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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 22 October 2003 and 02 February 2004.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
484-440-2
EC Name:
-
Cas Number:
502157-74-6
Molecular formula:
C84H68O12S3P2
IUPAC Name:
4-(4-hydroxybenzenesulfonyl)phenol bis(tetraphenylphosphanium) bis(4-(4-hydroxybenzenesulfonyl)benzen-1-olate)
Test material form:
solid: particulate/powder
Specific details on test material used for the study:
Description, Identification and Storage Conditions
Sponsor's identification SBCAT-03
Description white powder
Batch number UK030622B
Date received 09 October 2003
Storage conditions room temperature in the dark


Data relating to the identity, purity and stability of the test material are the responsibility of the Sponsor.

Preparation of Test Material
For the purpose of the study the test material was freshly prepared, as required, as a suspension at the appropriate concentration in arachis oil BP. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
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 International Product Supplies
Limited, Wellingborough, Northants, 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:
For the purpose of the study the test material was freshly prepared, as required, as a suspension at the appropriate concentration in arachis oil BP. Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.
Determination by analysis of the concentration, homogeneity and stability of the test material
preparations was not appropriate because it was not specified in the Study Plan and is not a
requirement of the Test Guideline.
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the
starting dose.
All animals were dosed once only by gavage, using a metal cannula attached to a graduated
syringe. 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 and each dose level to confirm the survival of the previously dosed
animals.
Doses:
See "Any other information".
No. of animals per sex per dose:
3
Control animals:
not specified
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 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.
The sequence of dosing may not always follow the Test Guideline as shown in the schematic
diagram in "Illustrations". It is Company Policy to minimise the number of animals used on each
study in accordance with UK Government Home Office guidelines. The sequence of testing does
not affect the final classification of the test material.
Data evaluations included the relationship, if any, between the exposure of the animal to the test
material and the incidence and severity of all abnormalities including behavioural and clinical
observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the
test material was made as shown in the schematic diagram in "Illustrations".

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 500 mg/kg bw
Based on:
test mat.
Mortality:
Individual mortality data are given in "Any other information on results".
All animals treated at a dose level of 2000 mg/kg were found dead two hours after dosing. There
were no deaths noted at a dose level of 300 mg/kg.
Clinical signs:
other: Individual clinical observations are given in "Any other information on results". Signs of systemic toxicity noted in all animals treated at a dose level of 2000 mg/kg were hunched posture and ataxia. Signs of systemic toxicity noted during the day of dos
Gross pathology:
Individual necropsy findings are given in "Any other information on results".
Abnormalities noted at necropsy of animals that died during the study were abnormally red lungs,
dark liver or patchy pallor of the liver, dark kidneys and white liquid present in the stomach. No
abnormalities were noted at necropsy of animals that were killed at the end of the study.

Any other information on results incl. tables

Mortality Data


 

































































Dose


Level mg/kg



Sex



Number of


Animals Treated



Deaths During Day of Dosing


(Hours)



Deaths During Period After Dosing


(Days)



 



Deaths



1/2



1



2



4



1



2



3



4



5



6



7



8-14



300



Female


 


 


Female



3


 


 


3



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0


 


 


0



0/3


 


 


0/3



2000



Female



3



0



0



3



-



-



-



-



-



-



-



-



-



3/3



- = All animals dead


 


 


Individual Clinical Observations - 300 mg/kg


 
































































































































































Dose Level mg/kg



Animal Number and Sex



Effects Noted After Dosing (Hours)



 



Effects Noted During Period After Dosing (Days)



1/2



1



2



4



1



2



3



4



5



6



7



8



9



10



11



12



13



14



300



1-0


Female



0



D



DDu



DDu



0



0



0



0



0



0



0



0



0



0



0



0



0



0



1-1


Female



0



0



D



D



0



0



0



0



0



0



0



0



0



0



0



0



0



0



1-2


Female



0



D



DDu



DDu



0



0



0



0



0



0



0



0



0



0



0



0



0



0



3-0


Female



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



3-1


Female



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



3-2


Female



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



0



O = No signs of systemic toxicity


D = Diarrhoea


Du Diuresis


 


