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Indole - 3 - acetic acid, 1 - (p - chlorobenzoyl) - 5 - methoxy - 2 - methyl -

RTECS #: NL3500000

CAS #: 53-86-1

UPDATE: February 2009 MW: 357.81 MF: C19H16ClNO4


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. STANDARDS AND REGULATIONS:
  9. NIOSH DOCUMENTATION AND SURVEILLANCE:
  10. STATUS IN FEDERAL AGENCIES:
  11. REFERENCES:

SYNONYMS:

  1. (1 - p - Chlorobenzoyl - 5 - methoxy - 2 - methylindol - 3 - yl) acetic acid
  2. 1 - (p - Chlorbenzoyl) - 5 - methoxy - 2 - methylindol - 3 - essigsaeure (German)
  3. 1 - (p - Chlorobenzoyl) - 2 - methyl - 5 - methoxy - 3 - indole - acetic acid
  4. 1 - (p - Chlorobenzoyl) - 2 - methyl - 5 - methoxyindole - 3 - acetic acid
  5. 1 - (p - Chlorobenzoyl) - 5 - methoxy - 2 - methylindole - 3 - acetic acid
  6. 1 - p - Cloro - benzoil - 5 - metoxi - 2 - metilindol - 3 - acido acetico (Spanish)
  7. Amuno
  8. Artracin
  9. Artrinovo
  10. Artrivia
  11. Confortid
  12. Dolovin
  13. Idomethine
  14. Imbrilon
  15. Inacid
  16. Indacin
  17. Indo - rectolmin
  18. Indo - tablinen
  19. Indocid
  20. Indomecol
  21. Indomed
  22. Indomee
  23. Indometacin
  24. Indometacine
  1. Indometacyna (Polish)
  2. Indomethacin
  3. Indomethacine
  4. Indometicina (Spanish)
  5. Indoptic
  6. Inflazon
  7. Infrocin
  8. Inteban SP
  9. Kwas 1 - (p - chlorobenzoilo) - 2 - metylo - 5 - metoksy - 3 - indolilooctowy (Polish)
  10. Lausit
  11. Liometacen
  12. Metacen
  13. Metartril
  14. Methazine
  15. Metindol
  16. Mezolin
  17. Mikametan
  18. Mobilan
  19. N - p - Chlorbenzoyl - 5 - methoxy - 2 - methylindole - 3 - acetic acid
  20. NCI - C56144
  21. Reumacide
  22. Sadoreum
  23. Tannex
  24. alpha - (1 - (p - Chlorobenzoyl) - 2 - methyl - 5 - methoxy - 3 - indolyl) acetic acid


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 oral
mouse 		84 mg/kg/1 week- continuous MUREAV 188,343,1987
dominant lethal test oral
rat 		17 mg/kg/13 week- continuous BZARAZ 32,1039,1979
DNA inhibition human lymphocyte 10 mg/L BOAEBM SGAE-2261,1974
DNA inhibition skin
mouse 		44 µmol/kg RCOCB8 24,533,1979
DNA inhibition mouse other cell types 10 mg/L BOAEBM SGAE-2261,1974
host-mediated assay rat
other cell types 		10 mg/kg BCPCA6 24,219,1975
mutation in microorganisms Salmonella typhimurium 100 µg/disc (+enzymatic activation step) JNUDAT 34,183,1992
micronucleus test oral
mouse 		72 mg/kg/24 hour MUREAV 188,343,1987
micronucleus test intraperitoneal
mouse 		72 mg/kg/24 hour MUREAV 188,343,1987
other mutation test systems oral
rat 		12 mg/kg/3 day- continuous REXMAS 189,173,1989
other mutation test systems rat other cell types 10 mg/L REXMAS 189,173,1989
sperm morphology intraperitoneal
mouse 		60 mg/kg/5 day- continuous MUREAV 188,343,1987
sperm morphology oral
mouse 		60 mg/kg/5 day- continuous MUREAV 188,343,1987


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intramuscular
monkey 		lowest published toxic dose: 6 mg/kg (2 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility CCPTAY 27,505,1983
intramuscular
rabbit 		lowest published toxic dose: 7,500 µg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility BIREBV 19,552,1978
intramuscular
rabbit 		lowest published toxic dose: 5,500 µg/kg (1-3 day pregnant) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) BIREBV 14,451,1976
intramuscular
rabbit 		lowest published toxic dose: 30 mg/kg (24-26 day pregnant) Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Effects on newborn: Biochemical and metabolic 		JPEMAO 6,240,1978
intraperitoneal
rat 		lowest published toxic dose: 2,500 µg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility PROMDL 7,29,1981
intraperitoneal
rat 		lowest published toxic dose: 28 mg/kg (7 day male) Reproductive: Effects on fertility: Male fertility index (e.g., # males impregnating females per # males exposed to fertile nonpregnant females) JRPFA4 76,65,1986
intraperitoneal
rat 		lowest published toxic dose: 4,150 µg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility PRGLBA 1,21,1972
intrauterine
guinea pig 		lowest published toxic dose: 66,640 µg/kg (9 day prior to copulation) Reproductive: Maternal effects: Menstrual cycle changes or disorders BJPCBM 49,98,1973
intrauterine
rat 		lowest published toxic dose: 500 µg/kg (4 day pregnant) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) CCPTAY 24,283,1981
intravaginal
rat 		lowest published toxic dose: 125 mg/kg (7 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)

Reproductive: Effects on fertility: Other measures of fertility 		RDCNBM 1,177,1974
intravenous
rabbit 		lowest published toxic dose: 148 mg/kg (1-9 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) 		JRPFA4 46,375,1976
intravenous
rabbit 		lowest published toxic dose: 20 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility FESTAS 39,85,1983
intravenous
rabbit 		lowest published toxic dose: 20 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility PRGLBA 1,89,1972
intravenous
woman 		lowest published toxic dose: 18 mg/kg (33-34 week pregnant) Reproductive: Specific developmental abnormalities: Homeostasis AOGSAE 61,183,1982
multiple
woman 		lowest published toxic dose: 22 mg/kg (33 week pregnant) Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Effects on newborn: Apgar score (human only) 		RFDEEH 3,489,1991
oral
mammal (species unspecified) 		lowest published toxic dose: 1 mg/kg (21 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system TJADAB 30(1),15A,1984
oral
monkey 		lowest published toxic dose: 496 mg/kg (21-26 week pregnant) Reproductive: Maternal effects: Parturition

