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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study; well documented study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)
EC Number:
218-679-9
EC Name:
Zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)
Cas Number:
2215-35-2
Molecular formula:
Too complex
IUPAC Name:
zinc O,O,O',O'-tetrakis(1,3-dimethylbutyl) bis(phosphorodithioate)

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Covance Research Products Inc.
- Weight at study initiation: 3254 to 3899 grams.
- Housing: Individual suspended wire mesh cages.
- Acclimation period: minimum of 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.8-18.8
- Humidity (%):50.1-75.7%.
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark.

IN-LIFE DATES: May 18, 1999 –June 1, 1999.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: Mineral Oil
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
The dosage level was 0.5 ml/site. There was one group of six rabbits, four intact sites per rabbit. Each rabbit received a single, 4 hour- semi-occluded exposure to each of the undiluted test material and a 50, 25, and 12.5% concentration of the test material in mineral oil.
Duration of treatment / exposure:
The test substance was administered once per site and remained in contact with the skin for 4 hours followed by removal with disposable paper towels moistened with deionized water.
Observation period:
The skin was examined and graded for dermal reaction at approximately 30-60 minutes and 24, 48 and 72 h following patch removal and daily thereafter up to 14 days if irritation persisted.
Number of animals:
6 females
Details on study design:
TEST SITE
On the day prior to dosing, the hair was removed from the backs and flanks of the rabbits using electric clipper. One 0.5 ml dose of each concentration of the test article was applied to an area of the skin approximately 2.5 x 2.5 cm at one of the four possible site locations. Doses were administered under a two-ply gauze patch secured with Micropore tape. The patches were overwrapped with a gauze binder and secured with Dermiform tape. Plastic restraint collars were applied and remained on the animals for the duration of the exposure period (4 hours). Following the exposure period, residual test substance was removed with disposable paper towels moistened with deionized water.

SCORING SYSTEM: Dermal Irritation was graded in accordance with the Draize method of scoring.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
3
Max. score:
4
Reversibility:
other: Not reversible in 4/6 animals at day 14
Remarks on result:
other: as supplied concentration
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.8
Max. score:
4
Reversibility:
other: Not reversible in 1/6 animals at day 14
Remarks on result:
other: as supplied concentration
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.9
Max. score:
4
Reversibility:
other: Not reversible in 4/6 animals at day 14
Remarks on result:
other: 50% in mineral oil
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hour
Score:
1.7
Max. score:
4
Reversibility:
other: reversible at day 10
Remarks on result:
other: 50% in mineral oil
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.9
Max. score:
4
Reversibility:
other: Not reversible in 2/6 animals at day 14
Remarks on result:
other: 25% in mineral oil
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
1.1
Max. score:
4
Reversibility:
other: Reversible at Day 8
Remarks on result:
other: 25% in mineral oil
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2.4
Max. score:
4
Reversibility:
other: reversible at day 13
Remarks on result:
other: 12.5% in mineral oil
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
0.9
Max. score:
4
Reversibility:
other: Reversible at day 7
Remarks on result:
other: 12.5% in mineral oil
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
4.3
Max. score:
8
Reversibility:
other: not applicable
Remarks on result:
other: as supplied concentration
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
4.6
Max. score:
8
Reversibility:
other: not applicable
Remarks on result:
other: 50% in mineral oil
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3.9
Max. score:
8
Reversibility:
other: not applicable
Remarks on result:
other: 25% in mineral oil
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24 and 72 hours
Score:
3.1
Max. score:
8
Reversibility:
other: not applicable
Remarks on result:
other: 12.5% in mineral oil
Irritant / corrosive response data:
Undiluted test material induced moderate erythema and slight edema and desquamation on all rabbits. There were no other dermal findings. By study termination (Day 14) very slight and slight erythema , very slight edema and desquamatation were noted for one, two, and four animals respectively.
The 50 % concentration of the test material induced moderate erythema, slight edema and desquamation in all animals. There were no other dermal findings. The edema completely subsided in all animals by Day 10. By study termination ( Day 14) very slight erythema and desquamation were noted in four animals.

The 25 % concentration of the test material induced moderate erythema and very slight to slight edema on all animals. There were no other dermal findings. The edema completely subsided in all animals by Day 8. By study termination ( Day 14) very slight erythema and desquamation were noted in two and one animals respectively.

The 12.5 % concentration of the test material induced slight to moderate erythema and very slight edema and desquamation on all animals. There were no other dermal findings. The erythema and edema completely subsided by days 13 and 7 respectively.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: other: EU and OECD GHS
Conclusions:
Based on the results of this study, the test substance would be classified as a Category 2 in accordance with the classification system of GHS.
Executive summary:

The primary dermal irritation potential of the test material was evaluated in this study with New Zealand White rabbits.There one group of six albino rabbits that received a single, four-hour, semi-occluded exposure of each test article concentration. Four concentrations of the test article were evaluated on each animal. Each 0.5 ml dose of the test article was were applied to the clipped, unabraded skin at four distinct test sites. . At completion of exposure the bandages were removed and the residual test substance was removedwith disposable paper towels moistened with deionized water.Application sites were evaluated in accordance with the method of Draize at approximately 24, 48, and 72 hours after patch removal and daily through day 14 if irritation persisted.

 

The Primary Irritation Index was calculated to be 4.3, 4.6, 3.9, and 3.1, for the sites dosed with undiluted test material, 50, 25, and 12.5% respectively.

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