sodium 3-((2,3-dicyanophenyl)sulfonyl)propane-1-sulfonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Remarks:

existing study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental test dates 2013-12-23 to 2014-01-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets the criteria for classification as reliable without restriction according to Klimich et al (1997)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

sodium 3-((2,3-dicyanophenyl)sulfonyl)propane-1-sulfonate

EC Number:

696-126-4

Cas Number:

886592-17-2

Molecular formula:

C11H9N2O5S2Na

IUPAC Name:

sodium 3-((2,3-dicyanophenyl)sulfonyl)propane-1-sulfonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals / tissue source

Species:

rabbit

Strain:

other: New Zealand white (Hsdlf:NZW)

Details on test animals or tissues and environmental conditions:

Two New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.52 or 2.61 kg and were twelve to twenty weeks old. After an acclimatization period of at least five days each animal was given a number unique within the study which was written with a black indelible marker pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Vehicle:

not specified

Controls:

other: The left eye remained untreated and was used for control purposes.

Amount / concentration applied:

A volume of 0.1 mL of the test item, which was found to weigh approximately 76 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye

Duration of treatment / exposure:

72h

Observation period (in vivo):

Immediately after administration of the test item, an assessment of the initial pain reaction was made.

Eight hours after test item application, a subcutaneous injection of post dose analgesia, buprenorphine 0.01 mg/kg and meloxicam 0.5 mg/kg, was administered to provide a continued therapeutic level of systemic analgesia. The treated animal was checked for signs of pain and suffering approximately 12 hours later. No further analgesia was required.

After consideration of the ocular responses produced in the first treated animal, a second animal was similarly treated.

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977).

Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Any clinical signs of toxicity, if present, were also recorded.

Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Number of animals or in vitro replicates:

2

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 73837 male

Time point:

other: highest score at 24,48 & 72h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 73843 male

Time point:

other: highest score at 24, 48 & 72h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

iris score

Basis:

animal: 73837 male

Time point:

other: highest score at 24, 48 & 72h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

iris score

Basis:

animal: 73843 male

Time point:

other: highest score at 24, 48 & 72h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24h

Results 5

Irritation parameter:

chemosis score

Basis:

animal: 73837 male

Time point:

other: highest score at 24, 48 & 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 48h

Results 6

Irritation parameter:

chemosis score

Basis:

animal: 73843 male

Time point:

other: highest score at 24, 48 & 72h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h

Results 7

Irritation parameter:

other: redness

Basis:

animal: 73837 male

Time point:

other: highest score at 24, 48 & 72h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48h

Results 8

Irritation parameter:

other: redness

Basis:

animal: 73843 male

Time point:

other: highest score at 24, 48 & 72h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 9

Irritation parameter:

other: discharge

Basis:

animal: 73837 male

Time point:

other: highest score at 24,48 & 72h

Score:

0

Max. score:

3

Reversibility:

fully reversible within: 24h

Results 10

Irritation parameter:

other: discharge

Basis:

animal: 73843 male

Time point:

other: highest score at 24, 48 & 72h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

No corneal effects were noted during the study.

Iridial inflammation was noted in one treated eye one hour after treatment.

Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation was noted in both treated eyes at the 24 Hour observation and in one treated eye at the 48 Hour observation.

One treated eye appeared normal at the 48 Hour observation and the other treated eye appeared normal at the 72 Hour observation.

Other effects:

Both animals showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item produced a maximum group mean score of 11.5 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

This study was designed to be compatible with the procedures indicated by the following internationally accepted guidelines and recommendations:

 

·     OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 02 October 2012)

·     Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

      

 Results & Conclusions

No corneal effects were noted during the study.

 

Iridial inflammation was noted in one treated eye one hour after treatment.

 

Moderate conjunctival irritation was noted in both treated eyes one hour after treatment. Minimal conjunctival irritation was noted in both treated eyes at the 24‑Hour observation and in one treated eye at the 48‑Hour observation.

 

One treated eye appeared normal at the 48‑Hour observation and the other treated eye appeared normal at the 72‑Hour observation.

The test item produced a maximum group mean score of11.5 and was classified as amildirritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

 

The test item does not meet the criteria for classification according to Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.