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Registry of Toxic Effects of Chemical Substances (RTECS)

Benzene, 2,4-diisocyanato-1-methyl-

RTECS #

CZ6300000

CAS #

584-84-9

Updated

April 2017

Molecular Weight

174.17

Molecular Formula

C9H6N2O2

Synonyms

2,4-Diisocyanato-1-methylbenzene (9CI)
2,4-Diisocyanatotoluene
2,4-TDI
2,4-Toluenediisocyanate
2,4-Tolylenediisocyanate
4-Methyl-phenylene diisocyanate
4-Methyl-phenylene isocyanate
Cresorcinol diisocyanate
Desmodur T80
Di-isocyanate de toluylene (French)
Di-iso-cyanatoluene
Diisocyanat-toluol (German)
Hylene T
Isocyanic acid, 4-methyl-m-phenylene ester
Mondur TD
Mondur TD-80
Mondur TDS
Nacconate IOO
NCI-C50533
RCRA waste number U223
TDI
TDI (OSHA)
TDI-80
Tolueen-diisocyanaat (Dutch)
Toluen-disocianato (Italian)
Toluene 2,4-diisocyanate
Toluene diisocyanate
Toluene-2,4-diisocyanate
Toluene-2,4-diisocyanate (ACGIH:OSHA)
Toluilenodwuizocyjanian (Polish)
Toluylene-2,4-diisocyanate
Tolyene 2,4-diisocyanate
Tolylene-2,4-diisocyanate
Tuluylendiisocyanat (German)

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /rabbit 100 mg severeEJTXAZ 9,41,1976
skin /rabbit 500 mg open irritation test severeUCDS** 3/8/1973
skin /rabbit 500 mg/24H moderateEJTXAZ 9,41,1976
skin /rat 12 mg/8H moderateTOLED5 199,364,2010

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
micronucleus testinhalation/rat0.05 ppm/6H/4WCRTXB2 31,737,2001
morphological transformfibroblast/mouse0.2 mg/L/21D (-enzymatic activation step)EMMUEG 37,231,2001
mutation in microorganisms/Salmonella typhimurium0.033 mg/plate (+enzymatic activation step)CRTXB2 31,737,2001
mutation in microorganisms/Salmonella typhimurium100 µg/plate (-enzymatic activation step)ENMUDM 9(Suppl 9),1,1987
sister chromatid exchangeovary/hamster300 mg/LEMMUEG 13,133,1989
specific locus testlymphocyte/mouse75 mg/LEMMUEG 17,196,1991

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Human, lung Inhibitor Concentration (50 percent kill): 207 gm/L/3HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 27,174,2013
In Vitro/Human, lung Inhibitor Concentration (50 percent kill): 100 gm/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 27,174,2013
In Vitro/Human, lung Inhibitor Concentration (50 percent kill): 63 gm/L/24HIn Vitro Toxicity Studies: Other assaysTIVIEQ 27,174,2013
In Vitro/Human, lung tumor Inhibitor Concentration (50 percent kill): 7.3 gm/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 27,174,2013
In Vitro/Human, monocyte Inhibitor Concentration (20 percent kill): 500 µmol/L/2HIn Vitro Toxicity Studies: Other assaysTOLED5 199,51,2010
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 12 gm/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 27,174,2013
inhalation/guinea pig lethal concentration (50 percent kill): 13 ppm/4HLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Lung, Thorax, or Respiration: Changes in pulmonary vascular resistance

Lung, Thorax, or Respiration: Pleural effusion
AIHAAP 23,447,1962
inhalation/human lowest published toxic concentration: 20 ppb/2YLung, Thorax, or Respiration: Cough

Lung, Thorax, or Respiration: Sputum
PRSMA4 63,372,1970
inhalation/human lowest published toxic concentration: 500 ppbOlfaction: Other olfaction effects

Lung, Thorax, or Respiration: Other changes
JOCMA7 1,448,1959
inhalation/human lowest published toxic concentration: 80 ppbOlfaction: Other olfaction effects

