Benzonitrile, 3,3'-(2,3,5,6-tetrahydro-3,6-dioxopyrrolo[3,4-c]pyrrole-1,4-diyl)bis-

Endpoint summary

Description of key information

Two studies in rabbits were performed to evaluate irritating or corrosive properties of the test material to skin or eyes. Application of the test substance did not provoke skin irritation. Treatment of rabbits eyes caused slight, transient opacity and conjuctival irritation. All reaction on skin and eyes has resolved within 8 days or were below treshold of regualtion. Therefore, the substance is considered to be as not-irritating.

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:

1992-06-24 to 1993-04-08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant Guideline study. Minor deficiency: 1st reading was done after 30 min instead of 60 min. This has no influence on the reliability of the study.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted Sep. 19, 1984

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

orange powder

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 12 to 14 weeks
- Weight at study initiation: 2.7 to 3.1 kg
- Housing: individually in metal cages with perforated floors
- Diet: standard laboratory diet SDS Stanrab (P) Rabbit Diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: yes, duration not specified

ENVIRONMENTAL CONDITIONS
- Temperature: approximately 19°C
- Humidity: 30 - 70%
- Air changes: approximately 19 per hour
- Photoperiod: 12 hours artificial light (0700 - 1900 hours) in each 24-hour period

IN-LIFE DATES: From: 1993-02-09 To: 1993-02-12

Type of coverage:

semiocclusive

Preparation of test site:

other: electric clippers

Vehicle:

water

Remarks:

distilled

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g per animal
- Concentration: 50% w/v

VEHICLE
- Amount applied: 0.5 mL distilled water

Duration of treatment / exposure:

4 hours

Observation period:

approximately 0.5, 24, 48 and 72 hours after exposure

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 100 mm x 100 mm (% not specified, but approximately 10% of the total body surface)
- Type of wrap if used: gauze pad covered with "Elastoplast" elastic adhesive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: the treated area of skin was washed with warm (30° to 40°C) water and blotted dry with absorbent paper
- Time after start of exposure: at the end of the 4 hours exposure period

SCORING SYSTEM:
Erythema/eschar and oedema formation: (scoring 0 - 4), according to OECD guideline 404

Irritation parameter:

erythema score

Basis:

mean

Remarks:

all animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

all animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

No dermal response to treatment was observed in any animal throughout the observation period.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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:

1992-06-24 to 1993-05-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant Guideline study.

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

adopted Sept. 19, 1984

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Analytical purity: 99%
- Appearance: orange powder

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 14 to 15 weeks
- Weight at study initiation: 3.2 to 3.5 kg
- Housing: individually in metal cages with perforated floors
- Diet: standard laboratory diet SDS Stanrab (P) Rabbit Diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: yes, duration not specified

ENVIRONMENTAL CONDITIONS
- Temperature: approximately 19°C
- Humidity: 30-70%
- Air changes: approximately 19 per hour
- Photoperiod: 12 hours artificial light (0700 - 1900 hours) in each 24-hour period

IN-LIFE DATES: From: 1993-02-15 To: 1993-03-01

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 50 mg, occupying a volume of 0.1 mL

Duration of treatment / exposure:

continuous

Observation period (in vivo):

approximately 1, 24, 48 and 72 hours after instillation as well as 4 and 7 days after instillation

Number of animals or in vitro replicates:

3 males

Details on study design:

SCORING SYSTEM: according to OECD 405 / EU Guidelines

TOOL USED TO ASSESS SCORE: not specified ("handheld light")

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours (mean)

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animals #2, #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

all three animals

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours (mean)

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animals #2, #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours (mean)

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animals #2, #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritant / corrosive response data:

A single instillation of the test item into the eye of the rabbit elicited corneal opacification and temporary slight to well-defined conjunctival irritation. All reactions had resolved one or seven days after instillation.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Procedure and observation

Two studies were performed to evaluate irritating potential of the test material to skin or eyes. In the first study, three male rabbits were each administered a single dermal dose of 0.5 g given as 50% suspension of the test substance. Semiocclusive application of the test material to intact rabbit skin for four hours did not cause any reaction on animals skin.

In a second study, six rabbits were each administered a single ocular dose of 50 mg of the test substance and observed for seven days after instillation. A single instillation of the test material into the eye of the rabbit elicited corneal opacification and temporary slight to well-defined conjunctival irritation. All reactions had resolved one or seven days after instillation.

Discussion

Application of the test substance onto skin did not cause corrosion or irritation. Appllication into the conjunctival sac of the eye caused slight to moderate conjuctival irritation. Conjunctival irritation was not reversible within 8 day post observation period but showed tendency to normalize and the score of irritation was below the treshold of regulation.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008.