Registration Dossier

Administrative data

Description of key information

Acute toxicity: Oral: LD50 male: 153 mg/kg (K, Reliability 1)
Acute toxicity: Dermal: LD50 combined: > 2000 mg/kg bw (K, Reliability 1)
Acute toxicity: Inhalation: LD50 combined: 3.25 mg/L (K, Reliability 2)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed accordingly to the OECD Guideline No. 401 and in accordance to the GLP compliance.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
: no information on the purity of the test substance.
Principles of method if other than guideline:
not applicable.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation: male: 122-145g; female: 108-121g
- Fasting period before study: yes
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 15%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 hrs/12 hrs

IN-LIFE DATES: From: To:
Route of administration:
oral: unspecified
Doses:
60, 125, 250, 500 and 1000 mg/kg bw.
No. of animals per sex per dose:
5 rats/sex/dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: clinical sign observation at 15, 30, 60, 180, 360 min and then every days. Weighing at day 1, 4, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gross pathology.
Statistics:
LD50 was determined for the male rats according to the Probit method whereas for the female rats LD50 is determined according to the Van der Waerden method.
Preliminary study:
not applicable
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
153 mg/kg bw
95% CL:
>= 102 - < 232
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
177 mg/kg bw
Mortality:
Yes: see details in Table 7.2.1/2.
Clinical signs:
In the dead rats, the male and females of the 250, 500 and 1000 mg/kg groups decline in spontaneous movement, and have an abnormal gait, an irregular respiration (bradypnea), lacrimation, soiled perineal position (only for 500 and 1000 mg/kg dose groups) and the prone position could be seen (not observed in the female 250 mg/kg dose group). These clinical signs are observed mainly from day 2 except for the 1000 mg/kg dose group for which the effects are visible from 30 min after the test item administration. The survival animals presented no clinical sign.
Body weight:
Animals were weighed at days 4, 8 and 15. Therefore, the body weight gain analysis is only applicable for the survival animals treated with the doses 60 and 125 mg/kg bw. For these animals, the body weight gain is positive along the study.
Gross pathology:
Swollen abdomens from hemorrhaging or water retention in the glandular stomach or forestomach were observed in a large portion of the dead rats. Other changes that were observed are shrinking of the thymus in the 250 mg/kg group, pulmonary congestion in low-dose groups over 250 mg/kg and tar contents in the jejunum/ileum or appendix in 1000 mg/kg groups. No abnormalities were seen for in the survival animals during the autopsy.
Other findings:
no data

Table 7.2.1/2: Mortality after an oral administration of 2,2,2 Trifluoroethanol

Dose (mg/kg)

Mortality (# dead/total)

Time range of death

Male

Female

Combined

60

0/5

0/5

0/10

-

125

1/5

0/5

1/10

Day 2

250

5/5

5/5

10/10

Day 2 (4 males and 2 females), Day 3 (3 females), Day 4 (1 male)

500

5/5

5/5

10/10

Day 2 (4 males), Day 3 (1 male and 5 females)

1000

5/5

5/5

10/10

Day 2 (5 males and 2 females), Day 3 (3 females)

 

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
With an oral acute DL50 between 50 and 300 mg/kg, under the test conditions, 2,2,2-trifluoroethanol is classified in category 3 (Toxic by ingestion, H301) according to the annex VI of the 1272/2008 CLP.
Executive summary:

In an acute oral toxicity study, performed according to the OECD guideline No. 401 (1987), and in compliance with the GLP, groups of Crj:CD(SD) male and female rats (5 animals/sex/dose) were given a single oral dose of 2,2,2-trifluoroethanol (TFE) at doses of 60, 125, 250, 500 and 1000 mg/kg bw. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days.

