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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:
1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Well documented, according to accepted guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

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)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): 1,4-Butanedioldiglycidylether (BDDGE)
- Physical state: liquid
- Analytical purity: 97.1%
- Lot/batch No.: DC 1294.2

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH 4414 Fuellinsdorf/Switzerland
- Age at study initiation: males: 14 weeks, female: 15 weeks
- Weight at study initiation: males: 2.0 - 2.9 kg, female: 2.6 kg
- Housing: Individually in stainless steel cages equipped with an automatic cleaning and drinking system
- Diet (e.g. ad libitum): Pelleted standard Kliba 341, Batch 37/88 and 38/88 rabbit maintenance diet ("Kliba", Klingentalmuehle AG, 4303 Kaiseraugst, Switzerland) ad libitum
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum
- Acclimation period: Four days under laboratory conditions after veterinary examination


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ±3 °C
- Humidity (%): 40 - 70%
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12


Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
The eyes of each animal were examined 1, 24, 48 and 72 hours, 7, 14 and 21 days after administration.

Number of animals or in vitro replicates:
3
Details on study design:
The eyes of the animals were observed 24 hours prior to test article administration. The test article (0.1 mL per animal) was placed in the conjunctival sac of the left 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 to prevent loss of the test article. The right eye remained untreated and served as the reference control. The eyes of each animal were examined 1, 24,48 and 72 hours, 7, 14 and 21 days after administration. The irritation was assessed according to the OECD Guidelines for testing of Chemicals, Section 4, number 405 "Acute Eye Irritation/Corrosion adopted February 24, 1987. The corrosive properties of the test article and the staining of the treated eye were described and recorded. Eye examinations were made with a slit-lamp 30 SL/M (C. Zeiss AG, Zuerich/Switzerland) and a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel/Switzerland).

The following numerical scoring system was used to grade the eye lesions: see attached tables.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 3
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 1
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 2
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 1
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 4
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.67
Max. score:
2
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 1
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 1
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
not reversible
Remarks on result:
other: score at 21 days was 2
Irritant / corrosive response data:
see attached table entitled eye irritation scores

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Conclusions:
Under the conditions of this experiment, 1,4-Butanedioldiglycidylether (BBDGE) was found to cause a primary irritation score of 5.92, when applied undiluted to the rabbit eye mucosa.
No staining of the cornea and conjunctivae of the treated eyes or colouring by the test article was observed.
Corneal opacity with different intensity was observed in all animals within 1 hour to 21 days after test article application.
According to EEC Council Directive, 83/467/EEC, July 1963 Brussels, Belgium, the mean value (24 – 72 hours) of the scores for each type of lesion, calculated for each of the three animals separately, is as follows: Cornea opacity: 1.33, 1.00, 1.33; Iris: 0.67, 1.00, 0.67; Conjunctivae redness: 2.00, 2.00, 2.67; Conjunctivae chemosis: 3.00, 2.00, 2.00.