Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 November to 23 December 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
GLP study conducted in compliance with OECD Guideline 423 without any deviation.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

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 01-03 July 2014 / signed on 15 September 2014)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: Colorless liquid
- Storage condition of test material: Stored at 2-8 °C temperature and protected by Nitrogen.
Specific details on test material used for the study:
- Purity test date: 04 November 2014
- Date of receipt: 06 November 2014
- Storage condition of test material: Refrigerated at 4°C in the dark under nitrogen

Test animals

Species:
rat
Strain:
Wistar
Remarks:
RccHan®:WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan (UK) Ltd
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: ca. 8-12 weeks
- Weight at study initiation: 154-185 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. The cages were solid bottomed polycarbonate cages with a stainless steel mesh lid.
- Diet: Animals were allowed free access to a standard rodent diet (Harlan Teklad 2014C Diet), except for overnight prior to and approximately four hours after dosing.
- Water: Potable water taken from the public supply, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19-23 °C
- Humidity: 40-70 %
- Air changes: 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: 20 November to 23 December 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 or 200 mg/mL in the vehicle and administered at a volume of 10 mL/kg bw. The test substance formulations were prepared on the day of dosing.

CLASS METHOD
- Rationale for the selection of the starting dose: The 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). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. 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 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 were seen in one or more animals dosed at 2000 mg/kg bw comprised of piloerection, decreased activity, unsteady gait and hunched posture. These signs were first noted on Day 1. Recovery of all animals, as judged by external appearance and behaviour, was complete by Day 3.
- No clinical signs were seen in any animal dosed at 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:
Oral LD50 (females) >2000 mg/kg bw
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP, 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. As results at this dose level indicated the acute (median) lethal oral dose of the test substance to be greater than 300 mg/kg bw, in compliance with the study guidelines a further two groups of three fasted females were similarly dosed at 2000 mg/kg bw to complete the study. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

 

There were no deaths during the study. Clinical signs of reaction to treatment were seen in one or more animals dosed at 2000 mg/kg bw comprised of piloerection, decreased activity, unsteady gait and hunched posture. These signs were first noted on Day 1. Recovery of all animals, as judged by external appearance and behaviour, was complete by Day 3. No clinical signs were seen in any animal dosed at 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 (females) >2000 mg/kg bw

 

Under the experimental conditions of this study, the acute median lethal oral dose (LD50) was demonstrated to be greater than 2000 mg/kg bw. Thus the test item is not classified according to Regulation (EC) No. 1272/2008 (CLP) and to GHS.

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