Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-08-30 - 2016-10-04
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 guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Certificate issued by the "Department of Health of the Government of the United Kingdom on 2016-10-28.
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 180 to 193g
- Fasting period before study: overnight fast immediately before dosing and for approximately 3-4 hours after dosing.
- Housing: Animals were housed in groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes. Environmental Enrichment Items whoch were considered not to contain any contaminant of a level that might have affected the purpose or integrety of the study are provided.
- Diet: ad libitum (2014C Teklad Global Rodent diet)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15 changes / hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential leaving sufficient time to confirm the survival of the previously dosed animals.
Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily at working days and once daily at weekends and public holidays.
Body Weight was recorded on day 0, day 7 and on day 14.
All animals were subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Using mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:
Not reported. Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study period.
Clinical signs:
No signs of systematic toxicity were noted during the observation period.
Body weight:
All animals gaines body weight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: EU GHS (CLP) criteria not met
Conclusions:
An acute oral median LD50 of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.
Executive summary:

A study on acute oral toxicity in the rat has been conducted with the test item according to OECD Guideline 420 and in compliance with GLP criteria. Five female rats (nulliparous and non-pregnant) of the Wistar strain with an initial body weight of 180 to 193g were used as test animals. The rats were deprived of food during the night immediately before dosing and for approximately 3-4 hours after dosing. The test item was injected into each animal by a gavage whereby the dose was 2000 mg / kg body weight. No rats were used as a control group. The observation period was 14 days and ended with the euthanization of the rats on day 14. Clinical observations were made 30 minutes, 1, 2 and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily at working days and once daily at weekends and public holidays. There were no deaths during the study period and no signs of systematic toxicity were noted during the observation period. Body weight was recorded on day 0, day 7 and on day 14: all animals gained body weight during the study period. The mean body weight of the 5 test animals was 185.6 g at day 1 and increased to 224 g at day 14. Each animal was subject to gross necropsy which consisted of an external examination and opening of the abdominal and thoracic cavities. No abnormalities were noted at necropsy.

An acute oral median LD50 of the test item in the female Wistar strain rat was found to be greater than 2000 mg/kg body weight.