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Physical 		FESTAS 27,588,1976
oral
monkey 		lowest published toxic dose: 747 mg/kg (21-26 week pregnant) Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord) AJOGAH 118,412,1974
oral
mouse 		lowest published toxic dose: 10 mg/kg (7 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Central nervous system

Reproductive: Specific developmental abnormalities: Eye, ear 		SEIJBO 17,177,1977
oral
mouse 		lowest published toxic dose: 10 mg/kg (7 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system 		SEIJBO 17,177,1977
oral
mouse 		lowest published toxic dose: 4 mg/kg (13 day pregnant) Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue) JCGBDF 10,83,1990
oral
pig 		lowest published toxic dose: 160 mg/kg (16 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility BIREBV 32,105,1985
oral
rat 		lowest published toxic dose: 1 mg/kg (21 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system OYYAA2 27,117,1984
oral
rat 		lowest published toxic dose: 300 µg/kg (21-22 day pregnant) Reproductive: Maternal effects: Parturition

Reproductive: Effects on newborn: Stillbirth

Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth) 		NATUAS 240,21,1972
oral
rat 		lowest published toxic dose: 10 mg/kg (17-22 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Specific developmental abnormalities: Respiratory system 		PEREBL 15,147,1981
oral
rat 		lowest published toxic dose: 12 mg/kg (5-16 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) RCOCB8 7,701,1974
oral
rat 		lowest published toxic dose: 20 mg/kg (1-21 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Other developmental abnormalities 		IRLCDZ 3,300,1975
oral
rat 		lowest published toxic dose: 325 mg/kg (65 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct 		VMJGEA 37,623,1989
oral
rat 		lowest published toxic dose: 21 mg/kg (1-7 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 21 mg/kg (8-14 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 105 mg/kg (1-7 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 105 mg/kg (8-14 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 105 mg/kg (14-20 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 2 gm/kg (multigenerations) Reproductive: Effects on newborn: Other postnatal measures or effects

Reproductive: Effects on newborn: Delayed effects 		EKFAE9 56,52,1993
oral
rat 		lowest published toxic dose: 21 mg/kg (1-7 day pregnant) Reproductive: Other developmental abnormalities FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 21 mg/kg (8-14 day pregnant) Reproductive: Other developmental abnormalities FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 10 mg/kg (18 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system EJPHAZ 485,289,2004
oral
rat 		lowest published toxic dose: 4 mg/kg (18-21 day pregnant) Reproductive: Effects on newborn: Biochemical and metabolic

Reproductive: Effects on newborn: Other postnatal measures or effects 		TXCYAC 232,257,2007
oral
rabbit 		lowest published toxic dose: 96 mg/kg (20-31 day pregnant) Reproductive: Maternal effects: Parturition BIREBV 15,551,1976
oral
rabbit 		lowest published toxic dose: 10 mg/kg (29 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system PRGLBA 9,585,1975
oral
rabbit 		lowest published toxic dose: 6 mg/kg (2 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility JJPAAZ 28,909,1978
oral
woman 		lowest published toxic dose: 1,500 µg/kg (36 week pregnant) Reproductive: Specific developmental abnormalities: Respiratory system

Reproductive: Effects on newborn: Other neonatal measures or effects 		JOPDAB 92,478,1978
oral
woman 		lowest published toxic dose: 1,500 mg/kg (27 week pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system NEJMAG 319,327,1988
oral
woman 		lowest published toxic dose: 12 mg/kg (33-34 week pregnant) Reproductive: Effects on newborn: Stillbirth JRPMAP 24,137,1980
oral
woman 		lowest published toxic dose: 525 mg/kg (16-32 week pregnant) Reproductive: Maternal effects: Parturition

Reproductive: Other effects on female

Reproductive: Specific developmental abnormalities: Urogenital system 		AJMGDA 39,252,1991
parenteral
mouse 		lowest published toxic dose: 8 mg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility JRPFA4 40,467,1974
parenteral
rat 		lowest published toxic dose: 3 mg/kg (19-21 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system

Reproductive: Specific developmental abnormalities: Respiratory system 		ERJOEI 8,209,1995
parenteral
rabbit 		lowest published toxic dose: 2,500 ng/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility LIFSAK 14,129,1974
rectal
woman 		lowest published toxic dose: 12 mg/kg (28 week pregnant) Reproductive: Specific developmental abnormalities: Blood and lymphatic systems (including spleen and marrow)

Reproductive: Specific developmental abnormalities: Gastrointestinal system

Reproductive: Specific developmental abnormalities: Urogenital system 		JOPDAB 113,738,1988
subcutaneous
guinea pig 		lowest published toxic dose: 240 mg/kg (12 day prior to copulation) Reproductive: Maternal effects: Menstrual cycle changes or disorders BJPCBM 49,98,1973
subcutaneous
hamster 		lowest published toxic dose: 144 mg/kg (18 day prior to copulation) Reproductive: Other effects on female ACENA7 78,343,1975
subcutaneous
mouse 		lowest published toxic dose: 9 mg/kg (2 day pregnant) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) PRGLBA 4,795,1973
subcutaneous
mouse 		lowest published toxic dose: 40 mg/kg (8-15 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Body wall 		ANANAU 136,349,1974
subcutaneous
mouse 		lowest published toxic dose: 40 mg/kg (8-15 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system ANANAU 136,349,1974
subcutaneous
mouse 		lowest published toxic dose: 8 mg/kg (1 day prior to copulation) Reproductive: Maternal effects: Uterus, cervix, vagina

