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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
The dose level applied was 25 mg instead of 100 mg for solids, as recommended in the guideline. However, it is considered that this deviation does not affect the outcome of the study.
Cross-reference
Reason / purpose:
read-across source
Remarks:
to
Reference
Endpoint:
eye irritation, other
Remarks:
read-across from supporting subtance
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from an analogue substance for which a guideline study (Klimisch 2) is available.
Reason / purpose:
read-across source
Principles of method if other than guideline:
Read-across from company data on an analogue
GLP compliance:
yes
Remarks on result:
other: Read across, see cross reference to source information

The results are presented in the cross reference to the source information (read-across).

Interpretation of results:
GHS criteria not met
Conclusions:
In the rabbit eye irritancy test, the test material (source chemical) caused slight conjunctival redness within 1 hour of dosing which had cleared by 24 hours. The test material is therefore not an eye irritant in rabbits. The read across is applied and the target chemical BHT is considered to be non-irritant for the eyes.
Executive summary:

The analogue CAS No. 118-82-1 (2,2',6,6'-tetra-tert-butyl-4,4'-methylenediphenol)which shares the same functional group (alkylphenol) with the substance CAS no. 128-37-0 (2,6-di-tert-butyl-p-cresol), also has comparable values for the relevant molecular properties. Therefore, the results obtained with the substance CAS No. 118-82-1 can be used for the read-across approach.

Based on company data, the read-across approach is applied from 2,2',6,6'-tetra-tert-butyl-4,4'-methylenediphenol and the substance 2,6 -di-tert-butyl-p-cresol (BHT) is considered to be non-irritant for the eyes.

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(However, it is considered that this deviation does not affect the outcome of the study).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: Pale yellow powder
- Analytical purity: 99.04%
- Lot/batch No.: 5/87; Indent 9200/9622
- Storage condition of test material: Following its arrival in Compound Control this test substance was stored in the dark at ambient temperature.
- Stability: Infra-red spectra of the test substance were taken. There were no significant differences between the spectra and so, on this basis, the test substance was judged to have been stable for the duration of this study.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Sittingbourne Research Centre Breeding unit
- Age at study initiation: 4-9 months old
- Weight at study initiation: males: 3872-4184 g; females: 3276-4806 g
- Housing: Animals were singly housed in hanging, stainless-steel cages with all-mesh floors and tops and half-mesh fronts; each cage measured 67 cm x 43 cm x 45 cm.
- Diet (e.g. ad libitum): Standard Rabbit Diet, S.Q.C., Special Diet Services Ltd., Essex, ad libitum.
- Water (e.g. ad libitum): Filtered from the public supply , ad libitum.
- Acclimation period: At least, two weeks.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-19 ºC
- Humidity (%): Not documented.
- Air changes (per hr): Not documented.
- Photoperiod (hrs dark / hrs light): Lighting was automatically switched on for the day (06.00 to 18.00 hours GMT) and off for the night (18.00 to 06.00 hours GMT).


Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 mg
Duration of treatment / exposure:
The eyes were not washed.
Observation period (in vivo):
A visual assessment of eye irritancy was made at 1, 4, 24, 48 and 72 hours and 7 days after instillation.
Number of animals or in vitro replicates:
Three per sex
Details on study design:
SCORING SYSTEM: Irritancy was scored for the cornea, iris and conjunctivae using the standard scores included in the study report.


TOOL USED TO ASSESS SCORE: At 24 hours and in the event of any corneal damage visualization was aided by the instillation of one drop of 2% fluorescein solution.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Irritation parameter:
other: Conjunctivae redness
Basis:
mean
Time point:
other: 24-72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Remarks:
The only occular effect was slight conjunctival redness in all rabbits within 1 hour of dosing.
Irritant / corrosive response data:
The instillation of the test substance powder into the conjunctival sac of one eye of each of six rabbits resulted in slight initial pain. The only occular effect was slight conjunctival redness in all rabbits within 1 hour of dosing which had cleared by 24 hours.

Any other information on results incl. tables

Table 7.3.2: Mean eye irritation scores

Redness

Chemosis

Discharge

Opacity

Iris

24 hours

0

0

0

0

0

48 hours

0

0

0

0

0

72 hours

0

0

0

0

0

7 days

0

0

0

0

0

Mean score

24-72 h

0.0

0.0

0.0

0.0

0.0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In the rabbit eye irritancy test, the test material caused slight conjunctival redness within 1 hour of dosing which had cleared by 24 hours. The test material is therefore not an eye irritant in rabbits.
Executive summary:

The test material (25 mg) was applied to the eyes of six New Zealand White rabbits (3 per sex). A visual assessment of eye irritancy was made at 1, 4, 24, 48 and 72 hours and 7 days after instillation. The test material caused slight conjunctival redness within 1 hour of dosing which had cleared by 24 hours.