CDC logo, Safer Healthier People  CDC HomeCDC SearchCDC Health Topics A-Z
NIOSH - National Institute for Occupational Safety and Health

Search NIOSH  |  NIOSH Home  |  NIOSH Topics  |  Site Index  |  Databases and Information Resources  |  NIOSH Products  |  Contact Us






Theophylline

RTECS #: XH3850000

CAS #: 58-55-9


UPDATE: February 2009 MW: 180.19 MF: C7H8N4O2


NOTE:

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

SYNONYMS:

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


SKIN AND EYE IRRITATION DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

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


MUTATION DATA AND REFERENCES:

SYSTEM TEST ROUTE/
ORGANISM/
TISSUE
DOSE REFERENCE
cytogenetic analysis hamster lung 450 mg/L GMCRDC 27,95,1981
cytogenetic analysis human lymphocyte 10 mg/L MUREAV 224,409,1989
cytogenetic analysis mouse mammary gland 3,200 mol/L/24 hour- continuous JTSCDR 5,141,1980
DNA inhibition hamster lung 6 mmol/L MUREAV 26,73,1974
DNA inhibition human fibroblast 7 mg/L NEOLA4 33,699,1986
DNA inhibition human other cell types 4 mmol/L BIOJAU 35,665,1981
DNA inhibition mouse lymphocyte 6 mmol/L MUREAV 26,73,1974
DNA inhibition mouse fibroblast 6 mmol/L MUREAV 26,73,1974
unscheduled DNA synthesis human other cell types 1 mmol/L BIOJAU 35,665,1981
mutation in microorganisms Bacillus subtilis 7,500 mg/L (-enzymatic activation step) MUREAV 117,55,1983
mutation in microorganisms Escherichia coli 150 mg/L (-enzymatic activation step) CSHSAZ 16,337,1952
mutation in microorganisms Euglena gracilis 600 mg/L (-enzymatic activation step) MUREAV 32,169,1975
mutation in microorganisms other microorganisms 6,000 ppm (-enzymatic activation step) NATUAS 162,573,1948
mutation in microorganisms Salmonella typhimurium 10 g/plate (+enzymatic activation step) MUREAV 444,17,1999
mutation in mammalian somatic cells hamster lung 7 mg/L NEOLA4 33,699,1986
other mutation test systems human lymphocyte 100 mol/L MUREAV 15,197,1972
other mutation test systems mouse other cell types 100 mol/L JIDEAE 66,313,1976
other mutation test systems rat other cell types 1 mmol/L INOPAO 13,210,1974
sister chromatid exchange hamster lung 360 mg/L SNSHBT (20),574,1980
sister chromatid exchange hamster ovary 2 mmol/L MUREAV 126,63,1984
sister chromatid exchange oral
hamster
300 mg/kg EXPEAM 38,600,1982
sister chromatid exchange human embryo 360 mg/L SNSHBT (20),574,1980
sister chromatid exchange human lymphocyte 10 mg/L MUREAV 224,409,1989
sister chromatid exchange intraperitoneal
mouse
12,500 g/kg MUREAV 444,17,1999
specific locus test mouse other cell types 1,500 mg/L/24 hour (-enzymatic activation step) MUTAEX 14,23,1999


REPRODUCTIVE EFFECTS DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
intraperitoneal
mouse
lowest published toxic dose: 175 mg/kg (13 day 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
lowest published toxic dose: 200 mg/kg (13 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Other developmental abnormalities
OFAJAE 46,167,1969
intraperitoneal
mouse
lowest published toxic dose: 225 mg/kg (13 day 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
lowest published toxic dose: 18,750 g/kg (24-26 day pregnant) Reproductive: Effects on newborn: Other neonatal measures or effects PEREBL 12,38,1978
intravenous
rabbit
lowest published toxic dose: 780 mg/kg (12-18 day 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
lowest published toxic dose: 3 gm/kg (6-15 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)

Reproductive: Effects on embryo or fetus: Fetal death
NTIS** PB86-103223
oral
mouse
lowest published toxic dose: 4,375 mg/kg (7 day male/7 day prior to copulation-3 week pregnant) Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth) FAATDF 10,525,1988
oral
mouse
lowest published toxic dose: 3,720 mg/kg (6-15 day pregnant) Reproductive: Effects on fertility: Post- implantation mortality (e.g., dead and/or resorbed implants per total number of implants)

Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus)
FAATDF 14,167,1990
oral
mouse
lowest published toxic dose: 17.5 gm/kg (7 day male/7 day prior to copulation/21 day 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
lowest published toxic dose: 19 gm/kg (7 day male/7 day prior to copulation/24 day pregnant) Reproductive: Maternal effects: Parturition NTIS** #PB85204659/AS
oral
mouse
lowest published toxic dose: 4.4 gm/kg (7 day male/7 day prior to copulation/21 day pregnant) Reproductive: Effects on newborn: Live birth index (Litter size (e.g., # fetuses per litter; measured after birth) NTIS** #PB85204659/AS
oral
mouse
lowest published toxic dose: 73,500 mg/kg (21 week 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
lowest published toxic dose: 10,050 mg/kg (67 day male) Reproductive: Paternal effects: Testes, epididymis, sperm duct FAATDF 10,525,1988
oral
rat
lowest published toxic dose: 1,500 mg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) TJADAB 33,70C,1986
oral
rat
lowest published toxic dose: 75,335 mg/kg (95 day male) Reproductive: Paternal effects: Spermatogenesis (including genetic material, sperm morphology, motility, and count) FAATDF 10,525,1988
oral
rat
lowest published toxic dose: 2,586 mg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetal death NTIS** #PB86-108172
oral
rat
lowest published toxic dose: 2,175 mg/kg (6-15 day pregnant) Reproductive: Effects on embryo or fetus: Fetotoxicity (except death, e.g., stunted fetus) NTIS** #PB86-108172
subcutaneous
rat
lowest published toxic dose: 1,700 mg/kg (1-17 day pregnant) Reproductive: Specific developmental abnormalities: Musculoskeletal system AIPTAK 172,219,1968


TUMORIGENIC DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

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


ACUTE TOXICITY DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
intramuscular
child
lowest published toxic dose: 50 mg/kg Behavioral: Excitement

Cardiac: Change in rate

Lung, Thorax, or Respiration: Respiratory stimulation
JOPDAB 90,827,1977
intramuscular
mouse
lethal dose (50 percent kill): 271 mg/kg N/R NIIRDN 6,34,1982
intraperitoneal
mouse
lethal dose (50 percent kill): 70 mg/kg Behavioral: Convulsions or effect on seizure threshold BJPCBM 73,887,1981
intraperitoneal
mouse
lowest published toxic dose: 0.25 mg/kg Behavioral: Analgesia EURNE* 13,165,2003
intraperitoneal
mouse
lowest published toxic dose: 10 mg/kg Behavioral: Change in motor activity (specific assay) PHREP* 58,101,2006
intraperitoneal
rat
lethal dose (50 percent kill): 150 mg/kg N/R USXXAM #4120947
intraperitoneal
rat
lowest published toxic dose: 80 g/kg Behavioral: Alteration of classical conditioning EURNE* 12,S66,2002
intraperitoneal
rat
lowest published toxic dose: 80 g/kg Brain 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/kg Kidney, Ureter, and Bladder: Other changes CEXPB9 30,242,2003
intraperitoneal
rat
lowest published toxic dose: 50 mg/kg Gastrointestinal: 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/kg Gastrointestinal: Changes in structure or function of salivary glands JTPAE7 16,215,2003
intraperitoneal
rat
lowest published toxic dose: 50 mg/kg Gastrointestinal: 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
intravenous
human
lowest published toxic dose: 10 mg/kg/ day Behavioral: Tremor

Cardiac: Arrythmias (indlucing changes in conduction)

Gastrointestinal: Nausea or vomiting
JAMAAP 235,1983,1976
intravenous
man
lowest published lethal dose: 3,429 g/kg Behavioral: 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/kg N/R PAHEAA 48,133,1973
intravenous
rat
lowest published lethal dose: 240 mg/kg N/R 27ZIAQ -,259,1973
intravenous
rat
lowest published toxic dose: 5 mg/kg Cardiac: 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: 10 mg/kg Lung, Thorax, or Respiration: Respiratory stimulation TOXID9 72,301,2003
intravenous
rat
lowest published toxic dose: 3 mg/kg Behavioral: Alteration of operant conditioning NEROEW 26,422,2002
intravenous
rat
lowest published toxic dose: 100 mg/kg Behavioral: Change in motor activity (specific assay)

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

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

Cardiac: Change in rate
TOXID9 90,266,2006
intravenous
rabbit
lethal dose (50 percent kill): 150 mg/kg N/R NIIRDN 6,34,1982
intravenous
woman
lowest published toxic dose: 120 mg/kg/3 day- continuous Cardiac: EKG changes not diagnostic of above

