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

Eye irritation

Administrative data

Endpoint:

eye 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 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Version / remarks:

August 1998

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF guidelines

Version / remarks:

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

Source: Charles River Deutschland, Kisslegg, Germany

Details on test animals or tissues and environmental conditions:

Age and body weight: The animal used within the study was at least 6 weeks old and its body weight was 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: 50 — 81%) 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 fluctuatlons 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

Vehicle:

unchanged (no vehicle)

Remarks:

Substance was ground to a powder using mortar and pestle prior to weighing

Amount / concentration applied:

59,7 mg in a volume approximately 1 ml

Observation period (in vivo):

1, 24, 48 and 72 hours after instillation

Number of animals or in vitro replicates:

1

Details on study design:

All available data relevant to the potential eye irritation/corrosivity of the substance indicated that no severe effects were to be expected. No severe reactions were noted in the skin irritation study (Notox Project 407756). An in-vitro test was considered, but a negative test result was anticipated that still had to be confirmed in an in-vivo study. Since no severe harm for the animals was to be expected, this in-vivo eye irritation study was performed and was started by treatment of a single rabbit (sentinel).

A health inspection was performed prior to commencement of treatment, to ensure that the animal was in a good state of health. Special attention was paid to the eyes, which were free from any abnormality.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not fully reversible within:

Remarks:

72 hours

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

not fully reversible within:

Remarks:

72 h

Results 3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 2 - <= 4

Max. score:

4

Reversibility:

not fully reversible within:

Remarks:

72 h

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 2 - <= 2

Max. score:

3

Reversibility:

not fully reversible within:

Remarks:

72 h

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 1 - <= 3

Max. score:

3

Reversibility:

not fully reversible within:

Remarks:

72 h

Results 6

Irritation parameter:

other: epithelial damage %

Basis:

animal #1

Time point:

24/48/72 h

Score:

>= 75 - <= 95

Max. score:

95

Reversibility:

not fully reversible within:

Remarks:

72 h

Other effects:

Decreased elasticity of the eyelids was noted at 24 and 48 hours after instillation of the test substance.
Gray discoloration (signs of necrosis) of eyelids and sclera were noted 48 and 72 hours after

Any other information on results incl. tables

Colouration / Remnants

No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.

Toxicity / Mortality

No symptoms of systemic toxicity were observed in the animal during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the degree and persistence of the corneal injury, it was concluded that ocular corrosion had occurred by instillation of V182675 into the rabbit eye in the 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 should be classified as: having irreversible effects on the eyes (Class 1).
- EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), V182675 should be labelled as: risk of serious damage to eyes (R 41).