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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:
2003-10-01 to 2003-11-06
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study is performed according to the OECD No 405 (1987) and EC (92/69/EEC, B.5) guidelines and is in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: OECD Guideline 405 (24 February 1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
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): 2,2,2 trifluoroethanol (TFE)
- Physical state: colorless liquid
- Lot/batch No.: 02 092 01
- Expiration date of the lot/batch: no data
- Stability under test conditions: assumed to be stable during the test (sponsor responsibility)
- Storage condition of test material: at room temperature
- Other: the pH of the undiluted test item, measured at CIT, was approximately 4.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 3.2 kg (+/- 0.3 kg)
- Housing: in individual polystyrene cages (48.2 cm x 58 cm x 36.5 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C (+/- 3°C)
- Humidity (%): 30-70%
- Air changes (per hr): approximately 12 cycles per hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h


IN-LIFE DATES: From: To: no data

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The right eye, which remained not treated served as negative control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): undiluted


VEHICLE: not applicable
Duration of treatment / exposure:
the eye was not rinsed after administration of test item up to the end of the study.
Observation period (in vivo):
Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until the end of the observation period (21 days).
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE: not applicable

SCORING SYSTEM: ocular reactions were scored according to the numerical scale described in the OECD guideline No.405

TOOL USED TO ASSESS SCORE: For the evaluation of corneal opacification (presence or absence, affected area), the eyes were examined under a UV lamp after instillation of one or two drops of 0.5 % sodium fluorescein solution (a clear fluorescence is visible in the areas of opacification). This evaluation was performed on day 2 and repeated thereafter whenever necessary.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
ca. 2.7
Max. score:
4
Reversibility:
fully reversible
Remarks:
day 7
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
ca. 2.7
Max. score:
4
Reversibility:
fully reversible
Remarks:
day 10
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
ca. 2.3
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: day 5
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: day 6
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: day 18
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: day 11
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: day 21
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not reversible
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
ca. 3.7
Max. score:
4
Reversibility:
fully reversible
Remarks:
day 11
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
ca. 2.7
Max. score:
4
Reversibility:
not fully reversible within: day 21
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not fully reversible within: day 21
Irritant / corrosive response data:
Very slight to severe conjunctival reactions, including a very slight to severe chemosis (grades 1 to 4), a very slight to moderate redness of the conjunctiva (grades 1 to 3) and a clear to whitish purulent discharge, were observed in all animals from day 1 up to day 11 (1/3 animals) or 21 (end of the observation period, 2/3 animals).
A slight iritis, which could have been masked by a corneal opacity between day 1 and day 2 in all animals and between days 9 and 18 in 1/3 animal, was noted in all animals from day 3 up to day 5, 6 or 8.
A very slight to severe corneal opacity (grades 1 to 4), which sometimes covered the area of the eye, was recorded in all animals from day 1 (2/3 animals) or 2 (1/3 animals) up to day 7, 10 or 22 (end of the observation period).
Whitish and/or brownish areas were observed on the conjunctiva of all animals from day 4 (2/3 animals) or 5 (1/3 animals) until day 10, 18 or 22 (end of the observation period).
Neovascularization was noted in 1/3 animals from day 10 until the end of the observation period (day 22).
Mean scores calculated for each animal over 24, 48 and 72 hours were 3.7, 2.7 and 4.0 for chemosis, 3.0, 3.0 and 3.0 for redness of the conjunctiva and 2.7, 2.7 and 2.3 for corneal opacity. Due to the corneal opacity which sometimes masked details of the iris, the mean scores for iris lesions could not be calculated.

See details in tables 7.3.2/1 and 7.3.2/2
Other effects:
Withish and/or brownish area on the conjonctiva, neovascularisation and withish purulent disharge.

Any other information on results incl. tables

Table 7.3.2/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/4/3

0/OP/OP

2/3/3

3/3/3

24 h

3/4/3

OP/OP/OP

3/3/3

4/3/4

48 h

3/2/2

1/1/1

3/3/3

4/3/4

72 h

2/2/2

1/1/1

3/3/3

3/2/4

Average 24h, 48h, 72h

2.7/2.7/2.3

Not calculated

3.0/3.0/3.0

3.7/2.7/4.0

Reversibility*)

c/c/n

c/c/c

c/n.c/n

c/n.c/n.c

Average time (day) for reversion

7/10/-

5/6/18

11/-/-

11/-/-

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

OP: Scoring masked by marked corneal opacity

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Under the test conditions, the 2,2,2-trifluorethanol is classified in Category 1 (Irreversible effects on the eye, H318) according to the Annex VI of the CLP Regulation 1272/2008/EC.
Executive summary:

In an eye irritation study performed according to the OECD No. 405 (1987) and EC (92/69/EEC, B.5) guidelines and in compliance to the GLP, 0.1 mL of undiluted 2,2,2-trifluoroethanol (TFE) was instilled into the conjunctival sac of left eye of 3 male New Zeland White Rabbit. After the instillation the substance was not remained. Animals were then observed for 21 days for eye edema and erythema of the conjunctive, corneal opacity and iris lesion. 

Eye rritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the instillation of the substance. The mean individual score were calculated within 3 scoring times (24, 48 and 72 hrs).

The mean individual scores were 3.7/2.7/4.0 for chemosis, 3.0/3.0/3.0 for conjunctival erythema, 2.7/2.7/2.3 for corneal opacity which were not completely reversible within the end of the study (21 days). The corneal opacity covered sometimes the whole area of the eye. Slight iridial lesions (mean individual score 1.0/1.0/1.0) were observed but were completely reversible in all animals.

Under the test conditions, the 2,2,2-trifluorethanol is classified in Category 1 (Irreversible effects on the eye, H318) according to the Annex VI of the CLP Regulation 1272/2008/EC.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.