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Registry of Toxic Effects of Chemical Substances (RTECS)

Acetanilide, 4'-hydroxy-

RTECS #

AE4200000

CAS #

103-90-2; 8055-08-1

Updated

December 2013

Molecular Weight

151.18

Molecular Formula

C8H9NO2

Synonyms

4-Acetamidophenol
4'-Hydroxyacetanilide
4-Hydroxyacetanilide
4-Hydroxyanilid kyseliny octove (Czech)
Abensanil
Acamol
Acetagesic
Acetalgin
Acetamide, N-(4-hydroxyphenyl)-
Acetamide, N-(p-hydroxyphenyl)-
Acetaminofen
Acetaminophen
Algotropyl
Alvedon
Amadil
Anaflon
Anelix
Apamid
Apamide
APAP
Ben-u-ron
Bickie-mol
Calpol
Cetadol
Clixodyne
Datril
Dial-a-gesic
Dirox
Dymadon
Eneril
Febrilix
Febro-gesic
Febrolin
Fendon
Finimal
Hedex
Homoolan
Lestemp
Liquagesic
Lonarid
Lyteca
Lyteca syrup
Multin
N-(4-Hydroxyphenyl)acetamide
N-Acetyl-p-aminophenol
N-Acetyl-para-aminophenol
NAPA (analgesic)
Napafen
Napap
Naprinol
NCI-C55801
Nobedon
Pacemo
p-Acetamidophenol
p-Acetaminophenol
p-Acetylaminophenol
Panadol
Panets
Paracetamol
Paracetamole
Paracetamolo (Italian)
Paracetamolum
Parmol
Pedric
Phendon
Phenol, p-acetamido-
p-Hydroxyacetanilide
Pyrinazine
SK-Apap
Tabalgin
Tapar
Temlo
Tempanal
Tempra
Tralgon
Tussapap
Tylenol
Valadol
Valgesic

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysislymphocyte/human200 mg/LNEZAAQ 37,673,1982
Cytogenetic Analysisoral/human42860 µg/kgMUREAV 209,161,1988
Cytogenetic Analysisoral/mouse50 mg/kgCYTBAI 27,27,1980
Cytogenetic Analysisintraperitoneal/mouse200 mg/kgMUREAV 278,253,1992
Cytogenetic Analysisovary/hamster70 mg/L/24HPCBRD2 209A,365,1986
Cytogenetic Analysisfibroblast/hamster60 mg/LESKHA5 (96),55,1978
Cytogenetic Analysislung/hamster10 mg/LATSUDG 4,41,1980
DNA Damagelung/hamster3 mmol/LMUREAV 204,333,1988
DNA Damageintraperitoneal/mouse300 mg/kgTOXID9 66,362,2002
DNA Damageliver/human1 mmol/l/48HMUREAV 696,21,2010
DNA Damageliver/mouse1 mmol/LTXAPA9 111,242,1991
DNA inhibitionlymphocyte/human300 µmol/LMUREAV 261,1,1991
DNA inhibitionlung/hamster160 µmol/LMUTAEX 3,51,1988
micronucleus testlung/hamster39 µmol/L/48H (-enzymatic activation step)MUTAEX 26,709,2011
micronucleus testlung/hamster626 µmol/L/6H (-enzymatic activation step)MUTAEX 26,709,2011
micronucleus testlung/hamster50 mg/LMUREAV 272,223,1992
micronucleus testoral/human42857 µg/kg/8H- intermittentMUREAV 227,147,1989
micronucleus testkidney/rat10 mmol/LMUREAV 189,299,1987
micronucleus testintraperitoneal/mouse100 mg/kgJPMSAE 80,761,1991
morphological transformembryo/mouse1 gm/LCNREA8 49,1038,1989
mutation in microorganisms/Salmonella typhimurium100 µg/disc (+enzymatic activation step)JNUDAT 34,183,1992
other mutation test systemslymphocyte/human200 mg/LNEZAAQ 37,673,1982
other mutation test systemslung/hamster3 mmol/LTIVIEQ 3,13,1989
sex chromosome loss and nondisjunctionoral/mouse25 mg/kgCARYAB 38,347,1985
sister chromatid exchangeovary/hamster200 mg/LPCBRD2 209A,365,1986
sister chromatid exchangelung/hamster1 mmol/LMUTAEX 3,51,1988
sister chromatid exchangeoral/human42860 µg/kgMUREAV 261,1,1991
sister chromatid exchangelymphocyte/human1 mmol/LMUREAV 261,1,1991
sister chromatid exchangeintraperitoneal/mouse50 mg/kgMUREAV 278,253,1992
Unscheduled DNA Synthesisoral/mouse84 gm/kg/40W-continuousTXAPA9 96,494,1988
Unscheduled DNA Synthesisliver/mouse7500 µmol/LMUREAV 164,167,1986
Unscheduled DNA Synthesisliver/rat10 mmol/LMUREAV 164,167,1986
Unscheduled DNA Synthesisoral/rat500 mg/kgMUREAV 320,189,1994

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
oral/woman 650 mg/kg (29W pregnant)Reproductive: Effects on newborn: Apgar score (human only)

Reproductive: Effects on newborn: Other neonatal measures or effects

Reproductive: Effects on newborn: Other postnatal measures or effects
ADCHAK 58,631,1983
oral/woman 417 mg/kg (20W pregnant)Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Hepatobiliary system
BJOGAS 91,286,1984
oral/woman 1300 mg/kg (31-32W pregnant)Reproductive: Other effects on female

Reproductive: Other effects to embryo or fetus

Reproductive: Effects on newborn: Other neonatal measures or effects
BJOGAS 96,491,1989
oral/rat 500 mg/kg (3D pregnant)Reproductive: Other effects to embryo or fetusZYDXDM 27,49,1998
oral/rat 1500 mg/kg (8-19D 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: Fetotoxicity (except death, e.g., stunted fetus)
JPMSAE 66,111,1977
oral/rat 12500 mg/kg (14D prior to copulation/1-11D pregnant)Reproductive: Effects on embryo or fetus: Cytological changes (including somatic cell genetic material)TJADAB 26(1),42A,1982
oral/rat 1 gm/kg (3D pregnant)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)

Reproductive: Effects on newborn: Behavioral

Reproductive: Effects on newborn: Other postnatal measures or effects
ZYDXDM 22,196,1993
oral/rat 35 gm/kg (70D male)Reproductive: Paternal effects: Testes, epididymis, sperm duct

Reproductive: Other effects on male
ATSUDG 7,164,1984
oral/mouse 25 mg/kg (1D male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)CYTBAI 27,27,1980
oral/mouse 600 mg/kg (1D male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)

Reproductive: Paternal effects: Testes, epididymis, sperm duct
TOXID9 4,170,1984
oral/mouse 2500 mg/kg (6-15D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system
TOXID9 4,166,1984
oral/mouse 2500 mg/kg (6-15D pregnant)Reproductive: Specific developmental abnormalities: Urogenital systemTOXID9 4,166,1984
oral/mouse 1430 mg/kg (2D pregnant)Reproductive: Other effects on femaleTOSCF2 56,150,2000
oral/mouse 15730 mg/kg (8D prior to copulation/1-3D pregnant)Reproductive: Effects on fertility: Other measures of fertility

Reproductive: Other effects to embryo or fetus
TOSCF2 56,150,2000
oral/rabbit 2 gm/kg (1D prior to copulation)Reproductive: Effects on fertility: Other measures of fertilityFESTAS 38,238,1982
oral/mouse 49 gm/kg (7D male/7D prior to copulation/21D pregnant)Reproductive: Effects on fertility: Litter size (e.g., # fetuses per litter; measured before birth)NTIS** #PB85204667/AS
oral/mouse 370 mg/kg (multigenerations)Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)NTIS** #PB85204667/AS
oral/mouse 1400 mg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Urogenital systemNTIS** #PB85204667/AS
oral/mouse 1400 mg/kg (multigenerations)Reproductive: Specific developmental abnormalities: Hepatobiliary systemNTIS** #PB85204667/AS
oral/rat 24.5 mg/kg (8-14D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TSPSA* -,258,2003

