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Aniline, 4,4' - methylenedi -

RTECS #: BY5425000

CAS #: 101-77-9


UPDATE: May 2009 MW: 198.29 MF: C13H14N2


NOTE:

TABLE OF CONTENTS:
  1. SYNONYMS:
  2. SKIN AND EYE IRRITATION DATA:
  3. MUTATION DATA:
  4. TUMORIGENIC DATA:
  5. ACUTE TOXICITY DATA:
  6. OTHER MULTIPLE DOSE DATA:
  7. REVIEWS:
  8. STANDARDS AND REGULATIONS:
  9. NIOSH DOCUMENTATION AND SURVEILLANCE:
  10. STATUS IN FEDERAL AGENCIES:
  11. REFERENCES:

SYNONYMS:

  1. 4,4' - Diaminodiphenylmethan (German)
  2. 4,4' - Diaminodiphenylmethane
  3. 4,4' - Diphenylmethanediamine
  4. 4,4' - Methylene dianiline
  5. 4,4' - Methylenebis (benzeneamine)
  6. 4,4' - Methylenebisaniline
  7. 4,4' - Methylenedianiline
  8. 4,4 - Methylenedianiline (ACGIH)
  9. 4 - (4 - Aminobenzyl) aniline
  10. Ancamine TL
  11. Araldite hardener 972
  12. Avaldite HT 972
  13. Benzenamine, 4,4' - methylenebis -
  14. Bis (4 - aminophenyl) methane
  15. Bis (p - aminophenyl) methane
  16. Bis - p - aminofenylmethan (Czech)
  17. Curithane
  1. DAPM
  2. Dadpm
  3. Di - (4 - aminophenyl) methane
  4. Diaminodiphenylmethane
  5. Dianilinomethane
  6. Epicure DDM
  7. Epikure DDM
  8. HT 972
  9. Jeffamine AP - 20
  10. MDA
  11. Methylenebis (aniline)
  12. Methylenedianiline
  13. Sumicure M
  14. Tonox
  15. p,p' - Diaminodifenylmethan (Czech)
  16. p,p' - Diaminodiphenylmethane
  17. p,p' - Methylenedianiline


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
eye
rabbit
100 mg/24 hour moderate 85JCAE -,481,1986


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE
DOSE REFERENCE
cytogenetic analysis hamster fibroblast 125 mg/L/3 hour MUREAV 497,29,2001
DNA adduct human other cell types 50 gm/L/24 hour TXCYAC 196,65,2004
DNA damage human liver 10 µmol/L/4 hour TXAPA9 182,219,2002
DNA damage human other cell types 10 µmol/L/4 hour TXAPA9 182,219,2002
DNA damage oral
mouse
250 mg/kg MUREAV 440,1,1999
DNA damage intraperitoneal
rat
370 µmol/kg CRNGDP 2,1317,1981
DNA damage rat liver 2 mmol/L MUREAV 368,59,1996
DNA damage rat liver 10 µmol/L/4 hour TXAPA9 182,219,2002
DNA damage rat other cell types 100 µmol/L/4 hour TXAPA9 182,219,2002
unscheduled DNA synthesis rat liver 10 µmol/L MUREAV 204,683,1988
mutation in microorganisms Salmonella typhimurium 250 µg/plate (+enzymatic activation step) MUREAV 67,123,1979
mutation in microorganisms Salmonella typhimurium 1 nmol/plate/20 minute EMMUEG 38,268,2001
mutation in microorganisms Salmonella typhimurium 50 µg/plate/20 minute (+enzymatic activation step) MUTAEX 20,217,2005
mutation in microorganisms Salmonella typhimurium 50 µg/plate/48 hour (+enzymatic activation step) MUTAEX 20,217,2005
micronucleus test hamster fibroblast 50 mg/L TOSCF2 58,102,2000
micronucleus test intraperitoneal
rat
400 mg/kg MUREAV 583,133,2005
sister chromatid exchange intraperitoneal
mouse
9 mg/kg MUREAV 108,225,1983


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
N/R
N/R N/R N/R


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
oral
rat
lowest published toxic dose: 320 mg/kg Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors

Kidney, Ureter, and Bladder: Kidney tumors
NATUAS 219,1162,1968
subcutaneous
rat
lowest published toxic dose: 1,410 mg/kg Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors
NATWAY 57,247,1970


