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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:
April 1980 to June 1980
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Remarks:
Test procedure performed in accordance with generally accepted scientific standards and well documented. Applicant assessment indicates that any deviation from current published guidelines would not be sufficient to affect the study outcome.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1981
Report Date:
1981

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: unspecified
- Weight at study initiation: 3 - 4 kg
- Housing: Individually housed in rabbit cages.
- Diet: Standard mixed rabbit feed, ad libitum.
- Water: Water, ad libitum.
- Acclimation period: Time not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Unspecified
- Humidity (%): Unspecified
- Air changes (per hr): Unspecified
- Photoperiod: Unspecified

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): 0.5 g
- Concentration (if solution): Test material was used as supplied.
Duration of treatment / exposure:
1 or 8 hours
Observation period:
Immediately after treatment and for the following 7 days.
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: dorsal
- Type of wrap if used: semi-occlusive (2.5 cm x 2.5 cm surgical gauze patch secured with surgical adhesive tape)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified; irrigation with water, soap and cotton wool mentioned elsewhere in the test report.
- Time after start of exposure: Not specified; immediate irrigation mentioned elsewhere in the test report.

SCORING SYSTEM:
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, if present, were also recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: All observations
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
Score is applicant assessment based on written description in study report.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: All observations
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 0 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Remarks:
Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 0 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Remarks:
Score is applicant assessment based on written description in study report.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
Score is applicant assessment based on written description in study report.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Remarks on result:
probability of severe irritation
Remarks:
Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
positive indication of irritation
Remarks:
Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
other: Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Max. score:
4
Remarks on result:
other: Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Remarks on result:
other: Score is applicant assessment based on written description in study report.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
0
Max. score:
4
Remarks on result:
other: Score is applicant assessment based on written description in study report.
Irritant / corrosive response data:
- Erythema: "Severe reddening with partial skin corrosion" (applicant assessment: severe erythema, score = 4) apparent immediately upon removal of bandage, persisting for the duration of the observation period, at both test sites.
- Edema: "Slightly swollen skin" (applicant assessment: Slight edema, score = 2) observed in both sites, immediately upon removal of bandage, with effects fully-reversed within 48 hours.
- Reversibility of effects: Erythema did not reverse during the observation period; oedema reversed within 48 hours.
Other effects:
There was no clinical signs of toxicity reported during the duration of the test, and no comments are recorded regarding bodyweight for these rabbits.

Any other information on results incl. tables

The study report provides written description of the reaction of the animals' skin to the test item. Applicant assessment of the written description indicates the following scores:

Table 1. Individual skin reactions  

Skin Reaction Observation Time
(following patch removal)
Individual Scores
Number and Sex
#1 (male) #2 (female)
Erythema/Eschar Formation 0 Hours 4 4
Intermediate observations 4 4
48 Hours 4 4
7 days 4 4
Edema Formation 0 Hours 2 2
Intermediate observations 2 2
48 Hours 2 2
7 days 0 0

Mean scores (N=2) per organism at 0 -48h and 7d:

0 -48h:

Erythemea/Escar Formation:

1: 4

2: 4

Edema Formation:

1: 2

2: 2

7d:

Erythemea/Escar Formation:

1: 4

2: 4

Edema Formation:

1: 0

2: 0

Applicant's summary and conclusion

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the test item is considered very strongly irritating and corrosive to the skin.
Executive summary:

The study was performed historically to a documented method similar to OECD TG 404 and EU Method B.4, to assess the primary skin irritancy potential of the test item in New Zealand White rabbits, following single 1 or 8 -Hour, semi-occluded applications to intact rabbit skin. Applicant assessment indicates that any deviation from current guidelines would be insufficient to affect the study outcome. 0.5 g of the test item was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the clipped skin to assess the irritancy potential of the test item. The patch was secured in position with a strip of surgical adhesive tape. After 1 or 8 hours of exposure to the test item (1 treatment/exposure-period per rabbit), the patches were removed and individual dose sites were observed immediately and over the following 7 days. A single, semi occluded application of the test item, of either 1 or 8 hours, to the intact skin of two rabbits produced severe erythema and partial corrosion immediately at the two treated skin sites, which did not reverse during the study. Slight erythema was detected immediately after patch removal in both sites, which was fully reversed within 48 hours. Corrosive effects were noted. Mean scores for following grading between 0 hours and 7 days were 4 and 4 in erythema and eschar scoring criteria; mean scores for following grading between 0 hours and 48 hours were 2 in edema scoring criteria; mean scores for following grading from 48 hours to 7 days were 0 in edema scoring criteria. The study authors note "Aufgrund der stark ausgepraegten Reiz- und Aetzwirkung ist jedoch jeder Haut- und Schleimhautkontakt (Auge) mit dem Pruefmuster unbedingth zu vermeiden.", i.e. "Due to the pronounced irritant and caustic effect, any skin and mucous-membrane contact (eye) with the test item must be avoided." Furthermore, the authors note, "...jeglicher Haut- und Schleimhautkontakt (Auge) ist unbedingt zu vermeiden.", i.e. "any contact with skin or mucous membranes (eye) should be avoided at all costs". Under the conditions of the study, the test item is therefore considered to be a strong skin irritant and skin corrosive.