Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 August 2010 - .........................................
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guideline; adeuqate coherence betwee data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Remarks:
deviations to study plan but not to guideline
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Remarks:
idem above
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products
- Physical state: yellow liquid
- Purity: not indicated (complex composition)
- Lot/batch No.: LR_OXO_2010-07-12
- Date of analysis: 12 July 2010
- Expiration date of the lot/batch: July 2011
- Storage conditions of test material: at +4°C and under nitrogen gas.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Breeder: Hypharm, La Corbière, Roussay, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 3.2 +/- 0.1 kg
- Housing: individually housed in Techniplast cages
- Diet (e.g. ad libitum): free access to breeding pelleted diet “type 110C”
- Water (e.g. ad libitum): tap water (filtered using a 0.22 µm filter) contained in bottles
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (7:00 - 19:00)

IN-LIFE DATES: From: 17 August 2010 To: 20 September 2010.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye, which remained untreated, served as control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL.
Duration of treatment / exposure:
Single application to the eye.
Observation period (in vivo):
6 days.
Number of animals or in vitro replicates:
Two males and one female.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

SCORING SYSTEM: Draize scale.

TOOL USED TO ASSESS SCORE: UV lamp and 0.5% sodium fluorescein solution.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 2 days
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1.7
Max. score:
1
Reversibility:
fully reversible within: 3 days
Remarks on result:
other: discharge also
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 6 days
Remarks on result:
other: whitish purulent discharge also
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 2 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 3 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
cornea opacity score
Remarks:
corneal opacity (intensity)
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 3 days
Irritation parameter:
cornea opacity score
Remarks:
corneal opacity (intensity)
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 3 days
Irritation parameter:
cornea opacity score
Remarks:
corneal opacity (intensity)
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
Slight to marked chemosis and redness of the conjunctiva (grades 1 to 3) were observed in all animals from day 1 until day 2, 4 or 6. Clear and/or whitish purulent discharge was observed in two animals from day 2 until day 3 or 4.
Iris lesions were noted in one animal from day 1 until day 3.
A slight or moderate corneal opacity was recorded in two animals on days 2 and 3.
Other effects:
None.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information not classified Criteria used for interpretation of results: EU
Conclusions:
The test item,distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was slightly irritant when administered by ocular route to rabbits. However it does not need to be classified according to EU.
Executive summary:

The objective of this study was to evaluate the potential of the test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, to induce irritation following a single ocular administration in rabbitsaccording to OECD (No. 405, 24th April 2002) and Commission Regulation (EC) (No. 440/2008, B.5, 30 May 2008) guidelines.

The study was conducted in compliance with the principles of Good Laboratory Practice.

 

Methods

The test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products,was first administered to a single male New Zealand White rabbit.

Since the test item was not severely irritant on this first animal, it was then evaluated simultaneouslyon two other animals.

The quantity of the test item administered was 0.1 mL.

The test item was introduced into the conjunctival sac of the left eye. The right eye, which remained untreated, served as control.

The eyes were not rinsed after administration of the test item.

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until the reversibility of the ocular reactions (at least day 7).

Body weight was recorded at the beginning and the end of the observation period. On completion of the observation period, the animals were sacrificed then discarded without macroscopic post‑mortem examination.

 

The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal.

The interpretation of results was carried out according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations).

 

Results

Slight to marked chemosis and redness of the conjunctiva (grades 1 to 3) were observed in all animals from day 1 until day 2, 4 or 6. Clear and/or whitish purulent discharge was observed in two animals from day 2 until day 3 or 4.

Iris lesions were noted in one animal from day 1 until day 3.

A slight or moderate corneal opacity was recorded in two animals on days 2 and 3.

 

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 2.3 and 0.3 for chemosis, 1.7, 2.3 and 0.3 for redness of the conjunctiva, 0.0, 0.7 and 0.0 for iris lesions and 1.0, 1.3 and 0.0 for corneal opacity.

 

Conclusion

Under the experimental conditions of the study, the test item, distillation residues of butyraldehyde, 2-ethylhexenal and isobutanal hydrogenation by-products, was slightly irritant when administered by ocular route to rabbits.

However, according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item should not be classified as irritating to the eyes.