The Registry of Toxic Effects of Chemical Substances

4 - Biphenylamine

RTECS #: DU8925000

CAS #: 92-67-1

UPDATE: May 2005 MW: 169.24 MF: C12H11N


NOTE:

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

SYNONYMS:

  1. (1,1' - Biphenyl) - 4 - amine
  2. 4 - Aminobifenyl (Czech)
  3. 4 - Aminobiphenyl
  4. 4 - Aminodifenil (Spanish)
  5. 4 - Aminodiphenyl
  6. 4 - Aminodiphenyl (ACGIH:OSHA)
  7. 4 - Bifenylamin (Czech)
  8. Biphenylamine
  1. Paraaminodiphenyl
  2. Xenylamin (Czech)
  3. Xenylamine
  4. p - Aminobiphenyl
  5. p - Aminodiphenyl
  6. p - Biphenylamine
  7. p - Phenylaniline


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

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


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE 		DOSE REFERENCE
body fluid assay dog
Salmonella typhimurium 		10 mg/kg CNREA8 37,1757,1977
body fluid assay rat
Salmonella typhimurium 		250 µmol/kg TXCYAC 16,113,1980
cytogenetic analysis intraperitoneal
mouse 		25 mg/kg MUREAV 268,255,1992
cytogenetic analysis mouse lymphocyte 50 mg/L MUREAV 320,69,1994
cytogenetic analysis intraperitoneal
rat 		10 mg/kg/72 hour NULSAK 23,36,1980
DNA adduct oral
dog 		5 mg/kg CNREA8 48,6336,1988
DNA adduct Escherichia coli 30 µmol/L MUREAV 89,95,1981
DNA adduct skin
mouse 		8.5 mg/kg/24 hour TOXID9 72(Supp 1),336,2003
DNA adduct oral
mouse 		80 mg/kg TOSCF2 73,279,2003
DNA adduct unreported route
mouse 		120 mg/kg CBINA8 146,51,2003
DNA damage hamster lung 300 µmol/L/2 hour BBRCA9 72,732,1976
DNA damage human other cell types 60 µmol/L EMMUEG 38,1,2001
DNA damage human other cell types 0.6 mmol/plate EMMUEG 38,1,2001
DNA damage human other cell types 0.125 mmol/L/20 hour TXCYAC 179,115,2002
DNA damage human lymphocyte 500 µmol/L/2 hour TOSCF2 72,283,2003
DNA damage rat liver 30 µmol/L SinJF# 26OCT1982
DNA damage rat other cell types 0.5 mmol/L/20 hour TXCYAC 179,115,2002
DNA repair Bacillus subtilis 200 µg/disc MUREAV 97,1,1982
DNA repair Escherichia coli 250 mg/L JJIND8 62,873,1979
unscheduled DNA synthesis human liver 100 µg/L MUREAV 206,91,1988
unscheduled DNA synthesis human fibroblast 800 µg/L TXCYAC 21,151,1981
unscheduled DNA synthesis oral
mouse 		200 mg/kg ENMUDM 6,474,1984
unscheduled DNA synthesis oral
rat 		200 mg/kg ENMUDM 6,474,1984
unscheduled DNA synthesis rat liver 3 µmol/L MUREAV 216,101,1989
unscheduled DNA synthesis rabbit liver 500 µmol/L CNREA8 43,3120,1983
host-mediated assay mouse
Escherichia coli 		67 mg/kg MUREAV 272,161,1992
host-mediated assay rat
Salmonella typhimurium 		1 mmol/kg MUREAV 93,317,1982
mutation in microorganisms Escherichia coli 900 µg/L (+enzymatic activation step) CNREA8 39,682,1979
mutation in microorganisms Salmonella typhimurium 2 µg/plate (-enzymatic activation step) ENMUDM 5(Suppl 1),3,1983
mutation in microorganisms Salmonella typhimurium 3 µg/plate (+enzymatic activation step) TOSCF2 56,351,2000
mutation in microorganisms Salmonella typhimurium 10 µg/plate/20 minute (+enzymatic activation step) MUREAV 515,15,2002
mutation in microorganisms Salmonella typhimurium 1 nmol/plate/20 minute EMMUEG 38,268,2001
mutation in microorganisms Salmonella typhimurium 600 µmol/L/3 hour TCMUD8 23,47,2003
micronucleus test intraperitoneal
mouse 		28 mg/kg/24 hour- continuous MUREAV 216,321,1989
micronucleus test oral
mouse 		50 mg/kg/48 hour- intermittent MUREAV 389,3,1997
gene conversion and mitotic recombination Saccharomyes cerevisiae 2 pph JJIND8 62,901,1979
mutation in mammalian somatic cells hamster lung 5 mg/L CNREA8 43,5194,1983
mutation in mammalian somatic cells human fibroblast 60 mg/L MUREAV 121,71,1983
mutation in mammalian somatic cells mouse lymphocyte 5 mg/L MUREAV 125,291,1984
mutation in mammalian somatic cells oral
mouse 		75 mg/kg MUREAV 400,245,1998
morphological transform hamster kidney 80 µg/L BJCAAI 37,873,1978
morphological transform hamster embryo 5 mg/L NCIMAV 58,243,1981
morphological transform mouse embryo 10 mg/L JNCIAM 52,1167,1974
morphological transform mouse fibroblast 0.1 mg/L/21 day (-enzymatic activation step) EMMUEG 35,300,2000
morphological transform oral
rat 		100 mg/kg CNREA8 40,1157,1980
morphological transform rat embryo 10 mg/L JNCIAM 51,799,1973
other mutation test systems intraperitoneal
mouse 		100 mg/kg MUREAV 268,255,1992
other mutation test systems mouse lymphocyte 50 mg/L MUREAV 320,69,1994
phage inhibition capacity Escherichia coli 25 mg/L CNREA8 41,532,1981
sister chromatid exchange intraperitoneal
hamster 		50 mg/kg MUREAV 113,33,1983
sister chromatid exchange oral
hamster 		50 mg/kg MUREAV 113,33,1983
specific locus test oral
Drosophila melanogaster 		500 µmol/L MUREAV 242,169,1990
specific locus test hamster ovary 5 mg/L/9 day EMMUEG 16,260,1990


