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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:
2011/06/07 to 2011/07/05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Method B4 Acute Toxicity (Skin Irritation) EC No. 440/2008
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): SD10
- Physical state: Clear Colorless Liquid
- Analytical purity: 96.9%
- Purity test date: 2010/11/04

Other: Measurement of pH of the test item prior to commencement of the study found that the neat material had a pH of 10.4. A 90% v/v aqueous preparation of the test item had a pH of 10.0 immediately after preparation, and 10.2 after 10 minutes.
- Lot/batch No.: 9147-192-3a
- Expiration date of the lot/batch: Retest date 2012/11/04
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.35 to 2.62 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): 2930 Teklad Global Rabbit Diet ad libitum
- Water (e.g. ad libitum): Mains drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 degrees C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 exchanges per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

IN-LIFE DATES: From: 2011/06/07 To: 2011/07/05

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: Clipped with veterinary clippers
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:
One animal initially treated: three suitable sites with test article applied. One patch removed at either 3 minutes, 1 hour or 4 hours after application. Any residual test article was removed by gentle swabbing with cotton wool soaked in distilled water.

After consideration of the reactions in the first animal, an additional two animals were treated with 0.5 ml of test item. One patch was applied to the back of each of the two animals and allowed to remain in contact for 4 hours.
Observation period:
Observations and scoring of the skin reactions were made immediately after removing the patch, at 1, 24, 48 and 72 hours. Additional observations were made on days 7 and 14 to assess the irreversibility of the lesions.

Body weights were recorded on the day of dosing and at the end of the observation period
Number of animals:
Three male New Zealand White rabbits
Details on study design:
TEST SITE
- Area of exposure: under 2.5 cm square cotton gauze patch.
- Type of wrap if used: Strip of surgical adhesive tape, with trunk wrapped in an elasticized corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gentle washing with cotton wool soaked in distilled water.
- Time after start of exposure: Immediately after patch removal (3 minutes, 1 hour or 4 hours).

SCORING SYSTEM: Draize J H (1959)
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema to eschar formation
preventing grading of erythema 4

Oedema formation
No oedema 0
Very slight oedema 1
Well-defined oedema 2
Moderate to severe oedema 3
Severe oedema 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
ca. 4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 4 hour exposure, all three animals
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean 24, 48, 72 h
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 4 h exposure, light brown discoloration of the epidermis at 48 and 72 h, loss of skin elasticity and flexibility at 72 h, hardened dark coloured and undulating scab at 72 h and 7d.
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean 24, 48, 72 h
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 4 h exposure, light brown discoloration of the epidermis at 48 and 72 h, moderate desquamation at day 7, no reading at day 14.
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean 24, 48, 72 h
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4 h exposure, light brown discoloration of the epidermis at 24, 48 and 72 h, hardened dark coloured scab at 24, 48 and 72 h, moderate desquamation on day 7, no reading on day 14.
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean 24, 48, 72 h
Time point:
other: 24, 48, 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: 4 h exposure
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean 24, 48, 72 h
Time point:
other: 24, 48, 72 h
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4 h exposure
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean 24, 48, 72 h
Time point:
other: 24, 48, 72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: 4 h exposure
Irritant / corrosive response data:
See Any other information on results section for data used in calculating primary irritation index.
Other effects:
All three animals showed expected body weight changes over the course of the study. Day 0 to Day 14 weight change in animal 1 was 0.23 kg. Animals 2 and 3 gained 0.08 and 0.17 kg over Days 0 to Day 7 of the study.

Any other information on results incl. tables

 Skin reaction  Observation time  1st rabbit  2nd rabbit  3rd rabbit  Total
 Eryethema/eschar  immediately  2  1  1  (4)
 Erythema/eschar  1 hour  2  1  1  (4)
 Erythema/eschar  24 hours  2  2  2StBr  6
 Erythema/Eschar  48 hours  2Br 2Br  2StBr  (6)
 Erythema/Eschar  72 hours  2BrLeLfStSw  2Br  2StBr  6
 Erythema/Eschar  7 days  ?eCfStSw  OD  OD  (0 -4)
 Erythema/Eschar  14 days  0  -  -  (0)
 ( ) = values not used in calculating PII Br = brown discoloration Le = loss of skin elasticity Lf = Loss of skin flexibility St = hardened dark brown scab Sw = Scab undulating Cf = crust formation D = moderate desquamation ?e = adverse reaction preventing evaluation of erythema ?od = adverse reaction preventing evaluation of edema - = not applicable

 

 
 

Skin reactions after 3 min and 1 hour of exposure (one male animal):

 
 Skin reaction observation time following patch removal Score 3 min exposure  Score 1 h exposure
Erythema/Escharformation  0 to 1 h  0  0
   24 h  0  1
   48 h  1  2
   72 h  2Bl  2Bl
   7 days  0D  ?eCf
   14 days  0G  0
       
 Edema formation  0 to 1 h  0  0
   24 h  0  0
   48 h  0  1
  72 h   2  2
   7 days  0  ?od
   14 days  0  0
 Bl: Blanching of the skinD: Moderate desquamationCF: crust formationG: glossy skin?e: Adverse reaction preventevaluation of erythema?od: Adverse reactions peventaccurate evaluation of edema      

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a primary irritation index of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification, when applied under a semi-occlusive dressing for 4 hours. 3 minute and 1 hour exposure of the test item to the intact skin of one rabbit produced no corrosive effects.

According to CLP criteria the the scores for erythema and/or edema are below the score of 2.3 in at least 2 of 3 animals after 4 h of exposure. The effects were reversible within the 14 day observation period. However as skin discoloration and scab formation occurred during the observation period, a classification as category 2 irritant is proposed.

According to Dir. 67/548/EC and adaptations the scores for erythema and/or edema were 2 or greater in 2 of three animals and the substance is consequently classified as irritant to skin R38.
Executive summary:

A rabbit dermal irritation study conducted by the method of OECD 404 was conducted using New Zealand White Rabbits. A single animal showed no corrosive effects from a 3 -minute or a 1 hour semi-occluded application of test article to intact skin. Scores for erythema increased from 24 to 72 hours, with maximum scores of 2 at the 72 hour reading. Blanching of the skin was noted at 72 hours in the 3 minute and 72 hour sites. Crusting was seen at 7 days after the 1 hour exposure, but other than glossy skin at the 3 minute exposure site, the skin had returned to normal by 14 days. Oedema readings increased to a maximum of 2 at 72 hours in the 3 minute and 1 hour exposure sites. Edema readings could not be assessed at 7 days in the 1 hour exposure site. Readings for edema were normal at 14 days in both exposure sites.

In the 4 hour exposure portion of the experiment, an additional 2 rabbits were added to the original for a total of 3 rabbits. A single 4 hour exposure of the test item to intact skin on these 3 animals produced well-defined erythema and slight to moderate edema. Maximum scores for erythema of 2 were seen for all rabbits at the 24 to 72 hour readings. Other skin readings observed were brown discoloration of the epidermis, hardened dark brown colored scab, loss of skin elasticity and flexibility, undulating scab, modreate desquamation and crust formation than hindered accurate evaluation of edema and erythema in one rabbit at 7 days. Two rabbits had normal readings except for some desquamation at 7 days, and the thrid rabbit had normal readings at 14 days. In t he opinion of the Study Director, these observations did not indicate corrosion.

Based on a Primary Irritation Index of 4.0, the test article was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.

According to CLP (Reg. 1907/2006 and amendments) criteria the the scores for erythema and/or edema are below the score of 2.3 in at least 2 of 3 animals after 4 h of exposure. The effects were reversible within the 14 day observation period. However as skin discoloration and scab formation occurred during the observation period, as classification as category 2 irritant is proposed.

According to Dir. 67/548/EC and adaptations the scores for erythema and/or edema were 2 or greater in 2 of three animals and the substance is consequently classified as irritant to skin R38.