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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:
11-04-2000 to 21-07-2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspected: September 1999 ; signature: December 1999

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Liquid
- Storage condition of test material: At room temperature, protected from light and under nitrogen gas
- Other: colourless

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: Young adult
- Weight at study initiation: 2.4 ±0.1 kg
- Housing: Individually housed in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet: certified rabbit diet ad libitum
- Water: filtered certified water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ±3
- Humidity (%): 30 - 70
- Air changes (per hr): ca. 12 cycles/hr
- Photoperiod: 12 hours light / 12 hours dark

IN-LIFE DATES: From: 11-04-2000 To: 25-04-2000

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5mL
- Concentration (if solution): Not applicable.
Duration of treatment / exposure:
4 hours
Observation period:
72 hours (initial observation); additional observations are made daily up to and including on Days 7 and 15 to assess the reversibility of skin reactions (as appropriate).
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal
- Type of wrap if used: semi-occlusive ; gauze patch secured with semi-occlusive dressing and restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No, since no residual test item was observed following dressing removal.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1, 24, 48, 72 hours (initial observations); additional observations are made daily up to and including on Days 7 and 15 to assess the reversibility of skin reactions (as appropriate).

SCORING SYSTEM:
Consistent with Draize. Erythema and Eschar Formation:
No erythema ____________________________0
Very slight erythema (barely perceptible) _____1
Well-defined erythema ____________________2
Moderate to severe erythema ______________3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) _____________4

Oedema Formation
No oedema _____________________________0
Very slight oedema (barely perceptible) ______1
Slight oedema (edges of area well-defined by definite raising) _________________________2
Moderate oedema (raised approximately 1 millimetre) _________________________________3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) __4
Any other skin reactions and clinical signs of toxicity (clinical signs/behaviour), if present, were also recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1h
Score:
0
Max. score:
4
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
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
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
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
- Erythema: Very slight or well defined erythema (score = 1 or 2) at all treated skin sites at 24 to 72 hours after patch removal and up to day 7 or 8 in two sites.
- Edema: No evidence of skin irritation was noted during the study.
- Reversibility of effects: All effects reversed within 9 days (3/3 sites) ; dryness of the skin was noted in all sites from day 5 (1/3), day 6 (2/3) or day 9 (1/3) which ceased in 2/3 sites by day 14.
Other effects:
- Other adverse local effects: None reported
- Other adverse systemic effects: None reported.

Any other information on results incl. tables

Table 1. Individual skin reactions

Skin Reaction

Observation Time

Individual Scores

 

 

1 (male)

2 (male)

3 (male)

Erythema/Eschar formation

1 hour

1

1

1

 

24 hours

2

2

2

 

48 hours

2

1

2

 

72 hours

2

1 S

2

 

7 days

1

1 S

1 S

 

14 days

0

0

0 S

 

 

 

 

 

Oedema formation

1 hour

0

0

0

 

24 hours

0

0

0

 

48 hours

0

0

0

 

72 hours

0

0

0

 

7 days

0 S

0 S

0

 

14 days

0

0

0 S

 

 

 

 

 

S = dryness of the skin

 

Mean scores per organism at 24, 48 and 72h:

Erythemea/Escar Formation:

1: total = 6; mean score = 2.0

2: total = 4; mean score = 1.3

3: total = 6; mean score = 2.0

Oedema Formation:

1: total = 0; mean score = 0.0

2. total = 0; mean score = 0.0

3. total = 0; mean score = 0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the test item is not considered to be irritating.
Executive summary:

The study was performed to OECD TG 404 and EU Method B.4 in accordance with GLP to assess the primary skin irritancy potential of the test item in New Zealand White rabbits. Following single 4-Hour, semi-occluded applications to the intact rabbit skin. 0.5 ml of the test material was introduced under a gauze patch and placed in position on the clipped skin via semi-occlusive dressing to assess the irritancy potential of the test item. The patch was secured in position with a strip of surgical bandage. After 4 hours of exposure to the test item, the patches were removed, and individual dose sites were scored at approximately 1, 24, 48, and 72 hours. Daily observations were made up to day 15 as applicable. A single 4-Hour, semi occluded application of the test item to the intact skin of three rabbits produced very slight or well-defined erythema (score = 1 or 2) at all treated skin sites at 24 to 72 hours after patch removal and up to day 7 or 8 in two sites. Mean scores for following grading at 24, 48 and 72h were 2.0, 1.3 and 2.00 in erythema and eschar and 0.0 in all sites for the edema scoring criteria. Under the conditions of the study, the test item is not considered to be a skin irritant.