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
intraperitoneal
mouse 		lowest published toxic dose: 85 µg/kg Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		CALEDQ 185,13,2002
oral
dog 		toxic dose : 5,580 mg/kg/4 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Kidney, Ureter, and Bladder: Bladder tumors 		NEOLA4 15,3,1968
oral
dog 		toxic dose : 8,200 mg/kg/90 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		JAMAAP 172,1611,1960
oral
dog 		toxic dose : 8,200 mg/kg/2 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		IMSUAI 27,25,1958
oral
dog 		toxic dose : 9,600 mg/kg/3 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		IMSUAI 27,25,1958
oral
dog 		toxic dose : 8,400 mg/kg/2 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		IMSUAI 27,25,1958
oral
dog 		toxic dose : 14 gm/kg/3 year- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors 		IMSUAI 27,25,1958
oral
mouse 		lowest published toxic dose: 1,520 mg/kg/39 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors

Kidney, Ureter, and Bladder: Bladder tumors 		BJCAAI 19,297,1965
oral
mouse 		toxic dose : 5,460 µg/kg Tumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors

Blood: Tumors 		EJCODS 21,865,1985
oral
rat 		lowest published toxic dose: 5 gm/kg/52 week- continuous Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Skin and Appendages: Tumors 		ARZNAD 12,270,1962
subcutaneous
mouse 		lowest published toxic dose: 216 mg/kg/3 day- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors 		JNCIAM 41,403,1968
subcutaneous
rat 		lowest published toxic dose: 4,560 mg/kg/44 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors

Kidney, Ureter, and Bladder: Kidney tumors 		NATUAS 175,1131,1955
subcutaneous
rat 		toxic dose : 5,000 mg/kg/1 week- intermittent Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Gastrointestinal: Tumors

Liver: Tumors 		BMBUAQ 14,141,1958


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lowest published lethal dose: 250 mg/kg Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia

Lung, Thorax, or Respiration: Dyspnea 		CBCCT* 6,54,1954
intraperitoneal
rat 		lowest published toxic dose: 10 µg/kg Blood: Other changes BECTA6 67,649,2001
oral
dog 		lowest published lethal dose: 25 mg/kg Blood: Methemoglobinemia- Carboxhemoglobinemia SCIEAS 167,992,1970
oral
mouse 		lethal dose (50 percent kill): 205 mg/kg N/R EJCODS 21,865,1985
oral
rat 		lethal dose (50 percent kill): 500 mg/kg Behavioral: Coma

