2,2,2-trifluoroethanol

Endpoint summary

Description of key information

- Skin irritation: Not irritating (OECD 404, Kr: 1)
- Eye irritation: Corrosive (OECD 405, Kr: 1)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-09-23 to 2003-10-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 404 (17 July 1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system 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: 2.7 kg (+/- 0.2 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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): undiluted


VEHICLE: not applicable
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

Duration of treatment / exposure:

The test item was first evaluated on a single animal. The duration was 3 minutes on one flank and 4 hours on the other flank. Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals.

Observation period:

The skin was examined approximately 1 hour, 24, 48 and 72 hours after the removal of the dressing. Since there were persistent irritation reactions at 72 hours, the observation period was extended. In the absence of complete reversibility of skin reactions on day 15, the study was ended.

Number of animals:

3 animals (male rabbit)

Details on study design:

TEST SITE
- Area of exposure: the flanks of animals
- % coverage: no data
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no residual test item was observed on removal of the dressing
- Time after start of exposure: 3 minutes or 4 hours


SCORING SYSTEM: according to the OECD guideline No. 404.

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

ca. 0.3

Max. score:

4

Reversibility:

fully reversible within: day 2

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: day 11

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean individual score

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean individual score

Time point:

other: overall 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean individual score

Time point:

other: overall 24, 48, 72 hrs

Score:

0

Max. score:

4

Irritant / corrosive response data:

For the 3-minute exposed animal (only one animal), except for a very slight erythema (grade 1) observed one hour after the removal of the dressing, no cutaneous reactions were noted (mean score 0.0)
See details in Table 7.3.1/1 for an exposure of 4 hours.

Other effects:

Dryness of the skin up to the end of the study and presence of crusts up to day 11 for the rabbit No. 936 (the rabbit the most affected by the treatment).

Table 7.3.1/1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test (4h)

Score at time point / Reversibility	Erythema	Edema
	Max. score: 4	Max. score: 4
60 min	1/1/2	0/0/0
24 h	0/1/2	0/0/0
48 h	0/0/2	0/0/0
72 h	0/0/2	0/0/0
Average 24h, 48h, 72h	0.0/0.3/2.0	0.0/0.0/0.0
Reversibility*)	c	-
Average time (day) for reversion**	11	-

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

**): correspond to the last day for which skin irritation signs in the last animal were observed

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test item 2,2,2-trifluoroethanol is not classified as skin irritant when applied topically to rabbits according to the Annex VI of the CLP regulation 1278/2000/EC.

Executive summary:

In a dermal irritation study performed according to the OECD guideline No. 404 (1992) 3 male New Zeland White rabbits, were dermally exposed to 0.5 mL of undiluted 2,2,2,-trifluoroethanol (TFE) (purity of 99.5%) to the shaved skin of the right flank. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 14 days for edema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 hrs after the removal of the patch.  

The mean individual scores calculated within 3 scoring times (24, 48 and 72 hrs) were 0.0/0.3/2.0 for erythema and 0.0/0.0/0.0 for edema.

Under the test conditions, the test item 2,2,2-trifluoroethanol is not classified as skin irritant when applied topically to rabbits according to the CLP Regulation 1278/200/EC.

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 405 (24 February 1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

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

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.

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.

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

1- Skin irritation:

A study was identified as the key study (Griffon, 2003). This study was performed according to the OECD guideline No. 404 and in compliance with the GLP.

Male New Zeland White rabbits were dermally exposed to undiluted 2,2,2-trifluoroethanol for 4 hours using a semi-occlusive patch. On the treated intact skin, the mean individual scores calculated within 3 scoring times (24, 48 and 72 hrs) were 0.0/0.3/2.0 for erythema and 0.0/0.0/0.0 for edema. Therefore under the test conditions, the 2,2,2-trifluoroethanol was not a skin irritant.

2- Eye irritation:

A study was identified as the key study (Griffon, 2004). This study was performed according to the OECD guideline No. 405 and in compliance with the GLP.

0.1 mL of undiluted 2,2,2-trifluoroethanol was instilled into the conjunctival sac of male New Zeland White rabbits. Under the test conditions, 2,2,2-trifluoroethanol induced severe chemosis (mean individual scores of 3.7/2.7/4.0), moderate conjunctival redness (mean individual scores of 3.0/3.0/3.0), and moderate corneal lesions (mean individual scores of 2.7/2.7/2.3) 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 scores of 1.0/1.0/1.0) were observed but were completely reversible in all animals.

Under the test conditions, 2,2,2-trifluoroethanol was highly irritating to eyes and induced irreversible effects.

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008.

Self-classification:

Based on the available data, 2,2,2-Trifluoroethanol is not classified for skin irritation according to the criteria of the Annex VI to Regulation (EC) No 1272/2008.

2,2,2-Trifluoroethanol is self-classified in Category 1 (H318: Irreversible effects to eyes) according to the Regulation (EC) No 1272/2008 (CLP).