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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data available
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 Type:
On the metabolism and toxicity of methyl salicylate
Davison C, Zimmerman EF, Smith PK
Bibliographic source:
J Pharmacol Expt Therap 132: 207-211

Materials and methods

Objective of study:
Test guideline
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

Constituent 1
Chemical structure
Reference substance name:
Methyl salicylate
EC Number:
EC Name:
Methyl salicylate
Cas Number:
Molecular formula:
Methyl 2-hydroxybenzoate

Test animals


Administration / exposure

Route of administration:
oral: gavage
other: methyl cellulose
Details on exposure:
no data
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
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:
Positive control reference chemical:
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
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:
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

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.