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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:
2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): n-dibutylether
- Physical state: colourless liquid
- Analytical purity: > 99.3%
- Purity test date:
- Lot/batch No.: 0000093881
- Expiration date of the lot/batch: December 19, 2004
- Stability under test conditions:
- Storage condition of test material: in tightly closed container, in a cool, well ventilated place, protected from light

Test animals

Species:
rabbit
Strain:
Himalayan
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: LPT laboratory of Pharmacology and Toxicology KG, branch Lohndorf, D-24601 Lohndorf/Post Wankendorf
- Age at study initiation: young adults - approximately 4 months
- Housing: during the exposure period, kept singly in restrainers, durimg the acclimatisation and after the 4-hour exposure period, the animals were housed singly in cages with dimensions (425 x 600 x 380 mm)
- Diet (e.g. ad libitum): ad libitumbefore and after the exposure period
- Water (e.g. ad libitum): ad libitumbefore and after the exposure period.
- Acclimation period: at least 20 adpatation days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Concentration: 0.5 ml undiluted
Duration of treatment / exposure:
4 hour(s)
Observation period:
After the 4-hour exposure period, the patch was removed and the resulting reactions were examined. Scores were noted at 60 minutes, 24, 48, 72 hours and 4 days after patch removal
Number of animals:
3
Details on study design:
The test was performed on three male rabbits (strain Himalayan, initial body weight 2.2 to 2.3 kg, age approx. 4 months at start of the adaptation period of at least 20 days). Approximately 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animals. Only animals with healthy intact skin were used. A dose of 0.5 ml was applied to the test site (area: approx. 6 cm³) and then covered with a gauze patch. The patch was held in contact with skin by means of a semi-occlusive dressing (non-irritating tape) for 4 hours. The surrounding untreated skin served as control. After the 4-hour exposure period the patch was removed and the resulting reactions were examined. Scores were taken 60 minutes, 24, 48, 72 hours and 4 days after patch removal.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 4 days
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 4 days
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no edema observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no edema observed
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no edema observed
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
A very slight erythema (barley perceptible, grade 1) was observed in all animals 60 minutes and 24 hours after patch removal. In two animals the very slight (barley perceptible) erythema persisted until 72 hours after patch removal. A very slight oedema (barley perceptible, grade 1) was observed in two animals 60 minutes after patch removal.  All effects were reversible within 4 days after patch removal. The mean scores of the 24, 48, and 72 hour readings for erythema were 1.0, 1.0, and 0.3 for the three test-animals, respectively, and for oedema 0.0 for all three test-animals. The mean scores of the 24, 48 and 72 hour readings do not exceed the limit values according to directive 93/21 EEC in any case.
Other effects:
There were no systemic intolerance reactions.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Considering the reported data in this irritation study it
can be stated that dibutyl ether showed very slight irritant
but no corrosive effects. According to the EC criteria for classification and
labelling requirements for dangerous substances and
preparations (Guidelines in Commission Directive 93/21 EEC) dibutyl ether does not have to be classified and has no
obligatory labelling requirements for skin irritation in
reference to this test result. Classification: not irritating
Executive summary:

The study was conducted according to OECD TG 404, EC Method B.4 and in accordance with the Principles of Good Laboratory Practice (GLP). The test was performed on three male rabbits (strain Himalayan, initial body weight 2.2 to 2.3 kg, age approx. 4 months at start of the adaptation period of at least 20 days). Approximately 24 hours before the test, the fur was removed by shaving from the dorsal area of the trunk of the animals. Only animals with healthy intact skin were used. A dose of 0.5 ml was applied to the test site (area: approx. 6 cm³) and then covered with a gauze patch. The patch was held in contact with skin by means of a semi-occlusive dressing (non-irritating tape) for 4 hours. The surrounding untreated skin served as control. After the 4-hour exposure period the patch was removed and the resulting reactions were examined. Scores were taken 60 minutes, 24, 48, 72 hours and 4 days after patch removal. A very slight erythema (barley perceptible, grade 1) was observed in all animals 60 minutes and 24 hours after patch removal. In two animals the very slight (barley perceptible) erythema persisted until 72 hours after patch removal. A very slight oedema (barley perceptible, grade 1) was observed in two animals 60 minutes after patch removal. All effects were reversible within 4 days after patch removal. The mean scores of the 24, 48, and 72 hour readings for erythema were 1.0, 1.0, and 0.3 for the three test-animals, respectively, and for oedema 0.0 for all three test-animals. There were no systemic intolerance reactions noted. Based on the results noted, n-dibutylether will not be classified as a skin irritant.