The Registry of Toxic Effects of Chemical Substances

Coumarin

RTECS #: GN4200000

CAS #: 91-64-5

UPDATE: May 2005 MW: 146.15 MF: C9H6O2


NOTE:

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

SYNONYMS:

  1. Cinnamic acid, o - hydroxy - , delta - lactone
  2. 2H - 1 - Benzopyran - 2 - one
  3. 2H - 1 - Benzopyran, 2 - oxo -
  4. Benzo - alpha - pyrone
  5. 1,2 - Benzopyrone
  6. Cumarin
  7. o - Hydroxycinnamic acid lactone
  8. o - Hydroxycinnamic lactone
  9. o - Hydroxyzimtsaure - lacton (German)
  1. Kumarin (Czech)
  2. NCI C07103
  3. Rattex
  4. Tonka bean camphor
  5. cis - o - Coumarinic acid lactone
  6. Coumarinic anhydride
  7. 2 - Oxo - 1,2 - benzopyran
  8. 2 - Propenoic acid, 3 - (2 - hydroxyphenyl) - delta - lactone


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
cytogenetic analysis hamster ovary 1,600 mg/L EMMUEG 10(Suppl 10),1,1987
cytogenetic analysis oral
mouse 		0.5 ppb EMMUEG 39,69,2002
cytogenetic analysis oral
rat 		0.5 ppb EMMUEG 39,69,2002
DNA damage mammal (species unspecified) lymphocyte 20 mmol/L PNASA6 48,686,1962
mutation in microorganisms Salmonella typhimurium 1 mg/plate (-enzymatic activation step) ENMUDM 5(Suppl 1),3,1983
morphological transform mouse fibroblast 1 mg/L/21 day (-enzymatic activation step) EMMUEG 37,231,2001
other mutation test systems Escherichia coli 62,500 ng/tube (-enzymatic activation step) MUREAV 445,81,1999
sister chromatid exchange hamster ovary 100 mg/L EMMUEG 10(Suppl 10),1,1987
specific locus test oral
mouse 		0.5 ppb EMMUEG 39,69,2002
specific locus test oral
rat 		0.5 ppb EMMUEG 39,69,2002


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 3,600 mg/kg (6-17 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) ARZNAD 17,97,1967


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
mouse 		lowest published toxic dose: 144 gm/kg/2 year- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Bronchogenic carcinoma 		NTPTR* NTP-TR-422,1993
oral
mouse 		lowest published toxic dose: 25,750 mg/kg/103 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Lung, Thorax, or Respiration: Tumors

Gastrointestinal: Tumors 		NTIS** PB94-215761
oral
mouse 		lowest published toxic dose: 103,000 mg/kg/103 week- intermittent Tumorigenic: Carcinogenic by RTECS criteria

Lung, Thorax, or Respiration: Tumors 		NTIS** PB94-215761
oral
rat 		lowest published toxic dose: 18,025 mg/kg/2 year- intermittent Tumorigenic: Neoplastic by RTECS criteria

Kidney, Ureter, and Bladder: Kidney tumors 		NTPTR* NTP-TR-422,1993
oral
rat 		toxic dose : 200 gm/kg/2 year- continuous Tumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors 		TXCYAC 1,93,1973
oral
rat 		lowest published toxic dose: 12,875 mg/kg/103 week- intermittent Tumorigenic: Neoplastic by RTECS criteria

Liver: Hepatitis (hepatocellular necrosis), diffuse

Kidney, Ureter, and Bladder: Kidney tumors 		NTIS** PB94-215761


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lethal dose (50 percent kill): 220 mg/kg Behavioral: Analgesia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase 		ARZNAD 15,897,1965
intravenous
rat 		lowest published toxic dose: 400 mg/kg Liver: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		BCPCA6 67,2141,2004
oral
guinea pig 		lethal dose (50 percent kill): 202 mg/kg Behavioral: Somnolence (general depressed activity)

Liver: Other changes 		FCTXAV 2,327,1964
oral
man 		lowest published toxic dose: 87 mg/kg/17 week- intermittent Liver: Liver function tests impaired HUTODJ 8,501,1989
oral
mouse 		lethal dose (50 percent kill): 196 mg/kg N/R YKKZAJ 83,1124,1963
oral
mouse 		lowest published toxic dose: 100 mg/kg Behavioral: Somnolence (general depressed activity) FCTOD7 837,39,2001
oral
mouse 		lethal dose : 200 mg/kg Behavioral: Somnolence (general depressed activity) FCTOD7 39,837,2001
oral
rat 		lethal dose (50 percent kill): 293 mg/kg N/R FCTXAV 12,385,1974
oral
woman 		lowest published toxic dose: 30 mg/kg/30 day- intermittent Liver: Liver function tests impaired HUTODJ 8,501,1989
subcutaneous
mouse 		lethal dose (50 percent kill): 242 mg/kg N/R YKKZAJ 83,1124,1963


