Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
01 December 2003 and 13 December 2003.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study performed according to OECD and EC test guidelines and GLP compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report date:
2004

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification : SB-322065
Description : cream coloured solid with orange coloured pieces
Batch number : MTN-B-07C
Date received : 12 November 2003
Storage conditions : room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three New Zealand White rabbits were supplied by David Percival Ltd, Moston, Sandbach,
Cheshire, UK. At the start of the study the animals were in the weight range of 2.0 to 3.5 kg and
were twelve to twenty weeks old. After an acclimatisation period of at least five 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 metal cages. Free access to mains drinking
water and food (Certified Rabbit Diet (Code 5322) supplied by International Product Supplies
Limited, Wellingborough, Northants, 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. Any occasional deviations from these targets were considered not to have affected
the purpose or integrity of the study. 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.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
At
each test site a quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was
introduced
Duration of treatment / exposure:
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after
application. Any residual test material was removed by gentle swabbing with cotton wool soaked
in distilled water.
After consideration of the skin reactions produced in the first animal, two additional animals were
treated with 0.5 g of test material moistened with 0.5 ml of distilled water. One patch was applied
to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four
hours.
Observation period:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the
test sites were examined for evidence of primary irritation
Number of animals:
3
Details on study design:
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At
each test site a quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was
introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.
Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal
interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset and the
animal was returned to its cage for the duration of the exposure period.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after
application. Any residual test material was removed by gentle swabbing with cotton wool soaked
in distilled water.
After consideration of the skin reactions produced in the first animal, two additional animals were
treated with 0.5 g of test material moistened with 0.5 ml of distilled water. One patch was applied
to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four
hours.
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the
test sites were examined for evidence of primary irritation

Results and discussion

In vivo

Results
Irritation parameter:
primary dermal irritation index (PDII)
Remarks:
4 hours exposure
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours in two and within 7 days in one animal
Irritant / corrosive response data:
Very slight erythema was noted at two treated skin sites one hour after patch removal and at all
treated skin sites at the 24 and 48-hour observations and at one treated skin site at the 72-hour
observation.
Very slight oedema was noted at two treated skin sites one hour after patch removal.
Two treated skin sites appeared normal at the 72-hour observation and the remaining treated skin
site appeared normal 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:
The test material produced a primary irritation index of 0.7 and was classified as a
MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive
effects were noted.