Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 19 June 2008 and 03 July 2008
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:
2008
Report date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection: 21/08/2007 Date of Signature:15/10/2007
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Barium di(bistridecylsulfosuccinate) in mixture with Barium hydrogen phosphate
- Substance type: pale yellow solid
- Physical state: Solid
-Batch number: Y-T-1
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK

- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age.

- Weight at study initiation: At the start of the study the animals weighed at least 200g.

- Fasting period before study: Overnight fasting 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): Certified Rat and Mouse Diet) was allowed throughout the study. The diet was routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

- Water (e.g. ad libitum): Free access to mains drinking water. The water was 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): Set to achieve limits of 19 deg C to 25 deg C.

- Humidity (%): Set to achieve limits of 30 to 70%.

- Air changes (per hr): The rate of air exchanges was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light): Light controlled by a time switch to give twelve hours continuous light (06:00 to 18:00 and twelve hours darkness.

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

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
TEST SITE
- Area of exposure: On the day before treatment the back and flanks of each animal were clipped free of hair. The appropriate amount of test material, moistened with arachis oil BP, was applied as evenly as possible to an area of shorn skin.
- % coverage: approximately 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material.
- Time after start of exposure:24-hour


TEST MATERIAL
- Amount(s) applied (volume or weight with unit):Not stated
- Concentration (if solution): treated with the test material at a dose level of 2000 mg/kg.
- Constant volume or concentration used: yes
- For solids, paste formed: Test material was moistened with arachis oil BP prior to application


VEHICLE
- Amount(s) applied (volume or weight with unit): Not stated
- Concentration (if solution):Not stated
- Lot/batch no. (if required): Not Stated
- Purity:Not stated
Duration of exposure:
24 hour exposure period
Doses:
dose level of 2000 mg/kg
No. of animals per sex per dose:
Five males at 2000 mg/kg
Five 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 ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.


Statistics:
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 dermal median lethal dose (LD50) of the test material was made.

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 95% CL not stated
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Bodyweight changes are given in the table below:
Animals showed expected gains in bodyweight over the study period except for one female which showed expected gain in bodyweight during the first week but no gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Other findings:
Dermal Reactions:
Individual dermal reactions are given in the tables below:
Moderate to severe erythema was noted at the treatment site of one female, well-defined erythema was noted at the treatment sites of six animals and very slight erythema was noted at the treatment sites of the remaining animals one day after dosing. Very slight erythema was noted at the treatment sites of all males and three females two and three days after dosing and in one male four days after dosing.

Small superficial scabs were noted at the treatment sites of all females up to 14-days after dosing. Crust formation was noted at the treatment site of one female four days after dosing and two females five days after dosing. Other skin reactions noted at the treatment sites of two females up to 14-days after dosing were hardened, light brown colored scab and scab lifting to reveal glossy skin. Adverse skin reactions prevented accurate evaluation of erythema and oedema at the treatment sites of two females, two to four days after dosing, and persisted in one female, five days after dosing.

The treatment sites of male animals appeared normal four or five days after dosing and the treatment sites of two females appeared normal six days after dosing.

Any other information on results incl. tables

Table               Individual Dermal Reactions - Males

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0

Male

Erythema

1

1

1

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1

Male

Erythema

1

1

1

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2

Male

Erythema

2

1

1

1

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-3

Male

Erythema

2

1

1

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-4

Male

Erythema

1

1

1

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0


0= No reactions

Table              Individual Dermal Reactions - Females

Dose Level mg/kg

Animal Number and Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

Female

Erythema

2

1

1

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

Ss

Ss

Ss

Cf

0

0

0

0

0

0

0

0

0

2-1

Female

Erythema

2

1

1

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

Ss

Ss

Cf

Cf

0

0

0

0

0

0

0

0

0

2-2

Female

Erythema

2

?e

?e

?e

?e

0

0

0

0

0

0

0

0

0

Oedema

0

?od

?od

?od

?od

0

0

0

0

0

0

0

0

0

Other

0

Sp

Sp

Sp

Sg

Ss

Ss

Ss

Ss

SsSg

SsSg

SsSg

SsSg

SsSg

2-3

Female

Erythema

2

1

1

0

0

0

0

0

0

0

0

0

0

0

Oedema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Other

0

0

0

Ss

Ss

Ss

Ss

Ss

Ss

Ss

Ss

Ss

Ss

Ss

2-4

Female

Erythema

3

?e

?e

?e

0

0

0

0

0

0

0

0

0

0

Oedema

0

?od

?od

?od

0

0

0

0

0

0

0

0

0

0

Other

0

Sp

Sp

Sp

SsSg

SsSg

SsSg

SsSg

SsSg

SsSg

SsSg

SsSg

SsSg

SsSg


0= No reactions                  

Cf = Crust formation         

Ss = Small, superficial scattered scabs                                            

Sp = Hardened, light brown coloured scab

Sg = Scab lifting to reveal glossy skin                            

?e = Adverse reactions prevent evaluation of erythema             

?od = Adverse reactions prevent evaluation of oedema

Table             Individual Bodyweights and Weekly Bodyweight Changes

Dose Level mg/kg

Animal Number and Sex

Bodyweight (g) at Day

Bodyweight Change (g) During Week

0

7

14

1

2

2000

1-0 Male

244

291

353

47

62

1-1 Male

253

298

3 58

45

60

1-2 Male

254

318

374

64

56

1-3 Male

236

272

311

36

39

1-4 Male

248

289

333

41

44

2-0 Female

256

271

283

15

12

2-1 Female

213

225

232

12

7

2-2 Female

247

261

261

14

0

2-3 Female

229

258

268

29

10

2-4 Female

223

249

260

26

11

The acute dermal median lethal dose (LD50) of the test material in the Sprague‑Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in the Sprague Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

Introduction. The study was performed to assess the acute dermal toxicity of the test material 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. 402 “Acute Dermal Toxicity” (adopted)

§        Method B3 Acute Toxicity (Dermal) of Commission Directive 92/69/EEC

Method. A group of ten animals (five males and five females) was given a single, 24-hour, semi‑occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. Very slight to moderate to severe erythema was noted at the treatment sites of all animals. Other skin reactions noted at the treatment sites of females were crust formation, small superficial scabs, hardened, light brown coloured scab and scab lifting to reveal glossy skin. Adverse skin reactions prevented accurate evaluation of erythema and oedema at the treatment sites of two females. The treatment sites of male animals appeared normal four or five days after dosing and the treatment sites of two females appeared normal six days after dosing.

Bodyweight. Animals showed expected gains in bodyweight over the study period except for one female which showed expected gain in bodyweight during the first week but no gain in bodyweight during the second week.

Necropsy. No abnormalities were noted at necropsy.

Conclusion. The acute dermal median lethal dose (LD50) of the test material in the Sprague‑Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight.