Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2005-09-12 to 2005-10-11
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Meets the criteria for classification as Reliable without restriction according to Klimisch et al (1997)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: FSM-003B
(FSM-003B is a synonym of S196439)
Nature of substance: powder
Batch number: CE-501-2
Date received: 23 August 2005

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Female Sprague-Dawley CD strain rats were supplied by a reputable supplier. On receipt the animals were randomly allocated to cages. The animals were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given an unique number within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The bodyweights fell within an interval of +/- 20% of the mean initial bodyweight of the first treated group.

The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Certified Rat and Mouse Diet) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other:
Details on oral exposure:
Concentration in vehicle: 35.1 mg/ml of test substance in distilled water
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
300 mg active ingredient/kg bodyweight (one group)
2000mg active ingredient/kg bodyweight (two groups)
No. of animals per sex per dose:
3 females 300 mg active ingredient/kg bodyweight
3 females 2000mg active ingredient/kg bodyweight
3 females 2000mg active ingredient/kg bodyweight
Control animals:
no
Details on study design:
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. 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:
act. ingr.
Mortality:
Female: 300 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Clinical signs: There were no signs of systemic toxicity noted in animals treated at a dose level of 351 mg/kg bodyweight (equivalent to 300 mg of active substance/kg bodyweight).

Hunched posture, pilo-erection and faeces and urine stained black were noted in animals treated at a dose level of 2337 mg/kg bodyweight (equivalent to 2000 mg of active substance/kg bodyweight). Animals at this dose level appeared normal three or four days after dosing.
Body weight:
Bodyweight changes:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
Effects on organs:
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 substance in the female Sprague-Dawley CD strain rats was estimated to be greater than 2000 mg active ingredient/kg bodyweight (2337 mg/kg bodyweight).
Executive summary:

Introduction

This study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD strain rat. The method was designed to meet the requirements of the following guidelines:

OECD Guideline for the Testing of Chemicals No. 423 'Acute Oral Toxicity - Acute Toxic Class Method' (adopted 17 December 2001)

Method B1 tris Acute Toxicity (Oral) of Commission Directive 2004/73/EC

Method

Three groups of three fasted females were treated with the test substance at a dose level of 300 mg active ingredient/kg bodyweight, 2000 mg active ingredient/kg bodyweight and 2000 mg active ingredient/kg bodyweight.The test item was administered orally as a solution in distilled water. Clinical signs and bodyweight were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality: There were no deaths.

Clinical Observations: There were no signs of systemic toxicity noted in animals treated at a dose level of 351 mg/kg (equivalent to 300 mg of notifiable substance/kg bodyweight). Hunched posture, pilo-erection and faeces and urine stained black were noted in animals treated at a dose level of 2337 mg/kg (equivalent to 2000 mg of notifiable substance/kg bodyweight). Animals at this dose level appeared normal three or four days after dosing.

Bodyweight: All animals showed expected gains in bodyweight over the study period.

Necropsy: No abnormalities were noted at necropsy.

Conclusion

The acute oral median lethal dose (LD50) of the test substance in the female Sprague-Dawley CD strain rats was estimated to be greater than 2000 mg active ingredient/kg bodyweight (2337 mg/kg bodyweight) (GHS category 5 >2000 -5000 mg/kg bodyweight).