Theophylline

Theophylline is a nonselective phosphodiesterase (PDE) inhibitor, adenosine receptor blocker, and histone deacetylase (HDAC) activator.

Signaling Pathways >> GPCR/G Protein >> Adenosine Receptor

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphodiesterase (PDE)

Natural Products >> Alkaloid

Research Areas >> Others

Human Endogenous Metabolite

[1]. Deree J, et al. Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition. Clinics (Sao Paulo). 2008 Jun;63(3):321-8.

[2]. Marques LJ, et al. Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages. Am J Respir Crit Care Med. 1999 Feb;159(2):508-11.

[3]. Daly JW, et al. Adenosine receptors: development of selective agonists and antagonists. Prog Clin Biol Res. 1987;230:41-63.

3-Methyladenine | Hydrocortisone | Acetylcysteine(N-acetylcysteine) | Retinoic acid | 3-Isobutyl-1-methylxanthine | Melatonine | Dinoprostone | Nicotinamide | Adenosine triphosphate | 4-Acetamidophenol | Prostaglandin E1 | rolipram | Dehydroepiandrosterone | Corticosterone | Progesterone

MOLECULAR FORMULA :

C7-H8-N4-O2

MOLECULAR WEIGHT :

180.19

WISWESSER LINE NOTATION :

T56 BM DN FNVNVJ F1 H1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

66 mg/kg

TOXIC EFFECTS :

Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

108 mg/kg

TOXIC EFFECTS :

Endocrine - hyperglycemia Nutritional and Gross Metabolic - changes in potassium Nutritional and Gross Metabolic - metabolic acidosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

388 mg/kg

TOXIC EFFECTS :

Behavioral - coma Cardiac - change in rate Nutritional and Gross Metabolic - metabolic acidosis

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - infant

DOSE/DURATION :

348 mg/kg/4D-I

TOXIC EFFECTS :

Behavioral - anorexia (human) Behavioral - irritability Lungs, Thorax, or Respiration - respiratory stimulation

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

5 mg/kg

TOXIC EFFECTS :

Behavioral - coma Cardiac - arrhythmias (including changes in conduction) Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

5 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

66 mg/kg

TOXIC EFFECTS :

Behavioral - muscle contraction or spasticity Gastrointestinal - nausea or vomiting Gastrointestinal - contraction (isolated tissue)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

129 mg/kg

TOXIC EFFECTS :

Endocrine - hyperglycemia Nutritional and Gross Metabolic - changes in potassium Nutritional and Gross Metabolic - metabolic acidosis

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

130 mg/kg

TOXIC EFFECTS :

Biochemical - Metabolism (Intermediary) - other

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

86 mg/kg

TOXIC EFFECTS :

Cardiac - change in rate Vascular - BP lowering not characterized in autonomic section Lungs, Thorax, or Respiration - respiratory stimulation

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

281 mg/kg/4W

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

10 mg/kg

TOXIC EFFECTS :

Behavioral - headache Cardiac - pulse rate increase, without fall in BP Gastrointestinal - nausea or vomiting

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Human

DOSE/DURATION :

3500 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human

DOSE/DURATION :

10 mg/kg/D

TOXIC EFFECTS :

Behavioral - tremor Cardiac - arrhythmias (including changes in conduction) Gastrointestinal - nausea or vomiting

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

3429 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Gastrointestinal - changes in structure or function of salivary glands

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Human - child

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Behavioral - excitement Cardiac - change in rate Lungs, Thorax, or Respiration - respiratory stimulation

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

120 mg/kg/3D-C

TOXIC EFFECTS :

Cardiac - EKG changes not diagnostic of specified effects Biochemical - Metabolism (Intermediary) - other

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Parenteral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

12 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Rectal

SPECIES OBSERVED :

Human

DOSE/DURATION :

6 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

225 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

188 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

325 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

240 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

235 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

70 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

138 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

136 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

271 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Rectal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

166 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - muscle contraction or spasticity Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

350 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

150 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

183 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

170 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

600 mg/kg/2W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - respiratory stimulation Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

5175 mg/kg/13W-I

TOXIC EFFECTS :

Liver - changes in liver weight Kidney, Ureter, Bladder - urine volume increased Blood - changes in leukocyte (WBC) count

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

39900 mg/kg/19W-C

TOXIC EFFECTS :

Nutritional and Gross Metabolic - weight loss or decreased weight gain

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4800 mg/kg/2W-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified Behavioral - somnolence (general depressed activity) Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

10350 mg/kg/13W-I

TOXIC EFFECTS :

Brain and Coverings - changes in brain weight Liver - other changes Blood - pigmented or nucleated red blood cells

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

10050 mg/kg

SEX/DURATION :

male 67 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

1500 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

75335 mg/kg

SEX/DURATION :

male 95 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - spermatogenesis (incl. genetic material, sperm morphology, motility, and count)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

1700 mg/kg

SEX/DURATION :

female 1-17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - musculoskeletal system

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3 gm/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - 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

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

4375 mg/kg

SEX/DURATION :

male 7 day(s) pre-mating female 7 day(s) pre-mating - 3 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - live birth index (measured after birth)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3720 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - 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)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

175 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - body wall

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

200 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - other developmental abnormalities

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

225 mg/kg

SEX/DURATION :

female 13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

18750 ug/kg

SEX/DURATION :

female 24-26 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - other neonatal measures or effects

TYPE OF TEST :

Sister chromatid exchange

TYPE OF TEST :

Sister chromatid exchange

MUTATION DATA

TYPE OF TEST :

Mutation in mammalian somatic cells

TEST SYSTEM :

Rodent - hamster Lung

DOSE/DURATION :

7 mg/L

REFERENCE :

NEOLA4 Neoplasma. (Karger-Libri, P.O. Box, CH-4009 Basel, Switzerland) V.4- 1957- Volume(issue)/page/year: 33,699,1986 *** REVIEWS *** IARC Cancer Review:Human Inadequate Evidence 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- Volume(issue)/page/year: 51,391,1991 IARC Cancer Review:Animal Inadequate Evidence 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- Volume(issue)/page/year: 51,391,1991 IARC Cancer Review:Group 3 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- Volume(issue)/page/year: 51,391,1991 TOXICOLOGY REVIEW JRPMAP Journal of Reproductive Medicine. (2 Jacklynn Ct., St. Louis, MO 63132) V.3- 1969- Volume(issue)/page/year: 12,27,1974 TOXICOLOGY REVIEW FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 13,747,1989 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - M0977 No. of Facilities: 1681 (estimated) No. of Industries: 3 No. of Occupations: 18 No. of Employees: 7418 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - M0977 No. of Facilities: 1091 (estimated) No. of Industries: 6 No. of Occupations: 13 No. of Employees: 29718 (estimated) No. of Female Employees: 21742 (estimated)