Isopentyl p-methoxycinnamate

Dermal absorption

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-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Isopentyl p-methoxycinnamate

EC Number:

275-702-5

EC Name:

Isopentyl p-methoxycinnamate

Cas Number:

71617-10-2

Molecular formula:

C15H20O3

IUPAC Name:

isopentyl p-methoxycinnamate

Radiolabelling:

yes

Remarks:

14C-labelled isopentyl p-methoxycinnamate

Test animals

Species:

human

Strain:

other: not applicable

Sex:

male/female

Details on test animals or test system 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.