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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:
17 June 2014 to 22 July 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
reference to other 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:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Appearance/physical state: Clear colourless liquid
- Storage conditions: Room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK.
At the start of the study the animals weighed 2.08 to 2.62 kg and were twelve to twenty weeks old. After an acclimatization period of at least five days each animal was given a number unique within the study.
The animais were individually housed in suspended cages. Free access to mains drinking water and food 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 twelve hours continuous light (06:00 to 18:00) and twelve 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.
On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal flank area using veterinary clippers. Only animais with a healthy intact epidermis by gross observation were selected for the study.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
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.
Observation period:
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
Number of animals:
3 (2 males + 1 female)
Details on study design:
The 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 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 retumed to their cages for the duration of the exposure period.
Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions. Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Male 74397
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Male 74398
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: Female 74485
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: Male 74397
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean score
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Male 74398
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean score
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: Female 74485
Irritant / corrosive response data:
Individual scores for erythema / eschar and edema are given in Table 1 (attached).
Well-defined erythema and slight edema were noted at one treated skin site (male no. 74398) with very slight erythema and very slight edema noted at one other treated skin site (male no. 74397) immediately, 1 and 24 hours after patch removal.
Well-defined erythema and slight edema persisted at one of these treated skin sites (male no. 74398) at the 48 and 72-Hour observations. Very slight erythema was noted at the remaining treated skin site (female no. 74485) 1 hour after patch removal with well-defined erythema and very slight edema noted at the 24 and 48-Hour observations and well-defined erythema at the 72-Hour observation. Moderate desquamation was noted at this treated skin site at the 7-Day observation.
One treated skin site (male no. 74397) appeared normal at the 48-Hour observation, one other treated skin site (male no. 74398) appeared normal atthe 7-Day observation and the remaining treated skin site (female no. 74485) appeared normal at the 14-Day observation.
Other effects:
All animals showed expected gain in body weight during the study (see Table 2, attached).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not a skin irritant in rabbits. In accordance with EU CLP Regulation (EC) No. 1272/2008 classification of this substance is not required for dermal irritation because scores for erythema and edema did not fulfill the criteria for classification. In addition the primary effects, erythema and edema, were fully reversible by the end of the 14-day observation period.
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.

Method

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. A quantity of 0.5 mL of the 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 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 according to the Draize scheme.

Results

A single 4-Hour, semi-occluded application of the test item to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight edema. Moderate desquamation was noted at one treated skin site. One treated skin site appeared normal at the 48-Hour observation, one other treated skin site appeared normal at the 7-Day observation and the remaining treated skin site appeared normal at the 14-Day observation.

Conclusion

The test item produced a primary irritation index of 2.5 and was considered to be a moderate irritant to rabbit skin according to the Draize scheme. No corrosive effects were noted.

According to GHS classification:

The test item produced a primary irritation index of respectively 0.33, 2 and 2 for erythema and Eschar formation for male 74397, male 74398 and female 74485 (considering observations at time 24h, 48h and 72h according to GHS requirements).

The test item produced a primary irritation index of respectively 0.33, 2 and 0.67 for oedema formation for male 74397, male 74398 and female 74485 (considering observations at time 24h, 48h and 72h according to GHS requirements).

In accordance with EU CLP Regulation (EC) No. 1272/2008 classification of this substance is not required for dermal irritation because scores for erythema and edema did not fulfil the criteria for classification. In addition the primary effects, erythema and edema, were fully reversible by the end of the 14-day observation period.