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Registry of Toxic Effects of Chemical Substances (RTECS)

Theophylline

RTECS #

XH3850000

CAS #

58-55-9

Updated

December 2013

Molecular Weight

180.19

Molecular Formula

C7H8N4O2

Synonyms

1,3-Dimethylxanthine
1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl- (9CI)
3,7-Dihydro-1,3-dimethyl-1H-purine-2,6-dione
Acet-theocin
Armophylline
Asmax
Austyn
Duraphy
Elixicon
Elixophyllin
Elixophylline
Euphylong
Lanophyllin
Liquophylline
NSC 2066
Nuelin
Optiphyllin
Parkophyllin
Pseudotheophylline
Quibron T/SR
Slo-Phyllin
Solosin
Spophyllin retard
Teofilina (Polish)
Teofyllamin
Theal tablets
Theocin
Theo-Dur
Theofol
Theograd
Theolair
Theolix
Theophyl-225
Theophyllin
Theophylline, anhydrous
Uniphyllin
Xanthine, 1,3-dimethyl-

Mutation Data and Reference

System TestRoute/Organism/TissueDoseReference
Cytogenetic Analysislymphocyte/human10 mg/LMUREAV 224,409,1989
Cytogenetic Analysismammary gland/mouse3200 µmol/L/24H-continuousJTSCDR 5,141,1980
Cytogenetic Analysislung/hamster450 mg/LGMCRDC 27,95,1981
DNA inhibitionlung/hamster6 mmol/LMUREAV 26,73,1974
DNA inhibitionfibroblast/human7 mg/LNEOLA4 33,699,1986
DNA inhibitionother cell types/human4 mmol/LBIOJAU 35,665,1981
DNA inhibitionlymphocyte/mouse6 mmol/LMUREAV 26,73,1974
DNA inhibitionfibroblast/mouse6 mmol/LMUREAV 26,73,1974
mutation in mammalian somatic cellslung/hamster7 mg/LNEOLA4 33,699,1986
mutation in microorganisms/Salmonella typhimurium10 µg/plate (+enzymatic activation step)MUREAV 444,17,1999
mutation in microorganisms/Escherichia coli150 mg/L (-enzymatic activation step)CSHSAZ 16,337,1952
mutation in microorganisms/Bacillus subtilis7500 mg/L (-enzymatic activation step)MUREAV 117,55,1983
mutation in microorganisms/Other microorganisms6000 ppm (-enzymatic activation step)NATUAS 162,573,1948
mutation in microorganisms/Euglena gracilis600 mg/L (-enzymatic activation step)MUREAV 32,169,1975
other mutation test systemsother cell types/rat1 mmol/LINOPAO 13,210,1974
other mutation test systemsother cell types/mouse100 µmol/LJIDEAE 66,313,1976
other mutation test systemslymphocyte/human100 µmol/LMUREAV 15,197,1972
sister chromatid exchangeintraperitoneal/mouse12500 µg/kgMUREAV 444,17,1999
sister chromatid exchangeembryo/human360 mg/LSNSHBT (20),574,1980
sister chromatid exchangelymphocyte/human10 mg/LMUREAV 224,409,1989
sister chromatid exchangelung/hamster360 mg/LSNSHBT (20),574,1980
sister chromatid exchangeovary/hamster2 mmol/LMUREAV 126,63,1984
sister chromatid exchangeoral/hamster300 mg/kgEXPEAM 38,600,1982
specific locus testother cell types/mouse1500 mg/L/24H (-enzymatic activation step)MUTAEX 14,23,1999
Unscheduled DNA Synthesisother cell types/human1 mmol/LBIOJAU 35,665,1981

Reproductive Effects Data and References

Route/OrganismDoseEffectReference
intraperitoneal/mouse 175 mg/kg (13D pregnant)Reproductive: Specific developmental abnormalities: Craniofacial (including nose and tongue)

Reproductive: Specific developmental abnormalities: Musculoskeletal system

Reproductive: Specific developmental abnormalities: Body wall
OFAJAE 46,167,1969
intraperitoneal/mouse 200 mg/kg (13D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Other developmental abnormalities
OFAJAE 46,167,1969
intraperitoneal/mouse 225 mg/kg (13D pregnant)Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)OFAJAE 46,167,1969
intravenous/rabbit 18750 µg/kg (24-26D pregnant)Reproductive: Effects on newborn: Other neonatal measures or effectsPEREBL 12,38,1978
intravenous/rabbit 780 mg/kg (12-18D pregnant)Reproductive: Other effects on female

Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)
MFEPDX 22,101,2000
oral/mouse 17.5 gm/kg (7D male/7D prior to copulation/21D pregnant)Reproductive: Effects on fertility: Other measures of fertility

Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)
NTIS** #PB85204659/AS
oral/mouse 19 gm/kg (7D male/7D prior to copulation/24D pregnant)Reproductive: Maternal effects: ParturitionNTIS** #PB85204659/AS
oral/mouse 4.4 gm/kg (7D male/7D prior to copulation/21D pregnant)Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)NTIS** #PB85204659/AS
oral/mouse 73500 mg/kg (21W prior to copulation)Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)

Reproductive: Effects on newborn: Growth statistics (e.g., reduced weight gain)
NTIS** #PB85204659/AS
oral/rat 2586 mg/kg (6-15D pregnant)Reproductive: Effects on embryo or fetus: Fetal deathNTIS** #PB86-108172
oral/rat 2175 mg/kg (6-15D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)NTIS** #PB86-108172
oral/rat 10050 mg/kg (67D male)Reproductive: Paternal effects: Testes, epididymis, sperm ductFAATDF 10,525,1988
oral/rat 1500 mg/kg (6-15D pregnant)Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)TJADAB 33,70C,1986
oral/rat 75335 mg/kg (95D male)Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count)FAATDF 10,525,1988
oral/mouse 3 gm/kg (6-15D 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)

Reproductive: Effects on embryo or fetus: Fetal death
NTIS** PB86-103223
oral/mouse 4375 mg/kg (7D male/7D pre-3W pregnant)Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth)FAATDF 10,525,1988
oral/mouse 3720 mg/kg (6-15D 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)
FAATDF 14,167,1990
subcutaneous/rat 1700 mg/kg (1-17D pregnant)Reproductive: Specific developmental abnormalities: Musculoskeletal systemAIPTAK 172,219,1968

Acute Toxicity Data and References

Route/OrganismDoseEffectReference
In Vitro/Chicken, neurons Inhibitor Concentration (50 percent kill): 20250 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): 3184 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): 17176 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): 5128 µmol/L/20HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 7,653,1993
In Vitro/Human, endothelium Inhibitor Concentration (50 percent kill): 9 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, fibroblast Inhibitor Concentration (50 percent kill): 20 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, HeLa cell Inhibitor Concentration (50 percent kill): 3350 mg/L/24HIn Vitro Toxicity Studies: Cell proliferation: DNA incorporation, mitotic index etc.TIVIEQ 5,225,1991
In Vitro/Human, HeLa cell Inhibitor Concentration (50 percent kill): 3150 mg/L/24HIn Vitro Toxicity Studies: Cell viability (mitochondrial reductase assays): MTT, XTT, MTS, WSTs assays etc.TIVIEQ 5,225,1991
In Vitro/Human, HeLa cell Inhibitor Concentration (50 percent kill): 2900 mg/L/24HIn Vitro Toxicity Studies: Cell membrane integrity: Cytoplasmic enzymes leakage (lactate dehydrogenase, ATP enzymes etc.)TIVIEQ 5,225,1991
In Vitro/Human, liver tumor Inhibitor Concentration (50 percent kill): 19 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, melanoma Inhibitor Concentration (50 percent kill): 18 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Human, skin Inhibitor Concentration (50 percent kill): 18 mmol/L/24HIn Vitro Toxicity Studies: Cell viability (lysosomal damage): neutral red assay etc.TIVIEQ 6,493,1992
In Vitro/Mouse, liver Inhibitor Concentration (50 percent kill): >5.5 mmol/L/2HBiochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Dehydrogenases

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Transaminases
TIVIEQ 4,783,1990
In Vitro/pzxInhibitor Concentration Low: 3 µmol/L/10MBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationJOETD7 135,463,2011
In Vitro/Rat, lung Inhibitor Concentration (10 percent kill): 0.1 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): 0.78 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): 2.75 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
intramuscular/child lowest published toxic dose: 50 mg/kgBehavioral: Excitement