Reproductive: Effects on fertility: Other measures of fertility 		FESTAS 25,636,1974
subcutaneous
rat 		lowest published toxic dose: 5 mg/kg (5 day pregnant) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) BIREBV 16,286,1977
subcutaneous
rat 		lowest published toxic dose: 2,500 µg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility PRGLBA 1,3,1972
subcutaneous
rat 		lowest published toxic dose: 12 mg/kg (3-4 day pregnant) Reproductive: Maternal effects: Uterus, cervix, vagina

Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea) 		JRPFA4 62,73,1981
subcutaneous
rat 		lowest published toxic dose: 9 mg/kg (9 day prior to copulation) Reproductive: Other effects on female ACENA7 78,343,1975
subcutaneous
rat 		lowest published toxic dose: 5 mg/kg (1 day prior to copulation) Reproductive: Maternal effects: Oogenesis

Reproductive: Maternal effects: Ovaries, fallopian tubes 		REPRD* 123,639,2002
subcutaneous
rat 		lowest published toxic dose: 5 mg/kg (1 day prior to copulation) Reproductive: Maternal effects: Menstrual cycle changes or disorders REPRD* 123,639,2002
subcutaneous
rabbit 		lowest published toxic dose: 1,590 µg/kg (6 day pregnant) Reproductive: Effects on embryo or fetus: Maternal- fetal exchange BIREBV 29,833,1983
subcutaneous
rabbit 		lowest published toxic dose: 48 mg/kg (23-28 day pregnant) Reproductive: Maternal effects: Parturition JOENAK 64,363,1975
subcutaneous
rabbit 		lowest published toxic dose: 32 mg/kg (5-6 day pregnant) Reproductive: Effects on fertility: Pre- implantation mortality (e.g., reduction in number of implants per female; total number of implants per corpora lutea)

Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) 		PRGLBA 20,587,1980
subcutaneous
rabbit 		lowest published toxic dose: 24 mg/kg (4-7 day pregnant) Reproductive: Effects on fertility: Other measures of fertility

Reproductive: Effects on embryo or fetus: Extra embryonic structures (e.g., placenta, umbilical cord)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) 		BIREBV 18,148,1978
subcutaneous
rabbit 		lowest published toxic dose: 64 mg/kg (9-12 day pregnant) Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth) BIREBV 18,148,1978
subcutaneous
rabbit 		lowest published toxic dose: 20 mg/kg (26-29 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death

Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system 		CJPPA3 58,212,1980
unreported route
cattle 		lowest published toxic dose: 40 µg/kg (1 day prior to copulation) Reproductive: Effects on fertility: Other measures of fertility JRPFA4 75,547,1985
unreported route
rat 		lowest published toxic dose: 3 mg/kg (20 day pregnant) Reproductive: Specific developmental abnormalities: Cardiovascular (circulatory) system TJADAB 30(1),20A,1984
unreported route
woman 		lowest published toxic dose: 6 mg/kg (39 week pregnant) Reproductive: Specific developmental abnormalities: Urogenital system JMFMEC 4,65,1995
unreported route
woman 		lowest published toxic dose: 4 mg/kg (10 week pregnant) Reproductive: Specific developmental abnormalities: Urogenital system MIPEA5 27,675,1975
unreported route
woman 		lowest published toxic dose: 2 mg/kg (28 week pregnant) Reproductive: Specific developmental abnormalities: Urogenital system

Reproductive: Specific developmental abnormalities: Homeostasis 		PEREBL 24,644,1988
unreported route
woman 		lowest published toxic dose: 12 mg/kg (32 week pregnant) Reproductive: Effects on newborn: Stillbirth JRPMAP 24,137,1980
unreported route
woman 		lowest published toxic dose: 14 mg/kg (34 week pregnant) Reproductive: Effects on newborn: Other neonatal measures or effects JRPMAP 24,137,1980


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
oral
rat 		lowest published toxic dose: 644 mg/kg/92 week- continuous Tumorigenic: Neoplastic by RTECS criteria

Skin and Appendages: Tumors 		CRNGDP 16,1493,1995


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraaural
mouse 		lowest published toxic dose: 20 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation EJPHAZ 495,201,2004
intraarterial
rat 		lowest published toxic dose: 10 mg/kg Lung, Thorax, or Respiration: Other changes

Gastrointestinal: Changes in structure or function of exocrine pancreas

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		TOXIA6 46,820,2005
intraduodenal
rat 		lowest published toxic dose: 10 mg/kg Gastrointestinal: Hypermotility, diarrhea JPETAB 303,1248,2002
intramuscular
mouse 		lethal dose (50 percent kill): 18,200 µg/kg N/R ARZNAD 30,1398,1980
intramuscular
rat 		lethal dose (50 percent kill): 26,300 µg/kg N/R ARZNAD 30,1398,1980
intramuscular
rat 		lowest published toxic dose: 10 mg/kg Brain and Coverings: Changes in surface EEG

Behavioral: Sleep 		TXCYAC 191,89,2003
intraperitoneal
guinea pig 		lethal dose (50 percent kill): 143 mg/kg N/R ARZNAD 30,1398,1980
intraperitoneal
mammal (species unspecified) 		lowest published toxic dose: 30 mg/kg Gastrointestinal: Nausea or vomiting JPHSC* 103,189,2007
intraperitoneal
mouse 		lethal dose (50 percent kill): 10 mg/kg N/R AFTOD7 8,201,1982
intraperitoneal
mouse 		lowest published toxic dose: 20 mg/kg Blood: Changes in spleen

Biochemical: Metabolism (intermediary): Effect on cyclic nucleotides 		TXAPA9 187,80,2003
intraperitoneal
mouse 		lowest published toxic dose: 5 mg/kg Gastrointestinal: Other changes

