Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 November 1988 to 23 December 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted to an appropriate test guideline with no or minor deviations.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Batch an other numbers SNC No. 1986: 88009
Toxicology reference No. St88/253Source: Shell Nederland Raffindarerij BV Rotterdam
Date received: 18 Oct 1988
Appearance: clear colourless liquid
Analysis: 94.51-97.51% cis isomer with 1.5% trans isomer
Density: 1.224 g/mL @ 15.2C
Date released 18 Nov 1988
Storage: dark at ambient temperature
Stability: stable for the duration of the study (no changes from 21 Nov 1988 to 19 Jan 1989

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
New Zealand White rabbits were obtained from a commercial supplier (Froxfield SPF Rabbits). Their bodyweight was between 3.0 and 4,0 kg and their age 3 to 5 months at the time of receipt. They were allowed to become accustomed to their new environment for at least two weeks before any experimentation commenced, The animals were singly housed in hanging, stainless cages with perforated dimple or wire-mesh flooring. Each cage measured 67 cm x 43 cm x 45 cm. A pelleted diet (Standard Rabbit Diet, S.Q.C., Special Diet Services Ltd.) and water from the public supply were provided ad libitum. There were no excursions of animal room environmental conditions beyond target values of 15° to 20°C and 30% to 70% R.H. that were considered to have influenced the outcome of the study. Lighting (fluorescent tube) was automatically controlled to provide a 12 hour day and 12 hour night. Animals assigned to the study were identified by cage-labels displaying the animal number, experiment number and treatment regime and by uniquely numbered ear-tags.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL undiluted test material on 6cm2 lint patch and held by semi-occlusive bandage
Duration of treatment / exposure:
4 h (then patch removed, washed with water, and dried)
Observation period:
14 days
Number of animals:
6 (sex not specified)
Details on study design:
Six rabbits were used. On the day before dosing the dorsal fur was removed using electric clippers. Any rabbit with signs of damage or irritation of the dorsum was replaced. The undiluted test material (0.5 ml) was applied to the skin on a 6 cm2 lint patch,, covered with gauze and held in place by a semi-occlusive elastic adhesive bandage. After a 4 hour exposure the dressings were removed, the skin washed with water and dried.

After treatment the animals were examined for erythema, oedema and other lesions. Erythema and oedema were each scored on a four point scale .
The mean scores at each time point and group mean scores at 24, 48 and 72 hours were calculated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
group mean
Time point:
other: 24, 48, 72 hour scores
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: dermal desaquamation observed day 7-14 (one animal to day 21)
Irritation parameter:
edema score
Basis:
mean
Remarks:
group mean
Time point:
other: 24, 48, 72 h scores
Score:
1.5
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks on result:
other: dermal desaquamation observed day 7-14 (one animal to day 21)
Irritant / corrosive response data:
Well defined erythema and moderate oedema at all dermal test sites 30 minutes after semi-occlusive dressing removal was observed. Subsequent examinations revealed progressive resolution of the irritation. All erythema and oedeam was reloved by day 14 of observation period. Desquamation of the treated skin was apparent in all rabbits on day 7 and 14, but persisted in only one animal on day 21.

Any other information on results incl. tables

Table 7 (amended) Dermal irriation following 4 hr application ot rabbit skin (n=6)
Time (post patch) 0.5 h 24 h 48 h 72 h 7 d 14 d 21 d
mean erythema score 2.0 1.7 1.2 1.2 1.2 0.0 0.0
mean oedema score 3.0 1.8 1.5 1.2 0.5 0.0 0.0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In the 4-hour rabbit skin irritancy test, the test material caused well-defined erythema and moderate oedema at all test sites shortly after removal of the semi-occlusive dressing; however, resolution of the irritation was complete by day 14.
Executive summary:

A GLP-compliant study has been conducted in accordance with OECD Guideline 404. In the 4-hour rabbit skin irritancy test, the test material caused well-defined erythema and moderate oedema at all test sites shortly after removal of the semi-occlusive dressing; however, resolution of the irritation was complete by day 14.