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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-05-27 to 1999-06-09
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

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)
Version / remarks:
the European Economic Communities (EEC) Guideline in the Official Journal of the European Communities [92/69, Annex V, B4 ( 1992)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Remarks:
the United States Environmental Protection Agency (EPA) Good Laboratory Practice Regulations (40 CFR Parts 160 and 792)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Substance type: benzenesulphonate
- Physical state: Dark brown, viscous liquid
- Analytical purity: test article purity data are the responsibility of the sponsor
- Impurities (identity and concentrations): not provided
- Composition of test material, percentage of components: UVCB
- Lot/batch No.: None provided
- Stability under test conditions: Test article stability data are the responsibility of the sponsor.
- Storage condition of test material: Original container at room temperature
- date received: April 28,1999

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA
- Age at study initiation: Young adult
- Weight at study initiation: 2523 to 3833 grams at initiation of dosing
- Housing: Individual in suspended wire-mesh cages
- Diet: PMI Nutrition International, Inc. Certified Rabbit LabDiet@ 5322 was offered at approximately 150 g per day during the study.
- Water (e.g. ad libitum): Reverse osmosis-treated municipal water was provided ad libitum.
- Acclimation period: for a minimum of 7 days prior to initiation of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 64.1- 67.2 °F (18 - 20 °C)
- Humidity (%): 50.1-76.7 The humidity was slightly above the protocol-specified range (30-70%) four times within the study period. A brief period of slightly increased humidity would not be expected to adversely affect the health of the rabbits. Therefore, this deviation did not affect the quality or integrity of the studv.
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
Prior to use, the original container of the test article was agitated to insure a homogeneous mixture. A sufficient amount of test article was dispensed and a stir bar was added. The test article was stirred continuously throughout use.
- Amount(s) applied (volume or weight with unit): 0.5 mL /site
Duration of treatment / exposure:
4 hours
Observation period:
approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and daily thereafter for up to 13 days
Number of animals:
Three males and three females
Details on study design:
TEST SITE
On the day prior to dosing, the hair was removed from the backs and flanks of the rabbits using an electric clipper. Each 0.5 mL dose was applied to an area of skin approximately 2.5 x 2.5 cm under a two-ply gauze patch secured in place with Micropore@ tape. The patches were overwrapped with a gauze binder and secured with Dermiform@ tape. Plastic restraint collars were applied to the animals to prevent ingestion of the test article andor bandages.
- Area of exposure: an area of skin approximately 2.5 x 2.5 cm on backs and flanks
- Type of wrap if used: Plastic restraint collars

REMOVAL OF TEST SUBSTANCE
At the end of four hours, the collars and bandages were removed and the sites wiped with disposable paper towels moistened with deionized water.

SCORING SYSTEM (in accordance with the method of Draize):
Erthema and Eschar Formation:
- No erythema: 0
- Very slight erythema (barely perceptible, edges of area not well defined): 1
- Slight erythema (pale red color and edges definable): 2
- Moderate to severe erythema (definite red in color and area well defined): 3
- Severe erythema (beet or crimson red) to slight eschar formation (injuries in depth): 4
- Maximum possible erythema score: 4

Oedema Formation:
- No oedema: 0
- Very slight oedema (barely perceptible, edges of area not well defined): 1
- Slight oedema (edges of area well defined by definite raising): 2
- Moderate oedema (raised approximately 1 mm): 3
- Severe oedema (raised more than 1 mm and extending beyond area of exposure): 4
- Maximum possible oedema score: 4

Maximum total possible Primary Irritation Score: 8

DESCRIPTIVE RATINGS
Mean Primary Dermal Irritation Index:
- Nonirritating: 0
- Slightly Irritating: 0.1 - 2.0
- Moderately Irritating: 2.1 - 5.0
- Severely Irritating: 5.1 - 8.0

Draize, J.H., 1965. The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Dermal Toxicity, pp. 46-59. Assoc. Of Food and Drug Officials of the U.S., Topeka, Kansas and the EPA-OPPTS Health Effects Test Guidelines (1998).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1h, 24h, 48h and 72h
Score:
1.4
Max. score:
8
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: slightly irritating in accordance with the descriptive rating of Draize
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
male
Time point:
other: mean of 24, 48 and 72-h
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: brown staining on dose site (24 and 48 h); desquamation on days 5-10
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
male
Time point:
other: mean of 24, 48 and 72-h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: brown staining on dose site (24 and 48 h); desquamation on days 6-7
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
male
Time point:
other: mean of 24, 48 and 72-h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: brown staining on dose site (24 h)
Irritation parameter:
erythema score
Basis:
animal #4
Remarks:
female
Time point:
other: mean of 24, 48 and 72-h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 13 days
Remarks on result:
other: brown staining on dose site (24 h); desquamation on days 4-11
Irritation parameter:
erythema score
Basis:
animal #5
Remarks:
female
Time point:
other: mean of 24, 48 and 72-h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 11 days
Remarks on result:
other: brown staining on dose site (24 and 48 h); desquamation on days 4-10
Irritation parameter:
erythema score
Basis:
animal #6
Remarks:
female
Time point:
other: mean of 24, 48 and 72-h
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: brown staining on dose site (24 and 48 h); desquamation on days 6-7
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
male
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
male
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
male
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #4
Remarks:
female
Time point:
other: mean of 24, 48 and 72 h
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
animal #5
Remarks:
female
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
animal #6
Remarks:
female
Time point:
other: mean of 24, 48 and 72 h
Score:
0
Max. score:
0
Irritant / corrosive response data:
The test article induced very slight to moderate erythema on all animals and very slight oedema for one rabbit. Desquamation and brown staining of the skin were noted for five and six rabbits, respectively. All dermal irritation completely subsided by day 13.
Other effects:
There were no deaths during the study.
There were no remarkable body weight changes during the study period.