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

Biochemical: Metabolism (intermediary): Histamines (including liberation not immunochemical in origin) 		EJPHAZ 460,63,2003
intraperitoneal
mouse 		lowest published toxic dose: 10 mg/kg Behavioral: Change in psychophysiological tests PSCHDL 171,382,2004
intraperitoneal
mouse 		lowest published toxic dose: 4 mg/kg Behavioral: Analgesia TOXIA6 45,585,2005
intraperitoneal
mouse 		lowest published toxic dose: 2 mg/kg Biochemical: Metabolism (intermediary): Effect on mitochondrial function CNREA8 65,7911,2005
intraperitoneal
mouse 		lowest published toxic dose: 10 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation FTRPAE 70,275,1999
intraperitoneal
rat 		lethal dose (50 percent kill): 13 mg/kg N/R TXAPA9 38,127,1976
intraperitoneal
rat 		lowest published toxic dose: 2.5 mg/kg Brain and Coverings: Other degenerative changes

Biochemical: Metabolism (intermediary): Other 		BJPCBM 139,1164,2003
intraperitoneal
rat 		lowest published toxic dose: 2 mg/kg Behavioral: Analgesia

Behavioral: Change in psychophysiological tests 		BJPCBM 141,1175,2004
intraperitoneal
rat 		lowest published toxic dose: 5 mg/kg Vascular: Measurement of regional blood flow

Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Other 		EJPHAZ 499,201,2004
intraperitoneal
rat 		lowest published toxic dose: 5 mg/kg Behavioral: Alteration of classical conditioning NEROEW 29,1597,2004
intraperitoneal
rat 		lowest published toxic dose: 2.5 mg/kg Behavioral: Analgesia TOXIA6 43,273,2004
intraperitoneal
rat 		lowest published toxic dose: 2 mg/kg Spinal Cord: Inflammatory changes

Nutritional and Gross Metabolic: Body temperature decrease

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		EJPHAZ 543,181,2006
intraperitoneal
rat 		lowest published toxic dose: 4 mg/kg Lung, Thorax, or Respiration: Structural or functional change in trachea or bronchi

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		TXAPA9 214,35,2006
intraperitoneal
rat 		lowest published toxic dose: 20 mg/kg Vascular: Measurement of regional blood flow

Gastrointestinal: Other changes 		BJPCBM 146,481,2005
intraperitoneal
rat 		lowest published toxic dose: 18 mg/kg Behavioral: Analgesia

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		PHMCAA 75,122,2005
intraperitoneal
rat 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Ulceration or bleeding from stomach PHMCAA 75,122,2005
intraperitoneal
rat 		lowest published toxic dose: 1.71 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BOMCL* 17,6439,2007
intraperitoneal
rat 		lowest published toxic dose: 10 mg/kg Immunological Including Allergic: Decrease in cellular immune response

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		FTRPAE 74,45,2003
intravenous
cat 		lowest published lethal dose: 20,200 µg/kg N/R ARZNAD 33,726,1983
intravenous
dog 		lethal dose (50 percent kill): 100 mg/kg N/R ARZNAD 30,1398,1980
intravenous
guinea pig 		lethal dose (50 percent kill): 180 mg/kg N/R JNPHAG 2,259,1971
intravenous
infant 		lowest published toxic dose: 200 µg/kg Blood: Hemorrhage JOPDAB 107,312,1985
intravenous
mouse 		lethal dose (50 percent kill): 30 mg/kg N/R ARZNAD 19,1198,1969
intravenous
mouse 		lowest published toxic dose: 2 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation TOXIA6 49,670,2007
intravenous
rat 		lethal dose (50 percent kill): 21 mg/kg N/R ARZNAD 31,655,1981
intravenous
rat 		lowest published toxic dose: 10 mg/kg Vascular: BP elevation not characterized in autonomic section

Kidney, Ureter, and Bladder: Changes in blood vessels or in circulation of kidney 		JPETAB 304,507,2003
intravenous
rat 		lowest published toxic dose: 5 mg/kg Vascular: Measurement of regional blood flow

Gastrointestinal: Other changes 		BJPCBM 139,263,2003
intravenous
rat 		lowest published toxic dose: 10 mg/kg Cardiac: Change in rate PHMCAA 76,84,2006
intravenous
rabbit 		lowest published toxic dose: 15 mg/kg Blood: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cabonic anhydrase 		CEXPB9 27,95,2000
intravenous
rabbit 		lowest published toxic dose: 5 mg/kg Vascular: Measurement of regional blood flow

Kidney, Ureter, and Bladder: Changes in blood vessels or in circulation of kidney 		CEXPB9 29,873,2002
multiple
man 		lowest published toxic dose: 3,557 mg/kg/5 year- intermittent Eye: Retinal changes pigmentary deposition, retinitis, other) AJOPAA 73,846,1972
oral
cat 		lethal dose (50 percent kill): 320 mg/kg N/R ARZNAD 30,1398,1980
oral
cat 		lowest published toxic dose: 4 mg/kg Cardiac: Changes in coronary arteries

Cardiac: Other changes 		FATOAO 48,54,1985
oral
cat 		lowest published toxic dose: 4 mg/kg Cardiac: Other changes

Vascular: Measurement of regional blood flow 		FATOAO 48,54,1985
oral
dog 		lethal dose (50 percent kill): 160 mg/kg N/R OYYAA2 2,70,1968
oral
guinea pig 		lethal dose (50 percent kill): 100 mg/kg N/R OYYAA2 2,70,1968
oral
guinea pig 		lowest published toxic dose: 10 mg/kg Lung, Thorax, or Respiration: Respiratory obstruction JPHSC* 105,251,2007
oral
hamster 		lethal dose (50 percent kill): 81 mg/kg N/R ATSUDG 7,365,1984
oral
human 		lowest published toxic dose: 113 mg/kg/8 week- intermittent Gastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Other changes 		ARZNAD 33,636,1983
oral
human 		lowest published toxic dose: 0.7 mg/kg Blood: Change in clotting factors BCPHBM 53,644,2002
oral
infant 		lowest published toxic dose: 400 µg/kg/2 day- intermittent Gastrointestinal: Necrotic changes JOPDAB 107,484,1985
oral
mammal (species unspecified) 		lethal dose (50 percent kill): 8 mg/kg N/R IJMRAQ 81,621,1985
oral
man 		lowest published toxic dose: 4,286 µg/kg/2 day- intermittent Skin: After systemic exposure: Dermatitis, other PGMJAO 72,186,1996
oral
man 		lowest published lethal dose: 15 mg/kg/2 week- intermittent Blood: Aplastic anemia IJMDAI 17,433,1981
oral
man 		lowest published toxic dose: 22,500 µg/kg/3 week- intermittent Liver: Hepatitis, fibrous (cirrhosis, post- necrotic scarring)

