2-nitro-4-(trifluoromethyl)benzonitrile

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

17 - 25 Feb 2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 28 Jul 2015

GLP compliance:

yes

Remarks:

The test complied with the Principles of Good Laboratory Practices (GLP) of the Certification and Accreditation Administration of the People’s Republic of China (2013 revised edition).

Test material

Test material information

Constituent 1

Reference substance name:

2-nitro-4-(trifluoromethyl)benzonitrile

EC Number:

212-298-1

EC Name:

2-nitro-4-(trifluoromethyl)benzonitrile

Cas Number:

778-94-9

Molecular formula:

C8H3F3N2O2

IUPAC Name:

2-nitro-4-(trifluoromethyl)benzonitrile

Test animals

Species:

rabbit

Strain:

other: Japanese long-eared white rabbit, general grade

Details on test animals or test system and environmental conditions:

- Source: Xinglong Experimental Animal Breeding Factory, Beijing, China
- Age at study initiation: 84 - 140 days
- Females nulliparous and non-pregnant: yes
- Weight at study initiation: 1.75 - 2.05 kg
- Housing: housed individually in hanging stainless steel rearing cages (L38 cm x W50 cm x H35 cm) affixed on rearing shelves (L200 cm x W65 cm x H170 cm)
- Diet: rabbit maintenance feed (Liaoning Changsheng Biotechnology Co., Ltd.,); ad libitum
- Water: every-day drinking water; ad libitum
- Acclimation period: 32 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.04 - 23.00
- Humidity (%): 40.28 - 63.40
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From 17 to 25 Feb 2019

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Remarks:

but moistened with purified water

Controls:

other:

Amount / concentration applied:

Test material: 0.5 g

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: skin area (2.5 x 2.5 cm) on the right side of the mid-line below the shoulder blade
- % coverage: not reported
- Type of wrap if used: The test sample was spread evenly on a piece of gauze to which a small piece of non-irritating medical tape (approximately 2.5 cm x 2.5 cm) was adhered and moistened with a small amount of purified water.

REMOVAL OF TEST SUBSTANCE
- Washing: Clear water was used to wash the skin at the test area.
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
1, 24, 48, 72 h and 4 - 6 days

SCORING SYSTEM: Draize scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 6 d

Remarks on result:

probability of weak irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 5 d

Remarks on result:

probability of weak irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 5 d

Remarks on result:

probability of weak irritation

Results 4

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Edema (score 1) 1 h after removal of the dressing; reversible within 24 h

Remarks on result:

probability of weak irritation

Irritant / corrosive response data:

In the first animal, erythema was observed immediately after removal of the dressing, and after 1 h (score: 2) and 24 h (score: 2) and it persisted until the fifth day; on the sixth day there were no abnormalities. Oedema was observed 1 h after the dressing was removed (score: 1).
In the second animal, erythema was observed immediately after removal of the dressing, and after 1h (score: 1) and 24 h (score: 2) and it persisted until the fourth day (score: 1 after 72 h); on the fifth day there were no abnormalities. Oedema was observed 1 h after the dressing was removed (score: 1).
In the third animal, erythema was observed immediately after removal of the dressing, and after 1h (score: 1) and 24 h (score: 2) and it persisted until the fourth day (score: 1 after 48 h); on the fifth day there were no abnormalities. Oedema was observed 1 h after the dressing was removed (score: 1). In the three animals, mean dermal erythema/eschar and oedema scores at 24 h, 48 h, and 72 h after the dressings were removed were 1.3/0; 1.7/0; and 1.3/0, respectively. For details on study results, see section "any other information on results incl. tables", tables 1 - 2.

Any other information on results incl. tables

Table 1: Individual data for the skin irritation test in rabbits

Animal no.	Skin response	Individual score - observation timepoint (dressing removed)
		1 h	24 h	48 h	72 h	4 d	5 d	6 d
1	Erythema and eschar	2	2	1	1	1	1	0
	Oedema	1	0	0	0	0	0	0
2	Erythema and eschar	1	2	2	1	1	0	-
	Oedema	1	0	0	0	0	0	-
3	Erythema and eschar	1	2	1	1	1	0	-
	Oedema	1	0	0	0	0	0	-

 

 

Table 2: Mean scores of individual data in the skin irritation test in rabbits

Animal no.	Skin response	Mean total score of individual skin responses
1	Erythema/eschar	1.3
	Oedema	0
2	Erythema/eschar	1.7
	Oedema	0
3	Erythema/eschar	1.3
	Oedema	0

Note: Means of the total points calculated at 24, 48 and 72 h after the dressings were removed.

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the present test conditions, the test substance 2-nitro-4-(trifluoromethyl)benzonitrile was not irritating to the skin according to Draize criteria. In the three animals, mean dermal erythema / eschar and oedema scores at 24 h, 48 h, and 72 h after the dressings were removed were 1.3 / 0; 1.7 / 0; and 1.3 / 0. Based on the GHS classification criteria for dermal corrosion and irritation, this test material was not classified.