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

Cardiac: Pulse rate increased without fall in BP

Gastrointestinal: Nausea or vomiting
SMJOAV 78,1000,1985
oral
guinea pig
lethal dose (50 percent kill): 183 mg/kg N/R USXXAM #4089959
oral
guinea pig
lowest published toxic dose: 27 mg/kg Lung, Thorax, or Respiration: Bronchiolar dilation JPETAB 297,165,2001
oral
guinea pig
lowest published toxic dose: 100 mg/kg Lung, Thorax, or Respiration: Bronchiolar constriction, including asthma JPETAB 302,127,2002
oral
guinea pig
lowest published toxic dose: 100 mg/kg Lung, Thorax, or Respiration: Respiratory stimulation BPBLEO 27,641,2004
oral
human
lowest published toxic dose: 5 mg/kg Behavioral: Convulsions or effect on seizure threshold

Gastrointestinal: Nausea or vomiting

Nutritional and Gross Metabolic: Body temperature decrease
34ZIAG -,92,1969
oral
human
lowest published toxic dose: 7.14 mg/kg Brain and Coverings: Changes in surface EEG

Behavioral: Change in psychophysiological tests
NEROEW 27,629,2002
oral
infant
lowest published toxic dose: 348 mg/kg/4 day- intermittent Behavioral: Food intake (animal)

Behavioral: Irritability

Lung, Thorax, or Respiration: Respiratory stimulation
PPHAD4 5,209,1985
oral
man
lowest published toxic dose: 66 mg/kg Cardiac: 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: 66 mg/kg Behavioral: Muscle contraction or spasticity

Gastrointestinal: Nausea or vomiting

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

Nutritional and Gross Metabolic: Changes in: K

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis
AIMEAS 104,284,1986
oral
man
lowest published toxic dose: 86 mg/kg Cardiac: Change in rate

Vascular: BP lowering not characterized in autonomic section

Lung, Thorax, or Respiration: Respiratory stimulation
AEMED3 20,1143,1991
oral
mouse
lethal dose (50 percent kill): 235 mg/kg N/R ARZNAD 45,569,1995
oral
mouse
lowest published toxic dose: 30 mg/kg Behavioral: Change in psychophysiological tests

Immunological Including Allergic: Decreased immune response
EJPHAZ 495,159,2004
oral
mouse
lowest published toxic dose: 30 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BJPCBM 145,178,2005
oral
rat
lethal dose (50 percent kill): 225 mg/kg N/R USXXAM #4089959
oral
rat
lowest published toxic dose: 30 mg/kg Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation BJPCBM 145,178,2005
oral
rat
lowest published toxic dose: 10 mg/kg Lung, Thorax, or Respiration: Respiratory stimulation

Kidney, Ureter, and Bladder: Urine volume increased
TOXID9 -,96,2008
oral
rabbit
lethal dose (50 percent kill): 350 mg/kg N/R 85JCAE -,865,1986
oral
woman
lowest published toxic dose: 108 mg/kg Endocrine: 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/kg Behavioral: Coma

Cardiac: Change in rate

Nutritional and Gross Metabolic: Changes in: Metabolic acidosis
AEMED3 20,1135,1991
oral
woman
lowest published toxic dose: 5 mg/kg Behavioral: Coma

Cardiac: Arrythmias (indlucing changes in conduction)

Gastrointestinal: Nausea or vomiting
BMJOAE 288,1497,1984
oral
woman
lowest published lethal dose: 130 mg/kg Biochemical: Metabolism (intermediary): Other AIMEAS 101,457,1984
oral
woman
lowest published toxic dose: 281 mg/kg/4 week Behavioral: Somnolence (general depressed activity) BMJOAE 281,1322,1980
parenteral
man
lowest published lethal dose: 12 mg/kg N/R DAKMAJ 80,510,1904
rectal
human
lowest published toxic dose: 6 mg/kg Behavioral: 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/kg Behavioral: 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/kg N/R HBTXAC 5,168,1959
subcutaneous
human
lowest published toxic dose: 3,500 g/kg Behavioral: 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/kg N/R ARZNAD 3,328,1953
subcutaneous
mouse
lowest published toxic dose: 5 mg/kg Biochemical: Metabolism (intermediary): Other BPBLEO 28,1989,2005
subcutaneous
rat
lowest published lethal dose: 325 mg/kg N/R EPXXDW #0134762
unreported route
mouse
lethal dose (50 percent kill): 400 mg/kg N/R USXXAM #4767763
unreported route
rat
lethal dose (50 percent kill): 300 mg/kg N/R USXXAM #4767763
unreported route
rat
lowest published toxic dose: 100 mg/kg Lung, Thorax, or Respiration: Respiratory stimulation HETOEA 24,109,2005


