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

RTECS #

CZ6300000

CAS #

584-84-9
See: NMAM or OSHA Methods

Updated

March 2019

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/Organism	Dose	Effect	Reference
eye /rabbit	100 mg	severe	EJTXAZ 9,41,1976
skin /rabbit	500 mg open irritation test	severe	UCDS** 3/8/1973
skin /rabbit	500 mg/24H	moderate	EJTXAZ 9,41,1976
skin /rat	12 mg/8H	moderate	TOLED5 199,364,2010

Mutation Data and Reference

System Test	Route/Organism/Tissue	Dose	Reference
micronucleus test	inhalation/rat	0.05 ppm/6H/4W	CRTXB2 31,737,2001
morphological transform	fibroblast/mouse	0.2 mg/L/21D (-enzymatic activation step)	EMMUEG 37,231,2001
mutation in microorganisms	/Salmonella typhimurium	0.033 mg/plate (+enzymatic activation step)	CRTXB2 31,737,2001
mutation in microorganisms	/Salmonella typhimurium	100 µg/plate (-enzymatic activation step)	ENMUDM 9(Suppl 9),1,1987
sister chromatid exchange	ovary/hamster	300 mg/L	EMMUEG 13,133,1989
specific locus test	lymphocyte/mouse	75 mg/L	EMMUEG 17,196,1991

Acute Toxicity Data and References

Route/Organism	Dose	Effect	Reference
In Vitro/Human, leukemia cells	Inhibitor Concentration Low: >10 µmol/L	In Vitro Toxicity Studies: Cell viability (dye exclusion): trypan blue assay etc.	TOLED5 239,32,2015
In Vitro/Human, leukemia cells	Inhibitor Concentration (50 percent kill): 1762 µmol/L/24H	In Vitro Toxicity Studies: Cell viability (dye exclusion): trypan blue assay etc.	TOLED5 239,32,2015
In Vitro/Human, lung	Inhibitor Concentration (20 percent kill): 0.15 mmol/L	In Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.	TIVIEQ 30,274,2015
In Vitro/Human, lung	Inhibitor Concentration (50 percent kill): 207 gm/L/3H	In 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/24H	In 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/24H	In Vitro Toxicity Studies: Other assays	TIVIEQ 27,174,2013
In Vitro/Human, lung tumor	Inhibitor Concentration (50 percent kill): 7.3 gm/L/24H	In 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/2H	In Vitro Toxicity Studies: Other assays	TOLED5 199,51,2010
In Vitro/Mouse, fibroblast	Inhibitor Concentration (50 percent kill): 12 gm/L/24H	In 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/4H	Lung, 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/2Y	Lung, Thorax, or Respiration: Cough Lung, Thorax, or Respiration: Sputum	PRSMA4 63,372,1970
inhalation/human	lowest published toxic concentration: 500 ppb	Olfaction: Other olfaction effects Lung, Thorax, or Respiration: Other changes	JOCMA7 1,448,1959
inhalation/human	lowest published toxic concentration: 80 ppb	Olfaction: 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/4H	Lung, 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/4H		ENTOX* -,204,2005
inhalation/rabbit	lethal concentration (50 percent kill): 11 ppm/4H	Behavioral: 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/m³/4H	Liver: Hepatitis (hepatocellular necrosis), zonal	TPKVAL 9,37,1967
inhalation/rat	lethal concentration (50 percent kill): 14 ppm/4H		ENTOX* -,204,2005
inhalation/rat	lethal concentration (50 percent kill): 14 ppm/4H	Eye: Lacrimation Behavioral: Excitement Lung, Thorax, or Respiration: Dyspnea	AIHAAP 23,447,1962
inhalation/woman	lowest published toxic concentration: 300 ppt/8H/5D	Lung, Thorax, or Respiration: Respiratory obstruction	LANCAO 1,756,1980
intravenous/mouse	lethal dose (50 percent kill): 56 mg/kg		CSLNX* NX#07807
oral/rat	lethal dose (50 percent kill): 5800 mg/kg	Gastrointestinal: Other changes	AMIHAB 15,324,1957
oral/rat	lethal dose (30 percent kill): 6.17 gm/kg		ENTOX* -,204,2005
oral/wild bird	lethal dose (50 percent kill): 100 mg/kg		AECTCV 12,355,1983
skin/rabbit	lethal dose (50 percent kill): >16 mL/kg		UCDS** 3/8/1973