Cardiac: Change in rate

Lung, Thorax, or Respiration: Respiratory stimulation
JOPDAB 90,827,1977
intramuscular/mouse lethal dose (50 percent kill): 271 mg/kgNIIRDN 6,34,1982
intraperitoneal/mouse lethal dose (50 percent kill): 70 mg/kgBehavioral: Convulsions or effect on seizure thresholdBJPCBM 73,887,1981
intraperitoneal/mouse lowest published toxic dose: 0.025 mg/kgBehavioral: AnalgesiaEURNE* 13,165,2003
intraperitoneal/mouse lowest published toxic dose: 10 mg/kgBehavioral: Change in motor activity (specific assay)PHREP* 58,101,2006
intraperitoneal/rat lowest published toxic dose: 50 mg/kgGastrointestinal: Changes in structure or function of salivary glandsJTPAE7 16,215,2003
intraperitoneal/rat lowest published toxic dose: 50 mg/kgGastrointestinal: Changes in structure or function of salivary glands

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other esterases
TOPADD 33,218,2005
intraperitoneal/rat lowest published toxic dose: 50 mg/kgGastrointestinal: Changes in structure or function of salivary glands

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

Biochemical: Metabolism (intermediary): Effect on cyclic nucleotides
JTPAE7 19,47,2006
intraperitoneal/rat lowest published toxic dose: 80 µg/kgBehavioral: Alteration of classical conditioningEURNE* 12,S66,2002
intraperitoneal/rat lowest published toxic dose: 80 µg/kgBrain and Coverings: Changes in surface EEG

Behavioral: Change in motor activity (specific assay)
EURNE* 12,S67,2002
intraperitoneal/rat lowest published toxic dose: 40 mg/kgKidney, Ureter, and Bladder: Other changesCEXPB9 30,242,2003
intraperitoneal/rat lowest published toxic dose: 30 mg/kgBehavioral: Anticonvulsant

Behavioral: Convulsions or effect on seizure threshold
NRTXDN 33,127,2012
intraperitoneal/rat lethal dose (50 percent kill): 150 mg/kgUSXXAM #4120947
intravenous/human lowest published toxic dose: 10 mg/kgBehavioral: Tremor

Cardiac: Arrythmias (indlucing changes in conduction)

Gastrointestinal: Nausea or vomiting
JAMAAP 235,1983,1976
intravenous/man lowest published lethal dose: 3429 µg/kgBehavioral: Convulsions or effect on seizure threshold

Lung, Thorax, or Respiration: Cyanosis

Gastrointestinal: Changes in structure or function of salivary glands
JAMAAP 136,397,1948
intravenous/mouse lethal dose (50 percent kill): 136 mg/kgPAHEAA 48,133,1973
intravenous/rabbit lethal dose (50 percent kill): 150 mg/kgNIIRDN 6,34,1982
intravenous/rat lowest published toxic dose: 10 mg/kgLung, Thorax, or Respiration: Respiratory stimulationTOXID9 72,301,2003
intravenous/rat lowest published lethal dose: 240 mg/kg27ZIAQ -,259,1973
intravenous/rat lowest published toxic dose: 100 mg/kgBehavioral: Change in motor activity (specific assay)

Lung, Thorax, or Respiration: Respiratory stimulation
PHMREP 44,81,2001
intravenous/rat lowest published lethal dose: 200 mg/kgBehavioral: Change in motor activity (specific assay)

Lung, Thorax, or Respiration: Respiratory stimulation
PHMREP 44,81,2001
intravenous/rat lowest published toxic dose: 10 mg/kgCardiac: Arrythmias (indlucing changes in conduction)

Cardiac: Change in rate
TOXID9 90,266,2006
intravenous/rat lowest published toxic dose: 5 mg/kgCardiac: Pulse rate increased without fall in BP

Vascular: BP elevation not characterized in autonomic section
BPBLEO 24,1137,2001
intravenous/rat lowest published toxic dose: 3 mg/kgBehavioral: Alteration of operant conditioningNEROEW 26,422,2002
intravenous/rat lowest published toxic dose: 1.083 mg/kg/10MVascular: BP elevation not characterized in autonomic sectionTOLED5 180S,S132,2008
intravenous/woman lowest published toxic dose: 120 mg/kg/3D- continuousCardiac: EKG changes not diagnostic of above

Biochemical: Metabolism (intermediary): Other
DICPBB 16,877,1982
oral/child lowest published toxic dose: 10 mg/kgBehavioral: Headache