OTHER MULTIPLE DOSE DATA AND REFERENCES:

ROUTE/
ORGANISM
DOSE
EFFECT

REFERENCE
intravenous
rat
lowest published toxic dose: 350 mg/kg/28 day- intermittent Behavioral: 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/28 day- intermittent Cardiac: 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/4 week- intermittent Lung, Thorax, or Respiration: Other changes

Biochemical: Metabolism (intermediary): Effect on inflammation or mediation of inflammation
CYLPDN 22,475,2001
oral
human
lowest published toxic dose: 160 mg/kg/4 week- intermittent Immunological Including Allergic: Decreased immune response CYLPDN 23,267,2002
oral
mouse
lowest published toxic dose: 4,800 mg/kg/2 week- intermittent Eye: 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: 10,350 mg/kg/13 week- intermittent Brain 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: 38,625 mg/kg/103 week- intermittent Liver: Tumors

Tumorigenic: Active as anti-cancer agent
NTIS** PB99-113342
oral
mouse
lowest published toxic dose: 4,410 mg/kg/35 day- continuous Skin and Appendages: Other: Hair NTIS** #PB85204659/AS
oral
mouse
lowest published toxic dose: 73,500 mg/kg/21 week- continuous Liver: Changes in liver weight

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** #PB85204659/AS
oral
mouse
lowest published toxic dose: 73,500 mg/kg/21 week- continuous Reproductive: 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
rat
lowest published toxic dose: 600 mg/kg/2 week- intermittent Lung, 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: 5,175 mg/kg/13 week- intermittent Liver: 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: 39,900 mg/kg/19 week- continuous Nutritional and Gross Metabolic: Weight loss or decreased weight gain JEPTDQ 2(3),687,1979
oral
rat
lowest published toxic dose: 3,500 mg/kg/5 week- intermittent Cardiac: 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: 12,875 mg/kg/103 week- intermittent Skin and Appendages: Tumors

Tumorigenic: Active as anti-cancer agent
NTIS** PB99-113342
oral
rat
lowest published toxic dose: 12,000 mg/kg/48 week- continuous Brain 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: 9,600 mg/kg/32 week- continuous Gastrointestinal: Tumors

Tumorigenic: Protects against induction of experimental tumors

Tumorigenic: Active as anti-cancer agent
EXONC* 15,23,1993
oral
rat
lowest published toxic dose: 1,238 mg/kg/10 day- continuous Skin and Appendages: Other: Hair

Nutritional and Gross Metabolic: Weight loss or decreased weight gain
NTIS** #PB86-108172
oral
rat
lowest published toxic dose: 2,586 mg/kg/10 day- continuous Nutritional and Gross Metabolic: Weight loss or decreased weight gain NTIS** #PB86-108172
oral
rat
lowest published toxic dose: 2,175 mg/kg/10 day- continuous Behavioral: Food intake (animal) NTIS** #PB86-108172
oral
rat
lowest published toxic dose: 1,238 mg/kg/10 day- continuous Behavioral: Fluid intake NTIS** #PB86-108172
unreported route
mouse
lowest published toxic dose: 2,160 mg/kg/3 day- intermittent Related to Chronic Data: Death in the "MULTIPLE DOSE" data type field FATOAO 49,74,1986


REVIEWS:

ORGANIZATION STANDARD
REFERENCE

International Agency for Research on Cancer (IARC) Cancer Review Human Inadequate Evidence IMEMDT 51,391,1991
International Agency for Research on Cancer (IARC) Cancer Review Animal Inadequate Evidence IMEMDT 51,391,1991
International Agency for Research on Cancer (IARC) Cancer Review Group 3 IMEMDT 51,391,1991
TOXICOLOGY REVIEW
JRPMAP 12,27,1974
TOXICOLOGY REVIEW
FAATDF 13,747,1989
TOXICOLOGY REVIEW
JTSCDR 25,1,2000
TOXICOLOGY REVIEW
MUREAV 488,151,2001
TOXICOLOGY REVIEW
MUREAV 543,201,2003
TOXICOLOGY REVIEW
TOLED5 144,383,2003
TOXICOLOGY REVIEW
TPHSDY 23,83,2002
TOXICOLOGY REVIEW
PHMREP 47,493,2003
TOXICOLOGY REVIEW
TPHSDY 24,66,2003
TOXICOLOGY REVIEW
JEMME* 11,415,1993
TOXICOLOGY REVIEW
ECPPH* 6,87,1998
TOXICOLOGY REVIEW
ECPPH* 6,87,1998
TOXICOLOGY REVIEW
ENTOX* -,167,2005
TOXICOLOGY REVIEW
AJEMEN 22,404,2004
TOXICOLOGY REVIEW
REPTED 25,192,2008


