Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 27 July 2006 and 16 August 2006.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Sponsor's identification: FSM-005W
Description: white solid
Batch number: 2005-01

Specific details on test material used for the study:
Sponsor's identification: FSM-005W
Description: white solid
Purity: 85.8%
Batch number: #2005-01
Date received: 23 August 2005
Storage conditions: room temperature in the dark over silica gel, under nitrogen

The integrity of supplied data relating to the identity, purity and stability of the test material is the responsibility of the Sponsor

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Animals and Animal Husbandry

Female Sprague-Dawley CD (Crl: CD® (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK. 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 a number unique 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 (Code 5LF2) supplied by BCM IPS Limited, London, UK) 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:
arachis oil
Details on oral exposure:
Using available information on the toxicity of the test material, 2332 mg/kg (equivalent to 2000 mg active ingredient/kg bodyweight) was chosen as the starting dose.

Dose volume= 10ml/kg
Concentration= 232.2 mg/ml
Doses:
All animals were dosed once only by gavage, using a metal cannula attached to a graduated syrmge.
No. of animals per sex per dose:
3 female rats per dose with two repicates.
Control animals:
not specified
Details on study design:
The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

The animals were observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days.

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

At the end of the observation period the surviving 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
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Mortality:
One animal was found dead two days after dosing and one other animal was killed in extremis four days after dosing.
Clinical signs:
Signs of systemic toxicity noted during the study were hunched posture, diuresis, diarrhoea, red/brown staining around the ano-genital region, eyes, snout and mouth, pilo-erection, lethargy, emaciation and dehydration. Surviving animals appeared normal four, five, six or nine days after dosing.
Body weight:
The surviving animals showed expected gains in bodyweight over the study period, except for one animal which showed a bodyweight loss during the first week but expected gain in bodyweight during the second week.
Gross pathology:
Abnormalities noted at necropsy of the animals that died or were killed in extremis during the study and one animal killed at the end of the study were abnormally red lungs, dark or patchy pallor of the liver, dark kidneys, gaseous stomach and stomach adhered to abdominal wall. No abnormalities were noted at necropsy of remaining animals that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
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 2332 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight) (Globally Harmonised Classification System Category 5 >2000 - 5000 mg/kg bodyweight).
Executive summary:

Introduction

The 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:

 

        OECD Guidelines for the Testing of Chemicals No. 423 "Acute Oral Toxicity- Acute Toxic Class Method" (adopted 17 December2001)

 

        Method B1IrisAcuteToxicity (Oral)ofCommissionDirective2004/73/EC

 

Method

A group of three fasted females was treated with the test material at a dose level of 2332 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight). This was followed by a further group of three fasted females at the same dose level.

 

The test material was administered orally as a suspension in dried arachis oil. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

 

Mortality

One animal was found dead two days after dosing and one other animal was  killed in extremis four days after dosing.

 

Clinical Observations

Signs of systemic toxicity noted during the study were hunched posture, diuresis, diarrhoea,red/brown staining around the ano-genital region,eyes,snout and mouth, pilo-erection,lethargy, emaciation and dehydration. Surviving animals appeared normal four to nine days after dosing.

 

Bodyweight

The surviving animals showed expected gains in bodyweight over the study period,except for one animal which showed a bodyweight loss during the first week but expected gain in bodyweight during the second week.


  

Necropsy

Abnormalities noted at necropsy of the animals that died or were killedin extremisduring the study and one animal killed at the end of the study were abnormally red lungs, dark or patchy pallor of the liver, dark kidneys, gaseous stomach and stomach adhered to abdominal wall. No abnormalities were noted at necropsy of remaining animals that were killed at the end of the study.

 

Conclusion

The acute oral median lethal dose (LDso) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2332 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight) (Globally Harmonised Classification System Category 5 >2000 - 5000 mg/kg bodyweight).