Oral LD50in male rats = 153 mg/kg bw, Oral LD50in female rats = 177 mg/kg bw

Death occured rapidly after TFE administration (from day 2). Dead animals presented severe toxic effects such as a decrease in locomotor activity, an abnormal gait, an irregular respiration (bradypnea), lacrimation, soiled perineal position (only for 500 and 1000 mg/kg dose groups) and a prone position. These effects were visible within the day 2 in the 250 and 500 mg/kg bw dose groups and 30 min after the TFE administration in the 1000 mg/kg bw dose group. Furthermore, swollen abdomens from hemorrhaging or water retention in the glandular stomach or forstomach were observed in a large portion of the dead rats. Other changes that were observed are shrinking of the thymus. Survival animals presented no abnormalities.

Under the test conditions, 2,2,2-trifluoroethanol is classified in category 3 (Toxic by ingestion, H301) according to the annex VI of the 1272/2008 CLP.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2003-09-23 to 2003-10-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study followed the OECD No.423 (22 March 1996) and EC (96/54/EC, B.1 ter, 30 July 1996) guidelines and was performed in compliance with the GLP.
Qualifier:
according to
Guideline:
other: OECD Guideline No. 423, 22 March 1996
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Janvier, le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks old
- Weight at study initiation: 310 g (+/- 38 g) for the males and 205 g (+/- 10 g) for the females
- Fasting period before study: yes - overnight period of approximately 18 hours before dosing. During this period the animals had free access to water.
- Housing: in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and three rats of the same sex and group during the treatment period.
- Diet (e.g. ad libitum): ad libitum except during the fasting period prior to the treatment.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C (+/- 2 °C)
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles of ventilation per hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12h/12h


IN-LIFE DATES: From: To:
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/kg bw and 2000 mg/kw bw
- Amount of vehicle (if gavage): 1 mL/100 g of animal body weight
- Justification for choice of vehicle: the tested substance is soluble in water
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 1 mL/100 g of animal body weight


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose of 200 mg/kg was chosen.
Doses:
The dose-level used as the starting dose was selected from one of three fixed levels, 25, 200 or 2000 mg/kg body weight. As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose of 200 mg/kg was chosen.
200 and then 2000 mg/kg bw were the both doses adminsitered. See details on Table 7.2.1/1
No. of animals per sex per dose:
3 males/dose and 3 females at the dose of 2000 mg/kg bw
Control animals:
other: The body weight of the rats exposed to the test items was compared to the body weight of CIT historical data of control animals exposed to 10mL/kg of water.
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test item. Thereafter, observation of the animals was made at least once a day. The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weight, macroscopic necropsy examination of the main organs (digestive tract, heart, kidneys, liver, pancreas, spleen and any other organs with obvious abnormalities).
Statistics:
No data
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Mortality:
At the 2000 mg/kg bw dose level, all males died within the day 2.
At 200 mg/kg bw dose level, no death occured.
Clinical signs:
Hypoactivity, piloerection, dyspnea were observed prior to death of males treated at the dose of 2000 mg/kg bw. For the males treated at 200 mg/kg bw, the same examinations were made from day 1 up to day 3, whereas such examinations were not made in females.
Body weight:
The body weight gain of the animals dosed at 200 mg/kg bw was not affected by treatment with the TFE.
Gross pathology:
Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.
Other findings:
No other finding

No remarks

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
As none of the 6 animals tested at the dose 200 mg/kg bw died during the study and according to Annex 2d of the OECD 423 allowing a judgement with respect to classifying the test substance, the substance should be classified in cat 4 based on the GHS criteria.
Executive summary:

In an acute oral toxicity study, performed according to the OECD guideline No. 423 (1996), and in compliance with the GLP, groups of Sprague-Dawley rats (3 animals/sex/dose) were given a single oral dose of 2,2,2-trifluoroethanol (99.95%) diluted in water at doses of 200 and 2000 mg/kg bw. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days.

Oral LD50in rats is comprised between 200 and 2000 mg/kg bw.