Cardiac: Pulse rate increased without fall in BP

Gastrointestinal: Nausea or vomiting
SMJOAV 78,1000,1985
oral/guinea pig lowest published toxic dose: 27 mg/kgLung, Thorax, or Respiration: Bronchiolar dilationJPETAB 297,165,2001
oral/guinea pig lowest published toxic dose: 100 mg/kgLung, Thorax, or Respiration: Bronchiolar constriction, including asthmaJPETAB 302,127,2002
oral/guinea pig lethal dose (50 percent kill): 183 mg/kgUSXXAM #4089959
oral/guinea pig lowest published toxic dose: 100 mg/kgLung, Thorax, or Respiration: Respiratory stimulationTXAPA9 247,191,2010
oral/human lowest published toxic dose: 7.14 mg/kgBrain and Coverings: Changes in surface EEG

Behavioral: Change in psychophysiological tests
NEROEW 27,629,2002
oral/human lowest published toxic dose: 5 mg/kgBehavioral: Convulsions or effect on seizure threshold

Gastrointestinal: Nausea or vomiting

Nutritional and Gross Metabolic: Body temperature decrease
34ZIAG -,92,1969
oral/infant lowest published toxic dose: 348 mg/kg/4D- intermittentBehavioral: Food intake (animal)

Behavioral: Irritability

Lung, Thorax, or Respiration: Respiratory stimulation
PPHAD4 5,209,1985
oral/man lowest published toxic dose: 66 mg/kgCardiac: Change in rate

Vascular: BP lowering not characterized in autonomic section

Gastrointestinal: Nausea or vomiting
AJEMEN 11,609,1993
oral/man lowest published toxic dose: 86 mg/kgCardiac: Change in rate

Vascular: BP lowering not characterized in autonomic section

Lung, Thorax, or Respiration: Respiratory stimulation
AEMED3 20,1143,1991
oral/man lowest published toxic dose: 66 mg/kgBehavioral: Muscle contraction or spasticity

Gastrointestinal: Nausea or vomiting

Gastrointestinal: Contraction (isolated tissue)
MJAUAJ 156,512,1992
oral/man lowest published toxic dose: 129 mg/kgEndocrine: Hyperglycemia

Nutritional and Gross Metabolic: Changes in: K

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis
AIMEAS 104,284,1986
oral/mouse lowest published toxic dose: 30 mg/kgBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationBJPCBM 145,178,2005
oral/mouse lethal dose (50 percent kill): 235 mg/kgARZNAD 45,569,1995
oral/mouse lowest published toxic dose: 30 mg/kgBehavioral: Change in psychophysiological tests

Immunological Including Allergic: Decreased immune response
EJPHAZ 495,159,2004
oral/mouse lowest published toxic dose: 50 mg/kgLung, Thorax, or Respiration: Respiratory stimulationTXAPA9 247,191,2010
oral/rabbit lethal dose (50 percent kill): 350 mg/kg85JCAE -,865,1986
oral/rat lowest published toxic dose: 30 mg/kgBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationBJPCBM 145,178,2005
oral/rat lowest published toxic dose: 10 mg/kgLung, Thorax, or Respiration: Respiratory stimulation

Kidney, Ureter, and Bladder: Urine volume increased
TOXID9 -,96,2008
oral/rat lethal dose (50 percent kill): 225 mg/kgUSXXAM #4089959
oral/rat lowest published toxic dose: 100 mg/kgLung, Thorax, or Respiration: Respiratory stimulationTXAPA9 247,191,2010
oral/woman lowest published toxic dose: 281 mg/kg/4WBehavioral: Somnolence (general depressed activity)BMJOAE 281,1322,1980
oral/woman lowest published lethal dose: 130 mg/kgBiochemical: Metabolism (intermediary): OtherAIMEAS 101,457,1984
oral/woman lowest published toxic dose: 5 mg/kgBehavioral: Coma

Cardiac: Arrythmias (indlucing changes in conduction)

Gastrointestinal: Nausea or vomiting
BMJOAE 288,1497,1984
oral/woman lowest published toxic dose: 108 mg/kgEndocrine: Hyperglycemia

Nutritional and Gross Metabolic: Changes in: K

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis
AJEMEN 3,408,1985
oral/woman lowest published toxic dose: 388 mg/kgBehavioral: Coma