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
dog 		lowest published toxic dose: 1,900 mg/kg/19 day- intermittent Liver: Jaundice, other or unclassified

Blood: Hemorrhage

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		JPETAB 118,348,1956
oral
hamster 		lowest published toxic dose: 109 gm/kg/13 week- continuous Liver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		FAATDF 34,105,1996
oral
hamster 		lowest published toxic dose: 7,728 mg/kg/12 week- continuous Liver: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		FCTOD7 40,809,2002
oral
hamster 		lowest published toxic dose: 74,382 mg/kg/42 week- continuous Liver: Changes in liver weight FCTOD7 40,809,2002
oral
hamster 		lowest published toxic dose: 21,252 mg/kg/12 week- continuous Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases FCTOD7 40,809,2002
oral
mouse 		lowest published toxic dose: 3,600 mg/kg/16 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-422,1993
oral
mouse 		lowest published toxic dose: 9,750 mg/kg/13 week- intermittent Liver: Changes in liver weight

Blood: Normocytic anemia 		NTPTR* NTP-TR-422,1993
oral
rat 		lowest published toxic dose: 1,400 mg/kg/7 day- intermittent Liver: Changes in liver weight

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases 		FCTXAV 3,457,1965
oral
rat 		lowest published toxic dose: 4,800 mg/kg/16 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field NTPTR* NTP-TR-422,1993
oral
rat 		lowest published toxic dose: 9,750 mg/kg/13 week- intermittent Liver: Hepatitis (hepatocellular necrosis), zonal

Blood: Changes in erythrocyte (RBC) count

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases 		NTPTR* NTP-TR-422,1993
oral
rat 		lowest published toxic dose: 88 gm/kg/42 week- continuous Liver: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases 		HETOEA 9,323,1990
oral
rat 		lowest published toxic dose: 27,300 mg/kg/39 week- continuous Liver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Liver function tests impaired

Blood: Changes in platelet count 		NTIS** OTS0555582
oral
rat 		lowest published toxic dose: 9,492 mg/kg/12 week- continuous Liver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.) 		FCTOD7 40,809,2002
oral
rat 		lowest published toxic dose: 25,032 mg/kg/12 week- continuous Liver: Other changes FCTOD7 40,809,2002


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
International Agency for Research on Cancer (IARC) Cancer Review Animal Limited Evidence IMEMDT 77,564,2000
International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 77,564,2000
International Agency for Research on Cancer (IARC) Cancer Review Human No Adequate Data IMEMDT 77,564,2000
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMEMDT 77,564,2000
TOXICOLOGY REVIEW
PMDCAY 10,85,1974
TOXICOLOGY REVIEW
MUREAV 47,161,1978
TOXICOLOGY REVIEW
FCTXAV 17,277,1979
TOXICOLOGY REVIEW
MUREAV 5432012003
TOXICOLOGY REVIEW
MUREAV 567,347,2004


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
N/R N/R N/R


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: 20340;
Number of Industries 14;
Total Number of Facilities 379;
Number of Occupations 39;
Total Number of Employees Exposed 31,272
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: 20340;
Number of Industries 113;
Total Number of Facilities 16,304;
Number of Occupations 99;
Total Number of Employees Exposed 239,705;
Total Number of Female Employees Exposed 110,313


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a cosmetic and perfume ingredient
EPA TSCA Section 8(d) unpublished health/safety studies
EPA TSCA TEST SUBMISSION (TSCATS) DATA BASE, JANUARY 2001
NCI Carcinogenesis Studies (gavage);clear evidence:mouse
NTP Carcinogenesis studies (gavage);some evidence:rat NTPTR* NTP-TR-422,1993
NCI Carcinogenesis Studies (gavage);equivocal evidence:rat


REFERENCES:

CODEN
REFERENCE
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
BCPCA6 Biochemical Pharmacology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1958-
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.
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1-40, 1981-97. For publisher information, see TOSCF2
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982-
FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7.
HETOEA Human & Experimental Toxicology. (Macmillan Press Ltd., Brunel Road, Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990-
HUTODJ Human Toxicology. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants., RG 21 2XS, UK) V.1- 1981-
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-
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
NTPTR* National Toxicology Program Technical Report Series. (Research Triangle Park, NC 27709) No.206-
PMDCAY Progress in Medical Chemistry. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1961-
PNASA6 Proceedings of the National Academy of Sciences of the United States of America. (National Academy of Sciences, Printing & Pub. Office, 2101 Constitution Ave., Washington, DC 20418) V.1- 1915-
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973-
YKKZAJ Yakugaku Zasshi. Journal of Pharmacy. (Nippon Yakugakkai, 2-12-15 Shibuya, Shibuya-ku, Tokyo 150, Japan) No.1- 1881-

Used as a cosmetic and perfume ingredient

RTECS Compound Description:
   Tumorigen
   Drug
   Mutagen
   Reproductive Effector
   Human Data
   Natural Product

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