Registration Dossier

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:
From 1991-07-09 to 1991-07-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age of animals at study initiation not reported
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
Inspected on 19 June 1990. Signed on 5 October 1990.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: colourless liquid
- Storage condition of test material: in the dark at about 4°C

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex.
- Age at study initiation: no data
- Weight at study initiation: 2.6-3.0 kg
- Housing: individually in grid bottomed metal cages.
- Diet (e.g. ad libitum): antibiotic free rabbit diet ad libitum (SQC standard rabbits pellets, produced by Special Diets Services, Witham, Essex)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C. On 3 occasions the temperature exceeded this range by 1°C.
- Humidity (%): 59-69 % with the exception of one occasion when a value of 76 % relative humidity was recorded.
- Air changes (per hr): no data
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: no data

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours after patch removal. Additional examination on day 7.
Number of animals:
4 animals
Details on study design:
TEST SITE
- Area of exposure: dorsal surface of the trunk
- % coverage: 2.5 cm square (6.25 cm2)
- Type of wrap if used: surgical lint held in position with "Elastoplast" elastic adhesive bandage 7.5 cm wide.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): cotton wool soaked in warm water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize scale according to OECD guideline No. 404

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.66
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
One hour after the end of the dosing period, erythema varying in degree from slight to well defined was apparent in all 4 rabbits and very slight oedema was noted in 2 of the 4 animals.
24 hours after patch removal erythema and oedema were observed in all 4 rabbits.
At the 72 hour assessment, irritation has entirely subsided in 2 animals. Erythema was slight to moderate in the remaining 2 rabbits.
7 days after the dosing, erythema and oedema were no longer apparent in any of the animal although skin thickening was noted in one of them.
Other effects:
none

Any other information on results incl. tables

Table 7.3.1/1: Mean irritant/corrosive response data (4 animals) at each observation time up to removal of animals from the test

 

Score at time point / Reversibility

Erythema

Max. score 4

Edema

Max. score 4

1 h

1.75

0.5

24 h

1.25

1.25

48 h

1.50

0.75

72 h

1.50

0.75

Average 24h, 48h, 72h

1.4

0.9

Reversibility*)

c

c

Average time (day) for reversion**

7 days

7 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

Table 7.3.1/2: Irritant/corrosive response data for each animal at each observation time up to removal of animals from the test

Score at time point / Reversibility

Erythema

Max. score 4

Oedema

Max. score 4

24 h

1 / 1 / 1 / 2

2 / 1 / 1 / 1

48 h

2 / 1 / 0 / 3

1 / 1 / 0 / 1

72 h

3 / 0 / 0 / 3

1 / 0 / 0 / 2

Average 24h, 48h and 72h

2 / 0.66 / 0.33 / 2.66

1.33 / 0.66 / 0.33 / 1.33

Reversibility*)

c

c

Average time for reversion

7 days

7 days

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Conclusions:
Under the test conditions, since a slight irritation being completely reversible within 7 days was observed:
- no additional self-classification is proposed for the registered substance regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP)
- the registered substance is classified as Category 3 (slight skin irritation) according to the GHS based on differences betwen the individual scores for each animal within 3 scoring times (24, 48 and 72 h) for erythema (2 / 0.66 / 0.33 / 2.66).
Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.5 mL of undiluted test material was dermally applied on the shaved skin of the dorsal surface of the trunk of 4 New Zealand White rabbits.Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for up to 7 days for edema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the removal of the patch and on day 7.

The individual scores for each animal within 3 scoring times (24, 48h and 72 hours) were 2 / 0.66 / 0.33 / 2.66 for erythema and 1.33 / 0.66 / 0.33 / 1.33 for oedema.

Under the test conditions, since a slight irritation being completely reversible within 7 days was observed:

- no additional self-classification is proposed for the registered substance regarding skin irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP)

- the registered substance is classified as Category 3 (slight skin irritation) according to the GHS based on differences betwen the individual scores for each animal within 3 scoring times (24, 48 and 72 h) for erythema (2 / 0.66 / 0.33 / 2.66).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.