Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 Nov - 19 Dec 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
National Institute of Environmental Research, Republic of Korea
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
(Crl:CD(SD)), SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females nulliparous and non-pregnant: not specified
- Age at study initiation: 8 weeks
- Weight at study initiation: 180.3 - 203.7 g
- Fasting period: overnight, approximately 16 h prior to dosing up to 4 h post dosing
- Housing: individually in stainless wire mesh cage, 260W×350D×210H (mm)
- Diet: Pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C), ad libitum
- Water: tap water filtered and irratiated by ultraviolet light, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5 - 24.5
- Humidity (%): 45.7 - 66.8
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.37 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Due to low expected toxicity of the test substance, 2,000 mg/kg bw was selected as the starting dose (limit test) for this study based on the information supplied by the sponsor.
Doses:
step 1 and 2: 2000 mg/kg bw
No. of animals per sex per dose:
3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for mortality, general condition and clinical signs such as tremor, convulsions, salivation, diarrhea, lethargy and vocalisation (type, severity, time of onset and recovery) at 30 min after dosing and at 1, 2, 4 and 6 h after dosing on Day 0 and once daily thereafter for 14 days (Day 1−Day 14). The body weight was recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy (Day 14)
- Necropsy of survivors performed: yes
Statistics:
Body weights and body weight gain: Calculation of group mean values and standard deviations.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths of animals at the dose of 2000 mg/kg bw throughout the study.
Clinical signs:
Mucous stool was observed in two animals of step 2 at 6 h after dosing and in all animals on Day 1 at 2000 mg/kg bw and disappeared on Day 2. This clinical sign was considered to be a test substance-related effect.
Body weight:
Normal body weight gain was observed in all animals at 2000 mg/kg bw throughout the study.
Gross pathology:
No visible findings were observed at gross pathology in any animal dosed with 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute oral toxicity study in rats an LD50 value of > 2000 mg/kg bw was found.
Executive summary:

The purpose of this study was to assess the potential toxicity test item following a single oral dose administration to female Sprague-Dawley rats. Two dose groups of three females received:

Steps 1−2: A dose of 2,000 mg/kg bw was administered and no mortality was observed (Step 1). A second dose of 2,000 mg/kg bw was administered. Again, no mortality was observed (Step 2). The study was finished at that point.

There were no deaths of animals at 2,000 mg/kg bw. Mucous stool was observed in animals on the day of dosing and Day 1 at the dose of 2,000 mg/kg bw. This change disappeared on Day 2.

No test substance-related effects were observed in body weight data or necropsy findings in any of the animals dosed with 2,000 mg/kg bw.

Based on the result of the acute oral toxicity study in Sprague-Dawley rats, the test substance was not classified according to the CLP regulation and the median lethal dose derived was: LD50 cut off ≥ 5,000 mg/kg bw.