3,4-dichlorobenzonitrile

Endpoint summary

Description of key information

No data are available on eye and skin irritation for 3,4-dichlorobenzonitrile.

Due to precautionary measures relevant endpoint data available for 2-chlorobenzonitrile and 2,6-Dichlorobenzonitril are read-across to 3,4-dichlorobenzonitrile based on structural similiarties of these two substances. Therefore, 3,4-Dichlorobenzonitrile is classified as H319 ("Causes serious eye irritation").

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

June 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

There is no data available on skin irritation/corrosion testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2,6-Dichlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural similarities. 2,6-Dichlorobenzonitrile is as well as 3,4-Dichlorobenzonitrile, is a disubstituted Benzonitrile. Both substances only differ in the position of the chloro substituents. Furthermore both substances are solid, practically insoluble in water and have a water octanol partition coefficient of 2.2 and 2.8. This might perhaps also lead to a similiar skin irritation/corrosion potential of both substances.
for Justification of read across see section 13.2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

other: Russian White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: own breed
- Weight at study initiation: at least 2.5 and 2.8 kg
- Housing: during the post oberservation period the animals were housed in V2A-steelcages with a floor area of 0.4 m2.
- Diet (e.g. ad libitum): KF-G 774 of Laboratorium für Pharmakologie und Toxikologie, 2104 Hamburg 92, Germany) ad libitum
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 60 +/- 5 %
- Photoperiod (hrs dark / hrs light): 12 hours light (150 Lux), 12 hours dark

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

30-60 minutes and 24, 48, 72 and 96 hours after exposure

Number of animals:

6 rabbits (3 male and 3 female)

Details on study design:

TEST SITE
- Area of exposure: max. 6 cm2 of the shaved dorsum skin
- Type of wrap if used: linen lobe with plastic film and bandage (Leukoplast, P. Beiersdorf & Co. AG, Unnastraße 48, 2000 Hamburg, Germany)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Skin reaction erythema and eschar generation:
0: no erythema
1: very slight, barely perceptible erythema
2: distinctive erythema
3: moderate till serious erythema
4: serious (deep red) erythema till light eschar generation (serious damage)

skin reaction edema generation:
0: no edema
1: very slight, barely perceptible erythema
2: moderate edema with clear definition
3: moderate edema (swelling approx. 1 mm)
4: serious edema (swelling greater than 1 mm and overlapping the area of exposure)

Furthermore the appearance of necrosis was examined.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

2,6-Dichlorobenzonitrile was tested to be not skin irritating in a test equivalent to OECD 404.

Executive summary:

As there is no data available on skin irritation testing with 3,4 -Dichlorobenzonitrile relevant endpoint data available for 2,6 -Dichlorobenzonitrile was read-acrossed to 3,4 -Dichlorobenzonitrile in order to classify the substance (without any unecessary animal testing) according to GHS. The Read-Across approach was based on structrual and physico chemical similarities (see rational for reliablitity).

2,6 -Dichlorobenzontrile was tested to be not skin irritating in a test equivalent to OECD 404. This agrees with the non skin irritating property of 2 -Chlorobenzonitrile. Therefore 3,4 -Dichlorobenzonitrile was also classified as non irritating to skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

There is no data available skin irritation/corrosion testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2-Chlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural and physico chemical similarities. 2-Chlorobenzonitrile, as well as 3,4 -Dichlorobenzonitrile is a Chloro substituted Benzonitrile. Although 2-Chlorobenzonitrile is only monosubstituted both substances are solid, practically insoluble in water and have similar water octanol partition coefficients (2.2 and 2.8). This might perhaps also lead to a similiar skin irritation/corrosion potential of both substances.
For justificatoin of read across see section 13.2

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

other: hair was removed with an electric clipper

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

Three rabbits

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

A single semi-occlusive application of 2-Chlorobenzonitrile to intact rabbit skin for four hours elicited no dermal irritation.

Executive summary:

A single semi-occlusive application of 0.5 g 2-Chlorobenzonitrile to intact skin of 3 New Zealand White rabbits for 4 hours according to OECD 404 elicited no dermal irritation.

Examination of the treated skin was made on Day 1 (i.e. approximately 30 min after removal of the patches) and on days 2, 3, and 4 after removing the gauze pads according to the OECD scoring system.

