mouse	lowest published toxic dose: 4.64 mg/kg/6D- intermittent	Skin: After topical application: Cutaneous sensitization (experimental)	FCTOD7 48,1704,2010

Reviews

Organization	Standard	Reference
American Conference of Governmental Industrial Hygienists (ACGIH)	Threshold Limit Value-time-weighted average 0.005 ppm	DTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)	Cancer Review:Human No Adequate Data	IMEMDT 19,303,1979
International Agency for Research on Cancer (IARC)	Cancer Review:Human Inadequate Evidence	IMEMDT 71,1049,1999
International Agency for Research on Cancer (IARC)	Cancer Review:Animal No Adequate Data	IMEMDT 19,303,1979
International Agency for Research on Cancer (IARC)	Cancer Review:Group 3	IMEMDT 71,1049,1999
TOXICOLOGY REVIEW		CRTXB2 31,737,2001
TOXICOLOGY REVIEW		TOLED5 140-141,213,2003
TOXICOLOGY REVIEW		RTOPDW 61,1,2011

Standards and Regulations

Organization	Standard	Reference
Mine Safety and Health Administration (MSHA) STANDARD	air-ceiling concentration 0.02 ppm (0.2 mg/m³)	DTLVS* 3,170,1971
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-AUSTRALIA	time-weighted average 0.02 mg(NCO)/m³, short term exposure limit 0.07 mg(NCO)/m³, JUL2008
Occupational Exposure Limit-AUSTRIA	MAK-TMW 0.005 ppm (0.05 mg/m³);KZW 0.01 ppm (0.1 mg/m³), sen, 2007
Occupational Exposure Limit-BELGIUM	time-weighted average 0.005 ppm (0.052 mg/m³), MAR2002
Occupational Exposure Limit-DENMARK	time-weighted average 0.005 ppm (0.05 mg/m³), MAY2011
Occupational Exposure Limit-FRANCE	VME 0.01 ppm (0.1 mg/m³), VLE 0.02 ppm (0.2 mg/m³), FEB2006
Occupational Exposure Limit-GERMANY	MAK 0.05 mg/m³, inhal, 2011
Occupational Exposure Limit-HUNGARY	time-weighted average 0.05 mg/m³, short term exposure limit 0.05 mg/m³, SEP2000
Occupational Exposure Limit-ICELAND	time-weighted average 0.005 ppm (0.05 mg/m³), short term exposure limit 0.01 ppm (0.1 mg/m³), sen, NOV2011
Occupational Exposure Limit-JAPAN	Occupational Exposure Limit 0.05 mg/m³, a1 sen, MAY2012
Occupational Exposure Limit-KOREA	time-weighted average 0.005 ppm (0.055 mg/m³), 2006
Occupational Exposure Limit-MEXICO	time-weighted average 0.005 ppm (0.051 mg/m³), 2004
Occupational Exposure Limit-NEW ZEALAND	time-weighted average 0.02 mg(NCO)/m³; short term exposure limit 0.07 mg(NCO)/m³, sen, JAN2002
Occupational Exposure Limit-PERU	time-weighted average 0,005 ppm (0,051 mg/m³), JUL2005
Occupational Exposure Limit-POLAND	MAC(time-weighted average) 0.05 mg/m³, MAC(C) 0.2 mg/m³, JAN1999
Occupational Exposure Limit-RUSSIA	short term exposure limit 0.5 mg/m³, Skin, JUN2003
Occupational Exposure Limit-SWEDEN	time-weighted average 0.002 ppm (0.03 mg/m³), ceiling concentration 0.005 ppm (0.05 mg/m³), Sen, JUN2005
Occupational Exposure Limit-SWITZERLAND	ceiling concentration 0.02 mg(NCO)/m³, skin, sen, JAN2011
Occupational Exposure Limit-THAILAND	time-weighted average 0.02 ppm (0.2 mg/m³), JAN1993
Occupational Exposure Limit-THE NETHERLANDS	MAC-TGG 0.05 mg/m³, 2003
Occupational Exposure Limit-THE PHILIPPINES	time-weighted average 0.02 ppm (0.2 mg/m³), JAN1993
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction)	ceiling concentration 0.02 ppm (0.2 mg/m³)	CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors)	ceiling concentration 0.02 ppm (0.2 mg/m³)	CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry)	ceiling concentration 0.02 ppm (0.2 mg/m³)	CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)	ceiling concentration 0.02 ppm (0.2 mg/m³)	CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

Organization	Standard	Reference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO MDI-air	10H time-weighted average 0.005 ppm;ceiling concentration 0.02 ppm/10M	NIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983	Hazard Code 27780; Number of Industries 41; Total Number of Facilities 2896; Number of Occupations 48; Total Number of Employees Exposed 53321; Total Number of Female Employees Exposed 13421

Status in Federal Agencies

Organization	Reference
EPA TSCA Section 8(b) CHEMICAL INVENTORY
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA Section 8(e) Risk Notification, 8EHQ-0892-9111
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH Analytical Method, 1994: Isocyanates, monomeric, 5521
NIOSH Analytical Method, 1996: Isocyanates, 5522
On EPA IRIS database
OSHA ANALYTICAL METHOD #33
OSHA ANALYTICAL METHOD #47

Page last reviewed: November 16, 2018

Content source: National Institute for Occupational Safety and Health