Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP. All relevant validity criteria were met.
Justification for type of information:
Information as to the availability of the in vivo study is provided in 'attached justification'.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

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:
inspected: June 2015; signature: September 2015
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Liquid
- Storage condition of test material: Approximately 4 °C, in the dark
- Other: clear colourless

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: 8 - 12 weeks.
- Weight at study initiation: 166 g (300 mg/kg bw sighting test; sentinel); 171 - 181 g (2000 mg/kg bw sighting test and main study); The weight variation did not exceed ±20% of the mean weight at the start of treatment.
- Fasting period before study: Overnight before dosing and three to four hours after dosing.
- Housing: Group housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Certified diet from recognised supplier, provided ad libitum (except for fasting period).
- Water (e.g. ad libitum): ad libitum (except for fasting period)
- Acclimation period: At least 5 days.

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

IN-LIFE DATES: From: To: 2015-12-16 to 2016-01-06

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
For the purpose of the 2000 mg/kg dose level the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. For the purpose of the 300 mg/kg dose level the test item was freshly prepared, as required, as a solution in arachis oil BP. Arachis oil BP was used because the test item did not dissolve/suspend in distilled water. The test item was formulated within 2 hours of being applied to the test system. In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg bw in Arachis oil BP vehicle (starting dose and initial sighting test); 2000 mg/kg bw (initial sighting test and main study)
No. of animals per sex per dose:
1 (sighting study) and 4 (main study); total 5 per dose according to sequential guideline testing strategy.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
300 mg/kg bw (sighting test): No mortality
2000 mg/kg bw (definitive test): No mortality.
Clinical signs:
300 mg/kg bw (sighting test): No signs of systemic toxicity were noted.
2000 mg/kg bw (definitive test): No signs of systemic toxicity were noted.
Body weight:
300 mg/kg bw (sighting test): Expected bodyweight gains were seen over the study period.
2000 mg/kg bw (definitive test): All animals showed expected bodyweight gains over the study period.
Gross pathology:
300 mg/kg bw (sighting test): No abnormalities were noted at necropsy.
2000 mg/kg bw (definitive test): No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in female Wistar rats. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.
Executive summary:

The study was performed according to OECD TG 420 and EU Method B.1 bis Acute Toxicity (Oral) and in accordance with GLP to assess the acute oral toxicity of the test material following a single oral administration in the female Wistar strain rat by the fixed dose method. The test substance was administered by oral gavage in an initial sighting study at 300 mg/kg. In the absence of significant toxicity the test substance was then administered by oral gavage in a further initial sighting at 2000 mg/kg. Subsequently a further group of four fasted females was given a single oral dose of test item, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study and gross necropsy performed. There was no mortality during the course of the study. No signs of systemic toxicity were noted in the remaining animals. Animals showed expected gains in bodyweight over the study period and there were no abnormalities noted at necropsy. Under the conditions of this study the oral LD50 was established to exceed 2000 mg/kg bw in the female Wistar rat. Under the conditions of this study, and according to the OECD TG 420 criteria, the LD50 cut-off value was considered to be greater than 5000 mg/kg body weight.