Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 December 2012 to 02 August 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Fully GLP compliant and in accordance with current test guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Acetic acid 2-oxo-2H-pyridin-1-yl ester
EC Number:
689-986-7
Cas Number:
1742-79-6
Molecular formula:
C7H7NO3
IUPAC Name:
Acetic acid 2-oxo-2H-pyridin-1-yl ester
Constituent 2
Reference substance name:
1742-78-6
IUPAC Name:
1742-78-6
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Name: Oxypyrionacetate
CAS number: 1742-78-6
Batch number: 11085913
Quantity supplied: 52 g
Purity: 100%
Date of receipt: 20 November 2012
Storage details: stored in a refrigerator at 2 to 8ºC, in a sealed container in the dark.

Test animals

Species:
rat
Strain:
other: HsdHan:WIST
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd., Bicester
- Age at study initiation: 8 to 10 weeks
- Weight at study initiation: The weight variation did not exceed ±20% of the mean weight.
- Fasting period before study: the evening of the day prior to dosing (Day -1) until approximately 3 hours after dosing
- Housing: The animals were housed in groups of up to five during the acclimatisation period and from Day -1 in groups of three in cages that conform to the ‘Code of Practice for the Housing and Care of Animals Used in Scientific Procedures’ (Home Office, London, 1989).
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No 1, Expanded (Special Diets Services Ltd, Witham, UK) was freely available
- Water (e.g. ad libitum): Mains water was provided, ad libitum, via cage-mounted water bottles.
- Acclimation period: 8 to 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 45 to 65%, on four occasions the relative humidity was just below the range specified in the protocol, with recordings of 39% and 42%. On one occasion the relative humidity was just above the range specified in the protocol, at 68%.
- Air changes (per hr): 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily

IN-LIFE DATES: From: 7 January 2013 To: 5 February 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 and 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Not reported
- Lot/batch no. (if required): Not applicable
- Purity: 100%

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: were no data to indicate that deaths may occur at dose levels of less than 2000 mg/kg
Doses:
Dose level: 2000 mg/kg, Concentration: 200 mg/mL, Dose volume: 10 mL/kg
Dose level: 300 mg/kg, Concentration: 30 mg/mL, Dose volume: 10 mL/kg
Dose level: 300 mg/kg, Concentration: 30 mg/mL, Dose volume: 10 mL/kg
No. of animals per sex per dose:
3 animals per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs were recorded immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. In a deviation from protocol, Group 3 animals were only observed once on Day 4. This deviation was considered not to have affected the integrity or outcome of the study as these animals had no clinical signs at this time.
All animals were examined at the beginning and end of the working day throughout the study to ensure they were in good health.
Rats were weighed on Day -1 (day before dosing) and on Days 1, 4, 8 and 15. Decedent carcass weights were also recorded prior to necropsy.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 500 mg/kg bw
Based on:
test mat.
Mortality:
All animals dosed at 2000 mg/kg died. Two animals were found dead 0.5 hours after dosing, and the remaining animal was found dead 5 hours after dosing.
No deaths were noted at a dose level of 300 mg/kg.
Clinical signs:
Clinical signs noted in animals dosed at 2000 mg/kg were tremors, twitching, clonic convulsions, gasping, piloerection, hunched posture, ptosis, decreased activity and prone posture.
Piloerection was noted in three animals treated with 300 mg/kg at two hours after dosing. No other clinical signs were noted at this dose level.
Body weight:
All surviving rats achieved body weight gains during the first and second weeks of the study.
Other findings:
No abnormalities were noted at necropsy of animals that died during the study.
A small heart and a thickened, abnormally shaped liver were noted in one animal dosed at 300 mg/kg that was killed at the end of the study. No other abnormalities were noted at necropsy of these animals.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute median lethal oral dose level of the test article, Oxypyrion-Acetate, was found to be between 300 and 500 mg/kg.
The test material was classified as Category 4 in respect of its acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).
Executive summary:

This study was conducted to asses the acute toxicity of the test article, Oxypyrion‑Acetate, following a single oral administration to small groups of rats. The study design provides information for hazard assessment and classification and enables a chemical to be assigned to toxicity classes but severely restricts animal usage.

Groups of three female fasted rats were given the test article as a single dose on Day 1 by oral gavage at dose levels of 2000 mg/kg and 300 mg/kg. The test article was dispersed in purified water and administered at a dose volume of 10 mL/kg. Surviving animals were killed on Day 15. All animals underwent a full necropsy.

Two animals dosed at 2000 mg/kg were found dead 0.5 hour after dosing and the remaining animal was found dead 5 hours after dosing. No deaths were noted at a dose level of 300 mg/kg.

Clinical signs noted in animals dosed at 2000 mg/kg were tremors, twitching, clonic convulsions, gasping, piloerection, hunched posture, ptosis, decreased activity and prone posture. Piloerection was noted in three animals treated with 300 mg/kg at two hours after dosing. No other clinical signs were noted at this dose level.

All surviving rats achieved body weight gains during the first and second weeks of the study.

No abnormalities were noted at necropsy of animals that died during the study.

A small heart and a thickened, abnormally shaped liver were noted in one animal dosed at 300 mg/kg that was killed at the end of the study. No other abnormalities were noted at necropsy of these animals.

The acute median lethal oral dose level of the test article, Oxypyrion-Acetate, was found to be between 300 and 500 mg/kg.

The test material was classified as Category 4 in respect of its acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).