sodium;2-hexadecylsulfanyl-1H-benzimidazole-5-sulfonate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF

Version / remarks:

Japanese test guidelines (2000)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

sodium;2-hexadecylsulfanyl-1H-benzimidazole-5-sulfonate

EC Number:

616-081-6

Cas Number:

743423-33-8

Molecular formula:

C23 H37 N2 Na O3 S2

IUPAC Name:

sodium;2-hexadecylsulfanyl-1H-benzimidazole-5-sulfonate

impurity 1

Reference substance name:

1-hexadecyl-2-hexadecylsulfanyl-benzimidazole-5-sulfonate sodium salt

Molecular formula:

C39 H69 N2 Na O3 S2

IUPAC Name:

1-hexadecyl-2-hexadecylsulfanyl-benzimidazole-5-sulfonate sodium salt

impurity 2

Reference substance name:

N,N-dimethylacetamide

EC Number:

204-826-4

EC Name:

N,N-dimethylacetamide

Cas Number:

127-19-5

Molecular formula:

C4H9NO

IUPAC Name:

N,N-dimethylacetamide

impurity 3

Reference substance name:

Ethyldiisopropylamine

EC Number:

230-392-0

EC Name:

Ethyldiisopropylamine

Cas Number:

7087-68-5

Molecular formula:

C8H19N

IUPAC Name:

N-ethyl-N-isopropylpropan-2-amine

Test material form:

solid: particulate/powder

Remarks:

off-white powder with lumps

Details on test material:

Traces of 1-bromohexadecane

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Source: Charles River Deutschland, Kisslegg, Germany

Details on test animals or test system and environmental conditions:

Age and body weight Animals used within the study were at least 6 weeks old and body weights were at least 1.0 kg.
Identification Earmark.

Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +- 3.0°C (actual range: 19.9 —22.0°C), a relative humidity of 30-70% (actual range: 44 - 84%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.

Accommodation
Individually in labelled cages with perforated floors (Scanbur, Denmark, dimensions 56x44x37.5 cm).
Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.

Diet
Standard laboratory rabbit diet (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Lage, Germany) approx. 100 g. per day. Certificates of analysis were examined and retained in the NOTOX archives. In addition, hay (BMI, Helmond, the Netherlands) was provided at least three times a week.

Water
Free access to tap-water. Certificates of quarterly analysis were examined and retained in the NOTOX archives.
Results of analysis for ingredients and/or contaminants of diet and water were assessed and did not reveal any findings that were considered to have affected study integrity.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Substance was ground to a powder with mortar and pestle before weighing and moistened with water (Milli-U) immediately before application to ensure close contact with the animal's skin

Amount / concentration applied:

0.5 grams of test substance, moistened with 3 ml of water

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours and 7 days after removal of the test substance

Number of animals:

3 males

Details on study design:

All available data relevant to the potential dermal irritation/corrosivity of the substance indicated that no severe effects were to be expected. An in—vitro test was considered, but a negative test result was anticipated that still would have to be confirmed in an in-vivo study. Since no severe harm for the animals was to be expected, this in-vivo skin irritation study was performed and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner two weeks later, after considering the degree of skin irritation observed in the first animal.

Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm"‘). Whenever considered necessary the treated skin areas were re-clipped at least 3 hours before the observations, to facilitate scoring.

A health inspection was performed prior to the commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from abnormalities.

Each animal was treated by dermal application of 0.5 grams of the test substance. The test substance was moistened with 0.3 ml of the vehicle and applied to the skin of one flank, using a metalline patch” of 2x3 cm. The patch was mounted on Micropore tape”, which was wrapped around the abdomen and secured with Coban elastic bandage“.
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using water.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within:

Remarks:

24 hours

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within:

Remarks:

7 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within:

Remarks:

24 hours

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within:

Remarks:

24 hours

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

Four hours exposure to 0.5 g of V182675 resulted in very slight and/or well-defined erythema and I or very slight oedema in the treated skin-areas of the three rabbits.
The skin irritation had resolved within 24 hours after exposure in two animals and within 7 days in the other animal.

Corrosion
There was no evidence of a corrosive effect on the skin.

Other effects:

Colouration I Remnants
No staining of the treated skin by the test substance was observed and no test substance remnants were seen.

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

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Exposure to V182675 resulted in very slight and/or well-defined erythema and I or very slight oedema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 24 hours after exposure in two animals and within 7 days in the other animal.

Based on these results and according to the:
- OECD Harmonized integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998), V182675 does not have to be classified for skin irritation.
- EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), V182675 does not have to be classified and has no obligatory labelling requirement for skin irritation.