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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:
21 April 2015 to 24 April 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
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:
liquid
Details on test material:
- Physical state/appearance: Yellow Liquid
- Storage conditions: Room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Hsdlf:NZW
Details on test animals and environmental conditions:
ANIMAL INFORMATION
- Two New Zealand White (Hsdlf:NZW) were supplied by Harlan Laboratories UK Ltd, Leicestershire, UK.
- At the start of the study the animals weighed 2.75 or 3.00 kg and were 12 to 20 weeks old.
- After an acclimatisation period of at least 5 days each animal was given a number unique within the study. The number was written with black indelible marker pen on the inner surface of the ear and on the cage label.

ANIMAL CARE AND HUSBANDRY
- The animals were individually housed in suspended cages.
- Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd, Oxon, UK) was allowed throughout the study.
- The diet and drinking water were not considered to contain any contaminant of a level that might have affected the purpose or integrity of the study.
- Temperature and relative humidity were set to achieve limits of 17 to 23 °C and 30 to 70 % respectively.
- Lighting was controlled by a timer switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.
- The rate of air exchange was at least 15 changes per hour.
- Animals were provided with environmental enrichment items which were not considered to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
absorption of the test item was not determined
Controls:
not required
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
Four hours
Observation period:
72 hours
Number of animals:
Two
Details on study design:
MEASUREMENT OF pH
- The pH of the test item was determined prior to commencement of the study and the findings are shown in the table below.

TEST SYSTEM
- On the day before the test, two rabbits were clipped free of fur on the dorsal/flank area using veterinary clippers.
- Only animals where gross observation showed healthy intact epidermis were selected for the study.
- On the day of the investigation a suitable test site was selected on the back of each rabbit.
- Test item (0.5 mL) was applied directly to the skin 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 animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset.
- 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 was 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 primary irritancy and scored according to the scale shown in the table below.
- 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
- 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. The test item was graded according to the following scheme devised by Draize, J.H.
(1959): Non-irritant (primary irritation index 0); mild irritant (primary irritation index > 0 to 2); moderate irritant (primary irritation index > 2 to 5); severe irritant (primary irritation index > 5 to 8).
- 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 considered to be corrosive to rabbit skin. Grading according to Draize may, therefore, not be applicable.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 75038 male
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 75039 male
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 75038 male
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: 75039 male
Irritant / corrosive response data:
SKIN REACTIONS
- The individual scores for erythema/eschar and edema are given in Table 1 (attached).
- Very slight erythema and very slight edema were noted at both treated skin sites 1 hour after patch removal.
- The treated skin sites appeared normal at the 24-Hour observation.
Other effects:
BODY WEIGHT
- Individual body weights and body weight change are given in Table 2 (attached).
- Both animals showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced a primary irritation index of 0.0 and was considered to be non-irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.
Executive summary:

GUIDELINE

The study was performed to assess the irritancy potential of the test item to the skin of the New Zealand White rabbit in compliance with the OECD Guideline for the Testing of Chemicals No 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002) and Method B.4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No 440/2008.

 

METHODS

Two animals were clipped free of fur on the dorsal/flank area using veterinary clippers and 0.5 mL of test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in place with a strip of surgical adhesive tape and the trunk of each rabbit was wrapped in an elasticated corset. Four hours after application, the corset and patches were removed from each animal and any residual test item was 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 primary irritancy and scored.

 

RESULTS

Very slight erythema and very slight oedema were noted at both treated skin sites one hour after patch removal. The treated skin sites appeared normal at the 24-hour observation.

 

CONCLUSION

The test item produced a primary irritation index of 0.0 and was considered to be non-irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.