Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 16 October 2012 to 15 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 420 and in compliance with GLP.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2013

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
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Monitoring Programme (inspection date: 10 July 2012/ signed on 30 November 2012)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
Description: clear colourless liquid
Specific details on test material used for the study:
Storage conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS (RccHanTM:WISTAR)
- Source: Harlan Laboratories UK Ltd, Oxon UK.
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 154-170 g
- Fasting period before study: overnight. Food will be returned approximately 3 to 4 hours after dosing.
- Housing: grouped in group of up to four in suspended solid-floor polypropylene cages furnished with wood flakes.
- Diet (e.g. ad libitum): Rodent 2014C Teklad Global Certified Diet ad libitum. Not contaminated.
- Water (e.g. ad libitum): Tap water ad libitum. Not contaminated.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): at least 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: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Sighting test: 1 female
Main test: 4 additional females
Control animals:
no
Details on study design:
SIGHTING TEST
- a single animal, 2000 mg/kg bw

MAIN TEST
- 5 animals per dose level (made up of one animal from the sighting test dosed at the selected dose level together with an additional 4 animals)
- Duration of observation period following administration: 14 days
- Frequency of mortality / morbidity inspection: twice daily, early and late, during normal working days, once daily at weekends and public holidays.
- Frequency of clinical observations: 30 min, 1, 2 and 4 hours after dosing, then at least once daily.
- Weighing: recorded on Day 0 (prior to dosing), Day 7 and 14, or at death.
- Necropsy of survivors performed: yes, gross necropsy on all animals
Statistics:
None

Results and discussion

Preliminary study:
In the absence of mortality at a dose level of 2000 mg/kg bw, an additional group of animals was treated at the same dose level.
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.
Clinical signs:
There were no signs of systemic toxicity noted in the initial treated animal. Hunched posture and ataxia were noted up to one day after dosing in the four additional treated animals.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS since the Rat Oral LD50 (females) > 2000 mg/kg bw and no
mortality or any adverse effects were observed.
Executive summary:

In an acute oral toxicity study performed according to the OECD test guideline No. 420 and in compliance with GLP, groups of fasted, eight to twelve weeks of age Wistar (RccHanTM:WIST) female rats were given a single oral dose of ST 15 C 12.

Following a sighting test using one animal at a dose level of 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of test item, at the same dose level. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Oral LD50 Females > 2000 mg/kg bw

There were no deaths during the study. Hunched posture and ataxia were noted in four animals. There were no signs of systemic toxicity noted in the initial treated animal

All animals showed expected gains in bodyweight. No abnormalities were noted at necropsy.

Under the experimental conditions of this study, the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS since the Rat Oral LD50 (females) > 2000 mg/kg bw and no mortality or any adverse effects were observed.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.