Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 27 July 2012 to 14 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 423 and in compliance with GLP.

Data source

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

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.
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on 2011-08-23/signed on 2011-12-12)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Physical state: colourless liquid
- Storage condition of test material: At ambient temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS: Crl:CD'SD' rats
- Source: Charles River (UK) Ltd.
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 188 to 219 g
- Fasting period before study: overnight prior to and approximately four hours after dosing.
- Housing: in groups of three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid
- Diet (e.g. ad libitum): standard rodent diet (Rat and Mouse No. 1 Maintenance Diet) ad libitum. Not contaminated.
- Water (e.g. ad libitum): Potable water taken from the public supply ad libitum. Not contaminated.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr): not reported (filtered fresh air)
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2012-08-02 To: 2012-08-28

Administration / exposure

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

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: LD50 > 5000 mg/kg bw on an analogue substance having the same constituents than the registered substance but at different ratios.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3+3 (females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: at least twice daily.
Clinical observation: 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).
Bodyweight: recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: yes, all animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Statistics:
Not required

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: from the flow chart from OECD Guideline 423 (Appendix 2d)
Mortality:
There were no deaths during the study.
Clinical signs:
Clinical signs of reaction to treatment comprised loose faeces seen in five females, urine staining in the perigenital region in three females and post salivation staining, hunched posture, fast breathing, piloerection and distended abdomen observed in individual females dosed at 2000 mg/kg bw. These signs were seen from approximately one hour after dosing. Recovery of animals, as judged by external appearance and behaviour, was complete by Day 3.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
Macroscopic examination at study termination on Day 15 revealed enlarged, swollen or thickened kidneys, pallor of the kidneys and clear fluid in the kidneys in one female. These findings are considered unlikely to be test substance related. No abnormalities were revealed in any of the other five animals at the macroscopic examination at this time.
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 Female rat > 5000 mg/kg bw. Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).
Executive summary:

In an acute oral toxicity study performed according to the OECD test guideline No. 423 and in compliance with GLP, a group of three fasted female Sprague-Dawley rats received a single oral gavage dose of the test material, formulated in corn oil, at a dose level of 2000 mg/kg bodyweight. As results at this dose level indicated the acute lethal oral dose of the test substance to be greater than 2000 mg/kg bodyweight, in compliance with the study guidelines, a further group of three fasted females was similarly dosed at 2000 mg/kg bodyweight to complete the study.

Clinical signs of reaction to treatment comprised loose faeces seen in five females, urine staining in the perigenital region in three females and post salivation staining, hunched posture, fast breathing, piloerection and distended abdomen observed in individual females dosed at 2000 mg/kg. These signs were seen from approximately one hour after dosing. Recovery of animals, as judged by external appearance and behaviour, was complete by Day 3.

All animals were considered to have achieved satisfactory bodyweight gains throughout the study.

Macroscopic examination at study termination on Day 15 revealed enlarged, swollen or thickened kidneys, pallor of the kidneys and clear fluid in the kidneys in one female. These findings are considered unlikely to be test substance related. No abnormalities were revealed in any of the other five animals at the macroscopic examination at this time.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat can be estimated from the flow chart from OECD Guideline 423 (Appendix 2d) as being greater than 5000 mg/kg bodyweight.

Under the test conditions, the test material is not classified according to the annex VI of the Regulation EC No. 1272/2008 (CLP).

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