Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18.10.2016 - 13.01.2017
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)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8-9 weeks
- Weight at study initiation: 178.8−227.9 g
- Housing: Stainless wire mesh cage, 260W×350D×210H (mm), 1 animal / cage
- Diet: ad libitum, pelleted rodent chow (Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C)
- Water: ad libitum, public tap water in Cheongju-si was filtered and irradiated by ultraviolet light
- Acclimation period: 7 days (quarantined for 4 days and acclimated for 3 days)
- Fasting period before study: 16 hours

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.7−22.9
- Humidity (%): 48.4−58.8
- Air changes (per hr): 10−15 clean, fresh, filtered air
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle (7 AM−7 PM via automated timer), 150−300 Lux

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
- The required amount of the test substance was weighed by an electronic balance and the vehicle, corn oil, was added and mixed gradually to yield the desired concentrations (60 and 400 mg/mL).
- All preparations were conducted just prior to use.
- Stability and concentration analyses of dosing formulations were not performed.
- Individual doses were calculated based on the animals’ body weight recorded prior to dosing at a dose volume of 5 mL/kg body weight. Animals were dosed via gastric intubation with a 1- or 3-mL syringe fitted with an intubation tube.
Doses:
300 and 2000
No. of animals per sex per dose:
6
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 0, 1, 3, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and histopathology
Statistics:
Statistical analysis was not performed. Mean scores and values were determined.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animals died during the course of the study.
Clinical signs:
Mucous stool was observed in 3 animals at 300 mg/kg and 2 animals at 2,000 mg/kg on Day 1, however, this disappeared on Day 2. It was considered to be a test substance-related temporary change.
Body weight:
Normal body weight gain was observed in all animals throughout the study.
A tendency for suppression of body weight gain was observed in 1 animal at 2,000 mg/kg on Day 1. However, the body weight gain normalized in this animal on Day 3. This change was considered to be a test substance-related effect.
Gross pathology:
No gross visible findings were observed in any animal at 300 and 2,000 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The median lethal dose was LD50 ≥ 2,000 mg/kg b.w. Based on the result the test substance does not need to be classified.
Executive summary:

In this study the potential toxicity of the test item was assessed following a single oral dose administration to female Sprague-Dawley rats. The test was carried out according to OECD 423 and GLP.

Four dose groups of three females were used as follows: Groups 1 and 2 (Steps 1 and 2): 300 mg/kg of the test substance and groups 3 and 4 (Steps 3 and 4): 2,000 mg/kg of the test substance. In steps 1 a dose of 300 mg/kg was administered. No mortality was observed, whereafter a second dose of 300 mg/kg was administered (Step 2).

In steps 3 and 4 a dose of 2,000 mg/kg was administered as no mortality was observed in the first 2 steps. In step 3 no animals died and therefore a fourth dose of 2,000 mg/kg was administered (Step 4).

All animals were monitored for clinical signs and body weight changes during the 14-day observation period after administration and subjected to gross necropsy at the end of the observation period.

There were no deaths at any dose and no gross pathologic findings were observed in any animal at 300 and 2,000 mg/kg.

Mucous stool was observed in 3 animals at 300 mg/kg and 2 animals at 2,000 mg/kg on Day 1, however, this disappeared on Day 2.

Normal body weight gain was observed in all animals throughout the study. A tendency for suppression of body weight gain was observed in 1 animal at 2,000 mg/kg on Day 1. However, the body weight gain normalized in this animal on Day 3. This change was considered to be a test substance-related effect.

The median lethal dose was LD50 ≥ 2,000 mg/kg b.w. Based on the result of the current acute oral toxicity study, the test substance does not need to be classified according to CLP regulation.