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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:
September 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): Javanol
- Physical state: Pale yellow viscous liquid
- Analytical purity: 88.4% (GC, sum of two peaks)
- Lot/batch No.: 008825
Specific details on test material used for the study:
- Name of test material (as cited in study report): Javanol
- Physical state: Pale yellow viscous liquid
- Analytical purity: 88.4% (GC, sum of two peaks)
- Lot/batch No.: 008825

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
1 male and 2 females.
Acclimatization four days under test conditions after health examination. Only animals without any visual signs of illness were used for the study.
Standard laboratory conditions: 10-15 air changes per hour, temeprature target at 22 +/- 3°C and relative humidity between 40-70% (values above 70% during cleaning process possible). 12 hour dark/light cycle. Recorded music was played for approximately 8 hours during the light period.
Accomodation: Individually in stainless steel cages with an automatic cleaning system equipped with feed hoppers, drinking water bowls and wood for gnawing.
Diet: Pelleted standard Kliba 341 rabbit maintenance diet ad libitum (batch no. 77/97).
Diet source: 'Kliba', Kliba Mulhen AG, Switzerland
Water: Community tap water for Itingen, ad libitum, in water bowls.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Amount / concentration applied:
0,5 ml (per animal) of the test article (100%) was applied to approximately 6cm2 of the intact skin of the clipped area. It was covered with 2.5 cm x 2.5 cm patch of surguca gauze and the gauze was covered with a semi-occlusive dressing.
Duration of treatment / exposure:
4 hours
Observation period:
Daily, during 14 days
Number of animals:
3
Details on study design:
Approximately three days before treatment, the dorsal fur was clipped with an electric clipper, exposing an area of approximately 100cm2. The skin of the animals was examined approximately 24 hours before treatment, and, if necessary, regrown fur was again clipped.
Animals with overt signs of skin injury or marked irritation which may have interfered with the interpretation of the results were not used in the test.
On the day of treatment, the test article was applied to approximately 6cm2 of the intact skin of the clipped area. It was covered with a semi-occlusive dressing. The dressing was wrapped around abdomen and anchored with tape.
The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal: 19
Time point:
24 h
Score:
0.67
Irritation parameter:
edema score
Basis:
animal: 20
Time point:
48 h
Score:
1
Irritation parameter:
edema score
Basis:
animal: 21
Time point:
72 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal: 19
Time point:
24 h
Score:
0.67
Irritation parameter:
erythema score
Basis:
animal: 20
Time point:
48 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal: 21
Time point:
72 h
Score:
1
Irritant / corrosive response data:
Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 1.78. Very slight reddening and very slight swelling were noted in two animals after 24 hours and in all animals from 48 hours to 7 days after application. All findings were reversible after 14 days. Local signs (mean values from 24 to 72 hours) consisted of grade 0.89 erythmea and grade 0.89 edema.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based upon the referred classification criteria, Javanol is considered to be 'not irritating' to rabbit skin.
Executive summary:

The primary skin irritation potential of the test article was investigated by a topical application of 0.5 ml to 6cm2 intact dorsal skin of each of three young adult New Zealand White rabbits. The duration of the treatment was 4 hours.The scoring of skin reactions was performed 1, 24, 48 and 72 hours as well as 7 and 14 days after removal of the dressing. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion.

The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 hours and then dividing by the number of data points. The primary eye irritation score was 1.78 (max 8.0). Local signs (mean values from 24 to 72 hours) consisted of grade 0.89 erythema and grade 0.89 edema.

Very slight reddening and swelling were noted in two animals after 24 hours and in all animals from 48 hours to 7 days after application. All findings were reversible after 14 days.

The test article did not cause staining of the treated skin.

No corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based upon the referred classification criteria (EEC comission directive 93/21/EEC of April 27, 1993), the test article is considered to be 'not irritating' to rabbit skin.