Tumorigenic Data and References

Route/OrganismDoseEffectReference
oral/mouse lowest published toxic dose: 135 gm/kg/77W- continuousTumorigenic: Carcinogenic by RTECS criteria

Liver: Hepatitis (hepatocellular necrosis), zonal

Liver: Tumors
CRNGDP 4,363,1983
oral/mouse toxic dose: 270 gm/kg/77W- continuousTumorigenic: Equivocal tumorigenic agent by RTECS criteria

Liver: Tumors

Endocrine: Other changes
CRNGDP 4,363,1983
oral/rat toxic dose: 329 gm/kg/78W- continuousTumorigenic: Carcinogenic by RTECS criteria

Liver: Tumors
ACPADQ 93,367,1985
oral/rat lowest published toxic dose: 218400 mg/kg/104W- continuousTumorigenic: Carcinogenic by RTECS criteria

Blood: Leukemia
NTIS** PB93-227478
oral/rat lowest published toxic dose: 164 gm/kg/78W- continuousTumorigenic: Carcinogenic by RTECS criteria

Kidney, Ureter, and Bladder: Bladder tumors
ACPADQ 93,367,1985

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Chicken, neurons Inhibitor Concentration (50 percent kill): 36683 µmol/L/21HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 7,653,1993
In Vitro/Chicken, neurons Inhibitor Concentration (10 percent kill): 10045 µmol/L/21HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 7,653,1993
In Vitro/Chicken, neurons Inhibitor Concentration (50 percent kill): 35026 µmol/L/20HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 7,653,1993
In Vitro/Chicken, neurons Inhibitor Concentration (10 percent kill): 7240 µmol/L/20HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 7,653,1993
In Vitro/Hamster, lung fibroblast Inhibitor Concentration (50 percent kill): 0.25 mmol/L/60HIn Vitro Toxicity Studies: Cell countingTIVIEQ 7,511,1993
In Vitro/Hamster, lung fibroblast Inhibitor Concentration (10 percent kill): 0.04 mmol/L/60HIn Vitro Toxicity Studies: Cell countingTIVIEQ 7,511,1993
In Vitro/Hamster, lung fibroblast Inhibitor Concentration Low: 1 mmol/L/2HIn Vitro Toxicity Studies: Cell metabolic activity: Alamar Blue assay etc.TIVIEQ 1,133,1987
In Vitro/Human, HeLa cell Inhibitor Concentration (50 percent kill): 0.87 mmol/L/60HIn Vitro Toxicity Studies: Cell countingTIVIEQ 7,511,1993
In Vitro/Human, HeLa cell Inhibitor Concentration (10 percent kill): 0.1 mmol/L/60HIn Vitro Toxicity Studies: Cell countingTIVIEQ 7,511,1993
In Vitro/Human, liver Inhibitor Concentration (50 percent kill): 6.6 µmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 6,47,1992
In Vitro/Human, liver Inhibitor Concentration (10 percent kill): 2.1 µmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 6,47,1992
In Vitro/Human, liver Inhibitor Concentration Low: 20 mmol/L/4HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)TXAPA9 249,148,2010
In Vitro/Human, melanoma Inhibitor Concentration (50 percent kill): 675 µmol/L/1HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.FCTOD7 50,1781,2012
In Vitro/Human, melanoma Inhibitor Concentration Low: 675 µmol/L/1HIn Vitro Toxicity Studies: Cell metabolic activity: Alamar Blue assay etc.

In Vitro Toxicity Studies: Apoptosis in vitro

In Vitro Toxicity Studies: Other assays
FCTOD7 50,1781,2012
In Vitro/Human, skin Inhibitor Concentration (50 percent kill): 1400 mg/L/48HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,367,1992
In Vitro/Human, skin Inhibitor Concentration (50 percent kill): >200000 mg/L/1MIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,367,1992
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 13.6 µmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 6,47,1992
In Vitro/Mouse, fibroblast Inhibitor Concentration (10 percent kill): 2.61 µmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 6,47,1992
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 5.5 mmol/L/48HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 5,449,1991
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 0.63 mmol/L/72HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 5,449,1991
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 6.4 mmol/L/48HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 5,449,1991
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 0.84 mmol/L/72HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 5,449,1991
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 2.4 mmol/L/48HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 5,449,1991
In Vitro/Mouse, fibroblast Inhibitor Concentration (50 percent kill): 0.55 mmol/L/72HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 5,449,1991
In Vitro/Mouse, liver Inhibitor Concentration (50 percent kill): 6 mmol/L/24HIn Vitro Toxicity Studies: Cell metabolic activity: Alamar Blue assay etc.TXAPA9 249,208,2010
In Vitro/Mouse, liver Inhibitor Concentration (50 percent kill): 2.4 mmol/L/24HIn Vitro Toxicity Studies: Other assaysTXAPA9 249,208,2010
In Vitro/Pig, liver Inhibitor Concentration Low: 10000 µmol/L/16HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)TIVIEQ 5,31,1991
In Vitro/Pig, liver Inhibitor Concentration Low: 3000 µmol/L/16HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 5,31,1991
In Vitro/Rat, liver Inhibitor Concentration (50 percent kill): 5 µmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 6,47,1992
In Vitro/Rat, liver Inhibitor Concentration (10 percent kill): 2.4 µmol/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 6,47,1992
In Vitro/Rat, liver Inhibitor Concentration Low: 1 mmol/L/48HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.

In Vitro Toxicity Studies: Other assays
TXAPA9 249,140,2010
In Vitro/Rat, liver Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)TIVIEQ 5,543,1991
In Vitro/Rat, liver Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 5,543,1991
In Vitro/Rat, liver Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 5,543,1991
In Vitro/Rat, liver Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 5,543,1991
In Vitro/Rat, liver tumor Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)TIVIEQ 5,543,1991
In Vitro/Rat, liver tumor Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 5,543,1991
In Vitro/Rat, liver tumor Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell protein synthesisTIVIEQ 5,543,1991
In Vitro/Rat, liver tumor Inhibitor Concentration (50 percent kill): >2000 mg/L/20HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 5,543,1991
In Vitro/Rat, lung Inhibitor Concentration (50 percent kill): 1.86 gm/L/24HIn Vitro Toxicity Studies: Cell membrane integrity (prelabeled cells): release of radioactive isotopes ([51Cr], [3H]-thymidine, [3H]-proline, [35S]- or [75Se]-methionine, 5-[125I]-2-deoxy-uridine) or fluorescent dyes (bis-carboxyethyl-carboxyfluorescein (BCECF) or calcein-AM)TIVIEQ 7,111,1993
In Vitro/Rat, lung Inhibitor Concentration (50 percent kill): 6.03 gm/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 7,111,1993
In Vitro/Rat, lung Inhibitor Concentration (10 percent kill): 0.13 gm/L/24HIn Vitro Toxicity Studies: Cell membrane integrity (prelabeled cells): release of radioactive isotopes ([51Cr], [3H]-thymidine, [3H]-proline, [35S]- or [75Se]-methionine, 5-[125I]-2-deoxy-uridine) or fluorescent dyes (bis-carboxyethyl-carboxyfluorescein (BCECF) or calcein-AM)TIVIEQ 7,111,1993
In Vitro/Rat, lung Inhibitor Concentration (75 percent kill): 9.77 gm/L/24HIn Vitro Toxicity Studies: Cell membrane integrity (prelabeled cells): release of radioactive isotopes ([51Cr], [3H]-thymidine, [3H]-proline, [35S]- or [75Se]-methionine, 5-[125I]-2-deoxy-uridine) or fluorescent dyes (bis-carboxyethyl-carboxyfluorescein (BCECF) or calcein-AM)TIVIEQ 7,111,1993
In Vitro/Rat, lung Inhibitor Concentration (10 percent kill): 1.6 gm/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 7,111,1993
In Vitro/Rat, lung Inhibitor Concentration (75 percent kill): 13.8 gm/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 7,111,1993
intracerebral/mouse lowest published toxic dose: 2143 µg/kgBehavioral: AnalgesiaEJPHAZ 503,209,2004
intraperitoneal/hamster lowest published toxic dose: 250 mg/kgLiver: Change in gall bladder structure or function