Liver: Other changes 		BMJOAE 3,155,1967
oral
man 		lowest published toxic dose: 22,500 µg/kg/3 week- intermittent Gastrointestinal: Ulceration or bleeding from large intestine APHRER 29,883,1994
oral
man 		lowest published toxic dose: 714 µg/kg Behavioral: General anesthetic

Behavioral: Convulsions or effect on seizure threshold

Behavioral: Ataxia 		LLRGDY 54,90,1999
oral
mouse 		lethal dose (50 percent kill): 11,841 µg/kg N/R GWXXBX #3005827
oral
mouse 		lowest published toxic dose: 5 mg/kg Kidney, Ureter, and Bladder: Other changes in urine composition FRMCE8 55,495,2000
oral
mouse 		lowest published toxic dose: 2.5 mg/kg Gastrointestinal: Ulceration or bleeding from stomach FRMCE8 56,939,2001
oral
mouse 		lowest published toxic dose: 0.3 mg/kg Gastrointestinal: Decreased motility or constipation BPBLEO 24,1122,2001
oral
mouse 		lowest published toxic dose: 10 mg/kg Gastrointestinal: Other changes

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

Biochemical: Metabolism (intermediary): Histamines (including liberation not immunochemical in origin) 		EJPHAZ 460,63,2003
oral
mouse 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Histamines (including liberation not immunochemical in origin) 		EJPHAZ 460,63,2003
oral
mouse 		lowest published toxic dose: 10 mg/kg Behavioral: Analgesia

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		BJMRDK 35,1229,2002
oral
mouse 		lowest published toxic dose: 5 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation JPETAB 304,1172,2003
oral
mouse 		lowest published toxic dose: 0.4 mg/kg Behavioral: Analgesia PHMCAA 68,96,2003
oral
mouse 		lowest published toxic dose: 5 mg/kg Nutritional and Gross Metabolic: Body temperature decrease

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		FTRPAE 70,25,1999
oral
rat 		lethal dose (50 percent kill): 2,420 µg/kg Gastrointestinal: Ulceration or bleeding from stomach ARZNAD 25,1526,1975
oral
rat 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		JPETAB 297,1010,2001
oral
rat 		lowest published toxic dose: 5 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation

Behavioral: Analgesia 		FRMCE8 55,383,2000
oral
rat 		lowest published toxic dose: 5 mg/kg Liver: Liver function tests impaired FATOAO 47,28,1985
oral
rat 		lowest published toxic dose: 5 mg/kg Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductases 		FATOAO 48,28,1985
oral
rat 		lethal dose (50 percent kill): 17 mg/kg N/R FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 10 mg/kg Gastrointestinal: Hypermotility, diarrhea

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects

Biochemical: Metabolism (intermediary): Lipids including transport 		JPETAB 303,1248,2002
oral
rat 		lowest published toxic dose: 10 mg/kg Gastrointestinal: Ulceration or bleeding from small intestine

Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		JPETAB 303,1248,2002
oral
rat 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Alteration in gastric secretion

Gastrointestinal: Ulceration or bleeding from stomach 		FCLPH* 16,311,2002
oral
rat 		lowest published toxic dose: 10 mg/kg Gastrointestinal: Ulceration or bleeding from small intestine

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

Biochemical: Metabolism (intermediary): Lipids including transport 		JPETAB 300,754,2002
oral
rat 		lowest published toxic dose: 3 mg/kg Gastrointestinal: Ulceration or bleeding from stomach

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		JPETAB 303,503,2002
oral
rat 		lowest published toxic dose: 1 mg/kg Behavioral: Analgesia BJPCBM 139,927,2003
oral
rat 		lowest published toxic dose: 7.5 mg/kg Gastrointestinal: Ulceration or bleeding from small intestine BJMRDK 37,333,2004
oral
rat 		lowest published toxic dose: 3 mg/kg Gastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Other changes 		JPETAB 314,302,2005
oral
rat 		lowest published toxic dose: 0.1 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation JPETAB 312,1206,2005
oral
rat 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Other changes

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		EJPHAZ 547,136,2006
oral
rat 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Ulceration or bleeding from small intestine

Gastrointestinal: Other changes 		EJPHAZ 552,143,2006
oral
rat 		lowest published toxic dose: 5.01 mg/kg Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Plasma proteins not involving coagulation 		JPETAB 318,1248,2006
oral
rat 		lowest published toxic dose: 30 mg/kg Nutritional and Gross Metabolic: Body temperature decrease BJPCBM 150,415,2007
oral
rat 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductases 		BJPCBM 146,481,2005
oral
rat 		lowest published toxic dose: 5 mg/kg Gastrointestinal: Ulceration or bleeding from stomach BPBLEO 29,361,2006
oral
rat 		lowest published toxic dose: 10 mg/kg Behavioral: Analgesia

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		FCLPH* 20,65,2006
oral
rat 		lowest published toxic dose: 25 mg/kg Gastrointestinal: Ulceration or bleeding from stomach

