Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, 2-ethylhexyl ester

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 23, 2017 - January 24, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

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:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147, November 24, 2000 as this is in line with OECD 405

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, 2-ethylhexyl ester

EC Number:

807-747-9

Cas Number:

144429-84-5

Molecular formula:

C25H42O3

IUPAC Name:

Benzenepropanoic acid, 3,5-bis(1,1-dimethylethyl)-4-hydroxy-, 2-ethylhexyl ester

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: Approx.3 months
- Weight at study initiation: 2.62 kg – 2.83 kg
- Housing: Single housing, atainless steel wire mesh cages with grating with shallow cage body; floor area: 4225 cm2
- Diet: STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye was used as control

Amount / concentration applied:

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

Duration of treatment / exposure:

single instillation

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with tap water
- Time after start of exposure: 24 h


SCORING SYSTEM: according to OECD guideline

TOOL USED TO ASSESS SCORE: fluorescein solution

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Irritant / corrosive response data:

Neither corneal nor iris lesions were noted in all animals at any examination time point. Even after instillation of a fluorescein solution no corneal lesions were detectable after 24 and 48 hours.
Slight conjunctival redness (grade 1) was noted in one animal at hour 1 after application only. The two other animals showed obvious conjunctival redness (grade 2) at hour 1, which decreased to slight conjunctival redness (grade 1) from hour 24 until hour 48. Slight conjunctival chemosis (grade 1) was seen in two animals at hour 1, while obvious or severe discharge (grade 2 or 3) was noted in all animals 1 hour after application.
Injected scleral vessels in a circumscribed area were noted in all animals at hour 1 after application.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described ocular reactions as well as the average score for irritation, the test item does not show an eye irritating potential under the test conditions chosen.

Executive summary:

The potential of the test item to cause damage to the conjunctiva, iris or cornea was assessed by a single ocular application of 0.1 mL of the undiluted test item to one eye of three New Zealand White rabbits (stepwise procedure starting with one animal and supplementing two additional animals). About, but not less than, 24 hours after application the eye was rinsed with tap water. The ocular reactions were assessed approximately 1, 24, 48 and 72 hours after application. Additional eye examinations were performed 24 and 48 h after application with the instillation of a fluorescein solution. Due to absence of detectable lesions following fluorescein instillation, all subsequent readings were performed without the aid of fluorescein. Neither corneal nor iris lesions were noted in all animals at any examination time point. Even after instillation of a fluorescein solution no corneal lesions were detectable after 24 and 48 hours. The following test item-related clinical observations were recorded during the course of the study: Slight to obvious conjunctival redness (grade 1 to 2), slight conjunctival chemosis (grade 1), obvious to severe discharge (grade 2 to 3), injected scleral vessels in a circumscribed area were noted in the animals at hour 1 after application only. The ocular reactions were reversible in one animal within 24 hours and in two animals within 72 hours after application. Mean scores calculated for each animal over 24, 48 and 72 hours were 0.0, 0.0 and 0.0 for corneal opacity and for iris lesions, 0.0, 0.7 and 0.7 for redness of the conjunctiva and 0.0, 0.0 and 0.0 for chemosis, respectively. Considering the described ocular reactions as well as the average score for irritation, the test item does not show an eye irritating potential under the test conditions chosen.