(2S)-5-amino-2-[(aminoacetyl)amino]-5-oxopentanoic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 December 2021 - 26 January 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2022

Report date:

2022

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2S)-2-(2-aminoacetamido)-4-carbamoylbutanoic acid

EC Number:

700-144-0

Cas Number:

13115-71-4

Molecular formula:

C7H13N3O4

IUPAC Name:

(2S)-2-(2-aminoacetamido)-4-carbamoylbutanoic acid

Test material form:

solid: crystalline

Test animals

Species:

rat

Strain:

other: Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 8-10 weeks old
- Weight at study initiation: 174 to 197 g
- Fasting period before study: no
- Housing: individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized wooden fibers as bedding material equipped with water bottles.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was
provided ad libitum
- Water: Municipal tap-water was freely available to each animal via water bottles
- Method of randomisation in assigning animals to test and control groups: all animals within ± 20% of the sex mean body weights

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C (target 20-24°C)
- Humidity (%): 50-60% (target 40-70%)
- Air changes (per hr): >10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 05 January 2022 To: 26 January 2022

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Remarks:

The samples were applied after moistening with 0.5. mL water (Elix), to ensure close contact to the skin.

Details on dermal exposure:

TEST SITE
- Area of exposure: 5 x 7 cm
- % coverage: 18 cm2 for females
- Type of wrap if used: surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2178 mg/kg bw (monohydrate form; test item; CAS 172669-64-6) equivalent to
2000 mg/kg bw (anhydrous form; CAS 13115-71-4)

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter; animals were weighed individually on Days 1 (pre-dose), 8 and 15
- Necropsy of survivors performed: yes
- Irritation: skin reactions were assessed at least once daily after removal of the dressing and test
item

Results and discussion

Preliminary study:

A range finding study was performed in order to select the dose causing no mortality or significant toxicity to be used in the main study. One animal was dosed at 2000 mg/kg.

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 178 mg/kg bw

Based on:

test mat.

Remarks:

monohydrate form (CAS 172669-64-6; test item)

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks:

anhydrous form (CAS 13115-71-4)

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortality occurred.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

The body weight gain shown by two of the animals during the observation period was within the range expected for rats used in this type of study. The lack of body weight gain between Days 1 and 15 in one animal was considered not indicative of toxicity, based on the absence of any corroborative findings in these animals.

Gross pathology:

No abnormalities were found at macroscopic postmortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Based on these results, Glycyl-L-Glutamine monohydrate does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Conclusions:

The dermal LD50 value of Glycyl-L-Glutamine monohydrate (CAS 172669-64-6) in Wistar Han rats was established to exceed 2178 mg/kg body weight, equivalent to 2000 mg/kg body weight of the anhydrous form Glycyl-L-Glutamine (CAS 13115-71-4).