Cardiac: Change in rate

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis
AEMED3 20,1135,1991
parenteral/man lowest published lethal dose: 12 mg/kgDAKMAJ 80,510,1904
rectal/human lowest published toxic dose: 6 mg/kgBehavioral: Convulsions or effect on seizure threshold

Gastrointestinal: Nausea or vomiting

Nutritional and Gross Metabolic: Body temperature decrease
34ZIAG -,92,1969
rectal/mouse lethal dose (50 percent kill): 166 mg/kgBehavioral: Convulsions or effect on seizure threshold

Behavioral: Muscle contraction or spasticity

Lung, Thorax, or Respiration: Other changes
PEREBL 11,783,1977
subcutaneous/guinea pig lowest published lethal dose: 170 mg/kgHBTXAC 5,168,1959
subcutaneous/human lowest published toxic dose: 3500 µg/kgBehavioral: Convulsions or effect on seizure threshold

Gastrointestinal: Nausea or vomiting

Nutritional and Gross Metabolic: Body temperature decrease
34ZIAG -,92,1969
subcutaneous/mouse lethal dose (50 percent kill): 138 mg/kgARZNAD 3,328,1953
subcutaneous/mouse lowest published toxic dose: 5 mg/kgBiochemical: Metabolism (intermediary): OtherBPBLEO 28,1989,2005
subcutaneous/rat lowest published lethal dose: 325 mg/kgEPXXDW #0134762
subcutaneous/rat lowest published toxic dose: 25 mg/kgBiochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammationJPHSC* 106,566,2008
unreported route/mouse lethal dose (50 percent kill): 400 mg/kgUSXXAM #4767763
unreported route/rat lethal dose (50 percent kill): 300 mg/kgUSXXAM #4767763
unreported route/rat lowest published toxic dose: 100 mg/kgLung, Thorax, or Respiration: Respiratory stimulationHETOEA 24,109,2005

Other Multiple Dose Data and References

Route/OrganismDoseEffectReference
intravenous/rat lowest published toxic dose: 350 mg/kg/28D- intermittentBehavioral: Food intake (animal)

Endocrine: Differential effect of sex or castration on observed toxicity

Nutritional and Gross Metabolic: Other changes
PHMREP 44,81,2001
intravenous/rat lowest published toxic dose: 700 mg/kg/28D- intermittentCardiac: Cardiomyopathy including infarction

Endocrine: Differential effect of sex or castration on observed toxicity

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
PHMREP 44,81,2001
oral/human lowest published toxic dose: 160 mg/kg/4W- intermittentImmunological Including Allergic: Decreased immune responseCYLPDN 23,267,2002
oral/human lowest published toxic dose: 160 mg/kg/4W- intermittentLung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
CYLPDN 22,475,2001
oral/mouse lowest published toxic dose: 4800 mg/kg/2W- intermittentEye: Other eye effects

Behavioral: Somnolence (general depressed activity)

Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field
FAATDF 10,477,1988
oral/mouse lowest published toxic dose: 10350 mg/kg/13W- intermittentBrain and Coverings: Changes in brain weight

Liver: Other changes

Blood: Pigmented or nucleated red blood cells
FAATDF 11,472,1988
oral/mouse lowest published toxic dose: 4410 mg/kg/35D- continuousSkin and Appendages: Other: HairNTIS** #PB85204659/AS
oral/mouse lowest published toxic dose: 73500 mg/kg/21W- continuousLiver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** #PB85204659/AS
oral/mouse lowest published toxic dose: 73500 mg/kg/21W- continuousReproductive: Paternal effects: Testes, epididymis, sperm duct

Reproductive: Paternal effects: Prostate, seminal vesicle, Cowper's gland, accessory glands

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** #PB85204659/AS
oral/mouse lowest published toxic dose: 38625 mg/kg/103W- intermittentLiver: Tumors

Tumorigenic: Active as anti-cancer agent
NTIS** PB99-113342
oral/rat lowest published toxic dose: 12000 mg/kg/48W- continuousBrain and Coverings: Tumors

Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent
EXONC* 15,23,1993
oral/rat lowest published toxic dose: 9600 mg/kg/32W- continuousGastrointestinal: Tumors

Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent
EXONC* 15,23,1993
oral/rat lowest published toxic dose: 600 mg/kg/2W- intermittentLung, Thorax, or Respiration: Respiratory stimulation

