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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:
15 July 1996 to 22 July 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 404 with minor deviations: no certificate of analysis, no data on the purity of the test substance, observation period of 7 days instead of 14 days.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: OECD Guideline No. 404 adopted in July 1992
Deviations:
yes
Remarks:
: no certificate of analysis, no data on the purity of the test substance, observation period of reversibility for 7 days instead of 14 days.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Physical state: clear liquid
- Analytical purity: no data
- Lot/batch No.: #HBE0946
- Expiration date of the lot/batch: no data
- Storage condition of test material: at room temperature and humidity

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Aace animals, Boyertown, PA, USA
- Age at study initiation: about 3 months
- Weight at study initiation: 2.2-2.5 kg
- Housing: individually in wire cages
- Diet (e.g. ad libitum): Fresh Purina Rabbit Chow (Diet #5321), provided daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 1996-03-31 to 1996-04-14

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
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 h
Observation period:
1, 24, 48 and 72 hours and on day 7 after the removal of the dressing.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 25 x 25 mm on the dorso area of the trunk
- Type of wrap if used: 25 mm x 25 mm gauze pad covered with a non-irritating tape. The torso was wrapped with plastic in a semi-occlusive manner and secured with non-irritating tape which completely covered the plastic.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle washing with distilled water
- Time after start of exposure: 4 h

SCORING SYSTEM:

Erythema & Eschar
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

Edema
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1.0 mm) 3
Severe edema (raised more than 1.0 mm, extending beyond the area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean score
Time point:
other: 24, 48, 72 h
Score:
ca. 1.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean score
Time point:
other: 24, 48, 72 h
Score:
ca. 1.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean score
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean score
Time point:
other: 24, 48, 72 h
Score:
ca. 0.3
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean score
Time point:
other: 24, 48, 72 h
Score:
ca. 0.7
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean score
Time point:
other: 24, 48, 72 h
Score:
ca. 1.3
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritant / corrosive response data:
Erythema scores ranged from very slight to well defined through 72 hours after patch removal, and from absent to very slight on day 7.
Edema scores ranged from absent to slight through 48 hours after patch removal, and from absent to very slight through day 7.
See details in Table 7.3.1/1
Other effects:
For one animal, 48 hours after the removal of the dressing, diarrhea and wetness of the anogenital area were observed. Seven days after the removal of the dressing all animals presented skin flaking.

Any other information on results incl. tables

Table 7.3.1/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Erythema and Eschar formation

Edema

Max. score: 4

Max. score: 4

1h

1/1/2

0/0/2

24 h

1/2/2

0/1/1

48 h

2/2/2

1/1/2

72 h

1/1/2

0/0/1

Average 24h, 48h, 72h

1.3/1.7/2

0.3/0.7/1.3

Reversibility (within 7 days)a

n.c.b

n.c.

Average time (unit) for reversion

?

?

aReversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

bFlaking skin

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, SR 351 is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).
Executive summary:

In a dermal irritation GLP study performed according to the OECD guideline No. 404 (approved in July 1992), three young adult male White New-Zealand rabbits were dermally exposed to 0.5 mL of test article for 4 hours to 6.25 cm² of clipped skin in semi-occlusive conditions. Animals then were observed for 7 days. Reactions were scored again at 24, 48 and 72 hours and on day 7. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods.

Under the test conditions, there were slightly irritant effects, with mean individual scores within 24, 48 and 72 hrs of 1.3/1.7/2.0 for erythema and 0.3/0.7/1.3 for edema. These effects were not fully reversible within 7 days for one animal only. Considering these scores the test substance is not classified as irritating to the skin according to the criteria of Annex VI to the Directive 67/548/EEC and CLP Regulation (EC) N° (1272-2008).

Primary Irritation Index is 2.00

The author concludes: The test article is a dermal irritant but not corrosive.