Dibismuth trioxide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2010-06-08 till 2010-06-14

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Dibismuth trioxide

EC Number:

215-134-7

EC Name:

Dibismuth trioxide

Cas Number:

1304-76-3

Molecular formula:

Bi2O3

IUPAC Name:

[(oxobismuthanyl)oxy]bismuthanone

Details on test material:

- Name of test material (as cited in study report): Dibismuth trioxide
- Molecular formula (if other than submission substance): Bi2O3
- Molecular weight (if other than submission substance): 465.96 g/mol
- Physical state: solid, yellow powder
- Storage condition of test material: At room temperature, in closed container, keep dry.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands
- Age at study initiation: 17 weeks
- Weight at study initiation: 2530 - 3435 g
- Housing: Individually in stainless steel cages.
- Diet: ad libitum; Pelleted standard Kliba Nafag 3418 rodent maintenance diet (batch no. 05/10 provided by Provimi Kliba AG, Switzerland)
- Water: ad libitum
- Acclimation period: at least 4 days

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

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied (volume or weight with unit): The test item was applied at 0.1 g/animal, the dose specified in the test guidelines for a solid test item.

VEHICLE
Not applicable, test item was applied undiluted as it was delivered.

Duration of treatment / exposure:

72 hours

Observation period (in vivo):

at approximately 1, 24, 48, 72 hours after administration

Number of animals or in vitro replicates:

3 males

Details on study design:

A single animal was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 1- and 24-hour examinations, the test was completed using the two remaining animals.

REMOVAL OF TEST SUBSTANCE
Substance was not removed.

SCORING SYSTEM: The eye reactions were assessed according to the numerical scoring system listed in the Commission Regulation (EC) No 440/2008, B.5. Scleral reddening and ocular discharge were also assessed.
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris light reflex, redness and chemosis of the conjunctivae, separately.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, 4153 Reinach / Switzerland).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of animal #1

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

for animal #2

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

for animal #3

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 4

Irritation parameter:

iris score

Basis:

mean

Remarks:

of animal #1

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 5

Irritation parameter:

iris score

Basis:

mean

Remarks:

for animal #2

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 6

Irritation parameter:

iris score

Basis:

mean

Remarks:

of animal #3

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of animal #1

Time point:

other: 72 hours after instillation

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Results 8

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of animal #2

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 9

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of animal #3

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 10

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of animal #1

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 11

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of animal #2

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Results 12

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of animal #3

Time point:

other: 72 hours after instillation

Score:

0

Max. score:

0

Irritant / corrosive response data:

Slight reddening of the conjunctivae and slight reddening of the sclerae were noted in all 3 males 1 hour after instillation. The slight reddening of the conjunctivae persisted in one animal up to the 24-hour reading. Slight ocular discharge was present in one animal 1 hour after instillation.
No abnormal findings were observed in the treated eyes of any animals 24 or 48 hours after treatment.
No staining produced by the test item was observed in the treated eyes.
No corrosion of the cornea was observed at any of the reading times.

Other effects:

No intercurrent deaths occurred during the course of the study. No clinical signs were recorded throughout the entire observation period. The body weight of the animals was within the range commonly recorded for this strain and age.
Green test item remnants were observed in the treated eyes of all animals at the 1-hour reading.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008), dibismuth trioxide does not have to be classified with respect to eye irritation in rabbits.

Executive summary:

The primary eye irritation potential of dibismuth trioxide was investigated according to OECD test guideline 405. The test item was applied by instillation of 0.1 g into the left eye of each of 3 young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation. The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris light reflex, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris light reflex were 0.00 for all three animals. The individual mean scores for the conjunctivae were 0.33, 0.00 and 0.00 for reddening and 0.00 for all animals for chemosis. The instillation of dibismuth trioxide into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, as well as ocular discharge. These effects were reversible and were no longer evident 24 or 48 hours after treatment. No abnormal findings were observed in the cornea or for the iris light reflex of any animals at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye.