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EC number: 204-260-8 | CAS number: 118-56-9
- 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
- Study period:
- no data available
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: This study is performed before guidelines and GLP establishment. This is sufficiently documented and is acceptable for evaluation of methyl salicylate hydrolysis.
Data source
Reference
- Reference Type:
- publication
- Title:
- On the metabolism and toxicity of methyl salicylate
- Author:
- Davison C, Zimmerman EF, Smith PK
- Year:
- 1 961
- Bibliographic source:
- J Pharmacol Expt Therap 132: 207-211
Materials and methods
- Objective of study:
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- method: other:
- Plasma analyses in rats after oral administration of methyl salicylate, sodium salicylate and acetylsalicylic acid.
Test material
- Reference substance name:
- Methyl salicylate
- EC Number:
- 204-317-7
- EC Name:
- Methyl salicylate
- Cas Number:
- 119-36-8
- Molecular formula:
- C8H8O3
- IUPAC Name:
- Methyl 2-hydroxybenzoate
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: methyl cellulose
- Details on exposure:
- no data
- Duration and frequency of treatment / exposure:
- single dose
Doses / concentrations
- Remarks:
- Doses / Concentrations:
500 mg/kg, calculated as free salicylic acid.
- No. of animals per sex per dose / concentration:
- 10/males/500 mg/kg as salicylic acid
- Control animals:
- no
- Positive control reference chemical:
- none
- Details on study design:
- no data
- Details on dosing and sampling:
- Pharmacokinetic study:
- Tissues and body fluids sampled: plasma (2mL) and 4 mL of brain homogenate (one part tissue and three parts water)
- time and frequency of sampling: the blood was removed by intracardiac puncture at 20 or at 60 min after administration
- From how many animals: samples pooled from 10 animals - Statistics:
- An analysis of variance of the Plasma and brain concentrations of total salicylate in rats after the oral administration of methyl salicylate, sodium salicylate and acetyl salicylic acid.
Results and discussion
- Preliminary studies:
- no data are available
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- - MeS, NaS, and ASA are all rapidly absorbed; with NaS being the most rapid.
- a significantly lower absorption of MeS than ASA was observed. - Details on distribution in tissues:
- Not performed
- Details on excretion:
- not performed
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- The results (see table 1) showed that MeS does not produce any higher plasma or brain concentrations than NaS and ASA, and is completely
hydrolyzed to free salicylate in as little as 20 minutes.
Any other information on results incl. tables
Table 1 presents the mean values obtained for total salicylate in groups of 10 animals. MeS values are not given because they were negligible.
Tissue Analyzed | Minutes after Administration | After MeS (500 mg/kg*) | After NaS (500 mg/kg*) | After ASA (500 mg/kg*) |
Plasma | 20 | 217 +/- 16.1(x) | 296 +/- 22.3 | 209 +/- 18.6 |
Brain | 20 | 8 +/- 2.7 | 38 +/- 5.9 | 22 +/- 4.4 |
Plasma | 60 | 278 +/- 16.7 | 316 +/- 24.8 | 274 +/- 23.5 |
Brain | 60 | 42 +/- 7.3 | 52 +/- 7.4 | 38 +/- 5.5 |
Table 1: Plasma and brain concentrations of total salicylate in mg/l* in rats after the oral administration of theree salicylates.
MeS: methyl salicylate
NaS: Sodium salicylate
ASA: acetysalicylic acid
*: calculated as free salicylic acid
(x): Mean +/- standard error. Each figure is an average of determinations in ten animals.
Applicant's summary and conclusion
- Conclusions:
- Under the test conditions, MeS, NaS and ASA are all rapidly absorbed even at high concentrations, with NaS absorpton being the most rapid. Also
plasma analysis showed rapid hydrolysis to free salicylate for all three compounds. - Executive summary:
Davison et al. (1961) reported that gavage of MeS to10 Wistar rats at doses equivalent to 500 mg/kg as SA resulted in the appearance of hydrolyzed free salicylate in both the plasma and brain tissue within 20 min.This study showed rapid hydrolysis to free salicylate for MeS, NaS and ASA, with comparable plasma concentrations of salicylate at 60 minutes post dosing. In the same study, the authors demonstrated that the major site of hydrolysis of methyl salicylate in the rat, rabbit, dog and monkey is the liver.
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