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Registry of Toxic Effects of Chemical Substances (RTECS)

Isocyanic acid, methylenedi-p-phenylene ester

RTECS #

NQ9350000

CAS #

101-68-8

Updated

July 2015

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/OrganismDoseEffectReference
eye /rabbit 100 mg moderateNTIS** OTS0516728
skin /rabbit 500 mg/24HEJTXAZ 9,41,1976

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysislymphocyte/human540 mg/LTOLED5 36,37,1987
Cytogenetic Analysislymphocyte/human0.64 mg/plateCRTXB2 31,737,2001
DNA adductinhalation/rat0.002 mg/L/17H/1YCRTXB2 31,737,2001
DNA adductinhalation/rat2 mg/m3/52W- intermittentCRNGDP 17,1069,1996
DNA Damageinhalation/human20 ppb/15M-continuousTOLED5 60,131,1992
micronucleus testinhalation/rat7.1 mg/m3/3HTOSCF2 58,102,2000
mutation in microorganisms/Salmonella typhimurium0.02 mg/plate (+enzymatic activation step)CRTXB2 31,737,2001
mutation in microorganisms/Salmonella typhimurium50 µg/plate (-enzymatic activation step)SWEHDO 6,221,1980
sister chromatid exchangelymphocyte/human2170 mg/LTOLED5 36,37,1987

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
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/OrganismDoseEffectReference
In Vitro/Human, lung Inhibitor Concentration Low: 7.575 µg/well/24HIn Vitro Toxicity Studies: Other assaysTIVIEQ 27,1151,2013
inhalation/human lowest published toxic concentration: 130 ppb/30MImmunological 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/m3AIHAAP 43,89,1982
inhalation/rat lowest published toxic concentration: 8 mg/m3/6HLung, 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/m3/6HLung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport
ARTODN 74,257,2000
inhalation/rat lowest published toxic concentration: 2.4 mg/m3/6HLung, 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/m3/6HBehavioral: 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/m3/6HLung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Other proteins
JJATDK 22,371,2002
inhalation/rat lowest published toxic concentration: 30 mg/m3/6HLung, 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/m3/1HARTODN 78,243,2004
oral/mouse lethal dose (50 percent kill): 2200 mg/kg85GMAT -,63,1982
oral/rat lethal dose (50 percent kill): 9200 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Ataxia

Nutritional and Gross Metabolic: Body temperature decrease
NTIS** OTS0516728

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/guinea pig lowest published toxic concentration: 2 mg/m3/3H/5D- intermittentLung, 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- intermittentBlood: Other changesMUREAV 723,1,2011
inhalation/rat lowest published toxic concentration: 3 mg/m3/18H/90D- intermittentOlfaction: Other olfaction effects

Lung, Thorax, or Respiration: Other changes

Blood: Other changes
NTIS** OTS0534539
inhalation/rat lowest published toxic concentration: 110 mg/m3/3W- intermittentLung, 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- intermittentOlfaction: 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- intermittentLung, 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- intermittentLung, 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- intermittentImmunological Including Allergic: Hypersensitivity delayed (multiple organ involvement)TOXID9 72,230,2003
skin/mouse lowest published toxic dose: 220 mg/kg/12D- intermittentSkin: 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- intermittentImmunological Including Allergic: Increase in humoral responseTOSCF2 94,108,2006
skin/mouse lowest published toxic dose: 4.64 mg/kg/6D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)FCTOD7 48,1704,2010

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 0.005 ppmDTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)Cancer Review:Human No Adequate DataIMEMDT 19,303,1979
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 71,1049,1999
International Agency for Research on Cancer (IARC)Cancer Review:Animal No Adequate DataIMEMDT 19,303,1979
International Agency for Research on Cancer (IARC)Cancer Review:Group 3IMEMDT 71,1049,1999
TOXICOLOGY REVIEWCRTXB2 31,737,2001
TOXICOLOGY REVIEWTOLED5 140-141,213,2003

Standards and Regulations

OrganizationStandardReference
Mine Safety and Health Administration (MSHA) STANDARDair-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-AUSTRALIAtime-weighted average 0.02 mg(NCO)/m3, short term exposure limit 0.07 mg(NCO)/m3, JUL2008
Occupational Exposure Limit-AUSTRIAMAK-TMW 0.005 ppm (0.05 mg/m3);KZW 0.01 ppm (0.1 mg/m3), sen, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 0.005 ppm (0.052 mg/m3), MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 0.005 ppm (0.05 mg/m3), MAY2011
Occupational Exposure Limit-FRANCEVME 0.01 ppm (0.1 mg/m3), VLE 0.02 ppm (0.2 mg/m3), FEB2006
Occupational Exposure Limit-GERMANYMAK 0.05 mg/m3, inhal, 2011
Occupational Exposure Limit-HUNGARYtime-weighted average 0.05 mg/m3, short term exposure limit 0.05 mg/m3, SEP2000
Occupational Exposure Limit-ICELANDtime-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-JAPANOccupational Exposure Limit 0.05 mg/m3, a1 sen, MAY2012
Occupational Exposure Limit-KOREAtime-weighted average 0.005 ppm (0.055 mg/m3), 2006
Occupational Exposure Limit-MEXICOtime-weighted average 0.005 ppm (0.051 mg/m3), 2004
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 0.02 mg(NCO)/m3; short term exposure limit 0.07 mg(NCO)/m3, sen, JAN2002
Occupational Exposure Limit-PERUtime-weighted average 0,005 ppm (0,051 mg/m3), JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 0.05 mg/m3, MAC(C) 0.2 mg/m3, JAN1999
Occupational Exposure Limit-RUSSIAshort term exposure limit 0.5 mg/m3, Skin, JUN2003
Occupational Exposure Limit-SWEDENtime-weighted average 0.002 ppm (0.03 mg/m3), ceiling concentration 0.005 ppm (0.05 mg/m3), Sen, JUN2005
Occupational Exposure Limit-SWITZERLANDceiling concentration 0.02 mg(NCO)/m3, skin, sen, JAN2011
Occupational Exposure Limit-THAILANDtime-weighted average 0.02 ppm (0.2 mg/m3), JAN1993
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 0.05 mg/m3, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-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

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO MDI-air10H time-weighted average 0.005 ppm;ceiling concentration 0.02 ppm/10MNIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard 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

OrganizationReference
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
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