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Registry of Toxic Effects of Chemical Substances (RTECS)

Aniline, 4,4'-methylenedi-

RTECS #

BY5425000

CAS #

101-77-9

Updated

October 2015

Molecular Weight

198.29

Molecular Formula

C13H14N2

Synonyms

4-(4-Aminobenzyl)aniline
4,4'-Diaminodiphenylmethan (German)
4,4'-Diaminodiphenylmethane
4,4'-Diphenylmethanediamine
4,4'-Methylene dianiline
4,4'-Methylenebis(benzeneamine)
4,4'-Methylenebisaniline
4,4'-Methylenedianiline
4,4-Methylenedianiline (ACGIH)
Ancamine TL
Araldite hardener 972
Avaldite HT 972
Benzenamine, 4,4'-methylenebis-
Bis(4-aminophenyl)methane
Bis(p-aminophenyl)methane
Bis-p-aminofenylmethan (Czech)
Curithane
Dadpm
DAPM
Di-(4-aminophenyl)methane
Diaminodiphenylmethane
Dianilinomethane
Epicure DDM
Epikure DDM
HT 972
Jeffamine AP-20
MDA
Methylenebis(aniline)
Methylenedianiline
p,p'-Diaminodifenylmethan (Czech)
p,p'-Diaminodiphenylmethane
p,p'-Methylenedianiline
Sumicure M
Tonox

Skin and Eye Irritation and References

Route/OrganismDoseEffectReference
eye /rabbit 100 mg/24H moderate85JCAE -,481,1986
skin /child 0.5%/2DCODEDG 60,346,2009
skin /man 0.5%/2DCODEDG 60,346,2009
skin /woman 0.5%/2DCODEDG 60,346,2009

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysisfibroblast/hamster125 mg/L/3HMUREAV 497,29,2001
DNA adductother cell types/human50 gm/L/24HTXCYAC 196,65,2004
DNA Damageliver/human10 µmol/L/4HTXAPA9 182,219,2002
DNA Damageother cell types/human10 µmol/L/4HTXAPA9 182,219,2002
DNA Damageliver/rat10 µmol/L/4HTXAPA9 182,219,2002
DNA Damageother cell types/rat100 µmol/L/4HTXAPA9 182,219,2002
DNA Damageintraperitoneal/rat370 µmol/kgCRNGDP 2,1317,1981
DNA Damageliver/rat2 mmol/LMUREAV 368,59,1996
DNA Damageoral/mouse250 mg/kgMUREAV 440,1,1999
micronucleus testfibroblast/hamster50 mg/LTOSCF2 58,102,2000
micronucleus testintraperitoneal/rat400 mg/kgMUREAV 583,133,2005
micronucleus testoral/rat875 mg/kg/14DMUREAV 780-781,2,2015
mutation in microorganisms/Salmonella typhimurium50 µg/plate/20M (+enzymatic activation step)MUTAEX 20,217,2005
mutation in microorganisms/Salmonella typhimurium50 µg/plate/48H (+enzymatic activation step)MUTAEX 20,217,2005
mutation in microorganisms/Salmonella typhimurium250 µg/plate (+enzymatic activation step)MUREAV 67,123,1979
mutation in microorganisms/Salmonella typhimurium1 nmol/plate/20MEMMUEG 38,268,2001
sister chromatid exchangeintraperitoneal/mouse9 mg/kgMUREAV 108,225,1983
Unscheduled DNA Synthesisliver/rat10 µmol/LMUREAV 204,683,1988

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/rat lowest published toxic dose: 320 mg/kgTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors

Kidney, Ureter, and Bladder: Kidney tumors
NATUAS 219,1162,1968
subcutaneous/rat lowest published toxic dose: 1410 mg/kgTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors
NATWAY 57,247,1970

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
intraperitoneal/rat lethal dose (50 percent kill): 193 mg/kgZHYGAM 20,393,1974
oral/Dog lowest published lethal dose: 300 mg/kgGastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Nausea or vomiting
TXCYAC 11,185,1978
oral/guinea pig lethal dose (50 percent kill): 260 mg/kgZHYGAM 20,393,1974
oral/man lowest published toxic dose: 8420 µg/kgBehavioral: Rigidity (includes catalepsy)

Liver: Jaundice, other or unclassified

Liver: Other changes
BMJOAE 1,514,1966
oral/mouse lethal dose (50 percent kill): 264 mg/kgNTIS** OTS0555063
oral/rabbit lethal dose (50 percent kill): 620 mg/kgZHYGAM 20,393,1974
oral/rat lethal dose (50 percent kill): 517 mg/kgNTIS** OTS0539752
oral/rat lowest published toxic dose: 50 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 44,393,2005
oral/rat lowest published toxic dose: 25 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Changes in liver weight

Endocrine: Changes in spleen weight
TOXID9 78,312,2004
oral/rat lethal dose (50 percent kill): 100 mg/kgLiver: Multiple effectsTOXID9 78,312,2004
oral/rat lowest published toxic dose: 25 mg/kgLiver: Liver function tests impaired

Liver: Other changes

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
TOLED5 169,13,2007
oral/rat lowest published toxic dose: 81 mg/kgKidney, Ureter, and Bladder: Other changesTXCYAC 246,91,2008
skin/rabbit lethal dose (50 percent kill): 200 mg/kgNTIS** OTS0555064
subcutaneous/Dog lowest published lethal dose: 400 mg/kgAEXPBL 58,167,1907
subcutaneous/rat lethal dose (50 percent kill): 200 mg/kgNATWAY 57,247,1970