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		JPHSC* 105,94,2007
oral
rabbit 		lethal dose (50 percent kill): 135 mg/kg N/R NIIRDN 6,90,1982
oral
woman 		lowest published toxic dose: 10 mg/kg Behavioral: Coma JJTOEX 12,337,1999
oral
woman 		lowest published toxic dose: 2,098 µg/kg/1 day- intermittent Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Kidney, Ureter, and Bladder: Urine volume decreased or anuria 		SMJOAV 78,1390,1985
rectal
man 		lowest published toxic dose: 2,586 mg/kg/3.5 year- intermittent Eye: Retinal changes pigmentary deposition, retinitis, other) AJOPAA 73,846,1972
rectal
rat 		lethal dose (50 percent kill): 31,900 µg/kg N/R YACHDS 14,2259,1986
subcutaneous
mouse 		lethal dose (50 percent kill): 18,300 µg/kg N/R ARZNAD 30,1398,1980
subcutaneous
mouse 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Ulceration or bleeding from stomach FATOAO 49,57,1986
subcutaneous
mouse 		lowest published toxic dose: 30 mg/kg Behavioral: Analgesia FATOAO 48,28,1985
subcutaneous
mouse 		lowest published toxic dose: 40 mg/kg Brain and Coverings: Recordings from specific areas of CNS JPETAB 305,755,2003
subcutaneous
mouse 		lowest published toxic dose: 0.5 mg/kg Behavioral: Food intake (animal) BPBLEO 29,1319,2006
subcutaneous
mouse 		lowest published toxic dose: 4 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation TOXIA6 49,1090,2007
subcutaneous
rat 		lethal dose (50 percent kill): 12 mg/kg N/R OYYAA2 2,70,1968
subcutaneous
rat 		lowest published toxic dose: 2 mg/kg Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: True cholinesterase

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Peptidases 		EURNE* 11,367,2001
subcutaneous
rat 		lowest published toxic dose: 20 mg/kg Gastrointestinal: Ulceration or bleeding from stomach FATOAO 49,57,1986
subcutaneous
rat 		lowest published toxic dose: 2.5 mg/kg Endocrine: Effect on menstrual cycle

Reproductive: Maternal effects: Ovaries, fallopian tubes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Proteases 		JRPFA4 123,639,2002
subcutaneous
rat 		lowest published toxic dose: 2 mg/kg Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		TOXIA6 42,183,2003
subcutaneous
rat 		lowest published toxic dose: 10 mg/kg Gastrointestinal: Other changes EJPHAZ 554,53,2007
subcutaneous
rat 		lowest published toxic dose: 10 mg/kg Gastrointestinal: Ulceration or bleeding from small intestine

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects

Biochemical: Metabolism (intermediary): Lipids including transport 		JPHSC* 103,40,2007
subcutaneous
rat 		lowest published toxic dose: 5 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BPBLEO 31,691,2008
subcutaneous
rat 		lowest published toxic dose: 1,333.3 µg/kg Behavioral: Analgesia BJMRDK 40,1141,2007
skin
guinea pig 		lethal dose : >100 mg/kg Behavioral: Excitement YACHDS 14,3185,1986
skin
mouse 		lowest published toxic dose: 10 mg/kg Immunological Including Allergic: Decrease in cellular immune response FATOAO 47,84,1984
skin
mouse 		lowest published toxic dose: 0.1 pph/8 hour Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation EJPHAZ 505,229,2004
skin
mouse 		lowest published toxic dose: 20 µg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BMECEP 11,1187,2003
skin
rat 		lethal dose : >250 mg/kg N/R YACHDS 14,3185,1986
skin
rat 		lowest published toxic dose: 12 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation FATOAO 47,84,1984
unreported route
man 		lowest published toxic dose: 499 mg/kg/87 week- intermittent Behavioral: Stiffness

Kidney, Ureter, and Bladder: Hematuria 		ARHEAW 20,917,1977
unreported route
mouse 		lethal dose (50 percent kill): 100 mg/kg N/R FATOAO 48,28,1985
unreported route
rat 		lowest published toxic dose: 30 mg/kg Gastrointestinal: Ulceration or bleeding from stomach FATOAO 51,64,1988
unreported route
rat 		lethal dose (50 percent kill): 200 mg/kg N/R FATOAO 48,54,1985
unreported route
rat 		lowest published toxic dose: 10 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation FCLPH* 18(Suppl 1),111,2004


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM 		DOSE
EFFECT

 REFERENCE
intraperitoneal
mouse 		lowest published toxic dose: 39 mg/kg/13 day- intermittent Lung, Thorax, or Respiration: Tumors

Skin and Appendages: Tumors

Tumorigenic: Active as anti-cancer agent 		BJCAAI 87,231,2002
intraperitoneal
mouse 		lowest published toxic dose: 2 mg/kg/2 day- intermittent Behavioral: Analgesia

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		JPETAB 314,111,2005
intraperitoneal
rat 		lowest published toxic dose: 9 mg/kg/3 day- intermittent Musculoskeletal: Joints

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		JPETAB 301,738,2002
intraperitoneal
rat 		lowest published toxic dose: 25 mg/kg/5 day- intermittent Kidney, Ureter, and Bladder: Renal function tests depressed

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		BJMRDK 37,979,2004
intravenous
infant 		lowest published toxic dose: 0.6 mg/kg/2 day- intermittent Kidney, Ureter, and Bladder: Renal function tests depressed

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		FCLPH* 19,187,2004
oral
dog 		lowest published toxic dose: 90 mg/kg/90 day- continuous Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Ulceration or bleeding from small intestine

Gastrointestinal: Hypermotility, diarrhea 		OYYAA2 7,333,1973
oral
dog 		lowest published toxic dose: 350 mg/kg/5 week- intermittent Gastrointestinal: Ulceration or bleeding from large intestine

Kidney, Ureter, and Bladder: Other changes in urine composition

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		YACHDS 17,1433,1989
oral
dog 		lowest published toxic dose: 40 mg/kg/4 day- intermittent Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Ulceration or bleeding from duodeum 		JPETAB 311,904,2004
oral
dog 		lowest published toxic dose: 40 mg/kg/4 day- intermittent Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		JPETAB 311,904,2004
oral
mammal (species unspecified) 		lowest published toxic dose: 168 mg/kg/4 week- intermittent Gastrointestinal: Necrotic changes

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Nutritional and Gross Metabolic: Changes in: Cl 		FAATDF 15,800,1990
oral
mammal (species unspecified) 		lowest published toxic dose: 120 mg/kg/30 day- intermittent Gastrointestinal: Gastritis PCJOAU 35,254,2001
oral
monkey 		lowest published toxic dose: 135 mg/kg/90 day- continuous Gastrointestinal: Ulceration or bleeding from stomach