As there is no data available on skin irritation/corrosion testing 3,4 -Dichlorobenzonitrile relevant endpoint data available for 2 -Chlorobenzonitrile was read-acrossed to 3,4 -Dichlorobenzonitrile in order to classify the substance (without any uneccesary animal testing) according to GHS. The Read-Across approach was based on structural and physico chemical similarities (see rational for reliability).

2 -Chlorobenzonitrile was tested to be non irritating to skin. This agrees with the non skin irritating property of 2,6 -Dichlorobenzonitrile. Therefore 3,4 -Dichlorobenzonitrile was also classified as non irritating to skin.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

June 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

There is no data available on skin irritation/corrosion testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2,6-Dichlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural similarities. 2,6-Dichlorobenzonitrile is as well as 3,4-Dichlorobenzonitrile, is a disubstituted Benzonitrile. Both substances only differ in the position of the chloro substituents. Furthermore both substances are solid, practically insoluble in water and have a water octanol partition coefficient of 2.2 and 2.8. This might perhaps also lead to a similiar skin irritation/corrosion potential of both substances.
for Justification of read across see section 13.2

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

other: Russian White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: own breed
- Weight at study initiation: at least 2.5 and 2.8 kg
- Housing: during the post oberservation period the animals were housed in V2A-steelcages with a floor area of 0.4 m2.
- Diet (e.g. ad libitum): KF-G 774 of Laboratorium für Pharmakologie und Toxikologie, 2104 Hamburg 92, Germany) ad libitum
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 60 +/- 5 %
- Photoperiod (hrs dark / hrs light): 12 hours light (150 Lux), 12 hours dark

Type of coverage:

not specified

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

30-60 minutes and 24, 48, 72 and 96 hours after exposure

Number of animals:

6 rabbits (3 male and 3 female)

Details on study design:

TEST SITE
- Area of exposure: max. 6 cm2 of the shaved dorsum skin
- Type of wrap if used: linen lobe with plastic film and bandage (Leukoplast, P. Beiersdorf & Co. AG, Unnastraße 48, 2000 Hamburg, Germany)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Skin reaction erythema and eschar generation:
0: no erythema
1: very slight, barely perceptible erythema
2: distinctive erythema
3: moderate till serious erythema
4: serious (deep red) erythema till light eschar generation (serious damage)

skin reaction edema generation:
0: no edema
1: very slight, barely perceptible erythema
2: moderate edema with clear definition
3: moderate edema (swelling approx. 1 mm)
4: serious edema (swelling greater than 1 mm and overlapping the area of exposure)

Furthermore the appearance of necrosis was examined.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

2,6-Dichlorobenzonitrile was tested to be not skin irritating in a test equivalent to OECD 404.

Executive summary:

As there is no data available on skin irritation testing with 3,4 -Dichlorobenzonitrile relevant endpoint data available for 2,6 -Dichlorobenzonitrile was read-acrossed to 3,4 -Dichlorobenzonitrile in order to classify the substance (without any unecessary animal testing) according to GHS. The Read-Across approach was based on structrual and physico chemical similarities (see rational for reliablitity).

2,6 -Dichlorobenzontrile was tested to be not skin irritating in a test equivalent to OECD 404. This agrees with the non skin irritating property of 2 -Chlorobenzonitrile. Therefore 3,4 -Dichlorobenzonitrile was also classified as non irritating to skin.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

There is no data available skin irritation/corrosion testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2-Chlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural and physico chemical similarities. 2-Chlorobenzonitrile, as well as 3,4 -Dichlorobenzonitrile is a Chloro substituted Benzonitrile. Although 2-Chlorobenzonitrile is only monosubstituted both substances are solid, practically insoluble in water and have similar water octanol partition coefficients (2.2 and 2.8). This might perhaps also lead to a similiar skin irritation/corrosion potential of both substances.
For justificatoin of read across see section 13.2

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

other: hair was removed with an electric clipper

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

4 hours

Observation period:

4 days

Number of animals:

Three rabbits

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

A single semi-occlusive application of 2-Chlorobenzonitrile to intact rabbit skin for four hours elicited no dermal irritation.

Executive summary:

A single semi-occlusive application of 0.5 g 2-Chlorobenzonitrile to intact skin of 3 New Zealand White rabbits for 4 hours according to OECD 404 elicited no dermal irritation.