Other Multiple Dose Data and References

Route/Organism	Dose	Effect	Reference
inhalation/guinea pig	lowest published toxic concentration: 3100 ppb/4H/5D- intermittent	Lung, 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- intermittent	Olfaction: Other olfaction effects	JJATDK 15,207,1995
inhalation/rabbit	lowest published toxic dose: 1500 ppb/71D- intermittent	Lung, 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- intermittent	Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi	AMIHAB 15,324,1957
inhalation/rat	lowest published toxic concentration: 204 µg/m³/24H/84D- continuous	Behavioral: 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- continuous	Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi	JJATDK 14,369,1994
inhalation/rat	lowest published toxic concentration: 26 ppm/6H/5W- intermittent	Lung, 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- intermittent	Skin: After topical application: Cutaneous sensitization (experimental)	EXPDE* 15,322,2006
intratracheal/rat	lowest published toxic dose: 48.84 µL/kg/21D- intermittent	Immunological 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- intermittent	Lung, 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- intermittent	Immunological 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- intermittent	Gastrointestinal: 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- intermittent	Immunological 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- intermittent	Skin: 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- intermittent	Skin: After topical application: Cutaneous sensitization (experimental)	FCTOD7 48,1704,2010
skin/mouse	lowest published toxic dose: 12 mg/kg/8D- intermittent	Blood: Other changes Skin: After topical application: Cutaneous sensitization (experimental)	TXCYAC 279,85,2011
skin/mouse	lowest published toxic dose: 30 mg/kg/3D- intermittent	Blood: Other changes Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation	TOLED5 280,133,2017
skin/mouse	lowest published toxic dose: 15 mg/kg/3D- intermittent	Skin: 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- intermittent	Immunological 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- intermittent	Immunological Including Allergic: Increase in humoral response	TOSCF2 94,108,2006
skin/mouse	lowest published toxic dose: 0.03 mL/kg/3D- intermittent	Skin: After topical application: Cutaneous sensitization (experimental)	TOLED5 177,1,2008
skin/mouse	lowest published toxic dose: 1.8 ul/kg/3D- intermittent	Skin: After topical application: Cutaneous sensitization (experimental)	TOLED5 180,1,2008
skin/mouse	lowest published toxic dose: 18 ul/kg/17D- intermittent	Skin: After topical application: Cutaneous sensitization (experimental)	TOLED5 180,1,2008
skin/mouse	lowest published toxic dose: 18.2 ul/kg/31D- intermittent	Skin: 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- intermittent	Immunological 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- intermittent	Immunological 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- intermittent	Lung, Thorax, or Respiration: Other changes Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation	TOXID9 -,11,2009

