Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 1991-07-26 to 1991-08-09
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP study in accordance with recognised test guideline but: Lot/batch No.: not stated Expiration date of the lot/batch: not stated NOTE: study deemed acceptable because spectral data for test item are available, covering approximately before and after the test period - see section 1.4 Analytical Information.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1997
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Purity: Ca. 100%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Age at study initiation: Approximately 5 weeks
- Weight at study initiation: 138 - 155 g for males and 127 - 134 g for females
- Fasting period before study: 18 hours
- Housing:The animals were housed in stainless steel grid cages measuring 54 x 33 x 20 cm (Steven Clarke Fabrications Limited, Alva, Clackmannanshire, Scotland).
- Diet (e.g. ad libitum): Laboratory Animal Diet No. 1 from Biosure, Manea, Cambridgeshire, England, fed ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target 21ºC, actual range 18º - 25ºC
- Humidity (%): Target 55% RH, actual range 40% - 70% RH
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 26 July 1991 To: 9 August 1991

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% (w/v) Aqueous Methylcellulose.
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5% w/v aqueous methylcellulose
- Amount of vehicle (if gavage): 20 mL / kg

MAXIMUM DOSE VOLUME APPLIED: 2000 mg / kg

DOSAGE PREPARATION (if unusual): The test material was prepared at the appropriate concentration in 0.5% w/v methylcellulose in purified water (obtained through the reverse osmosis of tap water). The dosage was calculated and expressed gravimetrically in terms of the material as received. A fresh formulation of the test material was prepared on the morning of administration and any surplus remaining after dosing was destroyed on the same day.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A preliminary study was carried out using one group of one male and one female rat given a single oral administration of test item at a dosage of 800 mg/kg bodyweight, at a volume-dosage of 20 mL/kg in 0.5% w/v aqueous methylcellulose. There was no death and no sign of reaction to treatment.
On the basis of this result, the main study was carried out using a single group of five male and five female rats given a single oral administration of test item at the maximum practicable dosage of 2000 mg/kg (Regulatory limit test), at a volume-dosage of 20 mL/kg. Since no rat died as a result of treatment the low toxicity of test item was demonstrated and no further groups of animals were employed.
Doses:
2000 mg / kg
No. of animals per sex per dose:
Five male and five female
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:Twice daily for 15 days, with weighing on day 1, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gastr-intestinal tract.
Statistics:
Not applicable

Results and discussion

Preliminary study:
A preliminary study was undertaken by administering one female rat and one male rat with a single oral dose of 800 mg / kg. There was no death and no sign of reaction to treatment.
Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
All animals achieved expected bodyweight gains.
Gross pathology:
No significant pathological findings

Applicant's summary and conclusion

Interpretation of results:
other: low oral toxicity
Conclusions:
Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg / kg.
Executive summary:

The acute oral toxicity of test item was investigated in a group of five male and five female CD rats at a dosage of 2000 mg/kg according to OECD 401. The animals were starved overnight prior to dosing. The test material was administered at a volume-dosage of 20 mL/kg in 0.5% w/v aqueous methylcellulose. Mortality and signs of reaction to treatment were recorded during a subsequent 14-day observation period. The animals were killed on the following day and subjected to necropsy.

There was no death and no sign of reaction to treatment. All animals achieved expected bodyweight gains and necropsy revealed no significant macroscopic lesion. Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.