Examination of the treated skin was made on Day 1 (i.e. approximately 30 min after removal of the patches) and on days 2, 3, and 4 after removing the gauze pads according to the OECD scoring system.

As there is no data available on skin irritation/corrosion testing 3,4 -Dichlorobenzonitrile relevant endpoint data available for 2 -Chlorobenzonitrile was read-acrossed to 3,4 -Dichlorobenzonitrile in order to classify the substance (without any uneccesary animal testing) according to GHS. The Read-Across approach was based on structural and physico chemical similarities (see rational for reliability).

2 -Chlorobenzonitrile was tested to be non irritating to skin. This agrees with the non skin irritating property of 2,6 -Dichlorobenzonitrile. Therefore 3,4 -Dichlorobenzonitrile was also classified as non irritating to skin.

Reference 5

Endpoint:

skin corrosion: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

June 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

There is no data available on eye irritation testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2,6-Dichlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural similarities. 2,6-Dichlorobenzonitrile is as well as 3,4-Dichlorobenzonitrile, is a disubstituted Benzonitrile. Both substances only differ in the position of the chloro substituents. Furthermore both substances are solid, practically insoluble in water and have a water octanol partition coefficient of 2.2 and 2.8. This might perhaps also lead to a similiar eye irritation potential of both substances.
For Justifcation of read across see section 13.2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

other: White Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: own breed
- Weight at study initiation: 2.5 - 2.8 kg
- Housing: single in V2A-steelcages with a floor area of 0.4 m2)
- Diet (e.g. ad libitum): KF-G 774 of Laboratorium für Pharmakologie und Toxikologie, 2104 Hamburg 92, Germany) ad libitum
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 60 +/- 5%
- Photoperiod (hrs dark / hrs light): 12 hours light (300 Lux), 12 hours dark

Vehicle:

not specified

Controls:

other: right eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

no data

Observation period (in vivo):

before the application, 1, 24 and 72 hours after the apllication

Number of animals or in vitro replicates:

6 rabbits (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data

SCORING SYSTEM:
on the basis of DRAIZE

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

other: Fluorecein Test

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Interpretation of results:

GHS criteria not met

Conclusions:

2,6-Dichlorobenzonitrile was tested to be not eye irritatting in a test equivalent to OECD 405.

Executive summary:

2,6 -Dichlorobenzonitrile was tested to be not eye irritation in a test equivalent to OECD 405.

As therer is no data available on eye irritation testing with 3,4 -Dichlorobenzonitrile relevant endpoint data available for 2,6 -Dichlorobenzonitrile was read-acrossed to 3,4 -Dichlorobenzonitrile in order to classify the substance (without any unecessary animal testing) according to GHS. The Read-Across approach was based on structural and physico chemical similarities (see rational for reliability).

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

There is no data available on eye irritation testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2-Chlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural and physico chemical similarities. 2-Chlorobenzonitrile, as well as 3,4 -Dichlorobenzonitrile is a Chloro substituted Benzonitrile. Although 2-Chlorobenzonitrile is only monosubstituted both substances are solid, practically insoluble in water and have similar water octanol partition coefficients (2.2 and 2.8). This might perhaps also lead to a similiar eye irritation potential of both substances.
For Justification of read across see section 13.2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes

Duration of treatment / exposure:

Single instillation of 0.1 ml of the test substance (approx. 90 mg of 2-Chlorobenzonitrile) into the lower everted eye lid of one eye of each animal.

Observation period (in vivo):

Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation

Number of animals or in vitro replicates:

3 females

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

named in the report as 813

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

named in the report as 813

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

named in the report as 813

Time point:

24/48/72 h

Score:

>= 1 - < 2

Max. score:

2

Reversibility:

fully reversible within: 2 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

named in the report as 840

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

named in the report as 840

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

named in the report as 840

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 2 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

named in the report as 841

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

named in the report as 841

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

named in the report as 841

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 2 days

Ocular reactions elicited by 2-Chlorobenzonitrile

Rabbit Number and sex	Body weight (Day 1)	Region of Eye		One hour	Day after instillation
					1	2	3	4	7
813 female	2665 g	Cornea	Density	0	0	0	0	0	0
			Area	0	0	0	0	0	0
		Iris		0	0	0	0	0	0
		Conjunctivae	Redness	2	1	0	0	0	0
			Chemosis	1	1	0	0	0	0
840 female	2770 g	Cornea	Density	0	2	2	1	0	0
			Area	0	1	1	1	0	0
		Iris		0	0	0	0	0	0
		Conjunctivae	Redness	2	1	0	0	0	0
			Chemosis	1	0	0	0	0	0
841 female	3020 g	Cornea	Density	0	1	1	1	1	0
			Area	0	1	1	1	1	0
		Iris		0	0	0	0	0	0
		Conjunctivae	Redness	2	1	0	0	0	0
			Chemosis	1	0	0	0	0	0

