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 29 September 2005 and 20 October 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevant results.

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
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection: 2nd December 2002 Date of signature: 13/2/03
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Identification : Barium di(bistridecylsulfosuccinate) in mixture with barium hydrogen phosphate
Description : Clolurless waxy solid block
Batch number : Y-T-1
Storage Conditions : room temperature in the dark.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Female Sprague-Dawley CD (Crl: CD (SD) IGS BR) strain rats were supplied by Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: Eight to twelve weeks of age.
- Weight at study initiation: 193 - 224g. The bodyweights fell within an interval of ± 20% of the mean initial bodyweight of the first treated group.
- Fasting period before study: An overnight fast immediately before dosing and for approximately three to four hours after dosing.
- Housing: The animals were housed in groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Free access to food (Certified Rat and Mouse Diet (Code 5LF2) supplied by BCM IPS Limited, London, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water 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.
- Acclimation period: At least five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): The temperature was set to achieve limits of 19 to 25°C.
- Humidity (%): Relative humidity was set to achieve limits of 30 to 70%.
- Air changes (per hr): At least fifteen changes per hour.
- Photoperiod (hrs dark / hrs light): The lighting was controlled by a time switch to give twelve hours continous light (06:00 to 18:00) and twelve hours darkness.


IN-LIFE DATES: From: Day 0 To: Day 14

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing.
- Justification for choice of vehicle: Dimethyl sulphoxide was used because the test material did not dissolve/suspend in distilled water.
- Lot/batch no. (if required): Not avaialable.
- Purity: Not available.


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION (if unusal): For the purpose of the study the test material was freshly prepared, as required, as a solution at the appropriate concentration in dimethyl sulphoxide. To aid preparation the test material formulation was heated to 80°C in a water bath. The formulation was allowed to cool before dosing.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using all available information on the toxicity of the test material, 2000 mg/kg was chosen as the starting dose.
Doses:
Dose level of 2000 mg/kg.
No. of animals per sex per dose:
6 females at 2000 mg/kg.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen day.
- Necropsy of survivors performed: yes
- Other examinations performed: Individual bodyeights were recorded prior to dosing and seven and fourteen days after treatment or at death.
Statistics:
None reported.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 500 mg/kg bw
Remarks on result:
other: LD50 estimated to be approximately 2500 mg/kg bodweight.
Mortality:
Individual mortality data are given in Table 1.
Two animals were found dead one day after dosing.
Clinical signs:
Individual clinical observations are given in Table 2.
Signs of systemic toxicity noted during the study were hunched posture, lethargy, pilo-erection, decreased respiratory rate, laboured respiration, ataxia, pallor of the extremities, dehydration, diarrhoea, increased lachrymation and splayed gait. Surviving animals appeared normal two, three, five or ten days after dosing.
Body weight:
Individual bodyweights and weekly bodyweight changes are given in Table 3.
The surviving animals showed expected gains in bodyweight over the study period, except for one animal which showed a bodyweight loss during the fisrt week but expected gain in bodyweight during the second week of the study.
Gross pathology:
Individual necropsy findings are given in Table 4.
Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Other findings:
None.

Any other information on results incl. tables

Table1               Mortality Data

Dose Level mg/kg

Sex

Number of Animals Treated

Deaths During Day of Dosing
(Hours)

Deaths During Period After Dosing
(Days)

Deaths

½

1

2

4

1

2

3

4

5

6

7

8-14

2000

Female

3

0

0

0

0

1

0

0

0

0

0

0

0

1/3

Female

3

0

0

0

0

1

0

0

0

0

0

0

0

1/3

Table2               Individual Clinical Observations

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Female

0

0

0

HLPRd

X

 

 

 

 

 

 

 

 

 

 

 

 

 

1-1

Female

0

0

0

HP

HP

HLAPRdRlE
Dh

HLPEDh

HPEDh

HP

H

H

H

H

0

0

0

0

0

1-2

Female

0

0

0

H

HLPARdRl

HLPARdRl

HRdPRl

H

0

0

0

0

0

0

0

0

0

0

2-0

Female

0

HD

HD

HD

H

H

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

HRdLRl

HRdLRlAWs

HRdLRlALiWs

HRdRl

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

0

0

H

X

 

 

 

 

 

 

 

 

 

 

 

 

 

 



0= No signs of systemic toxicity                     A = Ataxia                                                            D = Diarrhoea                                      Dh = Dehydration

E = Pallor of the extremities                               H = Hunched posture                                         L = Lethargy                                       Li = Increased lachrymation

P =                                                  Rd= Decreased respiratory rate                       Rl = Laboured respiration                  Ws = Splayed gait

X = Animal dead

Table3               Individual Bodyweights and Weekly Bodyweight Changes

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

1-0 Female

222

-

-

205

-

-

1-1 Female

222

218

280

 

-4

62

1-2 Female

224

228

255

 

4

27

2-0 Female

205

223

240

 

18

17

2-1 Female

224

228

250

 

4

22

2-2 Female

193

-

-

186

-

-

Table4               Individual Necropsy Findings

Dose Level

mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

2000

1-0 Female

Found dead Day 1

Lungs: haemorrhagic

Liver: dark

Kidneys: dark

1-1 Female

Killed Day 14

No abnormalities detected

1-2 Female

Killed Day 14

No abnormalities detected

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Found dead Day 1

Lungs: haemorrhagic

Liver: dark

Kidneys: dark

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 material in the female Sprague-Dawley CD strain tat was estimated to be approximately 2500 mg/kg bodyweight (GHS 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 December 2001)
  • Method B1 tris Acute Toxicity (Oral) of Commission Directive 2004/73/EC

Method.

A group of three fasted females was treated with the test material at a dose level of 2000 mg/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 solution in dimethyl sulphoxide. Clinical signs and bodyweight development were monitered during the study. All animals were subjected to gross necropsy.

Mortality.

Two animals were found dead one day after dosing.

Clinical Observations.

Signs of systemic toxicity noted during the study were hunched posture, lethargy, pilo-erection, decreased respiratory rate, laboured respiration, ataxia, pallor of the extremities, dehydration, diarrhoea, increased lachrymation and splayed gait. Surviving animals appeared normal two, three, five or ten 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 of the study.

Necropsy.

Abnormalities noted at necropsy of animals that died during the study were haemorrhagic lungs, dark liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.

Conclusion.

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be approximately 2500 mg/kg bodyweight (GHS Category 5 >2000 - 5000 mg/kg bodyweight).