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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:
Study was undertaken between 7 and 21 January 1986.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with generally accepted scientific principles, possibly with incomplete or methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): D.I.X.T (Di-isopropyl xanthogentetrasulphide [poly sulphide])
- Physical state: Clear yellow, oily liquid
- Storage condition of test material: ambient temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Obtained from Froxfield Rabbits, Petersfield, Hampshire.
- Age at study initiation: Approximately 11 to 13 weeks of age.
- Weight at study initiation: Weight range 2.4 to 3.0 kg, prior to treatment on Day 1
- Housing: The rabbits were individually housed in metal cages with perforated floors
- Diet (e.g. ad libitum): Free access to SDS Standard Rabbit Diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The rabbits selected for the study were all acclimated to the laboratory environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Room temperature was maintained at approximately 19°C.
- Humidity (%): Relative humidity at 30-70%.
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A 0.5 ml aliquot of D.I.X.T. was applied.

Duration of treatment / exposure:
SIngle application for a four hour period.
Observation period:
Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4. Additional observations were made on Days 5 through 14.
Number of animals:
6
Details on study design:
TEST SITE
Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 10 cm square.

A 0.5 ml aliquot of D.I.X.T. was applied under a 2.5 cm square gauze pad to one intact skin site on each animal.

Each treatment site was occluded with "Elastoplast" elastic adhesive dressing for a four hour period. The animals were not restrained during the exposure period and were returned to their cages.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed using distilled water to remove any residual test substance.

SCORING SYSTEM:
Grading and scoring of the dermal reactions were performed using the prescribed numerical scoring system as follows:

Erythema and eschar formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation:
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of area well-defined by definite raising): 2
Moderate oedema (raised approximately 1 millimetre): 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure): 4

Any other lesion not covered by this scoring system, will be described.







Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
Mean of all animals (6 in total) scores for erythema
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
other: Erythema persisted up to day 14 in 4 animals. 2 animals showed no effects after 4 days.
Irritation parameter:
edema score
Basis:
mean
Remarks:
Mean of all animals (6 in total) scores for oedema
Time point:
24/48/72 h
Score:
1.1
Max. score:
4
Reversibility:
other: Oedema persisted up to day 14 in 4 animals. 2 animals showed no effects after 4 days.
Irritant / corrosive response data:
The numerical scores awarded to the dermal reactions elicited by D.I.X.T. are given in Table 1.

Very slight erythema and oedema was observed in all six rabbits following removal of the bandages on Day 1. Very slight to well-defined erythema with or without very slight oedema was seen in all six rabbits on Day 2. These reactions ameliorated in two animals and had resolved completely by Day 4 in these animals.

Well-defined erythema with slight to moderate oedema developed in the four remaining animals.

Well-defined dermal reactions persisted in four animals at Day 14.

Desquamation of the stratum corneum was seen in three animals.

Any other information on results incl. tables

Table 1: Dermal reaction elicited by DIXT

Rabbit Number (male)

E= Erythema

O – Oedema

Day

1*

2

3

4

5

6

7

8

9

10

11

12

13

14

1101

E

O

1

1

1

1

2

1

2

2

2

2

2

2

2A

2

2A

2

2

2

2

2

1

2

1

2

1

2

1

2

1102

E

O

1

1

2

1

2

2

2

2

2

2

2

2

2A

2

2A

2

2

2

2

1

2

2

2

2

1

2

1

2

1103

E

O

1

1

2

1

1

1

0

0

 

 

 

 

 

 

 

 

 

 

1104

E

O

1

1

1

1

2

1

2

2

2

2

2

2

1

2

1

2

1

2

1

1

1

2

2

2

2

2

2

2

1105

E

O

1

1

1

0

1

0

0

0

 

 

 

 

 

 

 

 

 

 

1106

E

O

1

1

1

1

2

2

2

2

2

2

2

2

2A

3

2

3

2

3

2

3

2

2

2

2

2

2

2

2

* Approximately 30 minutes after removal of the dressing

A: Desquamation of the stratum corneum.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single semi-occlusive application of D.I.X.T. to intact rabbit skin for four hours elicited well-defined to moderate dermal irritation.
Executive summary:

Introduction:

The experimental procedure used followed the Testing Guidelines as described in the Federal Register, Vol. 50, No. 188, Part 11 of 27 September 1985, Section 798.4470 - Primary Dermal Irritation.

Results:

A single 4-hour, semi-occluded application of the test item to the intact skin of 6 New Zealand White strain rabbits produced the following results:

Very slight erythema and oedema was observed in all six rabbits following removal of the bandages on Day 1. Very slight to well-defined erythema with or without very slight oedema was seen in all six rabbits on Day 2. These reactions ameliorated in two animals and had resolved completely by Day 4 in these animals.

Well-defined erythema with slight to moderate oedema developed in the four remaining animals.

Well-defined dermal reactions persisted in four animals at Day 14.

Desquamation of the stratum corneum was seen in three animals.

Conclusion:

A single semi-occlusive application of D.I.X.T. to intact rabbit skin for four hours elicited well-defined to moderate dermal irritation.