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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study performed between7 August 2012 and 6 September 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
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 (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Test material form:
other: Solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd.
- Age at study initiation: Eight to twelve weeks of age
- Weight at study initiation: 152 - 160g. The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group.
- Fasting period before study: Overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Food (2014C Teklad Global Rodent diet) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water was allowed throughout the study.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Set to achieve limits of 19 to 25°C
- Humidity (%): Set to achieve limits of 30 to 70%
- Air changes (per hr): At least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 42 mg/ml and 279.8 mg/ml

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusual):
To achieve the fixed starting doses (300 mg/kg and 2000 mg/kg) formulated concentrations were adjusted to allow for the stated solvent content (28.5% propane-1,2-diol) of the test item. However for reporting purposes the concentrations are given as test item as a whole. The test item was freshly prepared, as required, as a solution at the appropriate concentration in arachis oil BP.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
In the absence of data regarding the toxicity of the test item, 420 mg/kg bodyweight) was chosen as the starting dose.

PROCEDURE
All animals were dosed once by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential.

Doses:
420 and 2798 mg/kg
No. of animals per sex per dose:
1 for 420 mg/kg and 6 for 2798 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.
- Necropsy of survivors performed: yes; At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 798 mg/kg bw
Based on:
test mat.
Mortality:
Individual mortality data are given in attachment.
There were no deaths.
Clinical signs:
Individual clinical observations are given in attachment.
Hunched posture was noted in two animals at a dose level of 2,798 mg/kg. Noisy respiration/lethargy, ataxia and fasciculations were also noted in these two animals. NO other signs of systemic toxicity were noted.
Body weight:
Individuals bodyweights and weekly bodyweight changes are given in the attachment.
All animals showed expected gains in body weight over the study period.
Gross pathology:
Individual necropsy findings are given in the attachment.
No abnormalities were noted at necropsy

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2798 mg/kg bodyweight (Globally Harmonised Classification System – Unclassified).
Executive summary:

Introduction.

The study was performed to assess the acute oral toxicity of the test item following a single oral administration in the Wistar strain rat. The method was designed to be compatible with the following:

- OECD Guidelines for the Testing of Chemicals No. 423 “Acute Oral Toxicity – Acute Toxic Class Method” (adopted 17 December 2001)

- Method B1 tris Acute Toxicity (Oral) of Commission Regulation (EC) No. 440/2008

Method.

A group of one fasted femaleswas treated with the test item at a dose level of 420 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at a dose level of 2798 mg/kg bodyweight. Dosing was performed sequentially.

The test item was administered orally as a solution in Arachis Oil. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality.

There were no deaths.

Clinical Observations.

Hunchd posture was noted in two animals treated at a dose level of 2,798 mg/kg. Noisy respiration, lethargh, ataxia and fasciculations were also noted in these two animals. No other signs of systemic toxicity were noted.

Bodyweight.

Animals showed expected gains in bodyweight over the study period.

Necropsy.

No abnormalities were noted at necropsy.

Conclusion.

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2798 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).

The test item did not meet the criteria for classification according to the Classification, Labelling and Packaging Regulation (CLP).