Z-85

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:

2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Method B4 Acute Toxicity (Skin Irriation) of Commission Directive 2004/73/EC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid: viscous

Details on test material:

Description: tan, slightly viscous liquid
Storage: room temp in dark

See justification for read-across in Section 13

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK and Charles River (France) Charlaronne, France supplied 2 and 1 rabbit, respectively. This deviation did not affect the results of the study.
- Housing: Individual, suspended cages


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
The dosage level was 0.5 ml/site and an adjacent area of untreated skin served as the control site.

Duration of treatment / exposure:

In order to check for corrosivity, one rabbit was used initially and three patches of 0.5 ml test substance/site was applied on a 2.5 cm x 2.5 cm cotton guaze patch. One patch was removed following 3 minutes, 1 hour and 4 hours after application. After consideration of the skin reactions observed in animal 1, two additional animals were used for the study. For the second 2 animals, the test substance was administered once per site and remained in contact with the skin for 4 hours followed by removal of the patch containing the test article.

Observation period:

The skin was examined and graded for dermal reaction at approximately 1, 24, 48 and 72 h following patch removal.

Number of animals:

3 rabbits

Details on study design:

On the day prior to testing, the fur was removed from the dorsal/flank area of each rabbit using veterniary clippers. Only animals with a healthy intact epidermis were used.

Initially, only one rabbit was treated by selecting three suitable sites on the back of the test animal. At each test site, 0.5 ml undiluted test substance was applied using a cotton guaze patch and the patch was secured using surgical adhesive tape. Additionally, the trunk of the rabbit was wrapped in an elastic bandage to protect the test sites. One patch was removed following 3 minutes, 1 hour, and 4 hours of exposure. Any residual test material was remvoed using 74% Industrial Methylated Spirits.

Once it was determined that the test substance did not cause severe corrosivity or reaction to the initial test animal, two more rabbits were selected for the study. They were prepared and treated the same as the first rabbit. However, only one patch was applied with 0.5 ml of the test substance for a 4 hour exposure period.

The skin was examined and graded for dermal reaction at approximately 1, 24, 48 and 72 h following patch removal.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other: Sum of all readings at 24 and 72 hr time point

Time point:

24/48/72 h

Score:

1.5

Remarks on result:

other: 4 hour exposure

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hrs

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.5

Max. score:

4

Reversibility:

fully reversible within: 7 Days

Results 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.25

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.25

Max. score:

4

Reversibility:

fully reversible within: 42 hours

Irritant / corrosive response data:

See results tables attached for individual animal scores.
Very slight erythema was noted at all treated skin sites one hour after patch removal with very slight to well-defined erythema at all treated skin sites at the 24-hour observation and at two treated skin sites at teh 48-hour observation. Very slight erythema was noted at two treated skin sites at the 72-hour observation.
Very slight oedema was noted at the two treated skin sites at teh 24-hour observation and at one treated skin site at the 48-hour observation.
One treated skin site appeared normal at the 48-hour observation.

Other effects:

Slight desquamation was observed at two treated skin sites at the 7-day observation..

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for dermal irritation i.e. althoughthere wasslightdesquamation in 2 animals on Day 7, the primary effects, erythema and edema, were reversed by the end of the observation period. Furthermore, the acute dermal and the LLNA studies did not demonstrate any clinical effects such as erythema or edema following exposure to the test article and can provide weight of evidence that the test substance will not cause skin irritation.

Executive summary:

Test Guidance

OECD Guideline No. 404 and EU Method B4

Method and materials

An acute dermal irritation study was conducted using undiluted test substance on New Zealand white rabbits. Initially, one rabbit was used and three patches of 0.5 ml test substance/site was applied on a 2.5 cm x 2.5 cm cotton guaze patch. One patch was removed following 3 minutes, 1 hour and 4 hours after application. After consideration of the skin reactions observed in animal 1, two additional animals were used for the study. For the second 2 animals, the test substance was administered once and the patch remained in contact with the skin for 4 hours and then followed by removal of the patch containing the test article. A 0.5 ml dose of the test article was applied to the clipped, unabraded skin at the test site. Following the exposure periods, the bandages were removed and the 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 7.

Results

The mean total scores for erthema and oedema were 1.1 and 0.33 respectively.All erythema and oedema was reversible within 7 days. Slight desquamation persisted in two animals at the 7-day observation period.

Conclusion

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for dermal irritation i.e. althoughthere was slight desquamation in 2 animals on Day 7, the primary effects, erythema and edema, were reversed by the end of the observation period. Furthermore, the acute dermal and the LLNA studies did not demonstrate any clinical effects such as erythema or edema following exposure to the test article and can provide weight of evidence that the test substance will not cause skin irritation.