Lung, Thorax, or Respiration: Dyspnea

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		JIHTAB 29,1,1947
oral
rat 		lowest published toxic dose: 0.1 µg/kg Blood: Other changes BECTA6 67,649,2001
oral
rabbit 		lethal dose (50 percent kill): 690 mg/kg Behavioral: Coma

Lung, Thorax, or Respiration: Dyspnea

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		JIHTAB 29,1,1947
skin
mouse 		lowest published toxic dose: 16.9 mg/kg Liver: Other changes

Blood: Methemoglobinemia- Carboxhemoglobinemia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases 		TXAPA9 181,32,2002


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

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


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value time-weighted average L (skin) DTLVS* TLV/BEI,2003
American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value Confirmed Human Carcinogen DTLVS* TLV/BEI,2003
International Agency for Research on Cancer (IARC) Cancer Review Human Limited Evidence IMEMDT 1,74,1972
International Agency for Research on Cancer (IARC) Cancer Review Animal Sufficient Evidence IMEMDT 1,74,1972
International Agency for Research on Cancer (IARC) Cancer Review Human Sufficient Evidence IMEMDT 28,151,1982
International Agency for Research on Cancer (IARC) Cancer Review Group 1 IMSUDL 7,91,1987
TOXICOLOGY REVIEW
KHZHAZ 12(2),85,1976
TOXICOLOGY REVIEW
ADCSAJ 13,271,1970
TOXICOLOGY REVIEW
BLFSBY 24,253,1983
TOXICOLOGY REVIEW
ARPTDI 43,485,2003
TOXICOLOGY REVIEW
TOLED5 134,39,2002


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Mine Safety and Health Administration (MSHA) STANDARD skin-HUMAN CARCINOGEN, NO ASSIGNED time-weighted average DTLVS* 3,10,1971
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (General Industry) see Code of Federal Regulations (CFR) 29,1910.1011 CFRGBR 29,1910.1000,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Construction) see Code of Federal Regulations (CFR) 29,1926.1111 CFRGBR 29,1926.55,1994
Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (Shipyards) see Code of Federal Regulations (CFR) 29,1915.1011 CFRGBR 29,1915.1000,1993
Occupational Safety and Health Administration (OSHA) cancer suspect agent CFRGBR 29,1910.1011,1987
Occupational Exposure Limit - AUSTRALIA Skin, Carcinogen, JAN1993
Occupational Exposure Limit - AUSTRIA Carcinogen, JAN1999
Occupational Exposure Limit - FINLAND time-weighted average 10 mg/m3, short term exposure limit 20 mg/m3, Skin, Carcinogen, JAN1999
Occupational Exposure Limit - FRANCE VME 0.001 ppm (0.007 mg/m3), continuous1 Carcinogen, JAN1999
Occupational Exposure Limit - GERMANY Carcinogen, JAN1999
Occupational Exposure Limit - NORWAY time-weighted average 0.1 mg/m3, JAN1999
Occupational Exposure Limit - SWEDEN Carcinogen, JAN1999
Occupational Exposure Limit - SWITZERLAND Skin, Carcinogen, JAN1999
Occupational Exposure Limit IN ARGENTINA, BULGARIA, COLOMBIA, JORDAN, KOREA American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value;

Confirmed Human Carcinogen
Occupational Exposure Limit IN NEW ZEALAND, SINGAPORE, VIETNAM American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value
Confirmed Human Carcinogen


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Institute for Occupational Safety and Health (NIOSH) Recommended Exposure Level TO 4-AMINODIPHENYL-air Carcinogen use 29 Code of Federal Regulations (CFR) 1910.1011 NIOSH* DHHS #92-100,1992


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA GENETOX PROGRAM 1988, Positive: Body fluid assay; Carcinogenicity-mouse/rat
EPA GENETOX PROGRAM 1988, Positive: SHE-clonal assay; Cell transform.-mouse embryo
EPA GENETOX PROGRAM 1988, Positive: Cell transform.-RLV F344 rat embryo; Host-mediated assay
EPA GENETOX PROGRAM 1988, Positive: E coli polA with S9; Histidine reversion-Ames test
EPA GENETOX PROGRAM 1988, Positive: In vitro UDS in rat liver; S cerevisiae-homozygosis
EPA GENETOX PROGRAM 1988, Negative: In vitro UDS-human fibroblast
EPA GENETOX PROGRAM 1988, Inconclusive: Mammalian micronucleus; E coli polA without S9
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a rubber antioxidant
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NTP 11th Report on Carcinogens,2004:Known to be human carcinogen
OSHA ANALYTICAL METHOD #93


