Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014-07-15 to 2014-08-19
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
1 hour observation performed ca. 2.5 hours after patch removal.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
1 hour observation performed ca. 2.5 hours after patch removal.
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state:amber coloured viscous liquid
- Analytical purity: 100%
- Expiration date of the lot/batch: 17 March 2016
- Storage condition of test material: room temperature on the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlon Laboratories UK Ltd., Leicestershire, UK
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.46 kg and 2.66 kg
- Housing: individual suspended cages
- Diet (e.g. ad libitum): 2930C Teklad Global Rabbit Diet ad libitum
- Water (e.g. ad libitum): mains drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark

IN-LIFE DATES: From: 2014-07-15 To: 2014-08-19

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Concentration (if solution): 0.5 mL

Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure: 1st rabbit: 3 sites on back or rabbit, 2nd rabbit: 1 site
- Type of wrap if used: Cotton gauze patch secured with surgical adhesive tape. Trunk of rabbit wrapped in elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): swabbing with cotton wool soaked in distilled water
- Time after start of exposure: 1st rabbit: 3 mins, 1 hour (2.5 hour as per deviation) and 4 hours. 2nd rabbit: 4 hours

SCORING SYSTEM: Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible
Remarks:
14 days
Remarks on result:
other: glossy skin noted at both sites but erythema fully reversed.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible
Irritant / corrosive response data:
See attached document for table of scores and observations.

No corrosive effects were noted

3 minutes
No evidence of skin irritation was noted during the study.
1 hour exposure
Very slight erythema was noted at the treated skin site at the treated skin site at the 24-hour observation with well-defined erythema and very slight oedema noted at the 48-hour observation and very slight erythema and very slight oedema at the 72-hour observation.
The treated skin appeared normal atthe 7-day observation.
4-hour exposure
Very slight erythema and very slight oedema were noted at one treated site 1 hours after patch removal. Well-defined erythema and very slight oedema were noted at both treated skin sites at the 24-hour observation with well-defined erythema and slight oedema noted at the 8 and 72-hour observations. Well-defined erythema and very slight oedema were noted at one treated skin site at the 7-day observation.
Other effects:
4 hour exposure
Loss of skin elasticity and flexibility were noted at both treated skin sites at the 48 and 72-hour observations and at one treated skin site at the 7-day observation. Light brown discolouration of the epidermis was also noted at both treated skin sites at the 72-hour observation. Superficial cracking of the epidermis was also noted at one treated skin site at the 7-day observation. Crust formation was noted at one treated skin site at the 7 and 14-day observations and preventedaccurate evaluation of erythema and oedema at teh 7-day observation. Glossy skin was noted at the other treated skin site at the 14-day observation.

Body weight
Both animals showed expecetd gain in body weigt during the study.

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 as the primary effects, erythema and edema, were reversed by the end of the observation period and the scores for erythema did not fall within the range requiring classification..
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 to clipped unabraded skin under 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, one further animal was treated. 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. 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 14.

Results

The mean total scores for erythema and oedema were 2 and 1.67 respectively. All erythema and oedema was reversible by the 14 day observation period.

A single 4 -hour, semi-occluded application of the test item to intact skin of two rabbits produced well-defined erythema and slight oedema. Other dermal reactions noted were loss of skin elasticity and flexibility, light brown disolouration of the epidermis, superficial cracking of the epidermis, crust formation and glossy skin. On one occasion the reactions noted prevented the accurate evaluation of erythema and oedema. No corrosive effects were noted.

Conclusion

In accordance with EU CLP Regulation (EC) No. 1272/2008, classification of this substance is not required for dermal irritation as the primary effects, erythema and edema, were reversed by the end of the observation period and the scores for erythema did not fall within the range requiring classification.