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
intraperitoneal
rat
lethal dose (50 percent kill): 193 mg/kg N/R ZHYGAM 20,393,1974
oral
dog
lowest published lethal dose: 300 mg/kg Gastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Nausea or vomiting
TXCYAC 11,185,1978
oral
guinea pig
lethal dose (50 percent kill): 260 mg/kg N/R ZHYGAM 20,393,1974
oral
man
lowest published toxic dose: 8,420 µg/kg Behavioral: Rigidity (includes catalepsy)

Liver: Jaundice, other or unclassified

Liver: Other changes
BMJOAE 1,514,1966
oral
mouse
lethal dose (50 percent kill): 264 mg/kg N/R NTIS** OTS0555063
oral
rat
lethal dose (50 percent kill): 517 mg/kg N/R NTIS** OTS0539752
oral
rat
lowest published toxic dose: 50 mg/kg Liver: 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/kg Liver: 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/kg Liver: Multiple effects TOXID9 78,312,2004
oral
rat
lowest published toxic dose: 25 mg/kg Liver: 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/kg Kidney, Ureter, and Bladder: Other changes TXCYAC 246,91,2008
oral
rabbit
lethal dose (50 percent kill): 620 mg/kg N/R ZHYGAM 20,393,1974
subcutaneous
dog
lowest published lethal dose: 400 mg/kg N/R AEXPBL 58,167,1907
subcutaneous
rat
lethal dose (50 percent kill): 200 mg/kg N/R NATWAY 57,247,1970
skin
rabbit
lethal dose (50 percent kill): 200 mg/kg N/R NTIS** OTS0555064


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
oral
dog
lowest published toxic dose: 456 mg/kg/15 week- intermittent Liver: Fatty liver degeneration

Kidney, Ureter, and Bladder: Interstitial nephritis

Blood: Normocytic anemia
JJATDK 11,367,1991
oral
rat
lowest published toxic dose: 16,800 mg/kg/40 week- continuous Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
TXAPA9 48,145,1979
oral
rat
lowest published toxic dose: 6,972 mg/kg/12 week- intermittent Liver: Other changes

Blood: Changes in spleen

Biochemical: Metabolism (intermediary): Other proteins
APPFAR 26,352,1969
oral
rat
lowest published toxic dose: 1,386 mg/kg/1 week- intermittent Behavioral: Ataxia

Liver: Changes in liver weight

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
NTIS** OTS0555074
oral
rat
lowest published toxic dose: 7,980 mg/kg/19 week- continuous Endocrine: 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/3 day- intermittent Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases TXCYAC 246,91,2008
oral
rat
lowest published toxic dose: 405 mg/kg/5 day- intermittent Liver: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXCYAC 246,91,2008


REVIEWS:

ORGANIZATION STANDARD
REFERENCE

American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average 0.1 ppm (skin) DTLVS* TLV/BEI,2007
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value Confirmed animal carcinogen DTLVS* TLV/BEI,2007
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 39,347,1986
International Agency for Research on Cancer (IARC) Cancer Review Human No Adequate Data IMEMDT 39,347,1986
International Agency for Research on Cancer (IARC) Cancer Review Group 2B IMSUDL 7,56,1987
TOXICOLOGY REVIEW
NTIS** DE85-017376
TOXICOLOGY REVIEW
TOLED5 134,39,2002
TOXICOLOGY REVIEW
MUREAV 543,201,2003
TOXICOLOGY REVIEW
MUREAV 567,227,2004
TOXICOLOGY REVIEW
DIMON* 39,678,1993
TOXICOLOGY REVIEW
HUTOX* -,649,1996