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

Blood: Changes in leukocyte (WBC) count 		OYYAA2 7,333,1973
oral
monkey 		lowest published toxic dose: 126 mg/kg/18 week- intermittent Behavioral: Food intake (animal)

Gastrointestinal: Hypermotility, diarrhea

Gastrointestinal: Other changes 		YAKUD5 8,1076,1966
oral
mouse 		lowest published toxic dose: 150 mg/kg/5 week- intermittent Lung, Thorax, or Respiration: Other changes

Blood: Changes in spleen

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		KSRNAM 13,1901,1979
oral
mouse 		lowest published toxic dose: 48 mg/kg/24 day- continuous Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent 		BCPCA6 61,565,2001
oral
mouse 		lowest published toxic dose: 0.384 mg/kg/12 day- continuous Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BCPCA6 66,1055,2003
oral
mouse 		lowest published toxic dose: 39.2 gm/kg/2 week- intermittent Behavioral: Convulsions or effect on seizure threshold TOXID9 66,90,2002
oral
mouse 		lowest published toxic dose: 504 mg/kg/30 week- continuous Tumorigenic: Protects against induction of experimental tumors CRNGDP 26,571,2005
oral
rat 		lowest published toxic dose: 26 mg/kg/7 day- intermittent Gastrointestinal: Ulceration or bleeding from small intestine

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		INFLD4 22,243,1998
oral
rat 		lowest published toxic dose: 33 mg/kg/11 day- intermittent Gastrointestinal: Ulceration or bleeding from stomach

Gastrointestinal: Ulceration or bleeding from duodeum

Gastrointestinal: Other changes 		ARZNAD 44,1329,1994
oral
rat 		lowest published toxic dose: 168 mg/kg/4 week- continuous Lung, Thorax, or Respiration: Changes in lung weight

Endocrine: Changes in spleen weight

Blood: Normocytic anemia 		YACHDS 16,2763,1988
oral
rat 		lowest published toxic dose: 273 mg/kg/13 week- intermittent Blood: Normocytic anemia

Biochemical: Metabolism (intermediary): Other proteins

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		YACHDS 17,21,1989
oral
rat 		lowest published toxic dose: 1,820 mg/kg/52 week- continuous Gastrointestinal: Ulceration or bleeding from small intestine

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		OYYAA2 7,333,1973
oral
rat 		lowest published toxic dose: 210 mg/kg/35 day- continuous Gastrointestinal: Ulceration or bleeding from stomach

Endocrine: Other changes

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol) 		OYYAA2 22,665,1981
oral
rat 		lowest published toxic dose: 650 mg/kg/26 week- intermittent Behavioral: Food intake (animal)

Gastrointestinal: Ulceration or bleeding from small intestine

Nutritional and Gross Metabolic: Weight loss or decreased weight gain 		ARZNAD 28,445,1978
oral
rat 		lowest published toxic dose: 105 mg/kg/21 day- intermittent Liver: Changes in liver weight

Kidney, Ureter, and Bladder: Changes in bladder weight

Related to Chronic Data: Changes in ovarian weight 		ARZNAD 22,226,1972
oral
rat 		lowest published toxic dose: 24 mg/kg/4 day- intermittent Gastrointestinal: Ulceration or bleeding from stomach TXAPA9 52,454,1980
oral
rat 		lowest published toxic dose: 50 mg/kg/5 day- intermittent Kidney, Ureter, and Bladder: Other changes in urine composition

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		ARTODN 73,233,1999
oral
rat 		lowest published toxic dose: 17.5 mg/kg/7 day- intermittent Liver: Liver function tests impaired FATOAO 48,28,1985
oral
rat 		lowest published toxic dose: 21 mg/kg/7 day- intermittent Gastrointestinal: Peritonitis

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 30 mg/kg/2 day- intermittent Gastrointestinal: Peritonitis

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		FATOAO 48,66,1985
oral
rat 		lowest published toxic dose: 30 mg/kg/3 day- intermittent Liver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects 		FATOAO 53,52,1990
oral
rat 		lowest published toxic dose: 120,000 mg/kg/16 week- continuous Tumorigenic: Active as anti-cancer agent FATOAO 52,67,1989
oral
rat 		lowest published toxic dose: 25 mg/kg/5 day- intermittent Gastrointestinal: Ulceration or bleeding from stomach EKFAE9 58,33,1995
oral
rat 		lowest published toxic dose: 17.5 mg/kg/7 day- intermittent Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductases 		FATOAO 48,28,1985
oral
rat 		lowest published toxic dose: 25 mg/kg/5 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field FATOAO 48,28,1985
oral
rat 		lowest published toxic dose: 375 mg/kg/15 day- intermittent Musculoskeletal: Joints

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		TOXID9 44,241,2005
oral
rat 		lowest published toxic dose: 40 mg/kg/2 day- intermittent Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BPBLEO 30,63,2007
oral
rat 		lowest published toxic dose: 7.51 mg/kg/3 day- intermittent Gastrointestinal: Other changes JPETAB 318,1248,2006
oral
rat 		lowest published toxic dose: 30.06 mg/kg/3 day- intermittent Gastrointestinal: Peritonitis

Gastrointestinal: Other changes

Kidney, Ureter, and Bladder: Urine volume decreased or anuria 		JPETAB 318,1248,2006
oral
rat 		lowest published toxic dose: 15.03 mg/kg/3 day- intermittent Gastrointestinal: Other changes

Biochemical: Metabolism (intermediary): Plasma proteins not involving coagulation 		JPETAB 318,1248,2006
oral
rat 		lowest published toxic dose: 4 mg/kg/4 day- intermittent Reproductive: Other effects on female TXCYAC 232,257,2007
oral
rat 		lowest published toxic dose: 4.2 mg/kg/21 day- intermittent Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation PHMCAA 68,96,2003
oral
rat 		lowest published toxic dose: 18.9 mg/kg/21 day- intermittent Gastrointestinal: Ulceration or bleeding from stomach PHMCAA 68,96,2003
oral
rat 		lowest published toxic dose: 14 mg/kg/7 day- intermittent Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BPBLEO 30,1934,2007
oral
rat 		lowest published toxic dose: 6 mg/kg/3 day- intermittent Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BMCPH* 6,12,2006
oral
rat 		lowest published toxic dose: 450 mg/kg/12 week- intermittent Kidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Other proteins

