Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1957
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted non-GLP, with limited data on study design, however the study was conducted according to state of the art methods at that time period. The study is considered adequate, reliable and relevant.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1957
Report Date:
1957

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): Aerosol MA-80%, sodium dihexylsulfosuccinate
- Physical state: Clear, viscous liquid (80% solution)
- Analytical purity: 78-80%
- Impurities (identity and concentrations): See confidential details
- Composition of test material, percentage of components: See confidential details
- Purity test date: Not provided
- Lot/batch No.: BV-1193A NH
- Expiration date of the lot/batch: Not provided
- Stability under test conditions: Good stability in aqueous solution
- Storage condition of test material: Not provided

Test animals

Species:
rabbit
Strain:
other: albino
Sex:
male
Details on test animals and environmental conditions:
Not provided

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the cuff and any excess of the dose were removed
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 mL/kg; 5 mL/kg; 10 mL/kg
- Concentration (if solution): solution containing 80 % solids ( 80 % active ingredient)
- Constant concentration used: yes; different volumes

VEHICLE
Not applicable
Duration of exposure:
24 hours
Doses:
2.5 mL/kg, 5.0 mL/kg and 10.0 mL/kg
No. of animals per sex per dose:
4
Control animals:
no
Details on study design:
TEST SITE
- Area of exposure: trunk
- % coverage: Not provided
- Type of wrap if used: a cuff of polyethylene film

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the cuff and any excess of the dose were removed
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5 mL/kg, 5.0 mL/kg and 10.0 mL/kg
- Concentration (if solution): 80%
- Constant concentration used: different volumes
Statistics:
the method of moving averages

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
5 mL/kg bw
Based on:
test mat.
95% CL:
> 2.6 - < 9.6
Remarks on result:
other: test material is 80% solution
Sex:
male
Dose descriptor:
LD50
Effect level:
4 000 mg/kg bw
Based on:
act. ingr.
95% CL:
> 2 100 - < 7 700
Mortality:
At a dosage of 10 mL/kg there was severe erythema, edema and necrosis of the skin, and all animals died within one to three days following the removal of the dose . At the two lower dosages, there was one death each.
Clinical signs:
At a dosage of 10 mL/kg there was severe erythema, edema and necrosis of the skin, and all animals died within one to three days following the removal of the dose having exhibited extreme depression over this interval. Erythema and edema were initially quite severe at the lower dosages, but the edema subsided within 24 to 48 hours. Erythema, however, persisted for 4 to 5 days.
Body weight:
In the surviving animals there was a negative body weight gain.
Gross pathology:
Post-mortem examination in the high dose group gave additional evidence of severe injury to the skin and abdominal wall.
Survivors were observed for a total of 7 days after application of the dose, and then sacrificed. At autopsy there was no gross pathology that could be related to administration of the product.

Any other information on results incl. tables

Table 1. Dosage & Results

Animal Number

Body weight in Grams

Weight Change in 7 Days

Dosage in mL/kg

Dose in mL

Days to Death

H 815

3372

-

10.0

33.7

3

H 817

3562

-

10.0

35.6

2

H 818

3900

-

10.0

39.0

2

H 819

3580

-

10.0

35.8

<1

H 821

2720

-

10.0

27.2

<1

 

 

 

 

 

 

H 823

3680

-160

5.0

18.4

S

H 824

3142

-

5.0

15.7

4

H 825

4098

-987

5.0

20.5

S

H 826

3091

-182

5.0

15.5

S

 

 

 

 

 

 

H 832

3729

-161

2.5

9.3

S

H 833

3557

-237

2.5

8.9

S

H 835

3805

-

2.5

9.5

4

H 836

4120

-408

2.5

10.3

S

S= Survived

LD50 =5.0 (2.6-9.6) mL/kg as 80% solution

LD50 =4.0 (2.1-7.7) g/kg as contained solids

 

NOTE: For purposes of calculation of anLD50 by the method of moving averages, a mortality of 4/4 at

20 mL/kg is assumed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of the test item for male albino rabbits by single skin application under these circumstances is 5.0 (2.6-9.6) mL/kg, corresponding with 4.0 g/kg bw of the active ingredient.
For purposes of calculation of an LD50 by the method of moving averages a mortality of 4/4 at 20 mL/kg is assumed.

Executive summary:

The test item as received (solution containing 80% solids) was supplied to the closely-clipped skin of male albino rabbits in single doses that remained in contact with the skin for a period of 24 hours. Four animals were used at each of three dosage levels; namely, 2.5 mL/kg, 5 mL/kg and 10 mL/kg respectively. The dose was retained by means of a cuff of polyethylene film which encircled the trunk of the animal. At the end of the period of exposure, the cuff and any excess of the dose were removed, and the skin examined for primary irritation.

At a dosage of 10 mL/kg there was severe erythema, edema and necrosis of the skin, and all animals died within one to three days following the removal of the dose having exhibited extreme depression over this interval. Post-mortem examination gave additional evidence of severe injury to the skin and abdominal wall. At the two lower dosages, there was one death each, and the LD50 was calculated to be 5.0 (2.6-9.6) mL/kg, or 4.0 g/kg bw of the active ingredient.

Erythema and edema were initially quite severe at the lower dosages, but the edema subsided within 24 to 48 hours. Erythema, however, persisted for 4 to 5 days. Survivors were observed for a total of 7 days after application of the dose, and then sacrificed. At autopsy there was no gross pathology that could be related to administration of the product.