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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4'-cyclohexylidenedi-o-cresol
EC Number:
219-110-7
EC Name:
4,4'-cyclohexylidenedi-o-cresol
Cas Number:
2362-14-3
Molecular formula:
C20-H24-O2
IUPAC Name:
4-[1-(4-hydroxy-3-methylphenyl)cyclohexyl]-2-methylphenol
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Dimethyl cyclohexyl bisphenol (DMBPC; CAS No. 2362-14-3)
- Synonyms: Dimethyl bisphenolcyclohexane; 4,4’-cyclohexylidene di-o-cresol; 1,1-Bis(4-hydroxy-3-ethyl)cyclohexane; Bis-OC-Z
- Appearance: fine white powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Two male and two female (nulliparous and non-pregnant) New Zealand White rabbits, at least 10 weeks of age, weighing 2.12 to 2.24 kg were obtained from the supplier. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages with hardwood chips for bedding. They were provided food and tap water ad libitum. Room temperature was 68 ± 5 °F and the relative humidity ranged between 30 - 70 %. Room lights were on a 12-hour light/dark cycle.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL (~50 mg)
Duration of treatment / exposure:
The test substance was instilled into the left eye by gently pulling the lower lid away from the eye to form a cup into which the test substance was placed. The upper and lower lids were gently held together for approximately one second to prevent the loss of the test substance. The eyes of the test animals were not rinsed at any time following test substance application.
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours after treatment
Number of animals or in vitro replicates:
4 (1 preliminary and 3 main test animals)
Details on study design:
Within the 24 hours prior to dosing, the eyes of the animals selected for the test were examined to ensure that the eyes were free of abnormality, damage and disease, scored according to the Grades for Ocular Lesions and scored by Fluorescein Staining (details provided below). An initial procedure using a 10 % dilution of the test substance was performed on one animal. No irritation of the treated eye was observed and the study proceeded with the dosing of 3 additional animals with the neat test substance.

The animals were dosed in the left eye at a volume of 0.1 mL (~50 mg). The test substance was instilled into the left eye by gently pulling the lower lid away from the eye to form a cup into which the test substance was placed. The upper and lower lids were gently held together for approximately one second to prevent the loss of the test substance. The eyes of the test animals were not rinsed at any time following test substance application. The right eye remained untreated and served as a control. The eyes were examined at 1, 24, 48 and 72 hours after treatment and scored according to the Grades for Ocular Lesions provided below. In addition, after recording the scores at 24 hours, the eyes were further examined with the aid of fluorescein to further characterise corneal opacity. Evaluation of the eyes was facilitated by the use of a hand-held slit lamp. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start (Day 0) and completion (Day 3).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of the three animals
Time point:
24/48/72 h
Score:
0
Max. score:
20
Remarks on result:
other: total conjunctiva score = redness score + chemosis score x 2
Irritation parameter:
iris score
Basis:
mean
Remarks:
of the three animals
Time point:
24/48/72 h
Score:
0
Max. score:
10
Remarks on result:
other: total iris score = iris score x 5
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of the three animals
Time point:
24/48/72 h
Score:
0
Max. score:
80
Remarks on result:
other: total cornea score = opacity score + area score x 5
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of the three animals
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: total conjunctiva score = 2 (redness + chemosis x 2)
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: total conjunctiva score = 2 (redness + chemosis x 2)
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: total conjunctiva score = 2 (redness + chemosis x 2)
Irritant / corrosive response data:
No corneal or iridial involvement was observed in the test eyes of any animal at any time point. All three animals demonstrated mild conjunctival redness at the 1-hour scoring interval which resolved by the 24-hour observation period. No fluorescein staining was present in the test eyes at any time point during the study.
Other effects:
All animals gained weight and no systemic signs of toxicity were observed during the course of the study. No irritation was observed in the control eyes at any scoring interval.

Any other information on results incl. tables

Results 
































































































































































Summary of Results for the Treated (Left) Eyes



Animal No.



Effects at 1 hour



Cornea



Iris



Conjunctiva



Fluor Exam



O



A



V



R



C



IS



A



10611



0



0



0



1



0



n/a



n/a



10612



0



0



0



1



0



n/a



n/a



10613



0



0



0



1



0



n/a



n/a



Effects at 24 hours



10611



0



0



0



0



0



n/a



n/a



10612



0



0



0



0



0



n/a



n/a



10613



0



0



0



0



0



n/a



n/a



Effects at 48 hours



10611



0



0



0



0



0



0



0



10612



0



0



0



0



0



0



0



10613



0



0



0



0



0



0



0



Effects at 72 hours



10611



0



0



0



0



0



0



0



10612



0



0



0



0



0



0



0



10613



0



0



0



0



0



0



0



O: Opacity; A: Area Involved


V: Iritis Value


R: Redness; C: Chemosis;


Fluor: Fluorescein; IS: Intensity of staining; A: Area Involved


n/a: not applicable


Applicant's summary and conclusion

Interpretation of results:
other: Not classified according to EU criteria
Conclusions:
Under the conditions of this study, DMBPC is considered to be not irritating.
Executive summary:

The irritation potential of the test material was investigate din accordance with the standardised guidelines OECD 405 and EPA OPPTS 870.2400 under GLP conditions.

Test substance (0.1 mL, ~50 mg) was instilled into the left eye of 3 New Zealand White rabbits. The eyes of the test animals were not rinsed at any time following test substance application. The right eye remained untreated and served as a control. The eyes were examined at 1, 24, 48 and 72 hours after treatment. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start (Day 0) and completion (Day 3).   

No corneal or iridial involvement was observed in the test eyes of any animal at any time point. All three animals demonstrated mild conjunctival redness at the 1-hour scoring interval which resolved by the 24-hour observation period. No fluorescein staining was present in the test eyes at any time point during the study. All animals gained weight and no systemic signs of toxicity were observed. No irritation was observed in the control eyes at any scoring interval.

Under the conditions of this study, DMBPC is considered to be not irritating.