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Administrative data

skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10.9. - 17. 9. 2007
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD test guidelines followed and GLP compliant

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
according to guideline
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
tert-butyl N-[(1S,3S,4S)-4-hydroxy-4-[4-methoxy-3-(3-methoxypropoxy)phenyl]-1-[(2S,4S)-5-oxo-4-(propan-2-yl)oxolan-2-yl]-3-(propan-2-yl)butyl]carbamate
EC Number:
Cas Number:
Molecular formula:
tert-butyl N-[(1S,3S,4S)-4-hydroxy-4-[4-methoxy-3-(3-methoxypropoxy)phenyl]-1-[(2S,4S)-5-oxo-4-(propan-2-yl)oxolan-2-yl]-3-(propan-2-yl)butyl]carbamate
Details on test material:
Test substance name: SPPIOO C6
Mol. weight:551.73
CAS No.: not available
Batch No.:HH-853.35Kr
Purity: 99.2 % (A) - HPLC (Sum of isomers 1 and 2)
Significant impurities:sum of all impurities by HPLC: ........ 0.8 % (A)
Solvent content:
Isopropyl acetate: (CAS No. 108-21-4) ....... 1.9 % (w/w)
Methylcyclohexane: (CAS No. 108-87-2) ... 5.8 % (w/w)
Stability/Expiration: DEC-2007
findings of test facility:
Appearance: white, fine-crystallic powder
pH: approximately 5 (universal indicator papers pH 0 - 12)

Test animals

New Zealand White
Details on test animals or test system and environmental conditions:
Albino rabbits, strain New Zealand. Albino rabbit IS the preferred species according to the guidelines
breeding farm BioTest s.r.o., Komirovice, 281 25, Czech Republic
Body weight 3.7 - 4.1 kg, acclimatisation 6 days, 3 animals; 2 females and 1 male
individually in cages without bedding in conventional animal room; diet pelleted standard diet TM-MAK 1 for rabbits and guinea-pigs ad
libitum, made by Bergman, Kocanda Mill, 252 42 Jesenice uPrahy; drinking tap water ad libitum (quality corresponding to
Regulation No. 252/2004 Czech CoIl. of Law); room temperature 17 - 23°C, permanently monitored
30 -70 %, permanently monitored; 12-hour light/dark cycle
code number on inner side of ear of animal, number of study on each cage
certificate of good health condition - from breeding farm; no signs of diseases were observed at clinical check-in, In
acclimatization period and before the start of experiment.

Test system

Type of coverage:
Preparation of test site:
not required
Amount / concentration applied:
0.5 g (moistened with the smallest amount of water)
Duration of treatment / exposure:
first animal 3 minutes, 1 and 4 hour.
second and third animal 4 hours.
Observation period:
72 hours
Number of animals:
Details on study design:
Approximately 24 hours before application the fur on the dorsal area of the trunk was
removed by close clipping (area - 6 x 6 cm). Only animals with healthy intact skin were used.
After clipping the fur the animals were weighed.
3. 4. Application of the test substance
The test substance in the dose of 0.5 g (moistened with the smallest amount of water) was
applied on intact skin and then it was covered by gauze patch, foil and cellulose cotton and
held in place with non-irritating tape - Spofaplast. At the end of each exposure period the
patch was removed and remaining sample was washed with water.
In initial test three patches were applied sequentially to one animal (rabbit No.1). The first
patch was removed after three minutes. No serious skin reaction was observed, so the second
patch was applied for one hour. The observations at this stage indicated that exposure can
humanely be allowed to extend to four hours, so the third patch was applied for four hours.

After removing the patch, the response was graded. Because no corrosive or irritant effect was
observed after a 4-hour exposure, the response was verified in confirmatory test using two
additional animals, each with one patch for an exposure period of 4 hours.

Rabbits were examined for signs of erythema and oedema at 1, 24, 48 and 72 hours
after patch removal. Dermal irritation was graded

Results and discussion

In vivo

Irritant / corrosive response data:
No oedema or erythema was seen in any of the 4-hours treated skin sites.
Other effects:
No other skin reactions were seen. No signs of toxicity were noted.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Migrated information Criteria used for interpretation of results: EU
Three rabbits were exposed to 0.5 g oftest substance, applied onto clipped skin for 4 hours
using a semi-occlusive dressing. Skin reactions were evaluated after patch. removal and
observations were made 1, 24, 48 and 72 hours after exposure.
No skin irritation was caused by 4-hour exposure.
No other signs of intoxication were observed.