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
FAATDF 10,477,1988
oral/rat lowest published toxic dose: 5175 mg/kg/13W- intermittentLiver: Changes in liver weight

Kidney, Ureter, and Bladder: Urine volume increased

Blood: Changes in leukocyte (WBC) count
FAATDF 11,472,1988
oral/rat lowest published toxic dose: 39900 mg/kg/19W- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainJEPTDQ 2(3),687,1979
oral/rat lowest published toxic dose: 3500 mg/kg/5W- intermittentCardiac: Other changes

Biochemical: Enzyme inhibition, induction, or change in blood or tissue levels: Other transferases
TXCYAC 145,185,2000
oral/rat lowest published toxic dose: 12875 mg/kg/103W- intermittentSkin and Appendages: Tumors

Tumorigenic: Active as anti-cancer agent
NTIS** PB99-113342
oral/rat lowest published toxic dose: 1238 mg/kg/10D- continuousSkin and Appendages: Other: Hair

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** #PB86-108172
oral/rat lowest published toxic dose: 2586 mg/kg/10D- continuousNutritional and Gross Metabolic: Weight loss or decreased weight gainNTIS** #PB86-108172
oral/rat lowest published toxic dose: 2175 mg/kg/10D- continuousBehavioral: Food intake (animal)NTIS** #PB86-108172
oral/rat lowest published toxic dose: 1238 mg/kg/10D- continuousBehavioral: Fluid intakeNTIS** #PB86-108172
unreported route/mouse lowest published toxic dose: 2160 mg/kg/3D- intermittentRelated to Chronic Data: Death in the "MULTIPLE DOSE" data type fieldFATOAO 49,74,1986

Reviews

OrganizationStandardReference
International Agency for Research on Cancer (IARC)Cancer Review:Human Inadequate EvidenceIMEMDT 51,391,1991
International Agency for Research on Cancer (IARC)Cancer Review:Animal Inadequate EvidenceIMEMDT 51,391,1991
International Agency for Research on Cancer (IARC)Cancer Review:Group 3IMEMDT 51,391,1991
TOXICOLOGY REVIEWJRPMAP 12,27,1974
TOXICOLOGY REVIEWFAATDF 13,747,1989
TOXICOLOGY REVIEWJTSCDR 25,1,2000
TOXICOLOGY REVIEWMUREAV 488,151,2001
TOXICOLOGY REVIEWMUREAV 543,201,2003
TOXICOLOGY REVIEWTOLED5 144,383,2003
TOXICOLOGY REVIEWTPHSDY 23,83,2002
TOXICOLOGY REVIEWPHMREP 47,493,2003
TOXICOLOGY REVIEWTPHSDY 24,66,2003
TOXICOLOGY REVIEWJEMME* 11,415,1993
TOXICOLOGY REVIEWECPPH* 6,87,1998
TOXICOLOGY REVIEWENTOX* -,167,2005
TOXICOLOGY REVIEWAJEMEN 22,404,2004
TOXICOLOGY REVIEWREPTED 25,192,2008
TOXICOLOGY REVIEWAJKDDP 52,144,2008
TOXICOLOGY REVIEWNEUCL* 18,215,2000
TOXICOLOGY REVIEWNBREV* 5,1,1981
TOXICOLOGY REVIEWTXAPA9 243,134,2010
TOXICOLOGY REVIEWBJPCBM 155,308,2008
TOXICOLOGY REVIEWBJPCBM 157,892,2009
TOXICOLOGY REVIEWFITOT* 82,141,2011
TOXICOLOGY REVIEWMUREAV 721,27,2011

Standards and Regulations

OrganizationStandardReference
Occupational Exposure Limit-RUSSIAshort term exposure limit 0.5 mg/m3, JUN2003

NIOSH Documentation and Surveillance

OrganizationStandardReference
National Occupational Exposure Survey 1983Hazard Code M0977; Number of Industries 6; Total Number of Facilities 1091; Number of Occupations 13; Total Number of Employees Exposed 29718; Total Number of Female Employees Exposed 21742
National Occupational Hazard Survey 1974Hazard Code M0977; Number of Industries 3; Total Number of Facilities 1681; Number of Occupations 18; Total Number of Employees Exposed 7418

Status in Federal Agencies

OrganizationReference
EPA TSCA Section 8(b) CHEMICAL INVENTORY
NCI Carcinogenesis Studies (gavage);no evidence:mouse,rat
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