Eye: Other eye effects

Lung, Thorax, or Respiration: Other changes
ATXKA8 19,364,1962
inhalation/mouse lethal concentration (50 percent kill): 10 ppm/4HLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Lung, Thorax, or Respiration: Changes in pulmonary vascular resistance
AIHAAP 23,447,1962
inhalation/mouse lethal concentration (50 percent kill): 10 ppm/4HENTOX* -,204,2005
inhalation/rabbit lethal concentration (50 percent kill): 11 ppm/4HBehavioral: Excitement

Lung, Thorax, or Respiration: Dyspnea

Gastrointestinal: Changes in structure or function of salivary glands
AIHAAP 23,447,1962
inhalation/rat lowest published toxic concentration: 0.004 gm/m3/4HLiver: Hepatitis (hepatocellular necrosis), zonalTPKVAL 9,37,1967
inhalation/rat lethal concentration (50 percent kill): 14 ppm/4HENTOX* -,204,2005
inhalation/rat lethal concentration (50 percent kill): 14 ppm/4HEye: Lacrimation

Behavioral: Excitement

Lung, Thorax, or Respiration: Dyspnea
AIHAAP 23,447,1962
inhalation/woman lowest published toxic concentration: 300 ppt/8H/5DLung, Thorax, or Respiration: Respiratory obstructionLANCAO 1,756,1980
intravenous/mouse lethal dose (50 percent kill): 56 mg/kgCSLNX* NX#07807
oral/rat lethal dose (50 percent kill): 5800 mg/kgGastrointestinal: Other changesAMIHAB 15,324,1957
oral/rat lethal dose (30 percent kill): 6.17 gm/kgENTOX* -,204,2005
oral/wild bird lethal dose (50 percent kill): 100 mg/kgAECTCV 12,355,1983
skin/rabbit lethal dose (50 percent kill): >16 mL/kgUCDS** 3/8/1973

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
inhalation/guinea pig lowest published toxic concentration: 3100 ppb/4H/5D- intermittentLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Blood: Changes in leukocyte (WBC) count
EXLRDA 11,145,1986
inhalation/mouse lowest published toxic concentration: 990 ppb/6H/14D- intermittentOlfaction: Other olfaction effectsJJATDK 15,207,1995
inhalation/rabbit lowest published toxic dose: 1500 ppb/71D- intermittentLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
AMIHAB 15,324,1957
inhalation/rabbit lowest published toxic concentration: 1500 ppb/6H/79D- intermittentLung, Thorax, or Respiration: Structural or functional change in trachea or bronchiAMIHAB 15,324,1957
inhalation/rat lowest published toxic concentration: 204 µg/m3/24H/84D- continuousBehavioral: Muscle contraction or spasticity

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase

Biochemical: Metabolism (intermediary): Lipids including transport
GISAAA 28(6),8,1963
inhalation/rat lowest published toxic concentration: 102 ppb/24H/7D- continuousLung, Thorax, or Respiration: Structural or functional change in trachea or bronchiJJATDK 14,369,1994
inhalation/rat lowest published toxic concentration: 26 ppm/6H/5W- intermittentLung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Lung, Thorax, or Respiration: Chronic pulmonary edema or congestion

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
NTIS** OTS0570993
intradermal/mouse lowest published toxic dose: 500 mg/kg/3D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)EXPDE* 15,322,2006
intratracheal/rat lowest published toxic dose: 48.84 µL/kg/21D- intermittentImmunological Including Allergic: Other immediate (humoral): uticaria, allergic rhinitis, serum sickness (multiple organ involvement)

Biochemical: Metabolism (intermediary): Histamines (including liberation not immunochemical in origin)
JPHSC* 109,606,2009
multiple/mouse lowest published toxic dose: 0.3 pph/3D- intermittentLung, Thorax, or Respiration: Bronchiolar constriction, including asthma

Lung, Thorax, or Respiration: Acute pulmonary edema

Lung, Thorax, or Respiration: Changes in lung weight
TOXID9 72,43,2003
oral/guinea pig lowest published toxic dose: 70 mg/kg/7D- intermittentImmunological Including Allergic: Other immediate (humoral): uticaria, allergic rhinitis, serum sickness (multiple organ involvement)

