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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-reported non guideline study
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Percutaneous absorption of salicylates from some commercially available topical products containing methyl salicylate or salicylate salts in rats
Author:
Megwa SA, Benson HAE, Roberts MS
Year:
1995
Bibliographic source:
J Pharmacy Pharmacol 47:891-896

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Measurement of dermal absorption
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):
Metsal Cream (20% MeS)
Dencorub Cream (28.3% MeS)
Biosal Cream (12% MeS)
Deep heat Cream (12.74% MeS)
Goanna Rub (10% MeS)
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
no effects
Absorption in different matrices:
- Skin test site: MeS was well absorbed

Any other information on results incl. tables

For each of the 5 preparations containing MeS, MeS was absorbed and mainly converted to SA during transport through the skin.

Applicant's summary and conclusion

Conclusions:
Topically applied MeS can penetrate deeply into tissues. Local concentrations higher than circulating systemic concentrations are suggestive that direct diffusion and local blood redistribution contribute to this effect
Executive summary:

In a study to examine dermal penetration of MeS from a topical preparation, dogs (5 male greyhounds) were anaesthetised and microdialysis probes placed in the dermis and gluteal muscle over each coxofemoral (hip) joint.. MeS was applied topically over the left hip joint. Dialysate and plasma (blood samples from the cephalic and femoral veins) were obtained during the subsequent 5 hours. Dogs were euthanatized, and tissue samples and synovial fluid were collected and analyzed for MeS and SA by use of HPLC.

SA and MeS concentrations increased rapidly (<30 minutes after application) in dialysate obtained from treated dermis. SA also appeared in plasma within 30 minutes and reached a plateau concentration after 2 hours, although combined concentrations (SA plus MeS) in plasma obtained from femoral vein samples were twice concentrations (SA only) measured in plasma obtained from the cephalic vain. Treated muscles had a progressive decrease in concentration of SA plus MeS, but it was substantially higher than that in untreated muscle. Substantial amounts of SA and MeS were also measured in synovial fluid of treated joints.

Topically applied MeS can penetrate deeply into tissues. Local concentrations higher than circulating systemic concentrations are suggestive that direct diffusion and local blood redistribution contribute to this effect.