Hypoactivity, piloerection, dyspnea were observed prior to death of all males treated at the dose of 2000 mg/kg bw. For the males treated at 200 mg/kg bw, no death occured but the same clinical observations were made from day 1 up to day 3, whereas such observations were not made in females.

Macroscopic examination of the main organs of the animals revealed no apparent abnormalities.

Under the test conditions, 2,2,2-trifluoroethanol is classified in category 4 (Harmful if swallowed, H302) according to GHS.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
153 mg/kg bw
Quality of whole database:
Two reliable studies testing the substance and performed according to the OECD TG are available. One concluded on an acute oral DL50 between 50 and 300 mg/kg and the second one concluded on a acute oral LD 50 between 200 and 2000 mg/kg. The lowest value was retained to classify the substance for the acute oral toxicity.
Additional published data with validity 4 due to very limited details were also reported in this dossier. The are considered as supporting studies since they reported similar effects end led to similar classification.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1999-06-28 to 1999-7-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
May 1981
Deviations:
yes
Remarks:
: no detail on animals and environmental conditions. A 7 day observation period after the completion of exposure instead of 14 days.
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
no data
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapor generator ; model GEL-1A, Shibata Scientific Technology LTD). The test substance was introduced from the top part of the inhalation chamber through a pre-filter and HEPA filter after mixing and dilution with the air inside the breathing chamber and then ejected normally from the lower part (one pass method). The concentration of the test substance was adjusted by changing the mix ratio of the test substance gas and the dilution air.
- Exposure chamber volume: 384L
- Method of holding animals in test chamber: no data
- Source and rate of air: Airflow, 100L/min
- Method of conditioning air: The ejected test substance was processed through an activated charcoal filter, diluted through a dilution tank and then released into the atmosphere.
- System of generating particulates/aerosols: no data
- Method of particle size determination: no data
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: see details in table 7.2.2/1.

TEST ATMOSPHERE
- Brief description of analytical method used: Sampling of the animal-breathing chamber was taken and the concentration was measured by equipment analysis (see details in Table 7.2.2/2). Sampling was conducted using a sampling rate if approximately 1.0 L/min at 60 and 80 minutes from the start of exposure.
- Samples taken from breathing zone: yes

VEHICLE
No data

TEST ATMOSPHERE (if not tabulated)
Not applicable
Analytical verification of test atmosphere concentrations:
yes
Remarks:
see Table 7.2.2/3
Duration of exposure:
4 h
Concentrations:
Low, Middle and high dose: 150; 450 and 1350 ppm (0.62; 1.87 and 5.6 mg/L)
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: the animals were observed for clinical signs and to see if death occured at 1, 2, 3, and 4 hours after exposure completion and then each day up to day 7. The animals are weighed at day 1, 3, 5 and 7.
- Necropsy of survivors performed: yes
Statistics:
no data
Preliminary study:
not applicable
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
784 ppm
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: corresponding to 3.25 mg/L (1 ppm= 4.16 µg/mL)
Mortality:
yes - See details in Table 7.2.2/4.
Clinical signs:
other: At the low dose, no abnormalitie were detected in male and female rats. At the middle (males only) and the high doses (males and females) decreased spontaneous locomotion, decreased respiratory rate, ptosis, and staining around anus were observed.
Body weight:
At the middle dose, the animals survived at day 7 but they presented clinical signs of suffering.
The body weight gain at day 7 was less than for the animals exposed to the low dose.
See details in Table 7.2.2/5.
Gross pathology:
At the high dose, staining around nose and mouth (only for one female rat), pale kidney, dark reddish change of the lung, reddish region of mucosa of the glandular stomach and cecum were observed.
Other findings:
no other findings

Table 7.2.2/4: Mortality after an inhalation exposure for 4h

Sex

Exposure group

Mortality (Number of dead animals/Number of animals)

Time of death

LD50 (ppm)

Male

Low dose

0/5

-

784

Middle dose

0/5

-

High dose

5/5

Day 1 (4 rats), Day 2 (1 rat)

