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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:
The study was conducted between 04 August 2015 and 07 August 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Two male New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Envigo RMS (UK) Limited, Leicestershire, UK. At the start of the study the animals weighed 2.59 or 2.68 kg and were 12 to 20 weeks old. After an acclimatization period of at least 5 days each animal was given a number unique within the study which was written with a black indelible marker pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Envigo RMS (UK) Limited, Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.


Justification
The rabbit is the preferred species of choice as historically used for irritation studies and is specified in the appropriate test guidelines. The number of animals used was the minimum required to achieve the objectives of the study. Testing was conducted in two animals and the response in those animals was such that exposure of a third animal would not affect classification of the test item, no further testing was needed.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
test item moistened with 0.5 ml of distilled water.
Controls:
no
Amount / concentration applied:
0.5 g
Duration of treatment / exposure:
Four hours
Observation period:
72 hours
Number of animals:
Two males
Details on study design:
On the day before the test two rabbits were clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

On the day of the test a suitable test site was selected on the back of each rabbit. At each test site a quantity of 0.5 g of the test item, moistened sufficiently with 0.5 mL of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.

Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in distilled water.

Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored.
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.

Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Interpretation of results
Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme
The scores for erythema and edema at the 24 and 72‑Hour readings were totaled for the two test rabbits (8 values) and this total was divided by 4 to give the primary irritation index of the test item.
 
If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test item is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.
 
The results were also interpreted according to theGlobally Harmonized Systemof Classification and Labelling of Chemicals.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritant / corrosive response data:
Red colored staining, caused by the test item but not preventing evaluation of skin responses, was noted at both treated skin sites at all observations.
No evidence of skin irritation was noted during the study.
Other effects:
Body Weight
Both animals showed expected gain in body weight during the study.

Any other information on results incl. tables

Individual Skin Reactions

Skin Reaction

Observation Time
(following patch removal)

Individual Scores

Total

Rabbit Number and Sex

75165Male

75169Male

Erythema/Eschar Formation

Immediately

0STA

0STA

(0 )

1 Hour

0STA

0STA

( 0 )

24 Hours

0STA

0STA

0

48 Hours

0STA

0STA

( 0 )

72 Hours

0STA

0STA

0

Edema Formation

Immediately

0

0

( 0 )

1 Hour

0

0

( 0 )

24 Hours

0

0

0

48 Hours

0

0

( 0 )

72 Hours

0

0

0

Sum of 24 and 72‑Hour Readings (S) :        0

Primary Irritation Index (S/4)              :        0/4 = 0.0

Classification                                       :        NON‑IRRITANT

(   ) =    Total values not used for calculation of primary irritation index

STA =    Red colored staining

Individual Body Weights and Body Weight Change

Rabbit Number
and Sex

Individual Body Weight (kg)

Body Weight Change (kg)

Day 0

Day 3

75165
Male

2.68

2.71

0.03

75169
Male

2.59

2.61

0.02

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item produced a primary irritation index of 0.0 and was classified as non irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test item does not meet the criteria for classification according to the Globally Harmonized System of Classification and Labelling of Chemicals.
Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit.

 

Results

A single 4‑Hour, semi‑occluded application of the test item to the intact skin of two male rabbits produced no evidence of skin irritation.

 

Conclusion

The test item produced a primary irritation index of0.0and was classified as non‑irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

 

The test item does not meet the criteria for classification according to the Globally Harmonized Systemof Classification and Labelling of Chemicals.