Biochemical: Metabolism (intermediary): Histamines (including liberation not immunochemical in origin)
ACPSI* 24,251,2003
oral/rat lowest published toxic dose: 15 gm/kg/10D- intermittentGastrointestinal: Other changes

Liver: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
AMIHAB 15,324,1957
skin/mouse lowest published toxic dose: 1 pph/3D- intermittentImmunological Including Allergic: Increased immune response

Biochemical: Metabolism (intermediary): Other proteins

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXCYAC 261,103,2009
skin/mouse lowest published toxic dose: 90 mg/kg/3D- intermittentSkin: After topical application: Dermatitis, allergic

Biochemical: Metabolism (intermediary): Other proteins

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOLED5 190,231,2009
skin/mouse lowest published toxic dose: 7.2 mg/kg/6D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)FCTOD7 48,1704,2010
skin/mouse lowest published toxic dose: 12 mg/kg/8D- intermittentBlood: Other changes

Skin: After topical application: Cutaneous sensitization (experimental)
TXCYAC 279,85,2011
skin/mouse lowest published toxic dose: 15 mg/kg/3D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXAPA9 184,46,2002
skin/mouse lowest published toxic dose: 800 mg/kg/4D- intermittentImmunological Including Allergic: Increased immune response

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
EJPHAZ 446,195,2002
skin/mouse lowest published toxic dose: 240 mg/kg/28D- intermittentImmunological Including Allergic: Increase in humoral responseTOSCF2 94,108,2006
skin/mouse lowest published toxic dose: 0.03 mL/kg/3D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)TOLED5 177,1,2008
skin/mouse lowest published toxic dose: 1.8 ul/kg/3D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)TOLED5 180,1,2008
skin/mouse lowest published toxic dose: 18 ul/kg/17D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)TOLED5 180,1,2008
skin/mouse lowest published toxic dose: 18.2 ul/kg/31D- intermittentSkin: After topical application: Cutaneous sensitization (experimental)

Immunological Including Allergic: Increased immune response
TOLED5 180,1,2008
skin/mouse lowest published toxic dose: 1.7 mg/kg/17D- intermittentImmunological Including Allergic: Increase in cellular immune response

Immunological Including Allergic: Increase in humoral response
TOLED5 181,163,2008
skin/mouse lowest published toxic dose: 90 mg/kg/3D- intermittentImmunological Including Allergic: Increase in humoral response

Biochemical: Metabolism (intermediary): Other proteins

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXCYAC 250,116,2008
skin/mouse lowest published toxic dose: 4.8 mg/kg/8D- intermittentLung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 -,11,2009

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 0.005 ppm;short term exposure limit 0.02 ppm (sen)DTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Not classifiable as a human carcinogenDTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 39,287,1986
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 71,865,1999
International Agency for Research on Cancer (IARC)Cancer Review:Human No Adequate DataIMEMDT 39,287,1986
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 71,865,1999
International Agency for Research on Cancer (IARC)Cancer Review:Group 2BIMEMDT 71,865,1999
TOXICOLOGY REVIEWAOHYA3 17,143,1974
TOXICOLOGY REVIEWJJOMDZ 15,808,1973
TOXICOLOGY REVIEWCMTVAS 10(3),49,1973
TOXICOLOGY REVIEWCRTXB2 31,737,2001
TOXICOLOGY REVIEWMUREAV 539,77,2003
TOXICOLOGY REVIEWMUREAV 567,227,2004
TOXICOLOGY REVIEWDIMON* 46,551,2000
TOXICOLOGY REVIEWENTOX* -,204,2005
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWMUREAV 681,93,2009
TOXICOLOGY REVIEWMUREAV 802,1,2016

