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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 April 1999 - 30 April 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: done under GLP and OECD method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
July 1992
Qualifier:
according to guideline
Guideline:
other: EEC Directive 92/69/EEC, Annex V, Test 84, July 1992.
GLP compliance:
yes
Remarks:
OECD Principles of Good Laboratory Practice, Statutory Instrument No. 654, 1997, ISBN 0-11- 064105-1.

Test material

Constituent 1
Chemical structure
Reference substance name:
(1S)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propanol
EC Number:
608-251-3
Cas Number:
287930-77-2
Molecular formula:
C29H28NO2Cl
IUPAC Name:
(1S)-1-[3-[(1E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-2-yl)phenyl]propanol
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
White, 99.9% purity

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Age at study initiation: 3 months
- Weight at study initiation: 2.41 - 2.75 kg
- Housing: The animals were housed individually in stainless steel cages (dimensions
77.2 x 70.1 x 48 cm) with a Noryl moulded dual level interior and perforated floor beneath which was an absorbent paper lined tray.
- Water and Diet: Each cage was supplied with an automatic watering valve (domestic mains) and a food hopper. Each animal was also offered a supplement of hay or organically grown cabbage ca. twice weekly.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C - 21°C
- Humidity (%): 58%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycles

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Remarks:
Applied topically under water moistened gauze patches (2.5 cm x 2.5 cm)
Controls:
other: contralateral zone of same animal
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4hr
Observation period:
1hr, 24hr, 48hr and 72hr after dressing removed
Number of animals:
3
Details on study design:
All the animals were checked for viability early in the morning and again as late as possible on each day.
All the animals were examined for reaction to treatment. The onset, intensity and duration of any signs were recorded.
On the day prior to test material application, the hair was clipped from an area (approximately 8 cmx 8 cm) across the dorsal trunk of each rabbit. Care was taken to avoid abrading the skin.
On the following day, the dorsal trunk of each rabbit was wetted and treated with test material applied topically under water moistened gauze patches (2.5 cm x 2.5 cm).
Each patch was then covered with semi-occlusive tape (Micropore, 3M Medical Surgical Division, USA) and elastic bandage (Smith and Nephew, Hull, England) wrapped round the torso of the rabbit.
After a contact period of 4 hours, the patch was removed and the skin wiped with sterile water. The test site was delineated

Results and discussion

In vivo

Other effects:
There was no sign of dermal effects or define the dermal effects noted.

Any other information on results incl. tables

 

Animal

 

Body Weight at Dosing (kg)

Time after Patch Removal/Reaction Score

Erythema

Oedema

1h

24h

48h

72h

1h

24h

48h

72h

1

3.63

0

0

0

0

0

0

0

0

2

3.73

0

0

0

0

0

0

0

0

3

3.68

0

0

0

0

0

0

0

0

Acute Skin Irritation Test in Rabbits Scoring System

 

 

Ervthema and Eschar Formation

No erythema     .........................................................................................o

Very sligh terythema (barely perceptible}..................................................................1

Well defined erythema.............................................................................. 2

Moderate to severe erythema .......................................................................3

Severe erythema (beet redness} to slight eschar formation (injuries in depth)

preventing grading of erythema................................................................4

Oedema Formation

No oedema       ............................................................................................ o

Very slght oedema (barely perceptible}................................................ .........................1

Slight oedema (edges of area well defined by definite raising)......................................2

Moderate oedema (raised approximately 1mm}.............................................3

Severe oedema (raised more than 1mm and extending beyond the area

of exposure}............................................................................................4

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, L-744,341 is considered to be non irritating to rabbit skin.

Executive summary:
The acute dermal irritation potential of the test material was investigated in New Zealand White rabbits. No oedema or erythema was noted in any animal at any of the observation periods. There were no additional observations noted.