Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From July to October 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD, EPA, etc)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): XP-7866
- Substance type: Solid
- Physical state: white powder
- Analytical purity: 99.5 wt% obtained by H1-NMR
- Purity test date: 99.5 wt%
- Lot/batch No.: 10188-1 JM
- Expiration date of the lot/batch: 28 February 2015
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: supplied by Harlan Laboratories UK Ltd., Oxon, UK - Female Wistar (RccHan™:WIST) strain rats.
- Age at study initiation: eight to twelve weeks of age - the females were nulliparous and non-pregnant
- Weight at study initiation: 167.4 g +/- 6.5. The bodyweight variation did not exceed ±20% of the bodyweight of the initially dosed animal.
- Fasting period before study: overnight fast before dosing and for approximately three to four hours after dosing.
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): free access throughout the study
- Water (e.g. ad libitum): free access throughout the study
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 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:
other: suspension in distilled water
Details on oral exposure:
VEHICLE: No vehicle used
suspension in distilled water.
Note:
- The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.
- No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

MAXIMUM DOSE VOLUME APPLIED:
- Dose volume: 10 ml/kg
- Concentration: 200 mg/ml
- Dose level: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of clinical observations: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and subsequently once daily for fourteen days.
- Frequency of morbidity and mortality observations: twice daily
- Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Bodyweight:
- At day 7: Mean: 187.4 g ; SD: +/- 12.9
- At day 14: Mean: 195 g ; SD: +/- 15.4
Bodyweight gain:
- During week 1: Mean: 20 g ; SD: +/- 7.6
- During week 2: Mean: 7.6 g ; SD: +/- 3.1
Gross pathology:
No abnormalities detected in any of the rat

Applicant's summary and conclusion

Interpretation of results:
not classified
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 2000 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 in the Wistar strain rat. The method was designed to be compatible with the following:

• OECD Guidelines for Testing of Chemicals No 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 December 2001)

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

Method. Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test item, as a suspension in distilled water, at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Bodyweight. All animals showed expected gains in bodyweight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute oral median lethal dose (LDso) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight (Globally Harmonised Classification System - Unclassified).