Registration Dossier

Administrative data

Description of key information

Results from several studies on skin and eye irritation were reported. Benzonitrile is considered to have a low potential for skin and eye irritation.

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:
supporting study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test material was used to treat six rabbits each on the intact skin and the abraded skin.
Further details on the method are not available.
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
occlusive
Preparation of test site:
other: abraded and intact skin
Vehicle:
unchanged (no vehicle)
Controls:
no
Duration of treatment / exposure:
24 h (0.5 ml)
Observation period:
first reading after the 24 h exposure, a second after 48 h (72 h after application)
Number of animals:
6 adults
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
0.3
Reversibility:
fully reversible within: 7d
Remarks on result:
other: intakt skin
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 h
Score:
0.2
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: intact skin
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
1.3
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: abraded skin
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 h
Score:
1
Reversibility:
fully reversible within: 7 d
Remarks on result:
other: abraded skin

Irritation was scored by the method of Draize (J.Pharacol.82 (1944) 377-390).

The second reading is carried out on the basis of the CIVO –grading system.

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: other: CIVO grading system
Conclusions:
Benzonitrile is a slight skin irritant
Executive summary:

In a primary dermal irritation study 12 adult rabbits were exposed to 0,5 ml of benzonitrile for 24 hours to a 1 inch x 1 inch of body surface area. Animals then were observed for 2 days (48 hr). Irritation was scored by the method of Draize (J.Pharacol.82 (1944) 377- 390).

Since the Draize grading system does not comprise a 72h reading the second reading is carried out on the basis of the CIVO- grading system. Benzonitrile caused very slight erythema in two out of six rabbits treated on the intact skin. On the abraded skin it caused very slight or well- defined erythema in five out of six rabbits and very slight edema in one out of six rabbits. The average results suggest benzonitrile to be a very slight primary skin irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

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:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
other: FDA Fed.Reg. 28 (119), 5582, 1963
Deviations:
not specified
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Duration of treatment / exposure:
upon application eye closed for one second and subsequently not rinsed
Observation period (in vivo):
eyes examined at 24, 48, 72 hr and 7 days after instillation
Number of animals or in vitro replicates:
6
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
fully reversible
Irritation parameter:
iris 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:
1
Reversibility:
fully reversible
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible

Individual scores awarded to the ocular lesions elicited by benzonitril using FDA-scoring scale

 

 

 

Conjunctivae

Rabbit No.

Cornea

Iris

Redness

Chemosis

After 24 hours

13

0

0

1

0

14

0

0

1

0

15

0

0

1

0

16

0

0

1

1

17

0

0

1

0

18

0

0

1

1

After 48 hours

13

0

0

0

0

14

0

0

0

0

15

0

0

1

0

16

0

0

1

0

17

0

0

1

0

18

0

0

1

0

After 72 hours

13

0

0

0

0

14

0

0

0

0

15

0

0

1

0

16

0

0

1

0

17

0

0

1

0

18

0

0

1

0

After 7 days

13

0

0

0

0

14

0

0

0

0

15

0

0

0

0

16

0

0

0

0

17

0

0

0

0

18

0

0

0

0

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: US CPSC / US FDA
Conclusions:
Upon application into the eye benzonitril caused slight lesions of the conjunctivae in all 6 rabbits. After seven days all treated eyes were normal again.
Executive summary:

In a primary eye irritation study 0,1 ml of benzonitril as provided by the study owner without vehicle was instilled into the conjunctival sac of one eye of an adult New Zealand rabbits (in total 6) secured for one second (eyes subsequently not washed). The animal eyes were then examined after 24, 48 and 72 hours and finally after 7 days.  Irritation was scored by the method of FDA-scoring scale.

 

Upon application into the eye benzonitril caused slight lesions of the conjunctivae in all (six) rabbits. After seven days all treated eyes were normal again. According to the FDA-standards benzonitril is not considered to be an eye irritant.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a primary dermal irritation study 12 adult rabbits were exposed to 0.5 ml of benzonitrile for 24 hours and observed for 2 days (TNO, 1978). Irritation was scored by the method of Draize (1944). The 72h reading was carried out on the basis of the CIVO- grading system. Benzonitrile caused very slight erythema in two out of six rabbits treated on the intact skin. On the abraded skin it caused very slight or well- defined erythema in five out of six rabbits and very slight edema in one out of six rabbits. The average results suggest benzonitrile to be a very slight primary skin irritant.

In a second primary dermal irritation study 4 New Zealand Albino rabbits were exposed to 0.5 ml of undiluted benzonitrile (Mastri 1970). One of the two sites was abraded while the other remained intact. Test sites were covered with an occlusive dressing for 24 hours. No evidence of irritation was noted at 24- and 72 -hour scoring intervals. This result was confirmed by Zeller (1969).

In a primary eye irritation study according to FDA Fed.Reg. 28 ((119), 5582, 1963) 0.1 ml of benzonitrile was instilled into the conjunctival sac of one eye of 6 adult New Zealand rabbits (TNO, 1978). The eyes were not washed after application and examined after 24, 48, 72 hours and 7 days. Irritation was scored by the method of FDA-scoring scale. Upon application into the eye benzonitril caused slight lesions of the conjunctivae in all (six) rabbits. After seven days all treated eyes were normal again. According to the FDA-standards benzonitril was not considered to be an eye irritant.

In a primary eye irritation study 0.1 mg/l of benzonitrile was instilled into the conjunctival sac of the right eye of five New Zealand albino rabbits (Mastri 1970). The eyes were not washed after application. Animals then were observed one minute, 1, 24, 72 and 7 days. Irritation was scored by the method of standard scoring system of Draize et al. In the classification system used, special emphasis was placed upon irritation or damage to the cornea. Correspondingly less attention was placed upon conjunctival and iridal effects. Benzonitrile was rated slightly irritating. Transient iridal junctival irritation was noted within one minute after instillation of benzontrile. The irritation essentially peaked at this time and subsided the next 24 to 72 hours. In this study, benzonitrile is slightly irritating to the eye based on Draize scoring system (with a score of 16.8 of a total of 110 possible points). The result was confirmed by Zeller (1969).

Justification for classification or non-classification

Based on the available data benzonitrile is considered to be slightly irritating to the skin and eye. A classification is not warranted.