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Description of key information

The acute oral toxicity of N,N´-di-L-Alanyl-L-Cystine / (L-Ala-L-Cys)2 was tested in a study performed according to OECD TG 423. The oral LD50 value was established to exceed 2000 mg/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
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
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
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).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
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.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
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).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

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).

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