Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 February 2007 and 12 March 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

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 (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: Abacavir Glutarate
Description: extremely pale pink crystalline solid
Batch number: 06B2-129
Date received: 02 October 2006
Storage conditions: room temperature, in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: Eight to twelve weeks.
- Weight at study initiation: The bodyweights fell within an interval of ± 20% ofthe initial bodyweight of the first treated animal (213 g).
- 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 up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: ad libitum: Certified Rat and Mouse Diet.
- Water: ad libitum: Mains drinking water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): 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: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:
One dose at 2000 mg/kg.
No. of animals per sex per dose:
Following a sighting test in which there was no mortality at a dose level of 2000 mg/kg, an additional four female animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Control animals:
no
Details on study design:
Using all available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose (sighting test). In the absence of toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated (four further animals).
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made ½, I, 2, and 4 hours after dosing and subsequently once daily for fourteen days. Morbidity and mortality checks were made twice daily.
- Necropsy of survivors performed: yes
- Other examinations performed: body weight: Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
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 test period.
Gross pathology:
No abnormalities were noted at necropsy.

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 material In the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight.
Executive summary:

Introduction. The study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of 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 Directive 2004/73/EC

Method. Following a sighting test in which there was no mortality at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test material, as a suspension in arachis oil BP 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 discriminatory dose was identified as 2000 mg/kg bodyweight.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. The test material was considered to have no significant acute toxic risk if swallowed and did not meet the criteria for classification according to Commission Directive 200l/59/EC for classification and labelling of dangerous substances.