Ethyl L-threoninate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 10, 2000 - April 28, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Minor deviations in humidity were observed during the study period but these deviations did not affect the integrity of the study.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

EC method B4

Deviations:

yes

Remarks:

humidity

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

humidity

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

yes

Remarks:

humidity

Principles of method if other than guideline:

NA

GLP compliance:

yes (incl. QA statement)

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

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl:NZW/Kbl.BR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd, Margate
- Age at study initiation: 11 to 13 weeks old
- Weight at study initiation: 2.03 to 2,37 kg
- Housing: floor-pens, single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 to 22 °C
- Humidity (%): 40 to 80% RH (on the first eleven days of the study, humidity fell below 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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

moistening with approx. 0.1 mL of water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500mg

VEHICLE
- Amount(s) applied (volume or weight with unit): moistening with approx. 0.1 mL of water

Duration of treatment / exposure:

4 h

Observation period:

3 days

Number of animals:

3 animals (1 male, 2 females)

Details on study design:

TEST SITE
- Area of exposure: 30 x 20 mm
- % coverage: No data
- Type of wrap if used: semi-occlusive gauze patch and an open weave, elasticated adhesive bandage wrapped firmly around the torso

REMOVAL OF TEST SUBSTANCE
- Washing (if done): lightly brushed clean of any solid residues and swabbed with moist cotton wool
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Erythema and eschar (Grade):
- No erythema (0)
- Very slight erythema (1)
- Well-defined erythema (2)
- Moderate erythema (3)
- Severe erythema (beet redness) or eschar preventing reading of erythema (4)

Oedema (Grade):
- No oedema (0)
- Very slight oedema (barely perceptible) (1)
- Slight oedema (edges of area well-defined by definite raising) (2)
- Moderate oedema (edges raised approximately 1 mm) (3)
- Severe oedema (raised >1 mm and extending beyond area of exposure) (4)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

No dermal response to treatment or signs of toxicity or ill health were observed in any animal throughout the observation period

Other effects:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

The skin irritation/corrosion of L-TEE was evaluated using a single semi-occluded application to intact rabbit skin for four hours. The study was perforned in compliance with the testing guidelines OECD (404) and EC (method B4). L-TEE did not elicit any dermal reactions. Based on these data, L-TEE is not classified.

Executive summary:

This study was conducted to determine the irritation or corrosion caused to intact rabbit skin. L-TEE (500 mg) was applied to a 30 x 20 mm area on the clipped dorsum of each of three New Zealand White rabbits on Day 1. The treated area of skin was covered by a semi-occlusive bandage for four hours. Dermal reactions to treatment were assessed for three days after removal of the dressings.

No reactions were observed following a single semi-occluded, topical application of L-TEE to the intact skin of three rabbits for four hours.

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

humidity, and analgesic treatment ommitted

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

humidity, and analgesic treatment ommitted

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)

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

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.

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

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1

Reversibility:

fully reversible within: 72 h

Irritation parameter:

other: Conjunctivae - discharge

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

other: Conjunctivae - discharge

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

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.

None

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The skin irritation/corrosion of L-TEE was evaluated using a single semi-occluded application to intact rabbit skin for four hours. The study was perforned in compliance with the testing guidelines OECD (404) and EC (method B4). L-TEE did not elicit any dermal reactions.

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.

Justification for selection of skin irritation / corrosion endpoint:
This is a key study.

Justification for selection of eye irritation endpoint:
This is a key study.

Justification for classification or non-classification

L-TEE was found to be non-corrosive and non-irritating to skin and eye in tests performed on rabbits. Based on these results, L-TEE is not hazardous and is not classified according to CLP or DSD.