Female

Low dose

0/5

-

784

Middle dose

0/5

-

High dose

5/5

Day 1 (2 rats), Day 2 (3 rats)

 

Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
With a 4h LC50 between 2 and 10 mg/L (vapour), under the test conditions, 2,2,2 Trifluoroethanol is classified in category 3 (Toxic if inhaled, H331) according to the criteria of Annex VI of the Regulation (EC) No 1272/2008.
Executive summary:

In an acute inhalation toxicity study, performed according to the OECD guideline No. 403 with acceptable restrictions, groups of Crj: CD (SD) male and female rats (5 animals/sex/dose) were exposed by inhalation route by whole body exposure to 2,2,2 Trifluoroethanol for 4 hours at concentrations of 0.62; 1.87; 5.6 mg/L (150, 450 and 1350 ppm).  Animals then were observed for 7 days. Clinical signs (at 1, 2, 3, 4 hours and each day after exposure completion), body weight (at day 0, 1, 3, 5, and 7) and gross pathology (at the sacrifice or death of animal) were observed.

 

LC50Males = 3.25 mg/L

      Females = 3.25 mg/L

At the middle (only for male rats) and high doses (for male and female rats), a decreased spontaneous locomotion, a decreased respiratory rate, ptosis, a staining around anus were observed. At the middle dose, the surviving animals presented clinical signs of suffering at day 7 and showed a body weight gains lower than those of the animals exposed to the low dose. At the high dose, a staining around nose and mouth (only for one female rat), a pale kidney, a dark reddish change of the lung, a reddish region of mucosa of the glandular stomach and cecum were observed.

Under the test conditions, 2,2,2 Trifluoroethanol is classified in category 3 (Toxic if inhaled, H331) according to the criteria of Annex VI of the Regulation (EC) No 1272/2008.

This study is considered as acceptable as the main criteria of the guideline are respected.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
3 250 mg/m³
Quality of whole database:
One reliable key study performed according to the OECD TG 403 is available and provided a 4hLC50 of 784 ppm (vapour).
Other studies are available but with not sufficient information or not relevant method for classification.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2010-04-30 to 2010-06-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HsdHan:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester
- Age at study initiation: approximately 8 to 9 weeks old on Day 1
- Weight at study initiation: 220 to 312 g (males) and 166 to 194 g (females) on Day 1
- Fasting period before study:
- Housing: During the acclimatisation period, up to five rats of the same sex were accommodated in cages that conformed to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989). From the day prior to dosing (Day –1), each rat was individually housed in a similar cage. After completion of the Day 3 observations animals allocated to the main study were returned to group housing.
- Diet: SQC(E) Rat and Mouse Maintenance Diet No 1, from Special Diets Services Ltd, Witham, UK ad libitum
- Water: ad libitum
- Acclimation period: 7 to 15 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 24°C
- Humidity: 45 to 65%
- Air changes: 15 to 20 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: on the clipped dorsum of the rat
- % coverage: at least 10% of the total body surface
- Type of wrap if used: A dense gauze patch was placed over the treated skin and retained in place by an elasticated, open-weave, adhesive compression bandage

REMOVAL OF TEST SUBSTANCE
- Washing: The dermal test site of each rat was lightly brushed clean of any solid residues and swabbed with water-moistened cotton wool before the animal was returned to the holding cage.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Concentration (if solution): 1.43 mL/kg
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs were recorded immediately post dose, at approximately 15 and 30 minutes post dose, hourly between 1 and 4 hours post dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period.
Rats were weighed on Day 1 (day before dosing) and on Days 1, 4, 8 and 15.
- Necropsy of survivors performed: yes. The necropsy procedure included inspection of external surfaces and orifices, the dermal test site, all viscera and tissue within the abdominal, thoracic and cranial cavities, and free hand sectioning of the dermal test site, liver and kidneys
Statistics:
Not applicable
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal died following a single dermal application of Trifluoroethanol at 2000 mg/kg.
Clinical signs:
There were no clinical signs after a single dermal application of Trifluoroethanol.
Body weight:
All rats gained weight during the second weeks of the study. One male and two females lost weight during the first week of the study.
Gross pathology:
Macroscopic examination on Day 15 revealed reddening to the thymus (bilateral), green kidneys (bilateral) and kidney pelvic dilatation (unilateral). These macroscopic findings were limited to two animals only. There were no abnormalities seen in the remaining animals.
Other findings:
There were no dermal reactions.