REFERENCES:

CODEN
REFERENCE
ADCSAJ Advances in Chemistry Series. (American Chemical Soc., Distribution Office Dept. 223, POB 57136, West End Stn., Washington, DC 20037) No.1- 1950-
ARPTDI Annual Review of Pharmacology and Toxicology. (Annual Reviews, Inc., POB 10139, Palo Alto, CA 94303) V.16- 1976-
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
BBRCA9 Biochemical and Biophysical Research Communications. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959-
BECTA6 Bulletin of Environmental Contamination and Toxicology. (Springer-Verlag New York, Inc., Service Center, 44 Hartz Way, Secaucus, NJ 07094) V.1- 1966-
BJCAAI British Journal of Cancer. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.1- 1947-
BLFSBY Basic Life Sciences. (Plenum Pub. Corp., 223 Spring St., New York, NY 10003) V.1- 1973-
BMBUAQ British Medical Bulletin. (Longman Group UK Ltd., Longman House, Burnt Mill, Harlow, Essex CM20 2JE, UK) V.1- 1943-
CALEDQ Cancer Letters (Shannon, Ireland). (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1975-
CBCCT* "Summary Tables of Biological Tests," National Research Council Chemical-Biological Coordination Center. (National Academy of Science Library, 2101 Constitution Ave., NW, Washington, DC 20418)
CBINA8 Chemico-Biological Interactions. (Elsevier Scientific Pub. Ireland Ltd., POB 85, Limerick, Ireland) V.1- 1969-
CFRGBR Code of Federal Regulations. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402)
CNREA8 Cancer Research. (Public Ledger Building, Suit 816, 6th & Chestnut Sts., Philadelphia, PA 19106) V.1- 1941-
DTLVS* The Threshold Limit Values (TLVs) and Biological Exposure Indices (BEIs) booklet issues by American Conference of Governmental Industrial Hygienists (ACGIH), Cincinnati, OH, 1996
EJCODS European Journal of Cancer and Clinical Oncology. (Pergamon Press, c/o Elsevier Science, 660 White Plains Rd., Tarrytown, NY 10591) V.17(7)- 25, 1981-89. For publisher information, see EJCAEL
EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987-
ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG.
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-
IMSUAI Industrial Medicine and Surgery. (Northbrook, IL) V.18-42, 1949-73. For publisher information, see IOHSA5.
IMSUDL IARC Monographs, Supplement. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) No.1- 1979-
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883-
JIHTAB Journal of Industrial Hygiene and Toxicology. (Cambridge, MA) V.18-31, 1936-49. For publisher information, see AEHLAU.
JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ.
JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8.
KHZHAZ Khimiya i Zhizn. Chemistry and Life. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.1- 1965-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869-
NCIMAV National Cancer Institute, Monograph. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) No.1- 1959-
NEOLA4 Neoplasma. (Karger-Libri, P.O. Box, CH-4009 Basel, Switzerland) V.4- 1957-
NIOSH* National Institute of Occupational Safety and Health, U.S. Dept. of Health, Education, and Welfare, Reports and Memoranda.
NULSAK Nucleus (Calcutta). (Dr. A.K. Sharma, Centre of Advanced Studies in Cell and Chromosome Research, Calcutta, 35 Baliygunge Circular Rd., Calcutta 700 019, India) V.1- 1958-
SCIEAS Science. (American Assoc. for the Advancement of Science, 1333 H St., NW, Washington, DC 20005) V.1- 1895-
SinJF# Personal Communication from J.F. Sina, Merck Institute for Therapeutic Research, West Point, PA 19486, Oct. 26, 1982
TCMUD8 Teratogenesis, Carcinogenesis, and Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980-
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-

Used as a rubber antioxidant

RTECS Compound Description:
   Agricultural Chemical
   Tumorigen
   Drug
   Mutagen
   Human Data

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