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
BPBLEO 27,1792,2004
intraperitoneal/mouse lowest published toxic dose: 200 mg/kgBrain and Coverings: Other degenerative changes

Nutritional and Gross Metabolic: Body temperature decrease

Biochemical: Neurotransmitters or modulators (putative): Dopamine in striatum
PHTOEH 93,33,2003
intraperitoneal/mouse lowest published lethal dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
BJPCBM 143,33,2004
intraperitoneal/mouse lowest published lethal dose: 400 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesBPBLEO 29,472,2006
intraperitoneal/mouse lowest published toxic dose: 200 mg/kgBlood: Changes in spleen

Blood: Changes in leukocyte (WBC) count
CRTOEC 20,20,2007
intraperitoneal/mouse lowest published toxic dose: 250 mg/kgBlood: Changes in spleen

Blood: Changes in leukocyte (WBC) count

Immunological Including Allergic: Decreased immune response
CRTOEC 20,20,2007
intraperitoneal/mouse lowest published lethal dose: 300 mg/kgBlood: Changes in spleen

Blood: Changes in leukocyte (WBC) count

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
CRTOEC 20,20,2007
intraperitoneal/mouse lowest published toxic dose: 200 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 226,74,2008
intraperitoneal/mouse lowest published toxic dose: 250 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Changes in liver weight

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXCYAC 244,25,2008
intraperitoneal/mouse lowest published toxic dose: 10 mg/kgBehavioral: AnalgesiaFTRPAE 71,143,2000
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
BJPCBM 135,589,2002
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
BJPCBM 135,589,2002
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
TOLED5 177,188,2008
intraperitoneal/mouse lowest published lethal dose: 500 mg/kgBPBLEO 31,1523,2008
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Liver function tests impaired

Liver: Other changes
BPBLEO 31,1523,2008
intraperitoneal/mouse lowest published toxic dose: 200 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
TOPADD 37,193,2009
intraperitoneal/mouse lowest published toxic dose: 400 mg/kgLiver: Other changes

Blood: Change in clotting factors

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
TOXID9 -,171,2008
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Blood: Hemorrhage

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
JCINAO 119,305,2009
intraperitoneal/mouse lowest published toxic dose: 60 mg/kgBiochemical: Metabolism (intermediary): Lipids including transportJTSCDR 33,515,2008
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgEndocrine: Hypoglycemia

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

Biochemical: Metabolism (intermediary): Lipids including transport
JTSCDR 33,515,2008
intraperitoneal/mouse lowest published toxic dose: 529 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Liver function tests impaired

Biochemical: Neurotransmitters or modulators (putative): Catecholamine levels in sympathetic nerves
BJPCBM 153,820,2008
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Lipids including transport
FCTOD7 47,866,2009
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TOXID9 -,213,2009
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 -,234,2009
intraperitoneal/mouse lowest published toxic dose: 250 mg/kgLiver: Changes in liver weight

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
TOXID9 -,234,2009
intraperitoneal/mouse lowest published toxic dose: 250 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
TOXID9 -,235,2009
intraperitoneal/mouse lowest published toxic dose: 600 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Kidney, Ureter, and Bladder: Changes in both tubules and glomeruli

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
HETOEA 27,223,2008
intraperitoneal/mouse lowest published toxic dose: 530 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Other proteins
TXCYAC 262,8,2009
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Other proteins
TXCYAC 263,93,2009
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Liver function tests impaired

Liver: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport
FCTOD7 48,2361,2010
intraperitoneal/mouse lowest published lethal dose: 300 mg/kgPeripheral Nerve and Sensation: Sensory change involving peripheral nerve

Behavioral: Change in psychophysiological tests
JPETAB 307,67,2003
intraperitoneal/mouse lowest published lethal dose: 700 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
FCTOD7 50,3142,2012
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 246,8,2010
intraperitoneal/mouse lowest published toxic dose: 600 mg/kgLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 246,8,2010
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 245,36,2010
intraperitoneal/mouse lowest published toxic dose: 250 mg/kgLiver: Other changes

Liver: Changes in liver weight

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 247,1,2010
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 247,169,2010
intraperitoneal/mouse lowest published lethal dose: 600 mg/kgLiver: Other changesTOXID9 44,13,2005
intraperitoneal/mouse lowest published toxic dose: 200 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonalTXAPA9 197,301,2004
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TOXID9 44,14,2005
intraperitoneal/mouse lowest published toxic dose: 100 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 44,14,2005
intraperitoneal/mouse lowest published toxic dose: 350 mg/kgLiver: Other changes

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

Blood: Change in clotting factors
FCTOD7 44,393,2006
intraperitoneal/mouse lowest published lethal dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Other
BJPCBM 143,33,2004
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
TXAPA9 181,133,2002
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXAPA9 184,27,2002
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXAPA9 184,27,2002
intraperitoneal/mouse lowest published toxic dose: 600 mg/kgKidney, Ureter, and Bladder: Changes in both tubules and glomeruli

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

Biochemical: Metabolism (intermediary): Other proteins
TXCYAC 189,173,2003
intraperitoneal/mouse lowest published lethal dose: 600 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TOSCF2 73,220,2003
intraperitoneal/mouse lowest published toxic dose: 400 mg/kgLiver: Liver function tests impaired

Liver: Other changes
TOLED5 132,1,2002
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Other changesTOXID9 66,362,2002
intraperitoneal/mouse lethal dose (30 percent kill): 600 mg/kgLiver: Liver function tests impaired

Liver: Other changes
TOXID9 66,364,2002
intraperitoneal/mouse lowest published toxic dose: 350 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 210,157,2006
intraperitoneal/mouse lowest published toxic dose: 151 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Other
CRTOEC 17,1551,2004
intraperitoneal/mouse lowest published toxic dose: 529 mg/kgLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
CRTOEC 17,1551,2004
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TOLED5 160,204,2006
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgBiochemical: Metabolism (intermediary): Effect on mitochondrial functionTOXID9 60,352,2001
intraperitoneal/mouse lowest published toxic dose: 400 mg/kgGastrointestinal: Hypermotility, diarrhea

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
TOXID9 90,116,2006
intraperitoneal/mouse lowest published toxic dose: 200 mg/kgNutritional and Gross Metabolic: Body temperature decreasePHTOEH 93,33,2003
intraperitoneal/mouse lowest published toxic dose: 900 mg/kgLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
EJPHAZ 543,133,2006
intraperitoneal/mouse lowest published toxic dose: 900 mg/kgBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationEJPHAZ 543,133,2006
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Other changes

