Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
other: OECD Guideline 404 (17 July 1992)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal 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

Species:
rabbit
Strain:
New Zealand White
Details on test animals 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

Test system

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.

Results and discussion

In vivo

Resultsopen allclose all
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).

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.