Benzoic acid, 2-([1,1'-biphenyl]-4-ylcarbonyl)-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Feb 6 2014 - May 20 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to OECD Guideline and EU Method on testing and assessment in compliance with GLP.

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

Principles of method if other than guideline:

same as guideline

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

2-(4Phenylbenzoyl)benzoic acid

IUPAC Name:

2-(4Phenylbenzoyl)benzoic acid

Constituent 2

Reference substance name:

2-{[1,1'-biphenyl]-4-carbonyl}benzoic acid

EC Number:

700-862-4

Cas Number:

42797-18-2

Molecular formula:

C20 H14 O3

IUPAC Name:

2-{[1,1'-biphenyl]-4-carbonyl}benzoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Name of test material (as cited in study report): 2-(4Phenylbenzoyl)benzoic acid
- Physical state: white powder
- Analytical purity: 99.9%
- Lot/batch No.: 5307
- Expiration date of the lot/batch: 01 May 2015
- Storage condition of test material: room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Leicestershire, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.58 or 2.95kg
- Housing: individually in suspended cages
- Diet: ad libitum, 2930C Teklad Global Rabbit diet
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23°C
- Humidity (%): 30-70%
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: April 7 2014 To: April 17 2014

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the second eye of each rabbit

Amount / concentration applied:

0.1mL (~64mg)

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

after 1 hour, 24, 48 and 72 hours

Number of animals or in vitro replicates:

2

Details on study design:

Test Item Formulation and Experimental Preparation
For the purpose of the study the test item was used as supplied.

The pH of the test item was determined prior to commencement of the study and found to be as follows:
pH Measurement of 10% w/w aqueous preparation of the test item:
-immediately: 6.29
-after 10 minutes: 6.22

Procedure
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre-dose anesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.
A volume of 0.1 mL of the test item, which was found to weigh approximately 64 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctiva! sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1.
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) given in Appendix 2.
Procedure
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A subcutaneous injection of buprenorphine 0.01 mg/kg was administered 60 minutes prior to test item application to provide a therapeutic level of systemic analgesia. Five minutes prior to test item application, a pre-dose anesthesia of ocular anesthetic (two drops of 0.5% tetracaine hydrochloride) was applied to each eye.
A volume of 0.1 mL of the test item, which was found to weigh approximately 64 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctiva! sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale shown in Appendix 1.
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) given in Appendix 2.
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.

Results and discussion

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1 hours

Score:

ca. 9

Max. score:

10

Reversibility:

fully reversible

Irritant / corrosive response data:

see attached tables with results

Other effects:

Individual body weights and body weight change are given in Table 3.

One animal showed body weight loss and the other animal showed expected gain in body weight during the study.

Any other information on results incl. tables

see attached result tables

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The test item produced a maximum group mean score of 9.0 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 the Globally Harmonized System of Classification and Labelling of Chemicals.

Executive summary:

Introduction

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

 

Results

 A single application of the test item to the non-irrigated eye of two rabbits produced moderate conjunctival irritation. One treated eye appeared normal at the 48-Hour observation and the other treated eye appeared normal at the 72-Hour observation.

 

Conclusion

 The test item produced a maximum group mean score of 9.0 and was classified as a mild irritant (Class4 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 the Globally Harmonized System of Classification and Labelling of Chemicals.