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
FCTOD7 44,1138,2006
intraperitoneal/mouse lethal dose (80 percent kill): 600 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Liver function tests impaired
JPETAB 316,507,2006
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXAPA9 216,98,2006
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
TOLED5 160,204,2006
intraperitoneal/mouse lowest published toxic dose: 250 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
BPBLEO 29,1618,2006
intraperitoneal/mouse lowest published toxic dose: 350 mg/kgLiver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
TXAPA9 223,56,2007
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TOSCF2 92,33,2006
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Other
TOXID9 44,214,2005
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TOXID9 44,360,2005
intraperitoneal/mouse lowest published toxic dose: 450 mg/kgLiver: Liver function tests impairedTOXID9 66,87,2002
intraperitoneal/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes
TOXID9 66,279,2002
intraperitoneal/mouse lowest published toxic dose: 150 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Lipids including transport
CRTOEC 16,295,2003
intraperitoneal/mouse lethal dose (50 percent kill): 367 mg/kgBehavioral: Analgesia

Nutritional and Gross Metabolic: Body temperature decrease
ARZNAD 15,520,1965
intraperitoneal/mouse lowest published toxic dose: 400 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
CALEDQ 174,73,2001
intraperitoneal/mouse lowest published toxic dose: 600 mg/kgKidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Other
BCPCA6 61,925,2001
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases
FCTOD7 39,271,2001
intraperitoneal/mouse lowest published toxic dose: 150 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired
TOSCF2 65,135,2002
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgAutonomic Nervous System: Other (direct) parasympathomimeticTOSCF2 65,135,2002
intraperitoneal/mouse lowest published toxic dose: 500 mg/kgLiver: Other changes

Liver: Liver function tests impaired
VHTODE 42,146,2000
intraperitoneal/mouse lowest published lethal dose: 600 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonalTXAPA9 191,211,2003
intraperitoneal/mouse lowest published toxic dose: 200 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesTXAPA9 192,119,2003
intraperitoneal/mouse lowest published toxic dose: 150 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Other proteins
TOSCF2 65,135,2002
intraperitoneal/rat lowest published toxic dose: 1 gm/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Other proteins
TXAPA9 181,106,2002
intraperitoneal/rat lowest published toxic dose: 500 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport
EKFAE9 59,43,1996
intraperitoneal/rat lowest published toxic dose: 400 mg/kgLiver: Tumors

Endocrine: Tumors

Blood: Tumors
JJATDK 20,427,2000
intraperitoneal/rat lethal dose (50 percent kill): 1205 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Tremor
SSSEAK 57,561,1979
intraperitoneal/rat lowest published toxic dose: 1000 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Other
TOXID9 60,118,2001
intraperitoneal/rat lowest published toxic dose: 763 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesHETOEA 23,49,2004
intraperitoneal/rat lowest published toxic dose: 1089 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
HETOEA 23,49,2004
intraperitoneal/rat lowest published toxic dose: 1 gm/kgBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationTOXID9 90,341,2006
intraperitoneal/rat lowest published lethal dose: 1 gm/kgLiver: Liver function tests impaired

Kidney, Ureter, and Bladder: Changes in blood vessels or in circulation of kidney

Kidney, Ureter, and Bladder: Renal function tests depressed
JPETAB 315,987,2005
intraperitoneal/rat lowest published toxic dose: 1200 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Liver: Liver function tests impaired

Kidney, Ureter, and Bladder: Renal function tests depressed
CYLPDN 23,503,2002
intraperitoneal/rat lowest published toxic dose: 900 mg/kgLiver: Other changesTOXID9 60,346,2001
intraperitoneal/rat lowest published toxic dose: 900 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes
TOXID9 66,363,2002
intraperitoneal/rat lowest published toxic dose: 500 mg/kgLiver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
JOETD7 56,193,1997
intraperitoneal/rat lowest published toxic dose: 200 mg/kgBehavioral: AnalgesiaBJPCBM 139,49,2003
intraperitoneal/rat lowest published toxic dose: 1 gm/kgLiver: Liver function tests impaired

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
TOXID9 72,196,2003
intraperitoneal/rat lowest published lethal dose: 600 mg/kgTOXID9 72,196,2003
intraperitoneal/rat lowest published toxic dose: 835 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Catalases
FCTOD7 46,1771,2008
intraperitoneal/rat lowest published toxic dose: 1000 mg/kgKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Biochemical: Metabolism (intermediary): Lipids including transport

Biochemical: Metabolism (intermediary): Other proteins
FCTOD7 47,1480,2009
intraperitoneal/rat lowest published toxic dose: 750 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Blood: Hemorrhage
FCTOD7 46,3612,2008
intraperitoneal/rat lowest published toxic dose: 700 mg/kgLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
FCTOD7 46,3475,2008
intraperitoneal/rat lowest published toxic dose: 1 gm/kgLiver: Liver function tests impaired

Liver: Other changes

Biochemical: Metabolism (intermediary): Other proteins
PHREP* 57,596,2005
intraperitoneal/rat lowest published toxic dose: 400 mg/kgBrain and Coverings: Other degenerative changes

Behavioral: Analgesia
NSAPCC 369(Suppl 1),R174,2004
intraspinal/mouse lowest published toxic dose: 2143 µg/kgBehavioral: AnalgesiaEJPHAZ 503,209,2004
intravenous/Dog lowest published lethal dose: 826 mg/kgBehavioral: AnalgesiaAIPTAK 149,571,1964
intravenous/mouse lowest published toxic dose: 500 mg/kgLiver: Liver function tests impaired

Liver: Other changes

Biochemical: Metabolism (intermediary): Other
TOXID9 60,352,2001
intravenous/pig lowest published lethal dose: 1 gm/kgLiver: Other changes

Kidney, Ureter, and Bladder: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Phosphatases
VHTODE 30,324,1988
intravenous/rat lowest published toxic dose: 430 mg/kgKidney, Ureter, and Bladder: Other changes in urine composition

Nutritional and Gross Metabolic: Changes in: Na
JPETAB 306,478,2003
intravenous/rat lowest published toxic dose: 145133 µg/kgBehavioral: AnalgesiaBJPCBM 158,601,2009
multiple/mouse lowest published toxic dose: 2143 µg/kgBehavioral: AnalgesiaEJPHAZ 503,209,2004
oral/child lowest published lethal dose: 360 mg/kg/2DGastrointestinal: Nausea or vomiting

Liver: Other changes

Skin: After systemic exposure: Dermatitis, other
JOPDAB 92,832,1978
oral/child lowest published toxic dose: 801 mg/kgBehavioral: General anesthetic

Gastrointestinal: Nausea or vomiting

Liver: Other changes
PEDIAU 61,68,1978
oral/child lowest published lethal dose: 50 mg/kgCardiac: Other changes

Lung, Thorax, or Respiration: Acute pulmonary edema

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)
AJEMEN 6,510,1988
oral/child lowest published lethal dose: 140 mg/kg/7D- intermittentBehavioral: Coma

Liver: Hepatitis (hepatocellular necrosis), zonal

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
MJAUAJ 171,472,1999
oral/child lowest published toxic dose: 591 mg/kg/2D- intermittentLiver: Liver function tests impaired

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Blood: Aplastic anemia
CPEDAM 33,42,1994
oral/Dog lowest published lethal dose: 2 gm/kgBehavioral: Altered sleep time (including change in righting reflex)

Blood: Changes in spleen

Nutritional and Gross Metabolic: Body temperature decrease
IYKEDH 24,602,1993
oral/guinea pig lethal dose (50 percent kill): 2620 mg/kgBehavioral: Altered sleep time (including change in righting reflex)

Behavioral: Somnolence (general depressed activity)

Behavioral: Tremor
JAPMA8 47,479,1958
oral/human lowest published toxic dose: 8.3 mg/kgBiochemical: Metabolism (intermediary): OtherCLPTAT 67,591,2000
oral/human lowest published toxic dose: 166.7 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuseBMJOAE 288,50,1984
oral/human lowest published lethal dose: 357 mg/kgBehavioral: Anorexia (human)

