4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol; bisphenol AF

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 - 26 April 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study was conducted in accordance with International guidelines and in accordance with GLP. All guideline validity criteria were met.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2001

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol

Cas Number:

1478-61-1

Molecular formula:

C15H10F6O2

IUPAC Name:

4,4'-[2,2,2-trifluoro-1-(trifluoromethyl)ethylidene]diphenol

Test material form:

solid

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and in the dark.
- Stability under test conditions: Not reported
- Solubility and stability of the test substance in the solvent/vehicle: Not reported
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not reported

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No
- Preliminary purification step (if any): No
- Final dilution of a dissolved solid, stock liquid or gel: N/A
- Final preparation of a solid: N/A

FORM AS APPLIED IN THE TEST (if different from that of starting material): N/A

OTHER SPECIFICS: Test item instilled into test system as delivered by Sponsor.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: minimum of 6 weeks old
- Weight at study initiation: between 1.0 - 3.5 kg
- Housing: Animals individually housed in cages with perforated floors (Scanbur, Denmark - 53.5 x 63 x 38.5 cm)
- Diet (e.g. ad libitum): Stadard laboratory diet (Charles River breeding and maintenance diet for rabbits, Altromin, Germany). 100 g/ day supplied to each individual. Hay was also provided wice weekly.
- Water (e.g. ad libitum): Tap water supplied ad libitum
- Acclimation period: Minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12:12 light:dark

IN-LIFE DATES: From: To: Not reported

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): ca. 33 mg of unchanged test item
- Concentration (if solution): n/a

VEHICLE
- Amount(s) applied (volume or weight with unit): n/a
- Concentration (if solution): n/a
- Lot/batch no. (if required): n/a
- Purity: n/a

Duration of treatment / exposure:

24 h

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

3 (males)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No
- Time after start of exposure: n/a

SCORING SYSTEM:

Immediately after the 24 h observation, a solution of 2 % fluoroscein in water (pH 7) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Any stained areas (indicating epitheleal damage) was estimated as a percentage of the total corneal area.

Irritation was assessed once daily for 3 days. The key parameters measured were; corneal irritation (including % of cornea involved), changes to the iris, conjunctival irritation, chemosis and discharge. Each parameter was measured on a numerical scale as described in OECD 405 TG.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hrs

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks:

within 72 hrs

Other effects:

OTHER EFFECTS:
- Visible damage on test system:

Corneal injury was seen as opacity (max. grade 3) and epitheleal damage (max. 90 % of corneal area). The corneal injury persisted until termination (72 h).

Iridial irritation (grade 1) was observed and persisted until termination.

Irritation of the conjunctivae was seen as redness, chemosis and discharge and persisted until termination.

Grey/ white discolouration (sign of necrosis) of the nicititating membrane was noted in two animals at 48 and 72 h. Reduced elasticity of the eyelids was noted in one animal at 48 hours in all animals at 72 h after instillation.

Based on the severity of the ocular lesions observed, no reversibility was expected- the animals were humanely sacrificed at 72 h.

DEMONSTRATION OF TECHNICAL PROFICIENCY: Yes

ACCEPTANCE OF RESULTS:
- Acceptance criteria met for negative control: Not indicated
- Acceptance criteria met for positive control: N/A
- Range of historical values if different from the ones specified in the test guideline: N/A

Any other information on results incl. tables

Table 1:       Irritant/ corrosive response data for each animal at each observation time up to the removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis	Discharge
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4	Max. score: 3
60 min	1 / 1 / 1	0 / 1 / 0	1 / 1 / 1	2 / 2 / 2	1 / 1 / 2
24 h	2 / 1 / 2	1 / 0 / 1	2 / 2 / 3	2 / 3 / 2	1 / 2 / 2
48 h	2 / 1 / 2	1 / 1 / 1	3 / 3 / 3	2 / 3 / 2	1 / 2 / 2
72 h	3 / 2 / 3	1 / 1 / 1	3 / 3 / 3	2 / 2 / 2	1 / 2 / 2
Max. area effected (% of total cornea)	80 / 80 / 90	n/a	n/a	n/a	n/a
Reversibility*	nr	n/a	n/a	n/a	n/a
Average time (unit) for reversion	n/a	n/a	n/a	n/a	n/a

nr: not reversible

n/a: not applicable

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The test item can be classified as a Category 1 eye irritant based on GHS criteria.

Executive summary:

In a primary eye irritation study (OECD 405), ca. 33 mg (equivalent to ca. 0.1 mL) of test item was instilled into the conjunctival sac of young adult, New Zealand White rabbits (3 males). Animals then were observed for 3 days.  Irritation was scored by the numerical scoring system described in OECD 405 TG.

Severe and non-reversible corneal injury occurred in all three individuals. Irritation of the conjunctivae, chemosis, discharge and necrosis of the nictitating membrane was also observed and persisted until study termination.

In this study, test item was found to be extremely irritant to the eye based on the ocular corrosion that occurred.