STANDARDS AND REGULATIONS:

ORGANIZATION STANDARD
REFERENCE

Occupational Exposure Limit - RUSSIA short term exposure limit 0.5 mg/m3, JUN2003


NIOSH DOCUMENTATION AND SURVEILLANCE:

ORGANIZATION STANDARD or SURVEY
REFERENCE

National Occupational Hazard Survey 1974 National Occupational Hazard Survey 1974: Hazard Code: M0977;
Number of Industries 3;
Total Number of Facilities 1,681;
Number of Occupations 18;
Total Number of Employees Exposed 7,418
National Occupational Exposure Survey 1983 National Occupational Exposure Survey 1983: Hazard Code: M0977;
Number of Industries 6;
Total Number of Facilities 1,091;
Number of Occupations 13;
Total Number of Employees Exposed 29,718;
Total Number of Female Employees Exposed 21,742


STATUS IN FEDERAL AGENCIES:

ORGANIZATION
REFERENCE

EPA TSCA Section 8(b) CHEMICAL INVENTORY
Used as a diuretic, cardiac stimulant, smooth muscle relaxant
NCI Carcinogenesis Studies (gavage);no evidence:mouse,rat


REFERENCES:

CODEN
REFERENCE

27ZIAQ "Drug Dosages in Laboratory Animals - A Handbook," Rev. ed., Barnes, C.D., and L.G. Eltherington, Berkeley, Univ. of California Press, 1973
34ZIAG "Toxicology of Drugs and Chemicals," Deichmann, W.B., New York, Academic Press, Inc., 1969
85JCAE "Prehled Prumyslove Toxikologie; Organicke Latky," Marhold, J., Prague, Czechoslovakia, Avicenum, 1986
AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038)
AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927-
AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898-
AJEMEN American Journal of Emergency Medicine. (WB Saunders, Philadelphia, PA) V.1- 1983-
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
BIOJAU Biophysical Journal. (Rockefeller Univ. Press, 1230 York Ave., New York, NY 10021) V.1- 1960-
BJPCBM British Journal of Pharmacology. (Macmillan Press Ltd., Houndmills, Basingstoke, Hants. RG21 2XS, UK) V.34- 1968-
BMJOAE British Medical Journal. (British Medical Assoc., BMA House, Tavistock Sq., London WC1H 9JR, UK) V.1- 1857-
BPBLEO Biological and Pharmaceutical Bulletin. (Pharmaceutical Society of Japan, 2-12-15-201 Shibuya Shibuya-ku, Tokyo 150, Japan) V.16- 1993-
CEXPB9 Clinical and Experimental Pharmacology and Physiology. (Blackwell Scientific Publications, (Australia) Pty Ltd., 107 Barry St., Carlton, Vic. 3053, Australia) V.1- 1974-
CSHSAZ Cold Spring Harbor Symposia on Quantitative Biology. (Cold Spring Harbor Laboratory, POB 100, Cold Spring Harbor, NY 11724) V.1- 1933-
CYLPDN Zhongguo Yaoli Xuebao. Acta Pharmacologica Sinica. Chinese Journal of Pharmacology. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1980-
DAKMAJ Deutsches Archiv fuer Klinische Medizin. (Leipzig, Ger. Dem. Rep.) V.1-211, 1865-1965. For publisher information, see EJCIB8.
DICPBB Drug Intelligence and Clinical Pharmacy. (POB 42435, Cincinnati, OH 45242) V.3- 1969-
ECPPH* Experimental and Clinical Psychopharmacology (Washington Dc American Psychological Association) V.1- 1993-
EJPHAZ European Journal of Pharmacology. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1967-
ENTOX* Encyclopedia of Toxicology: Reference Book, Elsevier, 2005
EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231)
EURNE* European Neuropsychopharmacology (Elsevier Science, P.O.Box 7247-7682,Philadelphia,PA 19170 -7682,USA OR Elsevier Science B.V.,P.O.Box 1270,1000 BG Amsterdam,The Netherlands) V.1- Nov.1990-
EXONC* Experimental Oncology (Journal of ucrainian section of European institute of ecology and cancer, Kiev-22, Vaselkovskaya str., 25, Kiev-22) V.1- 1979-
EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945-
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1-40, 1981-97. For publisher information, see TOSCF2
FATOAO Farmakologiya i Toksikologiya (Moscow). For English translation, see PHTXA6 and RPTOAN. (V/O Mezhdunarodnaya Kniga, 113095 Moscow, USSR) V.2- 1939-
