L-Glutamine, L-alanyl-

Endpoint summary

Description of key information

Skin irritation (in vivo, OECD 404): not irritating

Eye irritation (in vivo, OECD 405): not irritating

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:

1990-04-02 to 1990-04-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981

Deviations:

yes

Remarks:

occlusive dressing

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

Deviations:

yes

Remarks:

occlusive dressing

GLP compliance:

yes

Species:

rabbit

Strain:

other: White Russian

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG, Bielefeld, Germany
- Age at study initiation: 9 - 10 months
- Weight at study initiation: 2.30 - 2.54 kg
- Housing: individually in stainless steel cages with grating floor
- Diet: standard Diet ssniff K ("special diet for rabbits") approx. 120 g/day/animal
- Water: drinking water, ad libitum
- Acclimation period: 1 day under test conditions before application of the product

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 24.4
- Humidity (%): 30 - 50
- Photoperiod: 6 a.m. - 6 p.m. artificial lighting; 6 p.m. - 6 a.m. natural light-dark-rhythm

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g moistened with 1.6 mL demineralized water

VEHICLE
- Amount(s) applied: 1.6 mL

Duration of treatment / exposure:

4 hours

Observation period:

Reading time points: 1, 24, 48 and 72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: applied on the shorn dorsal skin area between shoulder and sacrum (approx. 6.25 cm²)

REMOVAL OF TEST SUBSTANCE
- Washing: yes, after the end of the exposure time remaining test material was gently washed off
- Time after start of exposure: 4 h

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

None of the three rabbits exposed for 4 h to 500 mg test substance/patch and animal (occlusive condition) showed any substance-related changes at the reading time points 60 min, 24, 48 and 72 h.

Other effects:

No systemic effects occurred after dermal appliation of the test substance. The general condition of the test animals was not affected.

Interpretation of results:

GHS criteria not met

Conclusions:

No skin reactions occurred in any animal at any observation point; erythema score and edema score: each 0 (mean of all animals, 24/48/72 h).
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

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:

1990-04-03 to 1990-04-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: White Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG, Bielefeld, Germany
- Age at study initiation: 9 months (males and females)
- Weight at study initiation: 2.63 kg and 2.89 kg (males); 2.9 kg (females)
- Housing: individually in stainless steel cages with grating
- Diet: standard diet ssniff K ("special diet for rabbits") approx. 120 g/day/animal
- Water: drinking water, ad libitum
- Acclimation period: one day under test conditions before start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 24.5
- Humidity (%): 30 - 50
- Photoperiod: 6 a.m. - 6 p.m. artificial lighting; 6 p.m. - 6 a.m. natural light-dark-rhythm

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.023 gram (representing a volume of about 0.1 mL)

Duration of treatment / exposure:

the treated eye was not rinsed

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3

Details on study design:

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

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Cornea and iris were without any findings in any animal during the 3-day observation period. The conjunctiva exhibited hyperemia (grade 1) 1 h after application in 2/3 rabbits. This finding is not relevant for classification and labelling. The effect was fully reversible within 24 h post-application.

Other effects:

There were no systemic toxic effects after conjunctival application of the test substance. The general condition of all animals was unaffected.

Interpretation of results:

GHS criteria not met

Conclusions:

The conjunctivae of 2/3 animals were hyperemic 1 h after exposure (not relevant for the hazard assessment and classification and labelling). No effects on cornea, iris and cunjuntivae occurred in any animal at any observation point relevant for classification and labelling; cornea opacity score, iris score, conjunctivae score, and chemosis score: each 0 (mean of all animals, 24/48/72 h).
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The potential to induce skin irritation or corrosion of the registered substance has been tested in a study performed according to OECD guideline 404 and under GLP conditions (90-0004-DNT). 0.5 g of the test substance moistened with 1.6 mL demineralized water was applied to the shorn dorsal skin area between the shoulder and the sacrum of 3 White Russian rabbits, respectively. The skin was exposed for 4 h under occlusive conditions. The opposite area of the dorsal skin was treated in the same manner but without test substance and served as the control site. Local skin reactions (erythema and edema) were evaluated according to the Draize scoring system, 1, 24, 48 and 72 h post-application.

There were no local skin reactions at any reading time point in any of the animals. The mean score over 24/48/72 h was 0 for all animals, for erythema and oedema. There were no systemic effects and the general condition of the animals was unaffected. Based on the results of the present study and under the experimental conditions mentioned, the test substance is considered to be not irritating to the skin.

Eye irritation

The eye irritating potential of the test substance was evaluated in a study performed according to OECD guideline 405 and in compliance with GLP (90-0005-DNT). A single dose of 0.023 g (corresponding to 0.1 mL) was instilled into the conjunctival sack of the right eye (no wash out) of 3 White Russian rabbits, respectively. The other eye remained untreated and served as control. Local irritation of the eyes was evaluated according to Draize criteria 1, 24, 48 and 72 h post-administration.

During the 3-day observation period, no irritation effects were observed on the cornea and iris were in any animal. One hour after test substance instillation, 2/3 rabbits showed hyperemia of the conjunctiva (grade 1). The effect was fully reversible within 24 h post-application. The mean score over 24/48/72 h was 0 for all animals, for all measured parameters (cornea opacity, iris, conjunctivae and chemosis).  There were no signs of systemic toxicity. Under the experimental conditions of the study, the test item had no eye irritating properties.

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.

No classification for skin or eye irritation / corrosion is warranted according to the criteria of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.