Table 7.2.3/1: Individual body weights and weekly increments

Dose level (mg/kg)

Animal number and sex

Body weight (g) at:

Increment (g)

Day -1

Day 1

Day 4

Day 8

Day 15

Day 1 to 8

Day 8 to 15

2000

10M

227

230

225

231

236

1

5

11M

220

222

212

212

217

-10

5

12M

266

265

264

280

297

15

17

13M

246

249

244

259

281

10

22

14M

301

312

304

322

341

10

19

2000

15F

166

170

163

169

175

-1

6

16F

193

194

190

197

210

3

13

17F

181

175

177

179

191

4

12

18F

180

185

181

183

193

-2

10

19F

191

188

189

192

199

4

7

 

 Table 7.2.3/2: Dermal reactions

Day

Dermal reaction

Animal number and sex

10M

11M

12M

13M

14M

2

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

3

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

4

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

5 to 15

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

 

Day

Dermal reaction

Animal number and sex

15F

16F

17F

18F

19F

2

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

3

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

4

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

5 to 15

Erythema

Oedema
Other

0

0
-

0

0
-

0

0
-

0

0
-

0

0
-

 

Interpretation of results:
GHS criteria not met
Conclusions:
With a dermal acute DL50 above 2000 mg/Kg and no mortality at this dose, under the test conditions, 2,2,2 Trifluoroethanol is not classified for acute dermal toxicity according to the GHS criteria.
Executive summary:

In a limit acute dermal toxicity study performed according to the OECD test guideline No. 402 and in compliance with GLP, groups of young adult HsdHan:WIST rats (5/sex) were dermally exposed toTrifluoroethanol (99.9 %) at doses of 2000 mg/kg bw. The treated areas of dorsum (10%) were covered by a semi-occlusive dressing for 24 hours. Animals then were observed for 14 days.

 

Dermal LD50Combined > 2000 mg/kg bw.

 

No animal died and there were no clinical signs of reaction to treatment. No overt dermal changes were noted at the test site following a single application at 2000 mg/kg.

All rats achieved body weight gains during the second weeks of the study. One male and two females lost weight during the first week of the study.

Macroscopic examination on Day 15 revealed reddening to the thymus (bilateral), green kidneys (bilateral) and kidney pelvic dilatation (unilateral). These macroscopic findings were limited to two animals only. There were no abnormalities seen in the remaining animals.

 

Under the test conditions, Trifluoroethanol is not classified according to the Directive 67/548/EEC and according to the CLP Regulation (1272/2008).

This study was considered as acceptable as it satisfied the main criteria of the OECD guideline.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
A reliable key study has been performed according the the OECD TG 402 to clarify the dermal toxicity suggested in a report of Silberstein (1978) of limited information. This study demonstrated no mortality up to and included the highest tested concentration of 2000 mg/kg bw, as well as very limited adverse effects. So the LD50 is above 2000 mg/kg bw and the substance does not have to be classified.

Additional information

Oral route:

Two study reports were available: Tosoh, 1998 and Griffon, 2004. The studies were performed according to OECD guidelines No.401 (Tosoh) and No.423 (Griffon) and in compliance with GLP. The study report of Tosoh was flagged as the Key study based on worst case result. Indeed the LD50 determined in this study is lower than the one of the Griffon study and therefore was considered as a worst case for the hasard assessment by oral route. In the Key study, groups of Crj:CD(SD) male and female rats were given 2,2,2-trifluoroethanol (TFE) at single dose of 60, 125, 250, 500 or 1000 mg/kg bw. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days. The oral LD50 were determined to be 153 mg/kg bw and 177 mg/kg bw/d in male and females rats, respectively.

