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Diss Factsheets
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EC number: 203-157-5 | CAS number: 103-90-2
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
Data source
Reference
- Reference Type:
- publication
- Title:
- No information
- Author:
- McEvoy, G.K. (ed.).
- Year:
- 2 007
- Bibliographic source:
- American Society of Health-System Pharmacists, Bethesda, MD. 2007
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
- GLP compliance:
- not specified
Test material
- Reference substance name:
- Paracetamol
- EC Number:
- 203-157-5
- EC Name:
- Paracetamol
- Cas Number:
- 103-90-2
- Molecular formula:
- C8H9NO2
- IUPAC Name:
- .
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- human
- Sex:
- male
Administration / exposure
- Route of administration:
- oral: unspecified
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- In healthy men, steady-state oral bioavailability of 1.3-g doses of extended-release tablets of acetaminophen administered every 8 hours for a total of 7 doses was equal to 1-g doses of conventional tablets of acetaminophen given every 6 hours for a total of 7 doses.
- Duration and frequency of treatment / exposure:
- Every 8 hours for a total of 7 doses
Doses / concentrations
- Dose / conc.:
- 1.3 other: gm
- No. of animals per sex per dose / concentration:
- Details not available
- Control animals:
- no
Results and discussion
Main ADME resultsopen allclose all
- Type:
- absorption
- Results:
- Acetaminophen is rapidly and almost completely absorbed from the GI tract following oral administration. Food may delay slightly absorption of extended-release tablets of acetaminophen
- Type:
- distribution
- Results:
- Acetaminophen is rapidly and uniformly distributed into most body tissues. About 25% of acetaminophen in blood is bound to plasma proteins Following oral administration of immediate- or extended-release acetaminophen preparations, peak plasma concentratio
- Type:
- metabolism
- Results:
- About 80-85% of the acetaminophen in the body undergoes conjugation principally with glucuronic acid and to a lesser extent with sulfuric acid. Acetaminophen also is metabolized by microsomal enzyme systems in the liver.
- Type:
- excretion
- Results:
- Acetaminophen is excreted in urine principally as acetaminophen glucuronide with small amounts of acetaminophen sulfate and mercaptate and unchanged drug. Approximately 85% of a dose of acetaminophen is excreted in urine as free & conjugated acetaminophen
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Acetaminophen is rapidly and almost completely absorbed from the GI tract following oral administration. Food may delay slightly absorption of extended-release tablets of acetaminophen. Following oral administration of immediate- or extended-release acetaminophen preparations, peak plasma concentrations are attained within 10-60 or 60-120 minutes, respectively. Following oral administration of a single 500-mg conventional tablet or a single 650-mg extended-release tablet, average plasma acetaminophen concentrations of 2.1 or 1.8 ug/mL, respectively, occur at 6 or 8 hours, respectively. In addition, dissolution of the extended-release tablets may depend slightly on the gastric or intestinal pH. Dissolution appears to be slightly faster in the alkaline pH of the intestines compared with the acidic pH of the stomach; however, this is of no clinical importance. Following administration of conventional preparations of acetaminophen, only small amounts of the drug are detectable in plasma after 8 hours. The extended-release tablets of acetaminophen release the drug for up to 8 hours, but in vitro data indicate that at least 95% of the dose is released within 5 hours.
- Details on distribution in tissues:
- Acetaminophen is rapidly and uniformly distributed into most body tissues. About 25% of acetaminophen in blood is bound to plasma proteins. Following oral administration of immediate- or extended-release acetaminophen preparations, peak plasma concentrations are attained within 10-60 or 60-120 minutes, respectively. Following oral administration of a single 500-mg conventional tablet or a single 650-mg extended-release tablet, average plasma acetaminophen concentrations of 2.1 or 1.8 ug/mL, respectively, occur at 6 or 8 hours, respectively
- Details on excretion:
- Acetaminophen is excreted in urine principally as acetaminophen glucuronide with small amounts of acetaminophen sulfate and mercaptate and unchanged drug. Approximately 85% of a dose of acetaminophen is excreted in urine as free and conjugated acetaminophen within 24 hours after ingestion. Administration of acetaminophen to patients with moderate to severe renal impairment may result in accumulation of acetaminophen conjugates.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- acetaminophen glucuronide
acetaminophen sulfate
acetaminophen mercaptate
Any other information on results incl. tables
Details on metabolism : About 80-85% of the acetaminophen in the body undergoes conjugation principally with glucuronic acid and to a lesser extent with sulfuric acid. Acetaminophen also is metabolized by microsomal enzyme systems in the liver.
Data indicate that small quantities of acetaminophen are metabolized by a cytochrome P-450 microsomal enzyme to a reactive intermediate metabolite (N-acetyl-p-benzoquinoneimine, N-acetylimidoquinone, NAPQI) which is further metabolized via conjugation with glutathione and ultimately excreted in urine as a mercapturic acid. It has been suggested that this intermediate metabolite is responsible for acetaminophen-induced liver necrosis and that high doses of acetaminophen may deplete glutathione so that inactivation of this toxic metabolite is decreased. At high doses, the capacity of metabolic pathways for conjugation with glucuronic acid and sulfuric acid may be exceeded, resulting in increased metabolism of acetaminophen by alternative pathways. In addition, it also has been suggested that in fasting individuals conjugation of high doses of acetaminophen with glucuronic acid may be reduced, secondary to decreased hepatic carbohydrate reserves and microsomal oxidation may be increased, resulting in increased risk of hepatotoxicity.
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): low bioaccumulation potential based on study results
In healthy humans, paracetamol (synonym = acetaminophen) is expected to have low bio-accumulation potential since approximately 85% of a dose of acetaminophen is excreted in urine as free and conjugated acetaminophen within 24 hours after ingestion. However, administration of acetaminophen to patients with moderate to severe renal impairment may result in accumulation of acetaminophen conjugates.
Thus, the bio-accumulation potential of paracetamol is expected to be related to the health status and age of the humans that are administered oral doses of the chemical - Executive summary:
In healthy humans, paracetamol (synonym = acetaminophen) is expected to have low bio-accumulation potential since approximately 85% of a dose of acetaminophen is excreted in urine as free and conjugated acetaminophen within 24 hours after ingestion. However, administration of acetaminophen to patients with moderate to severe renal impairment may result in accumulation of acetaminophen conjugates. Thus, the bio-accumulation potential of paracetamol is expected to be related to the health status and age of the humans that are administered oral doses of the chemical
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