Individual Clinical Observations - 2000 mg/kg






















































































































Dose Level mg/kg



Animal Number and Sex



Effects Noted After Dosing (Hours)



Effects Noted During Period After Dosing (Days)



 


 

1/2



1



2



4



1



2



3



4



5



6



7



8



9



10



11



12



13



14



 


 

2000



2-0 Female



HA



HA



x



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 


 
  

2-1 Female



HA



HA



x



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 


  
  

2-2 Female



HA



HA



x



 



 



 



 



 



 



 



 



 



 



 



 



 



 



 


  
  

H= Hunched posture


A= Ataxia


X= Animal dead


 


 


Bodyweights and Weekly Bodyweight Changes - 300 mg/kg


 




































































Dose Level mg/kg



Animal Number and Sex



Bodyweight (g) at Day



Bodyweight Gain (g) During Week



0



7



14



1



2



300



1-0 Female



195



228



239



33



11



1-1 Female



207



229



244



22



15



1-2 Female



190



223



257



33



34



3-0 Female



179



209



232



30



23



3-1 Female



182



202



251



20



49



3-2 Female



208



248



270



40



22



 


 


Individual Bodyweights and Weekly Bodyweight Changes - 2000 mg/kg


 


 
















































Dose Level


(mg/kg)



Animal Number and Sex



Bodyweight (g) at Day



Bodyweight (g)


at Death



Bodyweight Gain (g) During Week



0



7



14



1



2



2000



2-0



210



-



-



203



-



-



2-1



206



-



-



200



-



-



2-2



220



-



-



215



-



-



- = Animal dead


 


 


Individual Necropsy Findings - 300 mg/kg


 











































Dose Level mg/kg



Animal Number and Sex



Time of Death



Macroscopic Observations



300



1-0 Female



Killed Day 14



No abnormalities detected



I-I Female



Killed Day 14



No abnormalities detected



1-2 Female



Killed Day 14



No abnormalities detected



3-0 Female



Killed Day 14



No abnormalities detected



3-1 Female



Killed Day 14



No abnormalities detected



3-2 Female



Killed Day 14



No abnormalities detected



 


 












 
  


Individual Necropsy Findings - 2000 mg/kg


 


 




























Dose Level mg/kg



Animal Number and Sex



Time of Death



Macroscopic Observations



2000



2-0 Female



Found dead Day 0



Lungs: abnormally red


Liver: dark


Kidneys: dark


Stomach: white fluid resent



2-1 Female



Found dead Day 0



Lungs: abnormally red


Liver: dark


Kidneys: dark


Stomach: white fluid resent



2-2 Female



Found dead Day 0



Lungs: abnormally red


Liver: patchy pallor


Kidneys: dark


Stomach: white fluid resent


Applicant's summary and conclusion

Interpretation of results:
Category 4 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 in the range of 300 - 500 mg/kg bodyweight.
Executive summary:

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 December 2001)



A group of three fasted females was treated with the test material at a dose level of 300 mg/kg bodyweight. Based on the results from this dose level further groups of fasted females were treated at dose levels of 2000 and 300 mg/kg bodyweight. Dosing was performed sequentially.
The test material was administered orally as a suspension in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.



All animals treated at a dose level of 2000 mg/kg were found dead two hours after
dosing. There were no deaths noted at a dose level of 300 mg/kg.



Signs of systemic toxicity noted in all animals treated at a dose level of
2000 mg/kg were hunched posture and ataxia. Signs of systemic toxicity noted in three animals treated at a dose level of 300 mg/kg were diuresis and/or diarrhoea. There were no signs of systemic toxicity noted in three animals treated at a dose level of 300 mg/kg.



The surviving animals showed expected gains in bodyweight over the study period.



Abnormalities noted at necropsy of animals that died during the study were
abnormally red lungs, dark liver or patchy pallor of the liver, dark kidneys and white liquid present in the stomach. No abnormalities were noted at necropsy of animals that were killed at the end of the study.



The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be in the range of 300 - 500 mg/kg bodyweight.