Death rapidly occurred after TFE administration (from day 2). Dead animals presented severe toxic effects such as a decrease in locomotor activity, abnormal gait, irregular respiration (bradypnea), lacrimation, soiled perineal position (only for 500 and 1000 mg/kg bw dose groups) and prone position. These effects were visible within 2 days in the 250 and 500 mg/kg bw dose groups and within 30 min in the 1000 mg/kg bw dose group. Furthermore, swollen abdomens from hemorrhaging or water retention in the glandular stomach or forstomach were observed in a large portion of the dead rats. Other changes that were observed are shrinking of the thymus. Survival animals presented no abnormalities.

This study is considered as acceptable as it is in accordance to the main criteria of the EU guidelines and satisfies the requirement for acute oral toxicity endpoint.

Dermal route:

A study was identified as a Key study (Wilcox, 2010). In a limit acute dermal toxicity study performed according to the OECD test guideline No. 402 and in compliance with GLP, groups of young adult HsdHan:WIST rats (5/sex) were dermally exposed toTrifluoroethanol (99.9 %) at dose of 2000 mg/kg bw.The treated areas of dorsum (10%) were covered by a semi-occlusive dressing for 24 hours. Animals were then observed for 14 days. 

Dermal LD50Combined > 2000 mg/kg bw. 

No animal died and there were no clinical signs of reaction to treatment. No overt dermal changes were noted at the test site following a single application at 2000 mg/kg.

All rats achieved body weight gains during the second week of the study. One male and two females lost weight during the first week of the study.

Macroscopic examination on Day 15 revealed reddening thymus (bilateral), green kidneys (bilateral) and kidney pelvic dilatation (unilateral). These macroscopic findings were limited to two animals only. There were no abnormalities in the remaining animals. 

This study was considered as acceptable as it satisfied the main criteria of the OECD guideline.

Inhalation route:

A study was identified as a Key study (Tosoh, 1999).This study was performed according to the OECD guideline No. 403 with acceptable restrictions. Groups of male and female rats were whole body exposed by inhalation route to 2,2,2 Trifluoroethanol for 4 hours at concentrations of 0.62; 1.87 or 5.6 mg/L (150, 450 or 1350 ppm).  Animals were then observed for 7 days. Clinical signs, body weight and gross pathology were observed. The LC50 in males and females was determined to be 3.25 mg/L.

At the middle (only for male rats) and high doses (for male and female rats), decreased spontaneous locomotion, decreased respiratory rate, ptosis, staining around anus were observed. At the middle dose, the survival animals presented clinical signs of suffering at day 7 and showed body weight gains lower than those of the animals exposed to the low dose. At the high dose, pale kidney, dark reddish change of the lung, reddish region of mucosa of the glandular stomach and cecum were observed.

This study is considered as acceptable as it is in accordance to the main criteria of the EU guidelines and satisfies the requirement for acute inhalation toxicity endpoint.

Justification for classification or non-classification

Harmonized classification:

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

Self classification:

Oral route:

Based on the available data, 2,2,2 Trifluoroethanol is classified in category 3, Toxic if swallowed (H301) according to the Regulation (EC) No1272/2008 (CLP) as the LD50.

Dermal route:

Based on the available data, 2,2,2 Trifluoroethanol is not classified for acute dermal toxicity according to the Regulation (EC) No 1272/2008 (CLP) as the LD50 is higher than 2000 mg/kg bw.

Inhalation route:

Based on the available data, 2,2,2 Trifluoroethanol is classified in category 3, Toxic if inhaled (H331) according to the Regulation (EC) No 1272/2008 (CLP) as the LC50 is between 2 and 10 mg/L (vapour).