GMCRDC Gann Monograph on Cancer Research. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) No. 11- 1971-
HBTXAC "Handbook of Toxicology," 4 vols., Philadelphia, W.B. Saunders Co., 1956-59
HETOEA Human & Experimental Toxicology. (Macmillan Press Ltd., Brunel Road, Houndmills, Basingstoke, Hampshire, RG21 2XS, UK) V.9- 1990-
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972-
INOPAO Investigative Ophthalmology. (St. Louis, MO) V.1-15, 1962-76. For publisher information, see IOVSDA.
JAMAAP JAMA, Journal of the American Medical Association. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1883-
JEMME* The Journal of emergency medicine (New York : Pergamon Press) V.1- 1983-
JEPTDQ Journal of Environmental Pathology and Toxicology. (Park Forest South, IL) V.1-5(3), 1977-81(?). For publisher information, see JEPOEC.
JIDEAE Journal of Investigative Dermatology. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1938-
JOPDAB Journal of Pediatrics. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63141) V.1- 1932-
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
JRPMAP Journal of Reproductive Medicine. (2 Jacklynn Ct., St. Louis, MO 63132) V.3- 1969-
JTPAE7 Journal of Toxicologic Pathology. (Nihon Dokusei Byori Gakkai, editor, 3-25-8 Nishi- shinbashi, Minato-ku, Tokyo 105, Japan) V.1- 1988
JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku, Tokyo 113, Japan) V.1- 1976-
MFEPDX Methods and Findings in Experimental and Clinical Pharmacology. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1979-
MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914-
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964-
MUTAEX Mutagenesis. (Oxford Univ. Press, Pinkhill House, Southfield Road, Eynsham, Oxford OX8 1JJ, UK) V.1- 1986-
NATUAS Nature. (Nature Subscription Dept., POB 1018, Manasguan, NJ 08736) V.1- 1869-
NEOLA4 Neoplasma. (Karger-Libri, P.O. Box, CH-4009 Basel, Switzerland) V.4- 1957-
NEROEW Neuropsychopharmacology. (Elsevier Science, 655 Avenue of the Americas, New York, NY 10010) V.1- 1987-
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan)
NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information.
OFAJAE Okajimas Folia Anatomica Japonica. (Keio Univ., School of Medicine, Dept. of Anatomy, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan) V.14- 1936-
PAHEAA Pharmaceutica Acta Helvetiae. (Schweizerische Apothekerzeitung, Postfach 3006, CH3000 Bern, 7, Switzerland) V.1- 1926-
PEREBL Pediatric Research. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1967-
PHMREP Pharmacological Research. (Academic Press, 24-28 Oval Rd. London NW1 7DX, UK) V.21- 1989-
PHREP*
PPHAD4 Pediatric Pharmacology. (New York, NY) V.1-5, 1980-86. For publisher information, see DPTHDL.
REPTED Reproductive Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1- 1987-
SMJOAV Southern Medical Journal. (Southern Medical Assoc., POB 2446, Birmingham, AL 35205) V.1- 1908-
SNSHBT Senshokutai. Chromosome. (Sensyokutai Gakkai, Kaokusai Kirisutokyo Daigaku, Mitaka, Tokyo-to, Japan) No.1- 1946- Adopted new numbering in 1976.
TJADAB Teratology, The International Journal of Abnormal Development. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1977-
TOPADD Toxicologic Pathology. (c/o Dr. F.A. de la Iglesia, Warner-Lambert Co., Pharmaceutical Research Div., POB 1047, Ann Arbor, MI 48106) V.6(3/4)- 1978-
TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981-
TPHSDY Trends in Pharmacological Sciences. (Elsevier Science Pub. Co., Inc., 52 Vanderbilt Ave., New York, NY 10017) V.1- 1979-
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973-
USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231)

Used as a diuretic, cardiac stimulant, smooth muscle relaxant

FDA-over the counter drug

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

Click Here for Additional Information about RTECS

NIOSH Home |  NIOSH Search  |  Site Index  |  Topic List |  Contact Us