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		JPHPH* 58,165,2007
oral
rat 		lowest published toxic dose: 50 mg/kg/5 day- intermittent Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation IRJPH* 5,141,2006
oral
rat 		lowest published toxic dose: 120 mg/kg/12 day- intermittent Gastrointestinal: Ulceration or bleeding from stomach

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		IRJPH* 5,141,2006
oral
rat 		lowest published toxic dose: 0.896 gm/kg/32 week- continuous Tumorigenic: Protects against induction of experimental tumors JTPAE7 20,245,2007
oral
rabbit 		lowest published toxic dose: 1,050 mg/kg/12 week- intermittent Kidney, Ureter, and Bladder: Other changes in urine composition

Biochemical: Metabolism (intermediary): Lipids including transport

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation 		CEXPB9 30,405,2003
oral
woman 		lowest published toxic dose: 45 mg/kg/3 day- intermittent Blood: Aplastic anemia

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		CMAJAX 117,118,1977
subcutaneous
mouse 		lowest published toxic dose: 40 mg/kg/2 day- intermittent Gastrointestinal: Ulceration or bleeding from small intestine

Gastrointestinal: Other changes

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field 		BPBLEO 30,495,2007
subcutaneous
rat 		lowest published toxic dose: 4 mg/kg/2 day- intermittent Behavioral: Change in motor activity (specific assay)

Endocrine: Changes in pituitary weight

Biochemical: Neurotransmitters or modulators (putative): Catecholamine levels in CNS 		EURNE* 11,367,2001
subcutaneous
rat 		lowest published toxic dose: 4.9 mg/kg/7 day- intermittent Musculoskeletal: Other changes FATOAO 51,73,1988
subcutaneous
rat 		lowest published toxic dose: 9,017 µg/kg/3 day- intermittent Kidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Other 		TOXID9 44,104,2005
skin
mouse 		lowest published toxic dose: 120 mg/kg/10 day- intermittent Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation FATOAO 47,84,1984


REVIEWS:

ORGANIZATION STANDARD
REFERENCE
TOXICOLOGY REVIEW
CTOXAO 17,85,1980
TOXICOLOGY REVIEW
REPTED 9,7,1995
TOXICOLOGY REVIEW
TOLED5 127,269,2002
TOXICOLOGY REVIEW
MUREAV 488,151,2001
TOXICOLOGY REVIEW
TOLED5 144,383,2003
TOXICOLOGY REVIEW
TPHSDY 23,153,2002
TOXICOLOGY REVIEW
TPHSDY 23,324,2002
TOXICOLOGY REVIEW
TPHSDY 23,426,2002
TOXICOLOGY REVIEW
TPHSDY 24,7,2003
TOXICOLOGY REVIEW
TPHSDY 24,245,2003
TOXICOLOGY REVIEW
TPHSDY 24,290,2003
TOXICOLOGY REVIEW
TPHSDY 24,524,2003
TOXICOLOGY REVIEW
JPSYM* 20,140,2000
TOXICOLOGY REVIEW
APHRER 37,1664,2003
TOXICOLOGY REVIEW
APHRER 37,1675,2003
TOXICOLOGY REVIEW
APHRER 38,1159,2004
TOXICOLOGY REVIEW
APHRER 38,700,2004
TOXICOLOGY REVIEW
APHRER 39,944,2005
TOXICOLOGY REVIEW
BPCEM* 17,237,2003
TOXICOLOGY REVIEW
CLTHE* 28,1123,2006
TOXICOLOGY REVIEW
EJIME* 17,529,2006
TOXICOLOGY REVIEW
DIMON* 39,678,1993
TOXICOLOGY REVIEW
BJPCBM 146,477,2005
TOXICOLOGY REVIEW
TOPADD 32(Suppl. 2),71,2004
TOXICOLOGY REVIEW
FCLPH* 17,393,2003
TOXICOLOGY REVIEW
APHRER 40,1785,2006
TOXICOLOGY REVIEW
APHRER 40,1924,2006
TOXICOLOGY REVIEW
TPHSDY 28,501,2007
TOXICOLOGY REVIEW
PHREP* 59,247,2007


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE
Occupational Exposure Limit - RUSSIA short term exposure limit 0.05 mg/m3, Skin, JUN2003


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: X4091;
Number of Industries 2;
Total Number of Facilities 123;
Number of Occupations 10;
Total Number of Employees Exposed 5,082;
Total Number of Female Employees Exposed 2,130


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE
EPA TSCA Section 8(b) CHEMICAL INVENTORY


REFERENCES:

CODEN
REFERENCE
ACENA7 Acta Endocrinologica (Copenhagen). (Periodica, Skolegade 12 E, DK-2500 Valby, Denmark) V.1- 1948-
AFTOD7 Archivos de Farmacologia y Toxicologia. (Universidad Complutense, Facultad de Medicina, Departamento Coordinado de Farmacologia, Ciudad Universitaria, Madrid 3, Spain) V.1- 1975-
AJMGDA American Journal of Medical Genetics. (John Wiley & Sons Ltd., 605 Third Ave., New York, NY 10158) V.1- 1977-
AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920-
AJOPAA American Journal of Ophthalmology. (Ophthalmic Pub. Co., 435 N. Michigan Ave., Suite 1415, Chicago, IL 60611) Series 3: V.1- 1918-
ANANAU Anatomischer Anzeiger. (VEB Gustav Fischer Verlag, Postfach 176, Jena DDR-6900, Ger. Dem. Rep.) V.1- 1886-
AOGSAE Acta Obstetricia et Gynecologica Scandinavica. (Box 443, S-90109 Umeaa, Sweden) V.1- 1921-
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Used as a non-steroidal anti-inflammatory substance

FDA-proprietary drug

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

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