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
oral/Dog lowest published toxic dose: 456 mg/kg/15W- intermittentLiver: Fatty liver degeneration

Kidney, Ureter, and Bladder: Interstitial nephritis

Blood: Normocytic anemia
JJATDK 11,367,1991
oral/rat lowest published toxic dose: 7980 mg/kg/19W- continuousEndocrine: Thyroid weight (goiter)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
JJIND8 72,471,1984
oral/rat lowest published toxic dose: 243 mg/kg/3D- intermittentBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesTXCYAC 246,91,2008
oral/rat lowest published toxic dose: 405 mg/kg/5D- intermittentLiver: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXCYAC 246,91,2008
oral/rat lowest published toxic dose: 218.4 mg/kg/14D- intermittentLiver: TumorsMUREAV 780-781,2,2015
oral/rat lowest published toxic dose: 875 mg/kg/14D- intermittentLiver: Changes in liver weightMUREAV 780-781,2,2015
oral/rat lowest published toxic dose: 1120 mg/kg/28D- intermittentLiver: Changes in liver weightMUREAV 780-781,2,2015
oral/rat lowest published toxic dose: 16800 mg/kg/40W- continuousLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
TXAPA9 48,145,1979
oral/rat lowest published toxic dose: 6972 mg/kg/12W- intermittentLiver: Other changes

Blood: Changes in spleen

Biochemical: Metabolism (intermediary): Other proteins
APPFAR 26,352,1969
oral/rat lowest published toxic dose: 1386 mg/kg/1W- intermittentBehavioral: Ataxia

Liver: Changes in liver weight

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
NTIS** OTS0555074

Reviews

OrganizationStandardReference
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-time-weighted average 0.1 ppm (skin)DTLVS* TLV/BEI,2013
American Conference of Governmental Industrial Hygienists (ACGIH)Threshold Limit Value-Confirmed animal carcinogenDTLVS* TLV/BEI,2013
International Agency for Research on Cancer (IARC)Cancer Review:Animal Sufficient EvidenceIMEMDT 39,347,1986
International Agency for Research on Cancer (IARC)Cancer Review:Human No Adequate DataIMEMDT 39,347,1986
International Agency for Research on Cancer (IARC)Cancer Review:Group 2BIMSUDL 7,56,1987
TOXICOLOGY REVIEWNTIS** DE85-017376
TOXICOLOGY REVIEWTOLED5 134,39,2002
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWMUREAV 567,227,2004
TOXICOLOGY REVIEWDIMON* 39,678,1993
TOXICOLOGY REVIEWHUTOX* -,649,1996
TOXICOLOGY REVIEWTXAPA9 243,154,2010

Standards and Regulations

OrganizationStandardReference
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 0.1 ppm (0.81 mg/m3), JUL2008
Occupational Exposure Limit-AUSTRIATRK-TMW 0.1 mg/m3;KZW 0.4 mg/m3, skin, sen, 2007
Occupational Exposure Limit-BELGIUMtime-weighted average 0.1 ppm (0.82 mg/m3), Skin, Carcinogen, MAR2002
Occupational Exposure Limit-DENMARKtime-weighted average 0.1 ppm (0.8 mg/m3), carc, MAY2011
Occupational Exposure Limit-HUNGARYceiling concentration 0.81 mg/m3, Carcinogen, SEP2000
Occupational Exposure Limit-ICELANDtime-weighted average 0.1 ppm (0.8 mg/m3), carc, NOV2011
Occupational Exposure Limit-JAPANOccupational Exposure Limit 0.4 mg/m3, 2B carc, skin, MAY2012
Occupational Exposure Limit-KOREAtime-weighted average 0.1 ppm (0.8 mg/m3), skin, 2006
Occupational Exposure Limit-NEW ZEALANDtime-weighted average 0.01 ppm (0.08 mg/m3), skin, JAN2002
Occupational Exposure Limit-NORWAYtime-weighted average 0.1 ppm (0.8 mg/m3), JAN1999
Occupational Exposure Limit-PERUtime-weighted average 0.1 ppm (0.81 mg/m3), JUL2005
Occupational Exposure Limit-SWEDENGroup B Carcinogen, JUN2005
Occupational Exposure Limit-SWITZERLANDMAK-week 0.1 mg/m3, carc 2, skin, sen, JAN2011
Occupational Exposure Limit-THE NETHERLANDSMAC-TGG 0.2 mg/m3, Skin, 2003
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 0.01 ppm (0.08 mg/m3), skin, OCT2007

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO 4,4'-METHYLENEDIANILINE-airCarcinogen lowest feasible conc.NIOSH* DHHS #92-100,1992
National Occupational Exposure Survey 1983Hazard Code 83609; Number of Industries 25; Total Number of Facilities 741; Number of Occupations 30; Total Number of Employees Exposed 15170; Total Number of Female Employees Exposed 3407
National Occupational Hazard Survey 1974Hazard Code 83609; Number of Industries 16; Total Number of Facilities 363; Number of Occupations 27; Total Number of Employees Exposed 9163

Status in Federal Agencies

OrganizationReference
ATSDR TOXICOLOGY PROFILE (NTIS** PB/99/102568/AS)
EPA TSCA 8(a) PRELIMINARY ASSESSMENT INFORMATION, FINAL RULEFEREAC 47,26992,82
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: 4,4'-Methylenedianiline, 5029
NIOSH CURRENT INTELLIGENCE BULLETIN 8, 1976 AND BULLETIN 47, 1986
NTP 10th Report on Carcinogens,2002:Reasonably anticipated to be a human carcinogen
On EPA IRIS database
OSHA ANALYTICAL METHOD #ID-57
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