Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 December 1990 to 27 December 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The methodology used in this study was equivalent to the current guideline requirements at the time the study was conducted. Although there are some minor deficiencies in reporting compared to modern requirements, the study is considered suitable as a key study for acute oral toxicity.

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
Qualifier:
equivalent or similar to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not applicable
Principles of method if other than guideline:
The procedures used in this study met the requirements of the test for acute oral toxicity described in document L251/1. an EEC Commission Directove of 25 April 1984.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Test Item Storage: +4 °C in the dark
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4 ºC / Dark
- Stability under test conditions: Assumed stable
- Solubility and stability of the test substance in the solvent/vehicle: N/A
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: N/A

Test animals

Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl:CD(SD)BR Strain (VAF plus)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
-Source: Recognised supplier
-Age/weight at study initiation: 4-6 weeks / 100 grams
-Fasting period before study: over night fasting
-Housing: groups of five in grid bottom cages
-Diet: Pelleted rodent diet ad libitum
-Water: main drinking water via polypropylene bottles
-Acclimation period: 6 days

ENVIRONMENTAL CONDITION
-Temperature: 18 -21°C
-Humidity: 30 - 70%
-Air changes (per hour): Air conditioned
Photoperiod (hrs dark/hrs light: 12 hrs dark/12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
test item suspended in corn oil giving dose of 10 ml/kg
Details on oral exposure:
The prepared test item was administered to one group of 10 rats (5/sex) at oral dose of 2000 mg/kg/bw. by peroral injection using a rubber catheter attached to a syringe.
Doses:
A single doise of 2000 mg/kg
No. of animals per sex per dose:
5 per sex per dose; 10 in total
Control animals:
no
Details on study design:
A single dose administration followed by 14 days observation periood.
Fregrancy of observation and weighing: the animals were examined at approximately 30 minutes and 1, 2 and 14 hours after dosing then once daily for 14 days. Animal weights were taken at a weekly intervals
Necropsy of surving animals: Yes

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female death reported on day two, no clinical signs were observed prior to its death.
Clinical signs:
Piloerection in one male after 2 - 4 hours of dosing which was noted in all surving animals. Hypoactivity in all males and two females.
Body weight:
all animals gained body weight.
Gross pathology:
Gastric non-glandular mucosa and salivary glands reddened in 4/5 males, left testis enlargemnet in one male and fluid distented uterus in 2/5 females, these were consitent with normal macroscopic background pathlogy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the condition of this study the LD50 was dertermined to be > 2000 mg/kg/bw in male and female rats.
Executive summary:

A GLP study was performed folowing a method similar to OECD 401 to assess the toxicity of the test item following oral administration to Sprague-Dawley rats. The test item was administered as a single dose to a group 5 males and 5 female rats at dose level of 2000 mg/kg bw, this is followed by 14 days observation period for any signs of toxicity or any other effects of treatment. All animals were examined for gross patholog, one female death noted on day two of treatment. Piloerection and hyperactivity were noted in majority of the animals, one male exhibited a hunched posture - all clinical signs subsided by day 3. Necropsy findings were consitent with normal macroscopic background pathathology. Under the conditions of this study the LD50 was determined to be > 2000 mg/kg bw in male/female Sprague-Dawley rats.