Behavioral: Coma

Gastrointestinal: Nausea or vomiting
LANCAO 1,66,1973
oral/human lowest published lethal dose: 143 mg/kgBehavioral: General anestheticBMJOAE 282,199,1981
oral/human lowest published toxic dose: 283.5 mg/kgKidney, Ureter, and Bladder: Interstitial nephritis

Kidney, Ureter, and Bladder: Renal function tests depressed
JTCTDW 39,441,2001
oral/human lowest published toxic dose: 10 mg/kgBehavioral: HeadacheCODEDG 43,60,2000
oral/human lowest published toxic dose: 307.2 mg/kgKidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)JTCTDW 39,441,2001
oral/human lowest published toxic dose: 71.4 mg/kgKidney, Ureter, and Bladder: Renal function tests depressedJTCTDW 1,31,2005
oral/human lowest published toxic dose: 0.257 gm/kgGastrointestinal: Nausea or vomiting

Nutritional and Gross Metabolic: Changes in: K
BCLPT* 102,325,2007
oral/infant lowest published toxic dose: 1440 mg/kg/6DBehavioral: Irritability

Gastrointestinal: Hypermotility, diarrhea

Nutritional and Gross Metabolic: Body temperature increase
AJDCAI 137,386,1983
oral/mammal (species unspecified) lowest published lethal dose: 512 mg/kgUSXXAM #4035499
oral/man lowest published toxic dose: 9286 µg/kgEye: Other eye effects

Ear: Tumors

Skin: After systemic exposure: Dermatitis, other
LLRGDY 50(Suppl 26),206,1995
oral/man lowest published lethal dose: 714 mg/kgLiver: Other changesHUTODJ 1,25,1981
oral/man lowest published toxic dose: 714 mg/kgCardiac: EKG changes not diagnostic of abovePGMJAO 69,52,1993
oral/man lowest published lethal dose: 143 mg/kg/24H- intermittentBehavioral: Anorexia (human)

Liver: Hepatitis (hepatocellular necrosis), zonal

Liver: Jaundice, other or unclassified
AJMEAZ 74,349,1983
oral/man lowest published toxic dose: 404 mg/kgLiver: Liver function tests impaired

Blood: Change in clotting factors

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
AANEAB 47,1145,2003
oral/man lowest published lethal dose: 1.27 gm/kgLiver: Hepatitis (hepatocellular necrosis), zonalJFSCAS 52,992,2007
oral/man lowest published toxic dose: 0.444 gm/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesCTOXAO 47,752,2009
oral/monkey lowest published toxic dose: 200 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Other proteins
TOXID9 78,261,2004
oral/mouse lethal dose (50 percent kill): 338 mg/kgTXAPA9 19,20,1971
oral/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired
TOXID9 72,10,2003
oral/mouse lowest published toxic dose: 300 mg/kgLiver: Liver function tests impaired

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
TOXID9 72(Suppl 1),350,2003
oral/mouse lowest published toxic dose: 146.1 mg/kgBehavioral: Analgesia

Behavioral: Change in psychophysiological tests
JPETAB 307,699,2003
oral/mouse lowest published toxic dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
TXCYAC 219,187,2006
oral/mouse lowest published toxic dose: 150 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
FCTOD7 50,1439,2012
oral/mouse lowest published lethal dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
FCTOD7 50,1439,2012
oral/mouse lowest published toxic dose: 150 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Liver function tests impaired

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductases
FCTOD7 49,3367,2011
oral/mouse lowest published lethal dose: 600 mg/kgLiver: Liver function tests impairedHETOEA 27,425,2008
oral/mouse lowest published toxic dose: 300 mg/kgLiver: Multiple effects

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

Biochemical: Metabolism (intermediary): Other proteins
TOXID9 12,400,2008
oral/mouse lowest published toxic dose: 300 mg/kgLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
JTSCDR 31,23,2006
oral/mouse lowest published toxic dose: 1000 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
JTSCDR 31,23,2006
oral/mouse lethal dose (50 percent kill): 559 mg/kgLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
BMECEP 15,2206,2007
oral/mouse lowest published toxic dose: 50 mg/kgBehavioral: AnalgesiaFTRPAE 74,486,2003
oral/mouse lowest published toxic dose: 250 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Lipids including transport
ETPAEK 59,319,2007
oral/rabbit lowest published toxic dose: 100 mg/kgNutritional and Gross Metabolic: Body temperature decreaseFTRPAE 71,147,2000
oral/rabbit lowest published toxic dose: 2 gm/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
FCLPH* 18(Suppl 1),121,2004
oral/rabbit lowest published toxic dose: 2 gm/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Endocrine: Hypoglycemia

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
JAPTO* 29,395,2009
oral/rat lowest published toxic dose: 1000 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesTOXID9 -,322,2009
oral/rat lowest published toxic dose: 2000 mg/kgLiver: Other changes

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

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
TOXID9 -,214,2009
oral/rat lowest published toxic dose: 420 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Lipids including transport
FCTOD7 48,605,2010
oral/rat lowest published toxic dose: 150 mg/kgBehavioral: AnalgesiaJPETAB 321,1208,2007
oral/rat lowest published toxic dose: 600 mg/kgLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other enzymes
BCLPT* 105(Suppl 1),121,2009
oral/rat lowest published toxic dose: 200 mg/kgLiver: Liver function tests impaired

Liver: Other changes

Biochemical: Metabolism (intermediary): Plasma proteins not involving coagulation
AJPHT* 1,17,2006
oral/rat lethal dose (40 percent kill): 2500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Liver function tests impaired

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)
TXCYAC 243,261,2008
oral/rat lowest published toxic dose: 4250 mg/kg/6HLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Other changes
MUREAV 549,147,2004
oral/rat lowest published toxic dose: 1000 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes
JTSCDR 31,491,2006
oral/rat lowest published toxic dose: 1000 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
JTSCDR 31,49,2006
oral/rat lowest published toxic dose: 1000 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Other changes
JTSCDR 32,401,2007
oral/rat lowest published toxic dose: 1000 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
JTSCDR 32,469,2007
oral/rat lowest published toxic dose: 750 mg/kgLiver: Changes in liver weight

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
IRJPH* 4,64,2005
oral/rat lowest published toxic dose: 2 gm/kgLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases
IRJPH* 6,63,2007
oral/rat lowest published toxic dose: 50 mg/kgNutritional and Gross Metabolic: Body temperature decreaseBJPCBM 135,589,2002
oral/rat lowest published toxic dose: 3 gm/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
FCTOD7 46,2611,2008
oral/rat lowest published toxic dose: 1000 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TXAPA9 247,211,2010
oral/rat lowest published toxic dose: 2.5 gm/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Liver function tests impaired

Kidney, Ureter, and Bladder: Renal function tests depressed
FCTOD7 49,1705,2011
oral/rat lowest published toxic dose: 1.5 gm/kgLiver: Liver function tests impaired

Liver: Other changes

Biochemical: Metabolism (intermediary): Lipids including transport
FCTOD7 48,2200,2010
oral/rat lowest published toxic dose: 1000 mg/kgLiver: Hepatitis (hepatocellular necrosis), diffuse

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TXCYAC 264,89,2009
oral/rat lowest published toxic dose: 50 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Other
TXAPA9 215,306,2006
oral/rat lowest published toxic dose: 1500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
JPETAB 318,792,2006
oral/rat lowest published toxic dose: 150 mg/kgBiochemical: Metabolism (intermediary): Plasma proteins not involving coagulationJPETAB 318,792,2006
oral/rat lowest published toxic dose: 150 mg/kgLiver: Other changesTOXID9 72(Suppl 1),340,2003
oral/rat lowest published toxic dose: 3 gm/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Liver: Hepatitis (hepatocellular necrosis), diffuse

