Acetic acid, anhydride, reaction products with 1,5,10-trimethyl-1,5,9-cyclododecatriene

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 May 2007 and 4 June 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

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:

-

EC Number:

482-330-9

EC Name:

-

Cas Number:

144020-22-4

Molecular formula:

C17H26O

IUPAC Name:

1-[(1E,5Z,9Z)-2,5,10-trimethylcyclododeca-1,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1R)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one; 1-[(1S)-2,5,10-trimethylcyclododeca-2,5,9-trien-1-yl]ethan-1-one; 1-[(1S)-4,9-dimethyl-12-methylidenecyclododeca-4,8-dien-1-yl]ethan-1-one

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Highgate Farm, Market Rasen, Lincolnshire, England
- Age at study initiation: 15 to 16 weeks of age
- Weight at study initiation: 3.03 - 3.23 kg
- Housing: housed individually in plastic cages with perforated floors
- Diet (e.g. ad libitum): Each rabbit was offered 125 g of a standard laboratory rabbit diet (Rabbit GD Diet Pellets supplied by Highgate Farm) per day. A dietary supplement of hay was offered during acclimatisation until two days prior to dose instillation; for the remainder of acclimatisation and throughout the study observation period whole-meal bread was offered
- Water (e.g. ad libitum): ad libitum
- Acclimation period: four to seven weeks prior to the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 20°C
- Humidity (%): 40 to 70%
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.1 ML

Duration of treatment / exposure:

Four days

Observation period (in vivo):

Four days

Number of animals or in vitro replicates:

3

Details on study design:

TREATMENT PROCEDURE
The eyes of each animal were examined prior to instillation of the test substance to ensure that there was no pre-existing corneal damage, iridial inflammation or conjunctival irritation. Each animal was gently restrained. The dose was instilled into the right eye by pulling the lower eyelid away from the eye ball to form a cup into which the test substance was dropped. The eyelids were then gently held together for one second before releasing; the left eye remained untreated.

OBSERVATIONS
- Clinical signs: The behavior of the sentinel rabbit was observed immediately following instillation of the test substance to allow assessment of the initial pain response. The animals were returned to their cages and checked at least twice during the first hour after dosing and at regular intervals throughout the day to ensure no severe injury passed unnoticed. Ocular reactions to treatment were assessed 1, 24, 48 and 72 hours after treatment. An additional observation was made on the sentinel animal seven days after instillation. Assessment was made according to the criteria overleaf.

- Ocular Responses: The untreated eye was used as a comparison with the treated eye during assessment of ocular lesions. An ophthalmoscope and a pencil beam torch were used to facilitate inspection of the eyes.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

animal: #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

chemosis score

Basis:

animal: #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 3 days

Other effects:

Injection of the conjunctival blood vessels or a crimson-red conjunctival appearance with or without very slight chemosis and slight or moderate discharge was apparent in all animals throughout the first 48 hours after instillation.

The treated eye of each animal was overtly normal 72 hours after instillation.

Instillation of the test substance gave rise to a slight initial pain response in one animal.

Applicant's summary and conclusion

Interpretation of results:

other: Not irritant according to EU CLP (1272/2008 and its amendments)

Conclusions:

The substance is not an eye irritant in the eye irritation in vivo study (OECD TG 405).

Executive summary:

The eye irritating potential of the substance was determined in an eye irritation study (in vivo) performed in accordance with OECD TG 405 and GLP. Three rabbits were each administered a single ocular dose of a volume of 0.1 ml of the test substance and observed for four days after instillation. Injection of the conjunctival blood vessels or a crimson-red conjunctival appearance with or without very slight chemosis and slight or moderate discharge was apparent in all animals throughout the first 48 hours after instillation. Instillation of the test substance gave rise to a slight initial pain response in one animal. The treated eye of each animal was overtly normal 72 hours after instillation. The results showed that the substance is not considered irritating.