2-(4-bromophenyl)-2-methylpropionic acid methyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed in accordance with validated guidelines and in GLP compliance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-(4-bromophenyl)-2-methylpropionic acid methyl ester

EC Number:

450-630-9

EC Name:

2-(4-bromophenyl)-2-methylpropionic acid methyl ester

Cas Number:

154825-97-5

Molecular formula:

C11H13BrO2

IUPAC Name:

methyl 2-(4-bromophenyl)-2-methylpropanoate

Test material form:

other: liquid

Details on test material:

The test material of FEXO-03 was a colourless oil with a degree of purity >95%

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

The test animals were New Zealand White Rabbit, SPF. The age of the animals at tratment was 12- 13 weeks (male) and 18 - 19 weeks (females).
Air-conditioned with target ranges for room temperature 17-23 °C, relative humidity 30-70% and approximately 10-15 air changes per hour. Room temperature and humidity
were monitored continuously and values outside of these ranges may have occasionally occurred, usually following room cleaning. These transient variations are considered not
to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.
lndividually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks 4646 were provided for gnawing.
Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 52/03). Results of analysis for contaminants are archived at RCC Ltd.
Community tap water ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as the reference control.

Amount / concentration applied:

0.1 ml (per animal) of FEXO-03 was measured with a syringe and applied undiluted as it was delivered by the sponsor.

Duration of treatment / exposure:

On the day of treatment

Observation period (in vivo):

1, 24, 48 and 72 hours, as well as 7, 10 and 14 days after instillation.

Number of animals or in vitro replicates:

3 (animals of both sexes were used)

Details on study design:

0.1 ml (per animal) of FEXO-03 was measured with a syringe and applied undiluted as it was delivered by the sponsor.
The pH of the test item was measured for a previous study (RCC Study number 851037, skin irritation with FEXO-03 in rabbits) and was found to be 6.
According to Directive 92/69 EEC, B.5. and OECD Guidelines 405, a test item needs not to be tested if the pH-value is less than 2 or greater than 11.5, owing to its predictable corrosive properties.
The eyes of the animals were examined one day prior to test item administration. Animals with overt signs of ocular injury or irritation which may have interfered with the
interpretation of the results were not used in the test.
On the day ol treatment, 0.1 ml of FEXO-03 was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss ol test item. The right eye remained untreated and served as the reference control. The treated eyes were not rinsed alter instillation.
As the first animal screamed just after the application only this single animal (one male) was treated according to the study plan schedule. As neither a corrosive effect nor a severe irritant effect was observed alter the 1- and 24-hour examinations, the test was completed using the two remaining animals (two females).

OBSERVATIONS
Viability/Mortality - Daily from acclimatization of the animals to the termination of test.
Clinical signs - Daily from acclimatization of the animals to the termination of test.
Body weights - At start of acclimatization, on the day of application and at termination of observation.

The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and
72 hours, as well as 7, 10 and 14 days alter instillation.
Eye examinations were made with a Varia Cliptrix diagnostic-lamp.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible

Results 2

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 3

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 5

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 6

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 10

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

(mean score 1)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 11

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

(mean score 2)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Results 12

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

(mean score 3)

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.67, 1.00 and 1.33 for reddening and 0.00 for chemosis for all three animals.
No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.
Moderate reddening of the conjunctivae was observed in all animals at the 1-hour reading.
Slight to moderate reddening of the conjunctivae was noted in all animals 24 hours after treatment. Slight reddening was present in all animals at the 48-hour reading and persisted in two animals up to 72 hours and in one animal up to 10 days after treatment.
Slight to moderate swelling was present in all animals at the 1-hour reading.
Moderate reddening of the sclerae was observed in all animals at the 1-hour reading and slight reddening was evident in two animals 24 hours after treatment and persisted in one animal up to the 48-hour examination. No ocular discharge was noted in any animal at any time.
No abnormal findings were observed in the treated eye of any animal 14 days after treatment, the end of the observation period for all animals.
No corrosion of the cornea was observed at any of the reading times.

Other effects:

Coloration : no staining of the treated eyes produced by the test item was observed

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

FEXO-03 is considered to be "not irritating" to the rabbit eye.