O-acetylsalicylic acid

Exposure related observations in humans: other data

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 for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Methyl salicylate

EC Number:

204-317-7

EC Name:

Methyl salicylate

Cas Number:

119-36-8

IUPAC Name:

methyl salicylate

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.