Ethyl L-threoninate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 13, 2000 - April 28, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study was performed in compliance with GLP standards. Minor deviations in humidity were observed during the study period but these deviations did not affect the integrity of the study. The pre-treatment of the rabbits with ophthaine was ommitted in error, and it was not considered to have enhanced/increased the pain experienced by the test animals.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

humidity, and analgesic treatment ommitted

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

humidity, and analgesic treatment ommitted

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

yes

Remarks:

humidity, and analgesic treatment ommitted

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Threonineethylester
- Analytical purity: 97%
- Purity test date: no data
- Lot/batch No.: 142-576-6
- Expiration date of the lot/batch: no data
- Stability under test conditions: considered to be stable under test conditions
- Storage condition of test material: frozen

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch number of test material: 142-576-6


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: < 10°C when not in use

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Final dilution of a dissolved solid, stock liquid or gel: 50% m/v dispersion

OTHER SPECIFICS
- measurement of pH, osmolality, and precipitate in the culture medium to which the test chemical is added: pH of 9.16

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl:NZW/Kbl.BR

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Margate
- Age at study initiation: 11 to 14 weeks old
- Weight at study initiation: 1.92 to 2.42 kg
- Housing: floor-pens, single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 or 10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 22°C
- Humidity (%): 40 to 80 % RH (on the first eight days of the study, the humidity fell below the range by up to 15% RH)
- Air changes (per hr): 10 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours with fluorescent strip-lights

IN-LIFE DATES: From 4 April 2000 to 28 April 2000.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye (right eye)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 34.3 mg (the weight equivalent to 0.1 mL)

VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle

Duration of treatment / exposure:

few seconds

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3 animals (females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing

SCORING SYSTEM:
See in the section below

TOOL USED TO ASSESS SCORE: 2% aqueous fluorescein solution applied to the corenea and then washed out with water for irrigation or purified water. The corneal surface was illuminated by an ultraviolet source

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Results 7

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 8

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 9

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1

Reversibility:

fully reversible within: 72 h

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Reversibility:

fully reversible within: 72 h

Results 13

Irritation parameter:

other: Conjunctivae - discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Results 14

Irritation parameter:

other: Conjunctivae - discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Results 15

Irritation parameter:

other: Conjunctivae - discharge

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Instillation of L-TEE provoked a moderate initial sting reaction from all animals.
Slight reddening and swelling of the conjunctivae were noted in the first four hours following instillation, together with production of small amounts of discharge from the treated eyes. The reactions had largely resolved by Day 2 although some swelling
remained evident through day 2 and 3. By day 4 both eyes were overtly normal.

The eyes of all rabbits were overtly normal by the one or 72 hour examinations.

Other effects:

No observations indicative of systemic toxicity or ill health were noted for any rabbits during the course of the study.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The eye irritation potential of L-TEE was evaluated using instillation of L-TEE into the conjunctival sac of three rabbits. The study was performed in compliance with the testing guidelines OECD (405) and EC (method B5). L-TEE caused slight changes in the conjunctivae that resolved within 72 hours. The cornea and iris of each treated eye remained overtly unaffected. Based on these data, L-TEE is not classified.

Executive summary:

The eye irritation potential of L-TEE was evaluated using instillation of L-TEE (34.3 mg: weight equivalent to 0.1 mL) into one conjunctival sac of each of three rabbits and ocular reactions were assessed for three days after treatment.

L-TEE provoked a moderate initial sting reaction from all three animals. Reactions in the sentinel eye were limited, the eye was overtly normal within one hour of dosing.

No iridial or corneal changes were evident or the other two treated eyes. Slight reddening and swelling of the conjunctivae were noted, together with production of small amounts of discharge from the treated eyes. The change resolved within 72 hours. The cornea and iris of each treated eye remained overtly unaffacted by instillation of L-TEE.

Based on these data, L-TEE is not classified.