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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye 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-referenceopen allclose all
Reason / purpose:
reference to same study
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 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
Cited as Directive 92/69/EEC, B.5
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes

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
Specific details on test material used for the study:
Name: n-dibutylether
CAS nr: 142-96-1
Batch nr: 0000093881
Content: > 99.3%

Test animals / tissue source

Species:
rabbit
Strain:
Himalayan
Details on test animals or tissues 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 3.5 months
- Weight at study initiation: 2.6-2.9 kg
- 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

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Amount applied: 0.1 ml (undiluted)
Duration of treatment / exposure:
single instillation into the conjunctival sac
Observation period (in vivo):
The eyes were examined ophthalmoscopically with a slit lamp prior to administration and 1, 24, 48 and 72 hours after the administration. 24 hours after administration, the eyes were treated additionally with fluorescein and examined.
Number of animals or in vitro replicates:
3
Details on study design:
The test was performed on three male rabbits (strain Himalayan, initial body weight 2.6 to 2.9 kg, age approximately 3.5 months at start of the adaptation period of at least 20 days). Dibutyl ether in a volume of 0.1 ml was placed in the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as control. For 8 hours following test item application, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eyes by excrements and urine.
The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48 and 72 hours after administration. 24 hours after administration the eyes were treated additionally with fluorescein and examined.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0.1
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
Corneal opacity of grade 1 (scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible) was observed in one animal 1 hour and 24 hours and in another animal 1 hour after instillation. The fluorescein test performed 24 hours after instillation of the test item revealed corneal staining (1/4 of the surface) in one animal. Irritation of the iris of grade 1 (markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)) was observed in one animal 1 hour after instillation.  Conjunctival redness of grade 1 (some blood vessels definitely hyperaemic (injected)) was observed in all animals 1 hour after instillation.  No changes, as compared to the untreated control eyes, were visible at 48-h and 72-h readings in any of the three test animals. The test substance produced no corrosion or irreversible effects in any of the animals. The mean scores of the 24, 48 and 72 hour readings were 0.0 regarding iris lesions, conjunctival redness, and conjunctival chemosis in all three rabbits. Regarding corneal opacity the mean score was also 0.0 in two of the three test-animals and 0.3 in one rabbit. 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:
GHS criteria not met
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 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 eye irritation potential of n-dibutylether was evaluated in this study conducted according to OECD TG 405 and EC Method B.5 and in accordance with the Principles of Good Laboratory Practice (GLP). The test was performed on three male rabbits (strain Himalayan, initial body weight 2.6 to 2.9 kg, age approximately 3.5 months at start of the adaptation period of at least 20 days). Dibutyl ether in a volume of 0.1 ml was placed in the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as control. For 8 hours following test item application, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eyes by excrements and urine.

The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48 and 72 hours after administration. 24 hours after administration the eyes were treated additionally with fluorescein and examined. Corneal opacity of grade 1 (scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible) was observed in one animal hour and 24 hours and in another animal 1 hour after instillation. The fluorescein test performed 24 hours after instillation of the test item revealed corneal staining (1/4 of the surface) in one animal. Irritation of the iris of grade 1 (markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive) was observed in one animal 1 hour after instillation. Conjunctival redness of grade 1 (some blood vessels definitely hyperaemic (injected)) was observed in all animals 1 hour after instillation.  No changes, as compared to the untreated control eyes, were visible at 48-h and 72-h readings in any of the three test animals. The test substance produced no corrosion or irreversible effects in any of the animals. 

The mean scores of the 24, 48 and 72 hour readings were 0.0 regarding iris lesions, conjunctival redness, and conjunctival chemosis in all three rabbits. Regarding corneal opacity the mean score was also 0.0 in two of the three test-animals and 0.3 in one rabbit.