Registration Dossier

Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994-03-15 to 1994-04-05
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
1992-07-31
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
1992-07-17
GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
α,α,α-trifluoro-4-nitro-m-cresol
EC Number:
201-818-2
EC Name:
α,α,α-trifluoro-4-nitro-m-cresol
Cas Number:
88-30-2
Molecular formula:
C7H4F3NO3
IUPAC Name:
4-nitro-3-(trifluoromethyl)phenol
impurity 1
Chemical structure
Reference substance name:
5-chloro-α,α,α-trifluoro-2-nitrotoluene
EC Number:
204-280-7
EC Name:
5-chloro-α,α,α-trifluoro-2-nitrotoluene
Cas Number:
118-83-2
Molecular formula:
C7H3ClF3NO2
IUPAC Name:
4-Chloro-1-nitro-2-(trifluoromethyl)benzene
impurity 2
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Dihydrogen oxide
impurity 3
Chemical structure
Reference substance name:
3-Carboxy-4-nitrophenol
Cas Number:
610-37-7
Molecular formula:
C7H5NO5
IUPAC Name:
3-Carboxy-4-nitrophenol
Test material form:
liquid
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Batch No.of test material: C02910506
- Expiration date of the batch: 1995-02

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature, in darkness, under fume cupboard

Test animals

Species:
rabbit
Strain:
New Zealand White
Remarks:
Chbb: NZW (SPF)
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Chemical pharmaceutical factory, 88400 Biberach
- Age at study initiation: ~3 - 5 month
- Weight at study initiation: 2.3 - 2.7 kg
- Housing: individually
- Diet: ad libitum, Altromin 2123 maintenance diet - rabbits, Altromin GmbH, Lage/Lippe, Germany and hay (~15 g daily).
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
21 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal region
- coverage: 2.5 cm x 2.5 cm
- Type of wrap: cellulose patch, surgical plaster, semi-occlusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing : warm tap water
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
30 - 60 min, 24 h, 48 h, 72 h, day 7, day 14, and day 21

SCORING SYSTEM:
- Method of calculation: according to the technique of Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks:
fully reversible within 21 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks:
fully reversible within 21 d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3.33
Max. score:
4
Reversibility:
not fully reversible within: 14 d
Remarks:
fully reversible within 21 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d

Any other information on results incl. tables

Sex: Female

Erythema (time after decontamination)

Animal No.

30 – 60 min

1 day

2 days

3 days

7 days

14 days

21 days

Mean Score

56

3

2

3

3

2

3

0

2.7

57

3

3

3

3

2

1

0

3.0

58

3

3

3

4

2

2

0

3.3

 

 

 

 

 

 

 

Overall Mean

3.0

 

Sex: Female

Oedema (time after decontamination)

Animal No.

30 – 60 min

1 day

2 days

3 days

7 days

14 days

21 days

Mean Score

56

4

3

3

3

2

0

0

3.0

57

3

2

2

2

1

0

0

2.0

58

4

3

3

3

2

0

0

3.0

 

 

 

 

 

 

 

Overall Mean

2.7

 

The means have been calculated using the day 1, 2, and 3 values

Applicant's summary and conclusion

Interpretation of results:
Category 1C (corrosive) based on GHS criteria
Conclusions:
In an in vivo study acording to EU Method B.4, the test substance showed skin corroding effects in rabbits.
Executive summary:

In a primary dermal irritation study according to EU Method B.4, a group (3♀) of 3 - 5 month old New Zealand White rabbits were dermally exposed to 0.5 mL of the test substance for 4 hours to 6.25 cm² skin (Hoechst AG, 1994). Animals then were observed for 21 days. Irritation was scored according to Draize et al. (1959). Erythrema was observed in all animals (individual mean score 24/48/72 h: animal #1 2.67, animal #2 3.0, animal #3 3.3), being completely reversible within 21 days. Edema was observed in all animals (individual mean score 24/48/72 h: animal #1 3.0, animal #2 2.0, animal #3 3.0), completely reversible within 14 days.

4-nitro-3-(trifluoromethyl)phenol was corrosive to the skin based on the individual mean score (24/48/72 h).