RD 14156

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 20 October 2015 and 14 January 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

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:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor Lot/Batch number 1004R17501

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and humidity


FORM AS APPLIED IN THE TEST (if different from that of starting material)

OTHER SPECIFICS:

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA, USA
- Age at study initiation: ~27 weeks
- Weight at study initiation: 2.9 - 3.4 kg
- Housing: The animals were housed one per cage in suspended cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL equivalent to 32.5 mg RD 14156

Duration of treatment / exposure:

72 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done
- Time after start of exposure:

SCORING SYSTEM: OECD 405
The ocular irritation scores were evaluated in conjunction with the nature and severity of lesions, and their reversibility or lack of reversibility. The scores were categorized/classified as outlined below.

Non irritant: Substances that are not classified as EPA Category I, II, or III ocular irritants; or GHS eye irritation Category 1, 2, 2A or 2B; or EU Category 1 or 2.

Ocular irritant: A substance that produces a reversible change in the eye; Substances that are classified as EPA Category II or III ocular irritants; or GHS eye irritants Category 2, 2A or 2B; or EU Eye irritant Category 2.

Ocular corrosive: A substance that causes irreversible tissue damage to the eye; Substances that are classified as GHS eye irritants Category 1, or EPA Category I ocular irritants, or EU Category1.

Ocular severe irritant: A substance that causes tissue damage in the eye that does not resolve within 21 days of application or causes serious physical decay of vision; Substances that are classified as GHS eye irritant Category 1, or EPA Category I ocular irritants, or EU Category 1.

TOOL USED TO ASSESS SCORE: Mini-Maglite® flashlight equipped with a high intensity bulb/ fluorescein at 24h observation interval

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: ALL

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

animal: ALL

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

2

Reversibility:

fully reversible

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 1 hr

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 1 hr

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 6

Irritation parameter:

chemosis score

Basis:

animal: all

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal: all

Time point:

24 h

Score:

1

Max. score:

3

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal: all

Time point:

72 h

Score:

1

Max. score:

2

Any other information on results incl. tables

1. Ocular findings

Corneal opacity and iritis were not noted at any observation period. Conjunctival irritation, noted in three out of three eyes, cleared in two eyes by 24 hours, and in one eye by 72 hours. Additional ocular observations of test article residue in the conjunctival sac was noted at the 1-hour observation period. The control eyes appeared normal at all observation periods.

2. Systemic Observations and Body Weights

One animal was noted with few feces on Days 2 and 3. All other animals appeared normal. Two animals lost weight and one animal gained weight.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Ocular irritant: A substance that produces a reversible change in the eye; Substances that are classified as EPA Category II or III ocular irritants; or GHS eye irritants Category 2, 2A or 28; or EU Eye irritant Category 2.

EU Classification Not classified
GHS Classification Not classified
US EPA Classification Category III

Executive summary:

Objective:

To determine the irritant or corrosive effects, if any, of a test article when instilled into the rabbit eye. This study was designed to comply with the standards set forth in the current EPA Health Effects Testing Guidelines, OCSPP Series 870.2400 and OECD Guidelines for Testing Chemicals, Number 405.

Method Synopsis:

Three healthy New Zealand White rabbits (two males - one female), free from evidence of ocular irritation and corneal abnormalities, were placed on the study. An analgesic, Buprenorphine was administered subcutaneously between the shoulder blades approximately 1 hour prior to instillation of the test article. A dose of 0.1 ml equivalent (32.5 mg) of RD 14156 was placed into the conjunctival sac of one eye of each rabbit. The eyes were examined pretest and scored by the Draize technique at 1, 24, 48 and 72 hours postdose. The control eyes were observed at the same time periods. Sodium fluorescein dye procedures were used at the 24-hour observation interval. Animals were evaluated for physical signs twice daily for the first three days of the study. Body weights were recorded immediately pretest and at termination.

Summary:

Corneal opacity and iritis were not noted at any observation period. Conjunctival irritation, noted in three out of three eyes, cleared in two eyes by 24 hours, and in one eye by 72 hours. Additional ocular observations of test article residue in the conjunctival sac was noted at the 1-hour observation period. The control eyes appeared normal at all observation periods. One animal was noted with few feces on Days 2 and 3. All other animals appeared normal. Two animals lost weight and one animal gained weight.

Conclusions:

OECD 405

Ocular irritant: A substance that produces a reversible change in the eye; Substances that are classified as EPA Category II or III ocular irritants; or GHS eye irritants Category 2, 2A or 2B; or EU Eye irritant Category 2.

EU Classification Not classified

GHS Classification Not classified

US EPA Classification Category III