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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:
14 - 28 May 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

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
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Sodium alkylnaphthalene sulfonate
- Substance type: Slightly yellow powder
- Physical state: Powder
- Purity:96.27 w/w%
- CAS number: 1258274-08-6
- Lot/batch No.: 1238887
- Expiration date of the lot/batch: 03 May 2021
- Storage condition of test material: At room temperature in the dark under nitrogen
- pH: 7.5 – 10 at concentration of 5%
- Hygroscopic: No
- Volatile: No
- Test substance handling: Flush container with nitrogen after handling
- Solubility in water: Yes

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: at least 6 weeks old.
- Weight at study initiation: at least 1.0 kg.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.
Temporary deviations from the maximum level of daily mean relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.

IN-LIFE DATES: From: 14 - 28 May 2012

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: The test substance was moistened with 0.4 mL water
Controls:
other: Adjacent areas of the untreated skin of the animal served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 grams

VEHICLE
The test substance was moistened with 0.4 mL water
Duration of treatment / exposure:
Single application.
Observation period:
14 days.
Number of animals:
1 male
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and started with the treatment of one animal (sentinel) with a stepwise exposure regime. Based on the severity of the skin reactions, no further animals were exposed.

TEST SUBSTANCE PREPARATION
The powdery test substance was moistened with water (Elix, Millipore S.A.S., Molsheim, France), immediately before application, to ensure close contact with the animal's skin. No correction was made for purity of the test substance.

TEST SITE
This animal received 0.5 grams of the test substance moistened with 0.4 mL of the vehicle, to the intact, clipped skin of one flank using a Metalline patch1# of 2x3 cm. The patch was mounted on Micropore tape#, which was wrapped around the abdomen and secured with Coban elastic bandage#.
The dressing was removed 3 minutes after application. Since no signs of severe skin reactions (i.e. necrosis or corrosion) were observed and it was
considered that exposure could be continued humanely, two samples of 0.5 grams of the test substance moistened with 0.4 mL of the vehicle were then applied to separate skin-sites on the intact, clipped skin of the same animal, using an identical procedure and one sample per dressing. One of the dressings was removed after a 1-hour exposure. After similar considerations (i.e. no severe skin reactions, necrosis or corrosion), the other dressing was removed after a 4-hour exposure. After each removal of a dressing, the treated skin was cleaned of residual test substance using water.

REMOVAL OF TEST SUBSTANCE
After the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS (kort allemaal!)
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application) and after the final observation.
- Necropsy:No necropsy was performed according to protocol.
- Irritation: The skin reactions of all visible treated sites were assessed immediately after removal of a dressing and approximately 1, 24, 48, 72 hours after the removal of the last dressing and test substance. For the duration of the skin reactions, further observations were made 7 and 14 (maximum) days after exposure. The irritation scores and a description of all other (local) effects were recorded. Adjacent areas of untreated skin of the animal serve as controls.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(mean)
Time point:
24/48/72 h
Score:
3.7
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
(mean)
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritant / corrosive response data:
A 3-minute exposure resulted in well-defined erythema and slight oedema. The irritation had resolved within 72 hours following exposure.
A 1-hour exposure resulted in well-defined erythema and slight oedema. The irritation had resolved within 7 days following exposure.
A 4-hour exposure resulted in brown discolouration of the skin (a sign of superficial necrosis; due to which the maximum grade for erythema (grade 4) was assigned) at 48 and 72 hours and 7 days after exposure, severe oedema, reduced flexibility of the skin at 72 hours after exposure, fissuring of the skin at 7 days after exposure, and a bald skin with scaliness at 14 days after exposure.

There was no evidence of a corrosive effect on the skin.
Other effects:
Coloration/remnants: No staining of or remnants on the treated skin was observed.

Toxicity/mortality: No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Any other information on results incl. tables

INDIVIDUAL SKIN IRRITATION SCORES

Animal 34# 

 3 minutes treatment site 

 1-hour treatment site 

 4-hours treatment site 

Time after bandage removal 

Erythema

Oedema

Comments 

Erythema

Oedema

Comments 

Erythema

Oedema

Comments 

Immediately 

2

2

-

2

2

-

2

3

 -

 1 hour 

1

2

-

 NS 

 NS

-

2

4

 -

 3 hours 

 NS 

 NS

-

1

2

-

 NS 

 NS 

 -

 4 hours 

1

1

-

1

2

-

 NS 

 NS 

 -

 5 hours 

1

1

-

 NS 

 NS

-

 NS 

 NS 

 -

 24 hours 

1

1

-

1

2

-

3

4

 -

 48 hours 

0

1

-

1

2

-

4

4

 k 

 72 hours 

0

0

-

0

1

-

4

4

 k, f 

 7 days 

0

0

-

0

0

-

4

 -

 k, g 

 14 days 

0

0

-

0

0

-

0

2

 h, l 

Comments:

NS. Not scored according to protocol.

-. No scoring possible due to fissuring of the skin and brown discolouration of the skin (sign of necrosis).

f. Reduced flexibility of the skin.

g. Fissuring of the skin.

h. Bald skin.

k. Brown discoloration, a sign of necrosis (superficial).

l. Scaliness.

MEAN VALUE IRRITATION SCORES AFTER 4 HOURS OF EXPOSURE

Animal #

Mean 24, 48 and 72 hrs

 

Erythema

Oedema

34

3.7

4.0

# Animal specifications:  

Animal no

Sex

Age at start

Body weights (grams)

 

 

(weeks)

prior to application

at termination

34

13-15

3419

3605

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Conclusions:
No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of Sodium alkylnaphthalene sulfonate to the intact rabbit skin. The extreme response following a 4-hour exposure to Sodium alkylnaphthalene sulfonate in a single animal was irreversible within the 14-day observation period.
Executive summary:

Primary skin irritation/corrosion study with Sodium alkylnaphthalene sulfonate in the rabbit (semiocclusive application). The GLP compliant study was carried out according to OECD No.404 (2002); "Acute Toxicity - Skin irritation". One rabbit was exposed to three samples of 0.5 grams of Sodium alkylnaphthalene sulfonate applied to separate skin-sites on intact, clipped skin using a semi-occlusive dressing. The exposure periods were 3 minutes, 1 hour and 4 hours, respectively. Skin reactions were assessed at least once daily on Days 1-4 and 7 and 14 days after exposure. Based on the severity of the skin reactions, no further animals were exposed.

A 3-minute and 1-hour exposure resulted in well-defined erythema and slight oedema. The irritation had resolved within 72 hours or 7 days following exposure, respectively.

A 4-hour exposure resulted in brown discolouration of the skin (a sign of superficial necrosis; due to which the maximum grade for erythema (grade 4) was assigned) at 48 and 72 hours and 7 days after exposure, severe oedema, reduced flexibility of the skin at 72 hours after exposure, fissuring of the skin at 7 days after exposure, and a bald skin with scaliness at 14 days after exposure.

No evidence of full thickness destruction of the skin or scar tissue was observed during the observation period, indicating that no corrosion of the skin had occurred by dermal application of Sodium alkylnaphthalene sulfonate to the intact rabbit skin.

The extreme response following a 4-hour exposure to Sodium alkylnaphthalene sulfonate in a single animal was irreversible within the 14-day observation period.