Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 December 2013 to 03 January 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted according to OECD Guideline 423 without deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, Test Data for Registration of Agricultural Chemicals, Acute oral toxicity (2-1-1), 12 Nousan No 8147, Agricultural Production Bureau, November 24, 2000.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on 20-22 November 2012 / signed on 24 April 2014)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Clear colorless liquid
- Storage Conditions: ca. 4 °C in the dark under nitrogen
Specific details on test material used for the study:
- Purity test date: 14 January 2014

Test animals

Species:
rat
Strain:
other: Crl:CD (SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd.
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: ca. 8-12 weeks
- Weight at study initiation: 223-272 g
- Fasting period before study: Animals were fasted overnight prior to and approximately four hours after dosing.
- Housing: Animals were housed in groups of three rats of the same sex in solid bottomed polycarbonate cages with a stainless steel mesh lid.
- Diet: Rat and Mouse No. 1 Maintenance Diet, ad libitum
- Water: Potable water taken from the public supply, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 40-70 %
- Animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: 05 December 2013 to 03 January 2014

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test substance was formulated at concentrations of 30 and 200 mg/mL in the vehicle. Test substance formulations were prepared on the day of dosing. Formulations were stirred before and throughout the dosing procedure.

CLASS METHOD
- Rationale for the selection of the starting dose: Dose levels for the study were chosen in compliance with the study guidelines. As no previous toxicological information was available the initial dose level was 300 mg/kg bw.
Doses:
300 and 2000 mg/kg bw
No. of animals per sex per dose:
6 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality: Cages of rats were checked at least twice daily for any mortalities.
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). All animals were observed for 14 days after dosing.
- Frequency of weighing: The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly body weight changes and group mean body weights were calculated.
- Necropsy of survivors performed: Yes; all animals were humanely killed on Day 15 by carbon dioxide asphyxiation and subjected to gross necropsy.
Statistics:
None

Results and discussion

Preliminary study:
Not applicable
Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality was observed
Mortality:
There were no deaths during the study.
Clinical signs:
- Clinical signs of reaction to treatment comprised salivation seen in one female dosed at 2000 mg/kg bw. This sign was noted immediately after dosing until 2 h post dose.
- No signs were observed for any other animals receiving 2000 mg/kg bw or in any animals receiving 300 mg/kg bw.
Body weight:
All animals were considered to have achieved satisfactory body weight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
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 test conditions, the oral LD50 for ST 11 C 13 is higher than 2000 mg/kg bw in female rats therefore it is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP, groups (6 female rats/dose) of Crl:CD (SD) albino rats were given a single oral (gavage) dose of test substance, ST 11 C 13 in corn oil at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination. Prior to this experiment, two groups of three fasted female rats received a single oral (gavage) dose of the test substance, formulated in corn oil, at a dose level of 300 mg/kg bw.

 

There were no deaths during the study. Clinical signs of reaction to treatment comprised salivation seen in one female dosed at 2000 mg/kg bw. This signs was noted immediately after dosing until 2 h post dose. No signs were observed for any other animals receiving 2000 mg/kg bw or in any animals receiving 300 mg/kg bw. All animals were considered to have achieved satisfactory body weight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.

Oral LD50 (female) > 2000 mg/kg bw

Under the test conditions, the test substance is not classified for acute oral toxicity according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

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