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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
Study period:
During 1987-01-13 and 1987-10-01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Remarks:
Study was conducted according to OECD-GLP regulation but not conducted as per any of the test guidelines.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
It was the aim of the study to investigate the in vitro cutaneous penetration of isopentyl p-methoxycinnamate in two different formulations. 14C-labelled test substance was used in order to simplify the methodology.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
yes
Remarks:
14C-labelled isopentyl p-methoxycinnamate

Test animals

Species:
human
Strain:
other: not applicable
Sex:
male/female
Details on test animals and environmental conditions:
The test was carried out with two male and four female volunteers. All test subjects were healthy and within the age range of 30 to 44 years.

Administration / exposure

Type of coverage:
other: Stripping procedure
Vehicle:
other: Two Formulation I and II used in the present study, were water in oil emulsions.
Duration of exposure:
30 minutes
Doses:
0.157 and 0.164 mg of the test substance applied per cm2.
No. of animals per group:
The test was carried out with two male and four female volunteers.
Control animals:
no
Remarks:
not applicable
Details on study design:
[14C]-labelled isopentyl p-methoxycinnamate was applied volar to the forearm of 6 human volunteers. The test substance was integrated in two different formulations (I and II). 3 mg of each of the formulations were applied to areas of 2 x 1 cm. 30 min after application the skin was stripped (20x) with an adhesive tape. Duration of this procedure: approx. 5 min. The [14C]-radioactivitiesof the strips were determined.
Details on in vitro test system (if applicable):
not applicable

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
yes
Remarks:
Skin exanimation prior to application: No skin abnormalities or lesions were seen. After application: skin irritation reactions were noted in some volunters.
Total recovery:
no data
Percutaneous absorption
Remarks on result:
other: no data
Conversion factor human vs. animal skin:
No data

Any other information on results incl. tables

Sex difference

The l4C-activity found in the strips was statistically significantly lower in males than in females for formulation I. There was no statistically significant difference between the males and females where formulation II was used.

Applicant's summary and conclusion

Conclusions:
Since the predominant amount of the 14C-radioactivity was detected on or in the epidermis and more 14C-activity was found in the upper layers of the dermis than in the lower ones, it was concluded that the results suggest that isopentyl p-methoxycinnamate had not significantly penetrated into the skin of human volunteers from either of the formulations examined.
Executive summary:

[14C]-labelled isopentyl p-methoxycinnamate was applied volar to the forearm of 6 human volunteers. The test substance was integrated in two different formulations (I and II). 3 mg of each of the formulations were applied to areas of 2 x 1 cm. 30 min after application the skin was stripped (20x) with an adhesive tape. Duration of this procedure: approx. 5 min. The [14C]-radioactivities within each of the strips were determined. In the area where formulation I was administered one test person showed distinct redness 2 and 24 h p.a. A further three persons had slight erythema two hours after stripping. This redness was also noted 24 h post dose but had disappeared 72 h later. The treated skin of 2 volunteers was unaffected. No effects were observed on any volunteer after application of formulation II. More than 50% of the administered 14C-radioactivity was recovered in the first two strips. This amount is considered to be superficially deposited. A mean of 94.3% of the administered amount of [14C]-radioactivity was recovered in the 20 strips with formulation I and 88.5% with formulation II. The difference between the formulations was not statistically significant. The predominant amount of the 14C-radioactivity was therefore detected on or in the epidermis. In the upper layers of the epidermis more[14C]-radioactivity was found than in the lower ones. 0.5% of the applied 14C-activity was still detected in the last strip. These results suggest that isopentyl p-methoxycinnamate has not significantly penetrated into the skin of human volunteers.There were no statistically significant differences between the distal and proximal sites of application. The[14C]-radioactivityfound in the strips was statistically significantly lower in males than in females for formulation I. There was no statistically significant difference between the males and females where formulation II was used. These results suggest that isopentyl p-methoxycinnamate has not significantly penetrated into the skin of human volunteers from either of formulations.