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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 JUL 1996 - 30 SEP 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
This study was conducted in compliance with the regulations for Good Laboratory Practice (GLP) in nonclinical laboratory studies and followed the OECD Guideline for Testing of Chemicals No 404.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
425-560-7
EC Name:
-
Cas Number:
174063-87-7
Molecular formula:
C33H32O10
IUPAC Name:
2-methylbenzene-1,4-diyl bis{4-[3-(acryloyloxy)propoxy]benzoate}
Test material form:
solid: crystalline

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: Albino rabbit, Crl:KBL(NZW)BR, female (f)
- Source: Charles River Wiga GmbH, Kißlegg
- Age at study initiation: about 16 weeks
- Weight at study initiation: 2.80 (2.51 - 2.96) kg
- Housing: They were kept separately in cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2, height: 40 cm; manufacturer: Hulskamp) on metal grids. The paper underneath the cages was changed three times a week. The cages were machine-cleaned before the start of the study.
- Diet (e.g. ad libitum): ad libitum, Altromin Standard Diet TPF(R) 2113, pellets and acidified (The diet is checked periodically according to the specifications of the manufacturer by an independent laboratory, approved by the German government. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics. The analytical results show that the limits set by German regulations for animal feed have been followed.)
- Water (e.g. ad libitum): ad libitum, fully demineralized water
- Acclimation period: more than 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21°C
- Humidity (%): 48 to 93
- Air changes (per hr): air-conditioned
- Photoperiod (hrs dark / hrs light): daylight

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 0.5 g test item was mixed with some drops aqua pro injectione

Duration of treatment / exposure:
4 hours
Observation period:
The rabbits were investigated for skin alterations, behaviour, and general condition 1 hour after removal of the patches, and then after 24, 48, 72 hours and then daily up to day 8 of the study.
Number of animals:
3 female rabbits
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: 6 cm2 patches. The patch was kept in place by a self-adhesive fabric, Fixomull® stretch, Beiersdorf.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any test material left was wiped off after removal of the patches.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1 h, 24 h, 48 h, 72 h after removal of the patches and the daily until day 8 of the study

SCORING SYSTEM:
- Method of calculation:

Grading scale for evaluation:

Erythema and eschar formation

Scores
--------------------------------------------------
No erythema 0

Very slight erythema (barely perceptible) 1

Well defined erythema 2

Moderate to severe erythema 3

Severe erythema (beet redness) to eschar
formation preventing grading of erythema 4
--------------------------------------------------
Maximum possible: 4
--------------------------------------------------

Edema formation
Scores
--------------------------------------------------
No edema 0

Very slight edema (barely perceptible) 1

Slight edema (edges of area well
defined by definite raising) 2

Moderate edema (raised approx. 1 mm) 3

Severe edema (raised more than 1 mm
and extending beyond area of exposure) 4
--------------------------------------------------
Maximum possible: 4
--------------------------------------------------

Total possible irritation score (maximum): 8

Mean score = Mean grading for erythema or edema of all the rabbits per time point
Mean cumulative score = Mean grading of all readings for erythema and edema per time point
Mean score per animal = Mean grading for each animal of erythema or edema (24, 48, and 72 hours after removal of the patches)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 h, 24 h, 48 h, 72 h
Score:
0
Max. score:
8
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
After a single application to the intact dorsal skin of rabbits, for a 4 hours period of exposure under semiocclusive conditions, no signs of irritation were observed in the treated areas.
Other effects:
None

Any other information on results incl. tables

Clinical findings

No signs of systemic toxicity were detected.

Mortality

All rabbits survived the 8 day observation period.

Body weight

Body weight development of the treated rabbits was inconspicuous.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
According to the result, the test material is not irritant to the skin.
Executive summary:

The registered substance was tested for skin irritation in an Acute Dermal Irritation / Corrosion test according to OECD Guideline 404 following GLP.

Purpose

The purpose of this assay was to identify the skin irritation/corrosion potential of the test item when applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. This study should provide a rational basis for risk assessment to the irritating potential of the test item in human.

Study design

To test for primary skin irritation, the test substance was mixed with some drops of aqua pro injectione to ensure good contact to the skin. Afterwards the test material was spread onto patches and applied to the intact skin of three previously shaven rabbits for a 4 hours period under semiocclusive conditions. The first examination of the treated skin sites followed 1 hour after removal of the patches. Then, examinations were performed daily for further 7 days.

Results

Under the conditions of the present study no signs of irritation were seen. The evaluation of all animals yields a zero mean score.

Conclusion

According to the result, the test material is not irritant to the skin.