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE

Occupational Exposure Limit - AUSTRALIA time-weighted average 0.1 ppm (0.81 mg/m3), JUL2008
Occupational Exposure Limit - AUSTRIA TRK 0.1 mg/m3, JAN 2006
Occupational Exposure Limit - BELGIUM time-weighted average 0.1 ppm (0.82 mg/m3), Skin, Carcinogen, MAR2002
Occupational Exposure Limit - DENMARK time-weighted average 0.1 ppm (0.8 mg/m3), OCT 2002
Occupational Exposure Limit - HUNGARY ceiling concentration 0.81 mg/m3, Carcinogen, SEP2000
Occupational Exposure Limit - JAPAN Occupational Exposure Limit 0.4 mg/m3, skin, 2B carcinogen, APR2007
Occupational Exposure Limit - KOREA time-weighted average 0.1 ppm (0.8 mg/m3), skin, 2006
Occupational Exposure Limit - THE NETHERLANDS MAC-TGG 0.2 mg/m3, Skin, 2003
Occupational Exposure Limit - NEW ZEALAND time-weighted average 0.01 ppm (0.08 mg/m3), skin, JAN2002
Occupational Exposure Limit - NORWAY time-weighted average 0.1 ppm (0.8 mg/m3), JAN1999
Occupational Exposure Limit - SWEDEN Group B Carcinogen, JUN2005
Occupational Exposure Limit - SWITZERLAND MAK- week 0.1 mg/m3, Skin, Carcinogen, DEC2006
Occupational Exposure Limit - UNITED KINGDOM time-weighted average 0.01 ppm (0.08 mg/m3) (skin), 2005
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

Confirmed animal carcinogen
Occupational Exposure Limit IN SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
Confirmed animal carcinogen


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE

National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO 4,4'-METHYLENEDIANILINE-air Carcinogen lowest feasible conc. NIOSH* DHHS #92-100,1992
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 83609;
Number of Industries 16;
Total Number of Facilities 363;
Number of Occupations 27;
Total Number of Employees Exposed 9,163
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 83609;
Number of Industries 25;
Total Number of Facilities 741;
Number of Occupations 30;
Total Number of Employees Exposed 15,170;
Total Number of Female Employees Exposed 3,407


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE

ATSDR TOXICOLOGY PROFILE (NTIS** PB/99/102568/AS)
EPA TSCA Section 8(b) CHEMICAL INVENTORY
EPA TSCA 8(a) PRELIMINARY ASSESSMENT INFORMATION, FINAL RULE FEREAC 47,26992,82
Used as an intermediate and as a curing agent
EPA TSCA Section 8(d) unpublished health/safety studies
On EPA IRIS database
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NIOSH CURRENT INTELLIGENCE BULLETIN 8, 1976 AND BULLETIN 47, 1986
NIOSH Analytical Method, 1994: 4,4'-Methylenedianiline, 5029
NTP 10th Report on Carcinogens,2002:Reasonably anticipated to be a human carcinogen
OSHA ANALYTICAL METHOD #ID-57


REFERENCES:

CODEN
REFERENCE

85JCAE "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986
AEXPBL Archiv fuer Experimentelle Pathologie und Pharmakologie. (Leipzig, Ger. Dem. Rep.) V.1-109, 1873-1925. For publisher information, see NSAPCC.
APPFAR Acta Poloniae Pharmaceutica (English Translation). Translation of APPHAX. (Warsaw, Poland) V.20-29, 1963-72. Discontinued.
BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857-
CRNGDP Carcinogenesis (London). (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1980-
DIMON* Disease-a Month (Chicago : Year Book Publishers) V. 24- 1978-
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
FEREAC Federal Register. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) V.1- 1936-
HUTOX*
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979-
JJATDK JAT, Journal of Applied Toxicology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK) V.1- 1981-
JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ.
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
MUTAEX Mutagenesis. (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1986-
NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869-
NATWAY Naturwissenschaften. (Springer-Verlag, Heidelberger Platz 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.1- 1913-
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TOSCF2 Toxicological Sciences (Oxford University Press, 6277 Sea Harbor Drive, Orlando, FL 32887 ) V. 41, Jan. 1998-
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981-
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973-
ZHYGAM Zeitschrift fuer die Gesamte Hygiene und Ihre Grenzgebiete. (VEB Verlag Volk und Gesundheit, Neue Gruenstr. 18, Berlin DDR-1020, Ger. Dem. Rep.) V.1- 1955-

Used as an intermediate and as a curing agent

NIOSH PROFILE (RUBBER MANUFACTURING, SYNTHETIC), SRI, 2/77

NIOSH PROFILE (RUBBER MANUFACTURING, SYNTHETIC), FIRL, 4/78

RTECS Compound Description:
   Tumorigen
   Mutagen
   Human Data
   Primary Irritant

Click Here for Additional Information about RTECS

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