Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
08 December 1997 - 05 January 1 998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
no deviations noted.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Principles of method if other than guideline:
The method complied with that described in the OECD Guidelines for Testing of Chemicals No. 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 July 1992) and Method Bi bis in Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
solid: bulk
Details on test material:
Buff-colored
Specific details on test material used for the study:
Sponsor's identification: UK-114,958
Batch number: 116044/D/16/X2/1
Date received: 28 October 1997
Description: buff solid
Storage conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: rats supplied by Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: eight to twelve weeks old
- Weight at study initiation: males weighed 201 to 225g, and the females 205 to 219g
- Fasting period before study: Yes, overnight
- Housing: solid-floor polypropylene cages furnished with woodflake
- Diet: ad libitum (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 21'C
- Humidity (%): 46 to 66%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours darkness

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Doses:
500 and 2000 mg/kg
No. of animals per sex per dose:
ten fasted animals (five males and five females)
Control animals:
not specified
Details on study design:
Animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross necropsy.

Results and discussion

Preliminary study:
Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and then daily for seven days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

There were no deaths at a dose level of 500 mg/kg bodyweight. Hunched posture was noted at this dose level. Animals treated with 2000 mg,/kg were found dead four or seven days after dosing. Clinical observations noted at a dose level of 2000 mg/kg were ataxia, diarrhoea, pallor of the extremities, emaciation, hunched posture, lethargy, pilo-erection, ptosis, decreased respiratory rate, laboured respiration, red/brown staining around the eyes, occasional body tremors and splayed gait.

Based on this information, a dose level of 500 mg/kg bodyweight was selected for the main study
Effect levels
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 500 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No clinical signs of toxicity were noted during the study
Body weight:
All animals showed expected gains in bodyweight over the 14-day study period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Conclusions:
A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method complied with that described in the OECD Guidelines for Testing of Chemicals No. 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 July 1992) and Method Bi bis in Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Following a preliminary study at dose levels of 500 and 2000 mg/kg, a group of ten fasted animals (five males and five females) was given a single oral dose of test material, as a suspension in arachis oil BP at a dose level of 500 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross necropsy.

There were no deaths or clinical signs of toxicity in the main study. All animals showed expected gains in bodyweight during the 14-day study period. No abnormalities were noted at necropsy. The discriminatory dose was identified as 500 mg/kg bodyweight. The acute oral median lethal dose (LD 50) of the test material in the SpragueDawley CD strain rat was estimated to be greater than 500 mg/kg bodyweight but less than 2000 mg/kg bodyweight. The test material may be of some concern if swallowed but did not meet the criteria for classification under EC labelling regulations. No symbol or risk phrase are required.
Executive summary:

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method complied with that described in the OECD Guidelines for Testing of Chemicals No. 420 "Acute Oral Toxicity - Fixed Dose Method" (adopted 17 July 1992) and Method Bi bis in Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). The acute oral median lethal dose (LD 50) of the test material in the SpragueDawley CD strain rat was estimated to be greater than 500 mg/kg bodyweight but less than 2000 mg/kg bodyweight.