Standards and Regulations

OrganizationStandardReference
Mine Safety and Health Administration (MSHA) STANDARDair-ceiling concentration 0.02 ppm (0.14 mg/m3)DTLVS* 3,260,1971
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN check ACGIH TLV;
Occupational Exposure Limit IN SINGAPORE, VIETNAM check ACGIH TLV
Occupational Exposure Limit-ARAB Republic of Egypttime-weighted average 0.02 ppm (0.14 mg/m3), JAN1993
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 (0.035 mg/m3);KZW 0.02 ppm (0.14 mg/m3), sen, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 0.005 ppm (0.037 mg/m3), MAR2002
Occupational Exposure Limit-BELGIUMshort term exposure limit 0.02 ppm (0.14 mg/m3), MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 0.005 ppm (0.035 mg/m3), carc, MAY2011
Occupational Exposure Limit-HUNGARYceiling concentration 0.035 mg/m3, Carcinogen, SEP2000
Occupational Exposure Limit-ICELANDtime-weighted average 0.005 ppm (0.04 mg/m3), short term exposure limit 0.01 ppm (0.07 mg/m3), sen, NOV2011
Occupational Exposure Limit-JAPANOccupational Exposure Limit 0.005 ppm, skin, 2B carc, s1 sen, MAY2012
Occupational Exposure Limit-JAPANceiling concentration 0.02 ppm (0.14 mg/m3), MAY2012
Occupational Exposure Limit-KOREAtime-weighted average 0.005 ppm (0.04 mg/m3), short term exposure limit 0.02 ppm (0.15 mg/m3), 2006
Occupational Exposure Limit-MEXICOtime-weighted average 0.02 ppm (0.14 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-NORWAYtime-weighted average 0.005 ppm (0.035 mg/m3), JAN1999
Occupational Exposure Limit-PERUtime-weighted average 0,005 ppm (0,036 mg/m3); short term exposure limit 0,02 ppm (0,014 mg/m3), JUL2005
Occupational Exposure Limit-POLANDMAC(time-weighted average) 0.035 mg/m3, MAC(short term exposure limit) 0.070 mg/m3, JAN1999
Occupational Exposure Limit-RUSSIAshort term exposure limit 0.05 mg/m3, JUN2003
Occupational Exposure Limit-SWEDENtime-weighted average 0.002 ppm (0.014 mg/m3), Carcinogen, Sen, JUN2005
Occupational Exposure Limit-SWEDENceiling concentration 0.005 ppm (0.04 mg/m3), JUN2005
Occupational Exposure Limit-SWITZERLANDceiling concentration 0.02 mg(NCO)/m3, skin, sen, JAN2011
Occupational Exposure Limit-THAILANDtime-weighted average 0.02 ppm (0.14 mg/m3), JAN1993
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 0.04 mg/m3, 2003
Occupational Exposure Limit-THE PHILIPPINEStime-weighted average 0.02 ppm (0.14 mg/m3), JAN1993
Occupational Exposure Limit-TURKEYtime-weighted average 0.02 ppm (0.14 mg/m3), JAN1993
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction)ceiling concentration 0.02 ppm (0.14 mg/m3)CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Federal Contractors)ceiling concentration 0.02 ppm (0.14 mg/m3)CFRGBR 41,50-204.50,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry)ceiling concentration 0.02 ppm (0.14 mg/m3)CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards)ceiling concentration 0.02 ppm (0.14 mg/m3)CFRGBR 29,1915.1000,1993

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO TOLUENE DIISOCYANATE-airCarcinogen lowest feasible concNIOSH* DHHS#92-100,1992
National Occupational Exposure Survey 1983Hazard Code 73390; Number of Industries 19; Total Number of Facilities 838; Number of Occupations 30; Total Number of Employees Exposed 10921; Total Number of Female Employees Exposed 545
National Occupational Hazard Survey 1974Hazard Code 73390; Number of Industries 47; Total Number of Facilities 2310; Number of Occupations 54; Total Number of Employees Exposed 26654

Status in Federal Agencies

OrganizationReference
EPA TSCA Section 8(b) CHEMICAL INVENTORY
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH Analytical Method, 1994: Isocyanates, monomeric, 5521
NIOSH Analytical Method, 1994: Toluene-2,4-diisocyanate, 2535
NTP 11th Report on Carcinogens,2004:Reasonably anticipated to be a human carcinogen
OSHA ANALYTICAL METHOD #18, SUPERSEDED BY #42
OSHA ANALYTICAL METHOD #33
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