Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

27th May 2013 to 15th August 2013.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to GLP and OECD Guideline.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

Principles of method if other than guideline:

Not applicable.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Sodium Isobutyrate Solution

IUPAC Name:

Sodium Isobutyrate Solution

Constituent 2

Reference substance name:

Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate

EC Number:

939-200-6

IUPAC Name:

Reaction mass of lithium 3-hydroxy-2,2,4-trimethylpentanoate and lithium isobutyrate and sodium 3-hydroxy-2,2,4-trimethylpentanoate and sodium isobutyrate

Test material form:

other: semi liquid

Details on test material:

- Name of test material (as cited in study report): Sodium Isobutyrate Solution
- Physical state: Light yellow semi liquid
- Analytical purity: 86.5%
- Composition of test material: confidential information

- Lot/batch No.: W195_02
- Expiration date of the lot/batch: 17th October 2013
- Storage condition of test material: Controlled room temperature (15-25°C, below 70% relative himidity).
- Other: The pH was assessed to identify if it was extreme prior to application to the animals. The pH was found to be 6.5, so the test test item was permitted for use in th the animal studies.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft., 2173 Kartal, Czászár út 135, Hungary.
- Age at study initiation: approximately 12 weeks old.
- Weight at study initiation: 2766 - 3236g
- Housing: Rabbits were individually housed in AAALAC approved metal wire cages. Cages were of an open wire structure and cages were placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet (e.g. ad libitum): UNI diet for rabbits ad libitum.
- Water (e.g. ad libitum): Municipal tap water ad libitum from an automatic system.
- Acclimation period: At least 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.1°C - 21.6°C.
- Humidity (%): 37 - 72%
- Air changes (per hr): 15-20 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours daily (from 6am to 6pm).

IN-LIFE DATES: From: 4th June 2013 To: 13th June 2013.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: Contralateral eye of test animal acted as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL

Duration of treatment / exposure:

24 hours.

Observation period (in vivo):

72 hours.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated eyes were rinsed with physiological saline solution.
- Time after start of exposure: 24 hours.

SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize and OECD 405.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Basis:

other: all test animals

Time point:

other: One hour after application

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

chemosis score

Basis:

other: all test animals

Time point:

other: One hour after application

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

other: Discharge

Basis:

other: all test animals

Time point:

other: One hour after application

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

conjunctivae score

Basis:

other: all test animals

Time point:

other: 24 hours after treatment

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

chemosis score

Basis:

other: all test animals

Time point:

other: 24 hours after treatment

Score:

> 1 - < 2

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 6

Irritation parameter:

other: Discharge

Basis:

other: all test animals

Time point:

other: 24 hours after treatment

Score:

> 1 - < 3

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

conjunctivae score

Basis:

other: all test animals

Time point:

other: 48 hours after treatment

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 8

Irritation parameter:

chemosis score

Basis:

animal: 2 test animals

Time point:

other: 48 hours after application

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

other: Discharge

Basis:

animal: 2 test animals

Time point:

other: 48 hours after treatment

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Results 10

Irritation parameter:

conjunctivae score

Basis:

other: all test animals

Time point:

other: 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 11

Irritation parameter:

chemosis score

Basis:

other: all test animals

Time point:

other: 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 12

Irritation parameter:

cornea opacity score

Basis:

other: all test animals

Time point:

other: 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

At 72 hours after treatment, no clinical signs or conjunctival or corneal effects were observed.
An Initial Pain Reaction score of 1 was observed in 2 animals tested.

Other effects:

There was no mortality observed during the study.
The body weights of the animals were considered to be within the normal range of variability.
During the daily general examinations, there were no clinical signs observed that could be related to treatment and the general state and behaviour of the animals were normal throughout the study period.
During the study, the control eye of each animal was symptom-free.

Any other information on results incl. tables

Mean Values of Eye Irritation:

Animal	Cornea Opacity	Iris	Conjunctivae
			Redness	Chemosis	Discharge
1	0.00	0.00	1.00	0.67	1.00
2	0.00	0.00	1.00	0.33	0.33
3	0.00	0.00	1.00	1.00	1.33

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item, Sodium Isobutyrate Solution, applied to rabbit eye mucosa caused conjunctival irritatnt effects at one hour which were reduced at 48 hours after application. The effects were fully reversible within 72 hours.
Under the conditions of this study and based on its results, the test material, Sodium Isobutyrate Solution is not considered to be an eye irritant and does not require classification according to Regulation (EC) No 1272/2008.

Executive summary:

An acute eye irritation study was conducted to determine the potential of Sodium Isobutyrate Solution to cause eye irritation in New Zealand White rabbits. The study was conducted in accordance with OECD Guideline 405 and was scored according to the Draize method. Three male test animals were used in the study, with the test material placed in the conjunctival sac of the left eye of each animal, with the right eye serving as the control. A single volume of 0.1 mL of test material was administered as a single dose.

The eyes were examined 1, 24, 48 and 72 hours after application of the test material. An Initial Pain Reaction of 1 was observed in 2 animals and one hour after application, conjunctival redness (score of 2), chemosis (score of 2) and discharge (score of 2 and 3) were observed in the treated eye of all test animals. 24 hours after application, conjunctival redness (score of 2), chemosis (score of 1 or 2) and discharge (score of 1, 2 and 3) were observed in the treated eye of all test animals. 48 hours after treatment, conjunctival redness (score of 1) was observed in all animals. Chemosis (score 1) and discharge (score of 1) were sen in 2 of the test animals.

In the absence of clinical signs 72 hours after treatment, the study was terminated. At all times during the study, the control eye of each animal was symptom free and the general state and behaviour of the animals was normal for the duration of the study.

Under the conditions of this study and based on its results, the test material, Sodium Isobutyrate Solution is not considered to be an eye irritant and does not require classification according to Regulation (EC) No 1272/2008.