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
JOETD7 49,119,1995
oral/rat lowest published toxic dose: 1500 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Other proteins
TOXID9 44,205,2005
oral/rat lowest published toxic dose: 4000 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Metabolism (intermediary): Other
TOXID9 60,303,2001
oral/rat lowest published toxic dose: 151 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Peptidases
TOLED5 135,S130,2002
oral/rat lowest published toxic dose: 250 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)ABCPO* 47,1129,2000
oral/rat lethal dose (50 percent kill): 1944 mg/kgUSXXAM #4636513
oral/rat lowest published toxic dose: 1500 mg/kgKidney, Ureter, and Bladder: Other changes in urine composition

Biochemical: Metabolism (intermediary): Lipids including transport

Biochemical: Metabolism (intermediary): Amino acids (including renal excretion)
TOXID9 78,173,2004
oral/rat lowest published toxic dose: 1000 mg/kgLung, Thorax, or Respiration: Other changesTOXID9 60,167,2001
oral/rat lowest published toxic dose: 1500 mg/kgLiver: Other changes

Biochemical: Effect on specific coenzyme: NAD, NADP

Biochemical: Metabolism (intermediary): Xanthine, purine or nucleotides including urate
TOXID9 78,173,2004
oral/rat lowest published toxic dose: 50 mg/kgKidney, Ureter, and Bladder: Other changes in urine composition

Biochemical: Metabolism (intermediary): Effect on cyclic nucleotides
TOXID9 78,173,2004
oral/rat lowest published toxic dose: 1000 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Other

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 44,389,2005
oral/rat lowest published toxic dose: 4500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 66,11,2002
oral/woman lowest published toxic dose: 4962 µg/kgGastrointestinal: Changes in structure or function of exocrine pancreas

Liver: Liver function tests impaired

Blood: Other changes
JTCTDW 29,223,1991
oral/woman lowest published toxic dose: 325 mg/kgBehavioral: Hallucinations, distorted perceptions

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)
PGMJAO 68,116,1992
oral/woman lowest published lethal dose: 650 mg/kgVascular: BP lowering not characterized in autonomic section

Vascular: Other changes

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis
AJEMEN 6,511,1988
oral/woman lowest published lethal dose: 260 mg/kgBehavioral: Coma

Gastrointestinal: Nausea or vomiting

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)
JAMAAP 236,1874,1976
oral/woman lowest published toxic dose: 490 mg/kgBehavioral: Somnolence (general depressed activity)

Gastrointestinal: Other changes

Kidney, Ureter, and Bladder: Other changes
SMJOAV 71,906,1978
oral/woman lowest published toxic dose: 13 mg/kgBehavioral: ExcitementLLRGDY 50(Suppl 26),206,1995
oral/woman lowest published lethal dose: 400 mg/kgBehavioral: Coma

Liver: Liver function tests impaired

Nutritional and Gross Metabolic: Changes in: Metabolic alkalosis
JTCTDW 35,325,1997
oral/woman lowest published toxic dose: 416.7 mg/kgLiver: Liver function tests impaired

Blood: Change in clotting factors

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
AANEAB 47,1145,2003
oral/woman lowest published lethal dose: 474 mg/kgBrain and Coverings: Other degenerative changes

Liver: Hepatitis (hepatocellular necrosis), diffuse
AANEAB 47,1145,2003
parenteral/mouse lowest published toxic dose: 300 mg/kgLiver: Other changesTOXID9 44,12,2005
parenteral/mouse lowest published toxic dose: 300 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TOXID9 44,13,2005
parenteral/mouse lowest published toxic dose: 300 mg/kgLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
TOXID9 78,105,2004
parenteral/mouse lowest published toxic dose: 500 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Other
TOXID9 44,215,2005
parenteral/mouse lowest published toxic dose: 300 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
TOXID9 44,215,2005
parenteral/mouse lowest published lethal dose: 500 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
MOCAE8 60,907,2001
parenteral/mouse lowest published toxic dose: 500 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Metabolism (intermediary): Effect on mitochondrial function
MOCAE8 60,907,2001
parenteral/rat lowest published toxic dose: 1500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonalTOXID9 44,27,2005
parenteral/rat lowest published toxic dose: 150 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Other proteins
TOXID9 44,13,2005
subcutaneous/frog lowest published lethal dose: 50 mg/kgBehavioral: Altered sleep time (including change in righting reflex)

Behavioral: Ataxia

Lung, Thorax, or Respiration: Other changes
AEXPBL 33,216,1894
subcutaneous/mouse lethal dose (50 percent kill): 310 mg/kgHUTODJ 3,13S,1984
subcutaneous/mouse lowest published toxic dose: 149 mg/kgBehavioral: AnalgesiaEJPHAZ 538,57,2006
subcutaneous/mouse lowest published toxic dose: 200 mg/kgBrain and Coverings: Other degenerative changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
EJPHAZ 538,57,2006
subcutaneous/mouse lowest published toxic dose: 116 mg/kgBlood: Eosinophilia

Blood: Changes in bone marrow not included in above

Blood: Changes in leukocyte (WBC) count
JPETAB 305,755,2003
subcutaneous/rabbit lowest published toxic dose: 100 mg/kgNutritional and Gross Metabolic: Body temperature decreaseBIPBU* 24,1149,2001
subcutaneous/rat lowest published toxic dose: 60 mg/kgBehavioral: AnalgesiaBJPCBM 153,760,2008
Tank with water/Zebrafish lowest published toxic concentration: 3.12 mmol/L 144HMusculoskeletal: Other changes

Skin and Appendages: Other glands
REPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 10.12 mmol/L 24HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 9.92 mmol/L 48HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 7.87 mmol/L 72HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
Tank with water/Zebrafish lowest published toxic concentration: 3.71 mmol/L 144HRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldREPTED 33,142,2012
unreported route/infant lowest published toxic dose: 453 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: TransaminasesCTOXAO 47,739,2009
unreported route/mammal (species unspecified) lethal dose (50 percent kill): 891 mg/kgGISAAA 48(6),22,1983
unreported route/mouse lowest published toxic dose: 500 mg/kgBlood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)

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

Biochemical: Metabolism (intermediary): Other
TOXID9 44,472,2005
unreported route/mouse lowest published toxic dose: 500 mg/kgBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases

Biochemical: Metabolism (intermediary): Other
TOXID9 90,100,2006
unreported route/mouse lowest published toxic dose: 500 mg/kgBrain and Coverings: Other degenerative changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 90,100,2006
unreported route/mouse lowest published toxic dose: 300 mg/kgLiver: Other changes

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

Biochemical: Metabolism (intermediary): Other
TOXID9 60,267,2001
unreported route/mouse lowest published toxic dose: 80 mg/kgLiver: Other changes

Immunological Including Allergic: Decreased immune response
TOXID9 44,185,2005
unreported route/mouse lowest published toxic dose: 370.4 mg/kgLiver: Liver function tests impaired

Blood: Changes in serum composition (e.g. TP, bilirubin, cholesterol)
TOXID9 72(Suppl 1),350,2003
unreported route/mouse lowest published lethal dose: 600 mg/kgLiver: Liver function tests impaired

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

Biochemical: Metabolism (intermediary): Other proteins
TOXID9 72,195,2003
unreported route/mouse lowest published toxic dose: 300 mg/kgLiver: Other changesTOXID9 -,235,2009
unreported route/mouse lowest published toxic dose: 37 mg/kgBehavioral: AnalgesiaJPETAB 321,1208,2007
unreported route/rat lowest published toxic dose: 1000 mg/kgLiver: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOLED5 188,91,2009
unreported route/rat lowest published toxic dose: 400 mg/kgBehavioral: Analgesia