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

2-Chlorobenzonitrile elicited transient, corneal opacification and temporary well-defined conjunctival reactions.

Executive summary:

In a GLP guideline study according to OECD 405 (1987) 0.1 ml (approx. 90 mg) 2-Chlorobenzonitrile was installed into the lower everted eye lid of one eye of each of 3 female New Zealand White rabbits. Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation. All animals were observed daily for signs of ill health or toxic signs.The test material elicited transient, corneal opacification and temporary well-defined conjunctival reactions.

Two of three animals show corneal effects >=1 after 24 -72h. Based on the scoring result the classification “H319: Causes serious eye irritation” is warranted.

This endpoint data from 2 -Chlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile in order to classify the substance according to GHS (without any unecessary animal testing). The Read-Across approach was based on structural and physico chemical similarities (see rational for reliability).

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

June 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

There is no data available on eye irritation testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2,6-Dichlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural similarities. 2,6-Dichlorobenzonitrile is as well as 3,4-Dichlorobenzonitrile, is a disubstituted Benzonitrile. Both substances only differ in the position of the chloro substituents. Furthermore both substances are solid, practically insoluble in water and have a water octanol partition coefficient of 2.2 and 2.8. This might perhaps also lead to a similiar eye irritation potential of both substances.
For Justifcation of read across see section 13.2

Reason / purpose for cross-reference:

read-across source

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

not specified

Species:

rabbit

Strain:

other: White Russian

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: own breed
- Weight at study initiation: 2.5 - 2.8 kg
- Housing: single in V2A-steelcages with a floor area of 0.4 m2)
- Diet (e.g. ad libitum): KF-G 774 of Laboratorium für Pharmakologie und Toxikologie, 2104 Hamburg 92, Germany) ad libitum
- Water (e.g. ad libitum): tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3 °C
- Humidity (%): 60 +/- 5%
- Photoperiod (hrs dark / hrs light): 12 hours light (300 Lux), 12 hours dark

Vehicle:

not specified

Controls:

other: right eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

no data

Observation period (in vivo):

before the application, 1, 24 and 72 hours after the apllication

Number of animals or in vitro replicates:

6 rabbits (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data

SCORING SYSTEM:
on the basis of DRAIZE

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

other: Fluorecein Test

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Interpretation of results:

GHS criteria not met

Conclusions:

2,6-Dichlorobenzonitrile was tested to be not eye irritatting in a test equivalent to OECD 405.

Executive summary:

2,6 -Dichlorobenzonitrile was tested to be not eye irritation in a test equivalent to OECD 405.

As therer is no data available on eye irritation testing with 3,4 -Dichlorobenzonitrile relevant endpoint data available for 2,6 -Dichlorobenzonitrile was read-acrossed to 3,4 -Dichlorobenzonitrile in order to classify the substance (without any unecessary animal testing) according to GHS. The Read-Across approach was based on structural and physico chemical similarities (see rational for reliability).

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Justification for type of information:

There is no data available on eye irritation testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2-Chlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural and physico chemical similarities. 2-Chlorobenzonitrile, as well as 3,4 -Dichlorobenzonitrile is a Chloro substituted Benzonitrile. Although 2-Chlorobenzonitrile is only monosubstituted both substances are solid, practically insoluble in water and have similar water octanol partition coefficients (2.2 and 2.8). This might perhaps also lead to a similiar eye irritation potential of both substances.
For Justification of read across see section 13.2

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

yes

Duration of treatment / exposure:

Single instillation of 0.1 ml of the test substance (approx. 90 mg of 2-Chlorobenzonitrile) into the lower everted eye lid of one eye of each animal.

