Barium dibenzoate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-12-04 to 2017-12-26

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2017-10-09

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2015-06-05

Test material

Test material information

Constituent 1

Reference substance name:

Barium dibenzoate

EC Number:

208-551-0

EC Name:

Barium dibenzoate

Cas Number:

533-00-6

Molecular formula:

C14H10O4Ba

IUPAC Name:

barium dibenzoate

Test material form:

solid

Details on test material:

- State of aggregation at room temperature: white solid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: dry place at ambient temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 32 weeks old
- Weight at study initiation: 4.9 kg
- Housing: individually housed in ABS-plastic or Noryl rabbit cages, floor 4200 cm²
- Diet (ad libitum): autoclaved hay and to Altromin 2123 maintenance diet for rabbits, rich in crude fibre
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Relative humidity: 55 ± 10%
- Air changes: at least 10 x / hour
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of the test item in the conjunctival sac of one eye. Untreated eye served as control.

Duration of treatment / exposure:

1 hour

Observation period (in vivo):

1, 24, 48 and 72 hours as well as 4 to 21 days after test item application

Duration of post- treatment incubation (in vitro):

not applicable

Number of animals or in vitro replicates:

One female rabbit

Details on study design:

PREPARATION OF THE ANIMALS
Within 24 hours before the test and immediately prior to the application both eyes of each animal were examined.
Approx. 17 hours before the application the eyes were examined with the aid of a fluorescein solution (Fluoreszein SE Thilo®). The eyes were rinsed with physiological saline 0.9 % NaCl after the examination. None of the animals showed eye irritation, ocular defects, or pre-existing corneal injury.

INITIAL AND CONFIRMATORY TEST
The in vivo test was performed initially using one animal. The results of the initial test indicated that the test item is corrosive or severe irritant to the eye using the procedure described. Therefore, no additional animals were treated due to animal welfare reasons.

USE OF TOPICAL ANESTHETICS AND SYSTEMIC ANALGESICS
One hour before the application of the test item, 0.01 mg/kg of buprenorphine (Temgesic® 0.3 mg/mL) was administered subcutaneously in order to achieve a therapeutic level of systemic analgesia. Approx. 5 minutes prior to the application of the test item, 1-2 drops of an ocular anaesthetic (Proparakaine-POS® hydrochloride ophthalmic 0.5% solution) were administered in both the treated and the control eye of the animal.
To prevent pain and distress after the application of the test item the animal was treated with doses of buprenorphine and meloxicam (Metacam® 5 mg/mL) to provide a continued therapeutic level of systemic analgesia. Treatment with the analgesic medication was conducted from 11 hours post-application (day 0) upto 8 days post-application.

REMOVAL OF TEST SUBSTANCE
- Washing: treated eye was rinsed with physiological saline 0.9 % NaCl.
- Time after start of exposure: 1 hour after the application

SCORING SYSTEM: according to Draize scale

TOOL USED TO ASSESS SCORE: slit lamp biomicroscope / fluorescein
The treated eyes were examined with the aid of a fluorescein solution and a slit lamp biomicroscope 24 hours post-application and from then on daily until end of the observation period. The eyes were rinsed with physiological saline 0.9 % NaCl after the examination.

OBSERVATIONS
- body weight: prior to the administration and at least at the end of the observation period
- clinical observations: nature, severity and duration were recorded

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 13 days

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 11 days

Irritant / corrosive response data:

Animal no. 1:
- conjunctival redness: moderate conjunctival redness (grade 2) was observed from 1 hour until day 12 post-application. The effect was fully reversible within day 13 after application of the test material.

- conjuctival chemosis: moderate conjunctival chemosis (grade 3) was detected 1 hour post-application before severity level decreased from 24 until 48 hours post-application (grade 2) and from 72 hours until day 10 post-application (slight conjuncitvla chemosis; grade 1). The effect was fully reversible within day 11 after application of the test material.

- corneal opacity: slight corneal opacity (grade 1) was observed throughout the whole observation period of 21 days, except for day 14 and 15 after application. The effect was not reversible within 21 days.

- iris: the iris was not affected by administration of the test item.

Local effects were observed. The observed local effects mainly comprise severe to slight hypersecretion, red spot on the outer surface of the upper eyelid and vascularisation between eye rim and cornea lesion.
Upon fluorescein examinations starting 24 hours post-application, the treated eye of the animal showed corneal lesions (starting with approx. 40% of the area) which have not fully reversed within an observation period of 21 days.

Other effects:

- clinical observations: neither mortality nor significant clinical signs of toxicity were observed.
- body weight: the body weight development was not within the expected range.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The substance is serious eye damaging.
According to the EC Regulation No. 1272/2008 and subsequent adaptations, the substance is classified as a serious eye damaging (Category 1; H318).