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Toxicological information

Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-conducted volunteer study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
On the metabolism and toxicity of methyl salicylate
Author:
Davison C; Zimmerman EF, Smith PK
Year:
1961
Bibliographic source:
J Pharmacol Expt Therap 132:207-211

Materials and methods

Type of study / information:
Oral absorption and hydrolysis in humans
Endpoint addressed:
basic toxicokinetics
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Plasma analyses for methyl salicylate and free salicylate after oral administration of the ester to humans.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: methyl salicylate
- Molecular formula: C8H8O3
- Substance type: Oily liquid

Method

Ethical approval:
not specified
Details on study design:
4 men, 2 women
Exposure assessment:
measured

Results and discussion

Results:
After 15 min, the mean MeS and free salicylate values were 4.9 and 7.9 mg/l, respectively. After 90 min, these values were 2.8 and 10.5 mg/l, respectively. 30% MeS remained unhydrolysed at 15 minutes, and 21% at 90 minutes.

Any other information on results incl. tables

Table 1: Comparison of plasma salicylate levels in humans in mg/l (dose averaged 7 mg/kg as SA) after oral administration of MeS or ASA

 

Subject ID

MeS administration

ASA administration

15 min

90 min

15 min

90 min

MeS

Free Sal.

Total Sal.

MeS

Free Sal.

Total Sal.

Total Sal.

Total Sal.

PS

6.4

8.8

15.2

3.2

5.0

8.2

 

 

DC

3.2

7.7

10.9

5.7

21.1

26.8

16.9

26.8

LE

4.7

7.4

12.1

2.5

7.3

9.8

7.3

22.3

LS

4.5

13.6

18.1

0

10.8

10.8

25.0

34.0

CD

4.5

6.0

10.5

1.3

9.6

10.9

16.9

20.4

EZ

6.3

4.4

10.7

4.1

9.1

13.2

25.0

18.4

Mean

4.9

7.9

12.8

2.8

10.5

13.3

18.2

24.5

SD

0.05

1.27

1.26

0.82

2.29

2.78

3.26

2.87

 

Applicant's summary and conclusion

Conclusions:
Under the test conditions, in humans, hydrolysis of MeS was demonstrated but was slower and less complete than that for ASA, with 30% MeS unhydrolysed at 15 minutes, and 21% at 90 minutes.
Executive summary:

Davison et al. (1961) reported that oral consumption of 0.42 ml of methyl salicylate by 6 human volunteers resulted in the rapid appearance of salicylic acid in the plasma. At 15 and 90 min, salicylic acid was two and fourfold higher respectively than methyl salicylate in plasma. This is indicative of extensive hydrolysis during oral absorption. However, hydrolysis of MeS to free salicylate was slower and less complete than that of ASA, with 30% MeS unhydrolysed at 15 minutes, and 21% at 90 minutes.