[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30.04.2020 - 23.06.2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(2R,2'R)-3,3'-disulfanediylbis(2-((S)-2-aminopropanamido)propanoic acid)

Cas Number:

115888-13-6

Molecular formula:

C12H22N4O6S2

IUPAC Name:

(2R,2'R)-3,3'-disulfanediylbis(2-((S)-2-aminopropanamido)propanoic acid)

Test material form:

solid

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: 8-10 weeks
- Weight at study initiation: 134 to 171 g
- Fasting period before study: overnight for a maximum of 20 hours
- Housing: group housed (up to 3 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type)
- Historical data: available
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days before the commencement of dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): 10 or greater air changes per hour with 100% fresh air (no air recirculation)
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark cycle

IN-LIFE DATES: From: 12.05.2020 To: 23.06.2020

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Trial preparations were performed to select the suitable vehicle and to establish a suitable formulation procedure. These trials were not performed as part of this study and these preparations were not used for dosing.
- Identification: Water (Elix)
- Supplier: Millipore S.A.S., Molsheim, France
- Specific gravity: 1.0

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

CORRECTION FACTOR: A factor of 1.0183 was used to correct for the purity/composition of the test item.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

300 and 2000 mg/kg bw

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: at least three times on the day of dosing and once daily thereafter
- Frequency of weighing: individually on day 1 (pre-dose), 8 and 15
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: At 300 mg/kg, hunched posture was noted for all animals between Days 1 and 5 and erected fur was observed for one animal on Day 1. At 2000 mg/kg, hunched posture and erected fur was noted for all animals between Days 1 and 3.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of N,N´-di-L-Alanyl-L-Cystine / (L-Ala-L-Cys)2 in Wistar Han rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, N,N´-di-L-Alanyl-L-Cystine / (L-Ala-L-Cys)2 does not have to be classified and has no obligatory labelling requirement for acute oral 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).