Any other information on results incl. tables

Table 1. Individual irritation scores (erythema)

ANIMAL

SEX

SITE

1H

24H

48H

72H

4D

5D

6D

7D

8D

9D

10D

11D

12D

13D

28438

M

A

1s

1s

2s

2

2

2d

2d

2d

1d

1d

1d

0d

-

-

28444

M

A

0s

0s

1s

2

2

2

1d

1d

0d

-

-

-

-

-

28465

M

A

0s

1s

1

0

-

-

-

-

-

-

-

-

-

-

27714

F

A

0s

1s

3

3

3d

3d

2d

2d

2d

1d

1d

1d

1d

0d

28448

F

A

1s

1s

2s

3

3

2d

2d

2d

2d

1d

1d

1d

-

-

28458

F

A

0s

1s

2s

2

2

2

1d

1d

0d

-

-

-

-

-

Total

2

5

11

12

12

11

8

8

5

3

3

1

1

0

H = hours; D = days; F = female; M = male; - = dermal irritation previously subsided; d = desquamation; s = brown staining on dose site

Table 2. Individual irritation scores (oedema)

SITE

SEX

SITE

1H

24H

48H

72H

4D

5D

6D

7D

8D

9D

10D

11D

12D

13D

A

M

A

0

0

0

0

0

0

0

0

0

0

0

0

0

0

A

M

A

0

0

0

0

0

0

0

0

0

-

-

-

-

-

A

M

A

0

0

0

0

-

-

-

-

-

-

-

-

-

-

A

F

A

0

0

1

1

1

1

0

0

0

0

0

0

0

0

A

F

A

0

0

0

0

0

0

0

0

0

0

0

0

-

-

A

F

A

0

0

0

0

0

0

0

0

0

-

-

-

-

-

Total

 

 

0

0

1

1

1

1

0

0

0

0

0

0

-

-

Primary Irritation Index (PII) was calculated using test periods: 1h, 24h, 48h, and 72h

PII = [(Total erythema scores (2 + 5 + 11 + 12)) / 24 (amount of test sites)] + [(Total oedema scores (0 + 0 + 1 + 1)) / 24 (amount of test sites)] = 1.4 (slightly irritating)

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the classification criteria outlined in the section 3.2.2.3.2.2. (Guidance on the Application of CLP criteria, 2013), if the mean value of ≥ 2.3 - ≤ 4.0 was reached for erythema/eschar or for oedema in at least 4 of 6 tested animals from gradings at 24, 48 and 72 hours after patch removal, the classification as Skin Irritant would be assigned. The evaluation of test results was performed according to the example 3 (test carried out with more than three animals; section 3.2.2.3.2.2.). Only 1/6 of the animals reached the cut-off value of 2.3 for erythema, i.e. only animal No. 27714 (female) is a positive responder. All other mean scores for erythema and oedema were under the cut-off value of 2.3. The dermal reactions were completely reversible within 13 days. Based on this knowledge, the target substance (Benzenesulfonic acid, mono-C20-24 (even)-sec-alkyl derivs., para-, sodium salts) does not meet criteria of Regulation (EC) No. 1272/2008 for classification and labelling as a skin irritant.
Executive summary:

The primary dermal irritation potential of C20-24 sodium sulfonate (TNB=448) was evaluated in this study with New Zealand White rabbits. There was one group of six albino rabbits that received a single, four-hour, semioccluded exposure. Each 0.5 mL dose of the test article was applied to the clipped, unabraded skin. At completion of exposure, the bandages were removed and the sites washed. Application sites were evaluated in accordance with the method of Draize at approximately 30-60 minutes and 24, 48 and 72 hours after patch removal and daily through day 13, if irritation persisted. There were no deaths or remarkable body weight changes during the study period. The test article induced very slight to moderate erythema on all animals and very slight oedema for one rabbit. Desquamation and brown staining of the skin were noted for five and six rabbits, respectively. All dermal irritation completely subsided by day 13. The Primary Irritation Index was calculated to be 1.4. The test article, C20 -24 sodium sulfonate (TBN=448), received a descriptive rating classification of slightly irritating.