Biochemical: Metabolism (intermediary): Other proteins
FCLPH* 19,239,2005
unreported route/rat lowest published toxic dose: 1000 mg/kgBehavioral: AnalgesiaTOXID9 90,331,2006
unreported route/rat lowest published toxic dose: 1000 mg/kgBehavioral: Somnolence (general depressed activity)

Behavioral: Analgesia
TOXID9 90,331,2006
unreported route/rat lowest published toxic dose: 1000 mg/kgNutritional and Gross Metabolic: Weight loss or decreased weight gainTOXID9 90,331,2006
unreported route/rat lowest published toxic dose: 1000 mg/kgTOXID9 90,331,2006
unreported route/rat lowest published toxic dose: 500 mg/kgLiver: Hepatitis (hepatocellular necrosis), zonal

Liver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases
TOXID9 44,379,2005
unreported route/rat lowest published toxic dose: 500 mg/kgBiochemical: Metabolism (intermediary): OtherTOXID9 44,379,2005

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
intraperitoneal/mouse lowest published toxic dose: 750 mg/kg/3D- intermittentBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other enzymesTOXID9 66,116,2002
intraperitoneal/rat lowest published toxic dose: 2.1 gm/kg/4D- intermittentBehavioral: Tolerance

Kidney, Ureter, and Bladder: Changes in blood vessels or in circulation of kidney
JPETAB 315,987,2005
intraperitoneal/rat lowest published toxic dose: 1600 mg/kg/2D- intermittentLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Cytochrome oxidases (indlucing oxidative phosphrylation)
UBZHD4 68(6),92,1996
intraperitoneal/rat lowest published toxic dose: 2800 mg/kg/7D- intermittentBrain and Coverings: Other degenerative changes

Behavioral: Analgesia
NSAPCC 369(Suppl 1),R174,2004
multiple/infant lowest published toxic dose: 232 mg/kg/3D- intermittentVascular: Thromobosis distant from injection site

Kidney, Ureter, and Bladder: Renal function tests depressed

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
HOKMJ* 10,61,2004
oral/human lowest published toxic dose: 20 mg/kg/3W- intermittentSkin: After systemic exposure: Dermatitis, allergic

Immunological Including Allergic: Hypersensitivity delayed (multiple organ involvement)
CODEDG 43,60,2000
oral/human lowest published toxic dose: 600 mg/kg/2W- intermittentKidney, Ureter, and Bladder: Other changes in urine composition

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

Biochemical: Metabolism (intermediary): Amino acids (including renal excretion)
FCLPH* 23(Suppl 1),61,2009
oral/infant lowest published toxic dose: 175 mg/kg/7D- intermittentBehavioral: Somnolence (general depressed activity)

Gastrointestinal: Nausea or vomiting

Liver: Hepatitis (hepatocellular necrosis), diffuse
AJEMEN 23,94,2005
oral/mouse lowest published toxic dose: 1800 mg/kg/3D- continuousBlood: Changes in spleenTXAPA9 226,46,2008
oral/mouse lowest published toxic dose: 1680 mg/kg/4W- continuousImmunological Including Allergic: Decreased immune responseTXAPA9 226,46,2008
oral/mouse lowest published toxic dose: 10080 mg/kg/2W- continuousLiver: Other changesCRNGDP 26,689,2005
oral/mouse lowest published toxic dose: 210 mg/kg/7D- intermittentImmunological Including Allergic: Increase in cellular immune responseTOXID9 -,314,2009
oral/mouse lowest published toxic dose: 136 gm/kg/13W- continuousLiver: Other changes

Kidney, Ureter, and Bladder: Changes in bladder weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTPTR* NTP-TR-394,1992
oral/mouse lowest published toxic dose: 336 gm/kg/40W- continuousLiver: Hepatitis (hepatocellular necrosis), diffuse

Liver: Other changes

Liver: Changes in liver weight
TXAPA9 96,494,1988
oral/mouse lowest published toxic dose: 19600 mg/kg/14D- continuousBehavioral: Food intake (animal)NTIS** #PB85204667/AS
oral/mouse lowest published toxic dose: 750 mg/kg/3D- intermittentBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other enzymesTOXID9 66,116,2002
oral/rabbit lowest published toxic dose: 1600 mg/kg/8D- intermittentLiver: Other changes

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

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other oxidoreductases
ETPAEK 59,139,2007
oral/rat lowest published toxic dose: 63700 mg/kg/13W- continuousLiver: Changes in liver weightMOCAE8 42,9,2005
oral/rat lowest published toxic dose: 9750 mg/kg/15D- intermittentLiver: Hepatitis (hepatocellular necrosis), diffuse

Kidney, Ureter, and Bladder: Renal function tests depressed

Blood: Changes in erythrocyte (RBC) count
FCTOD7 48,3246,2010
oral/rat lowest published toxic dose: 484 mg/kg/2D- intermittentLiver: Other changes

Biochemical: Metabolism (intermediary): Other proteins
TXAPA9 243,300,2010
oral/rat lowest published toxic dose: 3388 mg/kg/14D- intermittentLiver: Other changes

Biochemical: Metabolism (intermediary): Other proteins
TXAPA9 243,300,2010
oral/rat lowest published toxic dose: 21780 mg/kg/90D- intermittentLiver: Other changes

Biochemical: Metabolism (intermediary): Other proteins
TXAPA9 243,300,2010
oral/rat lowest published toxic dose: 910 mg/kg/1W- intermittentBrain and Coverings: Changes in cerebral spinal fluid

Behavioral: Analgesia

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
FCLPH* 18(Suppl 1),89,2004
oral/rat lowest published toxic dose: 10000 mg/kg/10D- intermittentLiver: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TOXID9 78,105,2004
oral/rat lowest published toxic dose: 15000 mg/kg/30D- continuousKidney, Ureter, and Bladder: Renal function tests depressed

Kidney, Ureter, and Bladder: Other changes
JPETAB 305,123,2003
oral/rat lowest published toxic dose: 5250 mg/kg/7D- intermittentLiver: Hepatitis (hepatocellular necrosis), zonal

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
TXCYAC 243,261,2008
oral/rat lowest published toxic dose: 105 gm/kg/35D- continuousLiver: Other changes

Nutritional and Gross Metabolic: Weight loss or decreased weight gain

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
KSRNAM 4,2536,1970
oral/rat lowest published toxic dose: 68 gm/kg/13W- continuousLiver: Other changes

Kidney, Ureter, and Bladder: Changes in bladder weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTPTR* NTP-TR-394,1992
oral/rat lowest published toxic dose: 6080 mg/kg/19D- intermittentGastrointestinal: Other changes

Liver: Changes in liver weight

Blood: Changes in leukocyte (WBC) count
IYKEDH 24,615,1993
oral/rat lowest published toxic dose: 5000 mg/kg/2D- intermittentLiver: Multiple effectsFATOAO 47,105,1984
oral/rat lowest published toxic dose: 7000 mg/kg/2D- intermittentLiver: Liver function tests impaired

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

Biochemical: Metabolism (intermediary): Lipids including transport
EKFAE9 61,48,1998
oral/rat lowest published toxic dose: 67.2 gm/kg/28D- continuousLiver: Other changesTOXID9 72,235,2003
oral/rat lowest published toxic dose: 16800 mg/kg/14D- intermittentLiver: Hepatitis (hepatocellular necrosis), zonal

Kidney, Ureter, and Bladder: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
TOXID9 -,216,2009
oral/woman lowest published toxic dose: 60 mg/kg/5D- intermittentBlood: Hemorrhage

