L-Glutamine, L-alanyl-

Endpoint summary

Description of key information

Oral (OECD 401): LD50 (rat, m/f) > 5110 mg/kg bw

Dermal (OECD 402): LD50 (rabbit, m/f) > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-01-23 to 1990-02-06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Bor: WISW (SPFCpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co.KG, Borchen, Germany
- Age at study initiation: 9 weeks (males); 10 weeks (females)
- Weight at study initiation: 155 - 202 g (males); 144 - 158 g (females)
- Fasting period before study: 16 h before treatment
- Housing: individually in Macrolon cages, type II
- Diet: standard diet, ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 40 - 60 (for short periods down to 25%)
- Photoperiod: 6 a.m. - 6 p.m. artificial lighting; 6 p.m. - 6 a.m. natural light-dark-rhythm

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 237 mg/mL
- Amount of vehicle: 21.5 mL/kg bw
- Lot/batch no.: E0844357

Doses:

5110 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: continously observed for the first 4 - 6 h after administration; mortality: twice daily; weighing: on Day 1 prior to treatment and also 7 and 14 days after administration; clinical signs: continously for 4 - 6 h after treatment and once daily thereafter
- Necropsy of survivors performed: yes

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 110 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No alterations were found.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study no acute toxic effect occurred after oral administration of 5110 mg/kg bw test substance. LD50 > 5110 mg/kg bw.
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Sprague–Dawley CD (Crl:CD(SD) IGS BR)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Margate, Kent, UK
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 200 - 227 g
- Fasting period before study: withdrawal of food the night before dosing
- Housing: in groups of 3 in solid-floor polypropylene cages containing wood flakes and bedding material
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females + 3 females for confirmation

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical signs: 0.5, 1, 2, and 4 h post-dosing, thereafter, once daily; body weights: prior to dosing and at 7 and 14 days post-dosing
- Necropsy of survivors performed: yes

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the 14-day observation period.

Clinical signs:

other: No clinical signs of toxicity were observed.

Gross pathology:

Necroscopy did not reveal any abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of the test substance was > 2000 mg/kg bw.
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 1) study with the registered substance. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, Item 8.5, of Regulation (EC) No. 1907/2006 (REACH).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-03-27 to 1990-04-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: White Russian

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Asta Pharma AG, Bielefeld, Germany
- Age at study initiation: 11 months (males); 10 - 11 months (females)
- Weight at study initiation: 2.24 - 2.77 kg (males); 2.41 - 2.84 kg (females)
- Fasting period before study: 16 h prior to treatment
- Housing: individually in stainless steel cages with grating floor
- Diet: standard diet approx. 120 g/day/animal
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 23
- Humidity (%): 35 - 65
- Photoperiod: 6 a.m. - 6 p.m. artificial lighting; 6 p.m. - 6 a.m. natural light-dark-rhythm

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: shorn skin between shoulder and sacral region

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 h

TEST MATERIAL
- For solids, paste formed: test substance was moistened with the vehicle (1mL/g test substance)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: continuously observed for clinical signs for the first 4 to 6 h after application and then daily; mortality was checked twice daily; body weights were recorded on Day 1 prior to administration, 7 and 14 days after application
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No alterations were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study no acute toxic effect occurred after dermal application of 2000 mg/kg bw test substance. LD50 > 2000 mg/kg bw.
CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable (Klimisch score 1) study with the registered substance. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.5, of Regulation (EC) No. 1907/2006 (REACH).

Additional information

Acute oral toxicity

The acute oral toxicity of the registered substance was assessed in a limit test performed according to OECD guideline 401 under GLP conditions (90-0003-DNT). Groups of 5 male and 5 female Bor: WISW (SPFCpb) rats received a single dose of 5110 mg/kg bw of the test substance via gavage. The post-administration observation period was 14 days. No mortality occurred and no signs of systemic toxicity were observed. Body weights increased throughout the study period and no alterations were found at necropsy. The oral acute LD50 of the test substance was, therefore, established to be > 5110 mg/kg bw.

In a publication Oda et al. (2008) assessed the acute oral toxicity of the registered substance according to the Acute Toxic Class method described in OECD guideline 423 and observing GLP provisions (Oda_et_al_2008). A dose of 2000 mg/kg bw of the test substance was administered to two groups of 3 female Sprague-Dawley rats each via gavage and the animals were observed for a period of 14 days. All animals survived the test and there were no signs of systemic toxicity. No effect on body weight was observed during the study period. No abnormalities were noted during necropsy. Based on these findings, the authors concluded that the LD50 for acute oral toxicity is > 2000 mg/kg bw.

Acute dermal toxicity

There is a study investigating the acute dermal toxicity of the registered substance in rabbits (White Russian). The study was conducted according to OECD guideline 402 and under GLP conditions (90-0002-DNT). 5 animals/sex were exposed to the test substance for 24 h under occlusive conditions, and the animals were observed for 14 days following the exposure. No deaths occurred and no clinical signs of toxicity were observed. Exposure to the test substance did not impact the body weight development of the animals. No treatment-related alterations were found at necropsy. The acute dermal LD50 was determined in this study to be > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity 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 acute oral and dermal toxicity is warranted according to the criteria of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.