Reviews

Organization	Standard	Reference
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 carcinogen	DTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)	Cancer Review:Animal Sufficient Evidence	IMEMDT 39,287,1986
International Agency for Research on Cancer (IARC)	Cancer Review:Animal Sufficient Evidence	IMEMDT 71,865,1999
International Agency for Research on Cancer (IARC)	Cancer Review:Human No Adequate Data	IMEMDT 39,287,1986
International Agency for Research on Cancer (IARC)	Cancer Review:Human Inadequate Evidence	IMEMDT 71,865,1999
International Agency for Research on Cancer (IARC)	Cancer Review:Group 2B	IMEMDT 71,865,1999
TOXICOLOGY REVIEW		AOHYA3 17,143,1974
TOXICOLOGY REVIEW		JJOMDZ 15,808,1973
TOXICOLOGY REVIEW		CMTVAS 10(3),49,1973
TOXICOLOGY REVIEW		CRTXB2 31,737,2001
TOXICOLOGY REVIEW		MUREAV 539,77,2003
TOXICOLOGY REVIEW		MUREAV 567,227,2004
TOXICOLOGY REVIEW		DIMON* 46,551,2000
TOXICOLOGY REVIEW		ENTOX* -,204,2005
TOXICOLOGY REVIEW		MUREAV 584,1,2005
TOXICOLOGY REVIEW		MUREAV 681,93,2009
TOXICOLOGY REVIEW		MUREAV 802,1,2016
TOXICOLOGY REVIEW		RTOPDW 56,54,2010
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 (0.14 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 Egypt	time-weighted average 0.02 ppm (0.14 mg/m³), JAN1993
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 (0.035 mg/m³);KZW 0.02 ppm (0.14 mg/m³), sen, 2007
Occupational Exposure Limit-BELGIUM	time-weighted average 0.005 ppm (0.037 mg/m³), MAR2002
Occupational Exposure Limit-BELGIUM	short term exposure limit 0.02 ppm (0.14 mg/m³), MAR2002
Occupational Exposure Limit-DENMARK	time-weighted average 0.005 ppm (0.035 mg/m³), carc, MAY2011
Occupational Exposure Limit-HUNGARY	ceiling concentration 0.035 mg/m³, Carcinogen, SEP2000
Occupational Exposure Limit-ICELAND	time-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-JAPAN	Occupational Exposure Limit 0.005 ppm, skin, 2B carc, s1 sen, MAY2012
Occupational Exposure Limit-JAPAN	ceiling concentration 0.02 ppm (0.14 mg/m³), MAY2012
Occupational Exposure Limit-KOREA	time-weighted average 0.005 ppm (0.04 mg/m³), short term exposure limit 0.02 ppm (0.15 mg/m³), 2006
Occupational Exposure Limit-MEXICO	time-weighted average 0.02 ppm (0.14 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-NORWAY	time-weighted average 0.005 ppm (0.035 mg/m³), JAN1999
Occupational Exposure Limit-PERU	time-weighted average 0,005 ppm (0,036 mg/m³); short term exposure limit 0,02 ppm (0,014 mg/m³), JUL2005
Occupational Exposure Limit-POLAND	MAC(time-weighted average) 0.035 mg/m³, MAC(short term exposure limit) 0.070 mg/m³, JAN1999
Occupational Exposure Limit-RUSSIA	short term exposure limit 0.05 mg/m³, JUN2003
Occupational Exposure Limit-SWEDEN	time-weighted average 0.002 ppm (0.014 mg/m³), Carcinogen, Sen, JUN2005
Occupational Exposure Limit-SWEDEN	ceiling concentration 0.005 ppm (0.04 mg/m³), 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 (0.14 mg/m³), JAN1993
Occupational Exposure Limit-THE NETHERLANDS	MAC-TGG 0.04 mg/m³, 2003
Occupational Exposure Limit-THE PHILIPPINES	time-weighted average 0.02 ppm (0.14 mg/m³), JAN1993
Occupational Exposure Limit-TURKEY	time-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

Organization	Standard	Reference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO TOLUENE DIISOCYANATE-air	Carcinogen lowest feasible conc	NIOSH* DHHS#92-100,1992
National Occupational Exposure Survey 1983	Hazard 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 1974	Hazard 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

Organization	Reference
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 14th Report on Carcinogens,2016:Reasonably anticipated to be human carcinogen
OSHA ANALYTICAL METHOD #18, SUPERSEDED BY #42
OSHA ANALYTICAL METHOD #33

Page last reviewed: November 16, 2018

Content source: National Institute for Occupational Safety and Health