Registration Dossier

Administrative data

Description of key information

No studies investigating the skin and eye irritation potential of the test item are available, however, suitable and reliable data exist for a structural analogue substance. Based on the results of the studies, the test item is not considered to be irritating to skin and/or eye.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation / corrosion, other
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
For this endpoint a one-to-one read across was performed to a chemical similar compound of the same chemical class with a comparable phys. chem. profile and similar response in biological assays. The relevant study was performed according to GLP and the methods applied are fully compliant with OECD TG 405. A detailed read across justification is provided in chapter 13 of this dossier.
Reason / purpose:
read-across source
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
The first examination of the treated skin sites followed 1 hour after removal of the patches. Then examinations of the skin sites were performed daily for further 14 days.
In the primary skin irritation test, erythema (scores 1 and 2) were observed from day 2 - 14, and edema (scores 1 and 2) from day 3 - 10 of the study. In two rabbits scales were observed from day 8 - 12 of the study.
Other effects:
No signs of systemic toxicity were detected. The body weight developent corresponded to that of the untreated rabbits of the same age. No mortality was observed during the course of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
According to the result of the irritation scores, the test material has not to be classified as irritant for the skin.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Oct 05 - Oct 19, 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Strain: Rabbit, IVA:NZW, males (m) and females (f)
Source: SAVO-Ivanovas, Kisslegg
Age: about 36 weeks
Initial Weight: 3,96 (3.36-4.67) kg
Total Number of Animals: 3 (2m, 1 f)
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: paraffin oil
Controls:
not required
Amount / concentration applied:
0,5 g
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hours after removal of patches and then daily up to day 14
Number of animals:
2m, 1f
Details on study design:
Identification and adaptation
Healthy young rabbits were allocated to the different groups.The animals were kept in the experimental room for more than 7 days to allow for acclimatization.

Assignment
2 male and 1 female rabbit were assigned for this study.


Housing and diet
All rabbits were housed in an air-conditioned room of 39 m2 in the rabbit experimental station with daylight. They were kept separately in cages type KK 017 (floor area: 75 x 54.5 = 4087 cm2 , height: 38 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 studies.

Temperature and humidity were measured using a thermo­ hygrograph (type 252, Wilhelm Lambrecht KG, Göttingen).
The room temperature varied from 19 to 21°C and the humidity from 33 to 57 %.

The rabbits received Altromin Standard Diet TPF(R) 2113, pellets and acidified, fully demineralized water from an automatic drinking device ad libitum.

The diet is checked periodically by an independent and German Government approved testing laboratory, according to the regulations of the manufacturer. Analysis includes both qualitative and quantitative evaluation for heavy metals, aflatoxins, pesticides, and antibiotics.


Vehicle
Name: Liquid paraffin


Observations for clinical symptoms
The rabbit was examined for skin alterations, behavior, and general condition 1 hour after removal of the patch, after 24, 48, 72 hours, and then daily up to experimental day 14.

Skin changes at the application sites were evaluated according to the DRAIZE-, OECD-and EEC recommendations.

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)
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
other: see text for details
Irritant / corrosive response data:
The first examination of the treated skin sites followed 1 hour after removal of the patches. Then examinations of the skin sites were performed daily for further 14 days.
In the primary skin irritation test, erythema (scores 1 and 2) were observed from day 2 - 14, and edema (scores 1 and 2) from day 3 - 10 of the study. In two rabbits scales were observed from day 8 - 12 of the study.
Other effects:
No signs of systemic toxicity were detected. The body weight developent corresponded to that of the untreated rabbits of the same age. No mortality was observed during the course of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
According to the result of the irritation scores, the test material has not to be classified as irritant for the skin.
Executive summary:

Purpose

The purpose of this assay was to identify the skin irritation/corrosion potential of the test material 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 man.

Study Design

To test for primary skin irritation, 0.5 g of the test material was mixed with some drops of liquid paraffin to ensure good contact with the skin. Afterwards the test material was spread onto 6 cm2 patches and applied to the intact skin of previously shaven rabbits for a 4 hours period under semiocclusive conditions. The study was started as an initial test with one animal. This animal showed signs of irritation (well defined erythema, edema, brittle skin, and scales) and no more animals were treated. The first examination of the treated skin sites followed 1 hour after removal of the patches. Thereafter, examinations were performed daily for further 14 days.

Results

No signs of pain were observed after administration. The body weight developent corresponded to that of the untreated rabbits of the same age. No mortality was observed during the course of the study.

In the primary skin irritation test, erythema (scores 1 and 2) were observed from day 2 - 14, and edema (scores 1 and 2) from day 3 - 10 of the study. In two rabbits scales were observed from day 8 - 12 of the study.

Conclusion

According to the result of the irritation scores, the test material has not to be classified as irritant for the skin.

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the data provided which are reliable and suitable, the test item is not classified for skin/eye irritation/corrosion according to Regulation (EC) No 1272/2008.