Blood: Change in clotting factors
APHRER 38,1432,2004
oral/woman lowest published toxic dose: 4.2 gm/kg/6W- intermittentBehavioral: Somnolence (general depressed activity)

Liver: Hepatitis (hepatocellular necrosis), zonal

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Multiple enzyme effects
JEMME* 23,253,2002
oral/woman lowest published toxic dose: 390 mg/kg/5D- intermittentSkin: After systemic exposure: Dermatitis, other

Nutritional and Gross Metabolic: Body temperature increase
TOLED5 180S,S140,2008
unreported route/woman lowest published toxic dose: 0.64 gm/kg/8D- intermittentLiver: Hepatitis (hepatocellular necrosis), diffuse

Kidney, Ureter, and Bladder: Changes in tubules (including acute renal failure, acute tubular necrosis)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
MJAUAJ 186,371,2007

Reviews

OrganizationStandardReference
International Agency for Research on Cancer (IARC)Cancer Review:Animal Limited EvidenceIMEMDT 50,307,1990
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 50,307,1990
International Agency for Research on Cancer (IARC)Cancer Review:Animal Inadequate EvidenceIMEMDT 73,401,1999
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 73,401,1999
International Agency for Research on Cancer (IARC)Cancer Review:Group 3IMEMDT 73,401,1999
TOXICOLOGY REVIEWREPTED 17,255,2003
TOXICOLOGY REVIEWTOLED5 127,135,2002
TOXICOLOGY REVIEWCTOXAO 12,601,1978
TOXICOLOGY REVIEWNTIS** PB282-666
TOXICOLOGY REVIEWOBGNAS 58,57S,1981
TOXICOLOGY REVIEWNEJMAG 342,186,2000
TOXICOLOGY REVIEWJTCTDW 38,291,2000
TOXICOLOGY REVIEWMUREAV 488,151,2001
TOXICOLOGY REVIEWTOLED5 140-141,3,2003
TOXICOLOGY REVIEWTOLED5 140-141,53,2003
TOXICOLOGY REVIEWAPHRER 381,46,2004
TOXICOLOGY REVIEWTOLED5 144,279,2003
TOXICOLOGY REVIEWTOLED5 144,383,2003
TOXICOLOGY REVIEWTPHSDY 24,55,2003
TOXICOLOGY REVIEWTPHSDY 23,548,2002
TOXICOLOGY REVIEWJEMME* 23,253,2002
TOXICOLOGY REVIEWEMMUEG 43,143,2004
TOXICOLOGY REVIEWTPHSDY 24,245,2003
TOXICOLOGY REVIEWTPHSDY 24,154,2003
TOXICOLOGY REVIEWTPHSDY 24,524,2003
TOXICOLOGY REVIEWARPTDI 45,177,2005
TOXICOLOGY REVIEWAPHRER 38,146,2004
TOXICOLOGY REVIEWAPHRER 38,1935,2004
TOXICOLOGY REVIEWJPETAB 315,1,2005
TOXICOLOGY REVIEWAINCM* 7,63,2006
TOXICOLOGY REVIEWBPCEM* 17,237,2003
TOXICOLOGY REVIEWENTOX* -,18,2005
TOXICOLOGY REVIEWDIMON* 39,678,1993
TOXICOLOGY REVIEWEJPHAZ 549,1,2006
TOXICOLOGY REVIEWMUREAV 584,1,2005
TOXICOLOGY REVIEWBJPCBM 143,1,2004
TOXICOLOGY REVIEWTOPADD 32(Suppl. 2),71,2004
TOXICOLOGY REVIEWFCLPH* 17,393,2003
TOXICOLOGY REVIEWAJEMEN 22,404,2004
TOXICOLOGY REVIEWMUREAV 654,114,2008
TOXICOLOGY REVIEWMUREAV 659,31,2008
TOXICOLOGY REVIEWHUTOX* -,247,1996
TOXICOLOGY REVIEWMUREAV 657,84,2008
TOXICOLOGY REVIEWHUTOX* -,411,1996
TOXICOLOGY REVIEWSIMEJ* 47,134,2006
TOXICOLOGY REVIEWMCLNA* 92,761,2008
TOXICOLOGY REVIEWMCLNA* 89,1145,2005
TOXICOLOGY REVIEWTPHSDY 29,391,2008
TOXICOLOGY REVIEWJPHPH* 59,117,2008
TOXICOLOGY REVIEWJTSCDR 34,1,2009
TOXICOLOGY REVIEWPTPAD4 113,229,2007
TOXICOLOGY REVIEWJPHPH* 59(Suppl 2),117,2008
TOXICOLOGY REVIEWBPRCR* 17,877,2003
TOXICOLOGY REVIEWBLREV* 3,71,1989
TOXICOLOGY REVIEWMUTAEX 22,161,2007
TOXICOLOGY REVIEWCLLID* 13,277,2009
TOXICOLOGY REVIEWCCACL* 22,357,2006
TOXICOLOGY REVIEWCGHEP* 5,648,2007
TOXICOLOGY REVIEWMUTAEX 23,271,2008
TOXICOLOGY REVIEWMUREAV 705,20,2010
TOXICOLOGY REVIEWNBREV* 5,1,1981
TOXICOLOGY REVIEWNBREV* 11,35,1987
TOXICOLOGY REVIEWTXAPA9 243,239,2010
TOXICOLOGY REVIEWTXAPA9 243,154,2010
TOXICOLOGY REVIEWTXAPA9 243,167,2010
TOXICOLOGY REVIEWPAREAQ 60,79,2008
TOXICOLOGY REVIEWFCLPH* 22(Suppl 1),30,2008
TOXICOLOGY REVIEWMUREAV 705,165,2010
TOXICOLOGY REVIEWFCLPH* 23(Suppl 1),31,2009
TOXICOLOGY REVIEWFCLPH* 23(Suppl 1),35,2009
TOXICOLOGY REVIEWFCLPH* 23(Suppl 1),42,2009
TOXICOLOGY REVIEWFCLPH* 23(Suppl 1),92,2009
TOXICOLOGY REVIEWFCLPH* 23,100,2009
TOXICOLOGY REVIEWREPTED 30,495,2010
TOXICOLOGY REVIEWREPTED 32,198,2011
TOXICOLOGY REVIEWMUREAV 723,108,2011
TOXICOLOGY REVIEWMUREAV 722,147,2011
TOXICOLOGY REVIEWMUREAV 722,147,2011
TOXICOLOGY REVIEWMUREAV 751,82,2012
TOXICOLOGY REVIEWMUREAV 746,104,2012
TOXICOLOGY REVIEWMUREAV 750,1,2012

Standards and Regulations

OrganizationStandardReference
Occupational Exposure Limit-RUSSIAshort term exposure limit 0.5 mg/m3, JUN2003
Occupational Exposure Limit-UNITED KINGDOMtime-weighted average 10 mg/m3 (inhal. dust), OCT2007

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Occupational Exposure Survey 1983Hazard Code 80396; Number of Industries 7; Total Number of Facilities 1261; Number of Occupations 26; Total Number of Employees Exposed 65107; Total Number of Female Employees Exposed 56260
National Occupational Hazard Survey 1974Hazard Code 80396; Number of Industries 7; Total Number of Facilities 1829; Number of Occupations 14; Total Number of Employees Exposed 9269

Status in Federal Agencies

OrganizationReference
EPA GENETOX PROGRAM 1988, Inconclusive: Histidine reversion-Ames test
EPA TSCA Section 8(b) CHEMICAL INVENTORY
NCI Carcinogenesis Studies (feed);equivocal evidence:rat
NCI Carcinogenesis Studies (feed);no evidence:mouse
TOP