Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin:

In an in vivo study according to EU Method B.4, the test substance showed skin corroding effects in rabbits (Hoechst AG, 1994).

Eye:

In an in vivo study similar to OECD guideline 405, the test substance showed severe eye damaging effects in rabbits (Hazleton Laboratories, 1990).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
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
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
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
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
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
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

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

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).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
to 1990-08-28
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
2012-10-02
Principles of method if other than guideline:
According to Draize
GLP compliance:
yes
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

OTHER SPECIFICS: dark brown liquid
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Hazleton Research Products, Inc.
- Age at study initiation: young adult, ~ 14 weeks
- Weight at study initiation: 2.362 - 3.068 kg
- Housing: Individually, in screen-bottm stainless steel cages
- Diet: measured amount, High Fiber Rabbit Chow #5326, Purina Mills, Inc.
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1990-06-14 To: 1990-07-06
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL


Duration of treatment / exposure:
sinlge treatment
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
1
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
In an in vivo study similar to OECD guideline 405, the test substance showed serious eye damaging effects in rabbits.
Executive summary:

In a primary eye irritation study similar to OECD guideline 405, 0.1 mL of the test substance (undiluted test substance) was instilled into one conjunctival sac of one young adult, ~14 weeks old New Zealand White rabbit (2590 g) (Hazleton Laboratories, 1990). No washing procedure was performed. The animal was then observed for 21 days. Irritation was scored by the method of Draize (1959). Based on the individual mean score (24/48/72 h) following scores were determined: Cornea opacity score 4.0, iris score 2.0, conjunctiva score 3.0, chemosis score 2.67.

The test substance was corrosive to the eye based on the individual mean score (24/48/72 h).

Due to the level of irritation observed in this one animal, the other five animals slated for this study were not treated.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin:

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). Erythema 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.

The test substance was corrosive to the skin regarding the individual mean score (24/48/72 h).

These findings are supported by another dermal irritation study according to EU Method B.4 under GLP conducted in rabbits (Hazleton Laboratories, 1990). A group (6 male) of ca. 14 weeks old New Zealand White rabbits were dermally exposed to 0.5 mL of the test substance for 4 hours to 6.25 cm² skin with a semi-occlusive wrap. Animals then were observed for 21 days. Irritation was scored according to Draize et al. (1959). Erythema was observed in all animals (individual mean score 24/48/72 h: animal #1 2.0, animal #2 2.0, animal #3 3.0, animal #4 3.0, animal #5 3.0, animal #6 3.0), being completely reversible within 21 days. Edema was observed in all animals (individual mean score 24/48/72 h: animal #1 2.67, animal #2 3.0, animal #3 3.0, animal #4 2.0, animal #5 3.0, animal #6 3.0), completely reversible within 21 days.

Eye:

In a primary eye irritation study similar to OECD guideline 405, 0.1 mL of the test substance (undiluted test substance) was instilled into one conjunctival sac of one young adult, ~14 weeks old New Zealand White rabbit (2590 g) (Hazleton Laboratories, 1990). No washing procedure was performed. The animal was then observed for 21 days. Irritation was scored by the method of Draize (1959). Based on the individual mean score (24/48/72 h) following scores were determined: Cornea opacity score 4.0, iris score 2.0, conjunctiva score 3.0, chemosis score 2.67. Due to the level of irritation observed in this one animal, the other five animals slated for this study were not treated.

The test item was seriously eye damaging based on the individual mean score (24/48/72 h).

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008.

Skin corrosive and severe eye damaging properties were documented. As a result the test substance is considered to be classified as serious eye damaging (Category 1, H318) and skin corrosive (Category 1C, H314) under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.

Categories Display