Observation period (in vivo):

Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation

Number of animals or in vitro replicates:

3 females

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

named in the report as 813

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

named in the report as 813

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

named in the report as 813

Time point:

24/48/72 h

Score:

>= 1 - < 2

Max. score:

2

Reversibility:

fully reversible within: 2 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

named in the report as 840

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 4 days

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

named in the report as 840

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

named in the report as 840

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 2 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

named in the report as 841

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

named in the report as 841

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

named in the report as 841

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

2

Reversibility:

fully reversible within: 2 days

Ocular reactions elicited by 2-Chlorobenzonitrile

Rabbit Number and sex	Body weight (Day 1)	Region of Eye		One hour	Day after instillation
					1	2	3	4	7
813 female	2665 g	Cornea	Density	0	0	0	0	0	0
			Area	0	0	0	0	0	0
		Iris		0	0	0	0	0	0
		Conjunctivae	Redness	2	1	0	0	0	0
			Chemosis	1	1	0	0	0	0
840 female	2770 g	Cornea	Density	0	2	2	1	0	0
			Area	0	1	1	1	0	0
		Iris		0	0	0	0	0	0
		Conjunctivae	Redness	2	1	0	0	0	0
			Chemosis	1	0	0	0	0	0
841 female	3020 g	Cornea	Density	0	1	1	1	1	0
			Area	0	1	1	1	1	0
		Iris		0	0	0	0	0	0
		Conjunctivae	Redness	2	1	0	0	0	0
			Chemosis	1	0	0	0	0	0

 

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

2-Chlorobenzonitrile elicited transient, corneal opacification and temporary well-defined conjunctival reactions.

Executive summary:

In a GLP guideline study according to OECD 405 (1987) 0.1 ml (approx. 90 mg) 2-Chlorobenzonitrile was installed into the lower everted eye lid of one eye of each of 3 female New Zealand White rabbits. Examination of the eyes was made after 1 hour and 1, 2, 3, 4 and 7 days after instillation. All animals were observed daily for signs of ill health or toxic signs.The test material elicited transient, corneal opacification and temporary well-defined conjunctival reactions.

Two of three animals show corneal effects >=1 after 24 -72h. Based on the scoring result the classification “H319: Causes serious eye irritation” is warranted.

This endpoint data from 2 -Chlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile in order to classify the substance according to GHS (without any unecessary animal testing). The Read-Across approach was based on structural and physico chemical similarities (see rational for reliability).

Reference 5

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Justification for classification or non-classification

Justification for Read-Across:

There is no data available on eye or skin irritation/corrosion testing with 3,4-Dichlorobenzonitrile. In order to classify the substance according to GHS relevant endpoint data available for 2-Chlorobenzonitrile and 2,6-Dichlorobenzonitrile was read-acrossed to 3,4-Dichlorobenzonitrile based on structural and physico chemical similarities.

2,6-Dichlorobenzonitrile, as well as 3,4 -Dichlorobenzonitrile is a disubstituted Benzonitrile. Both substances only differ in the position of the chloro substituents. 2 -Chlorobenzonitrile is a next lower homologon of 2,6 -Dichlorobenzonitrile. Furthermore all three substances are solid, practically insoluble in water and have a water octanol partition coefficient between 2.2 and 2.8. This might perhaps also lead to a similiar toxicological behavior. The Read-Across approach assumes that if a Monochlorobenzonitrile and a Dichlorobenzonitrile show effects on skin or eyes, it is likely that a second Dichlorobenzonitrile also shows this similar behavior, particularly if it has the shows the same physico chemical properties (solid, practically insoluble in water and log Kow between 2.2 and 2.8).

Skin irritation:

2 -Chlorobenzonitrile was tested to be non irritating to skin. This agrees with the non skin irritating property of 2,6 -Dichlorobenzonitrile. Therefore 3,4 -Dichlorobenzonitrile was also classified as non irritating to skin.

Eye irritation:

2 -Chlorobenzonitrile was tested in a OECD 405 guideline study to cause elicited transient, corneal opacification and temporary well-defined conjunctival reactions.Based on the scoring result the classification “H319: Causes serious eye irritation” is warranted. This does not agree with the non eye irritating property of 2,6 -Dichlorobenzonitrile. Nevertheless, in considerations of safety, 3,4 -Dichlorobenzonitrile was classified as eye irritation cat.2 H319 following the results of the study with 2 -Chlorobenzonitrile.