2,2,2-trifluoroethanol

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

2,2,2-trifluoroethanol

EC Number:

200-913-6

EC Name:

2,2,2-trifluoroethanol

Cas Number:

75-89-8

Molecular formula:

C2H3F3O

IUPAC Name:

2,2,2-trifluoroethan-1-ol

Test material form:

liquid

Details on test material:

- Name of test material (as cited in study report): Trifluoroethanol
- Physical state: colorless liquid
- Storage condition of test material: in a sealed container, at room temperature in the dark.

Test animals

Species:

rat

Strain:

other: HsdHan:WIST

Sex:

male/female

Details on test animals or test system 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

Administration / exposure

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

Results and discussion

Preliminary study:

Not applicable

Effect levels

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:

other: There were no clinical signs after a single dermal application of Trifluoroethanol.

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.

Any other information on results incl. tables

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 -

 

Applicant's summary and conclusion

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.