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Acute Toxicity: dermal

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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 guidelineopen allclose all
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.

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.