4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline)

Endpoint summary

Description of key information

Skin irritation (according to OECD TG 404, GLP): not irritating to skin
Eye irritation (according to OECD TG 405, GLP): not irritating to eyes

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:

30 Dec 1987 - 02 Jan 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Comparable to guideline study with acceptable restrictions (purity of test substance not specified, first reading time point 30 minutes after patch removal).

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 12. May 1981

Deviations:

yes

Remarks:

purity of test substance not specified, first reading time point 30 minutes after patch removal

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products Inc., Denver, PA, USA
- Age at study initiation: young adult
- Weight at study initiation: 2381 - 2433 g
- Housing: individually in screen-bottom stainless steel cages (heavy gauge)
- Diet: measured amount of Purina High Fiber Rabbit Chow
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 21
- Humidity (%): 29 - 30
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5g (moistened with 0.9% saline) at the site of application

Duration of treatment / exposure:

4 hours

Observation period:

72 hours
reading time points: 0.5, 24, 48 and 72 hours

Number of animals:

3 (2 males and 1 female)

Details on study design:

TEST SITE
- Area of exposure: back and flank (approximately 6 cm2)
- Type of wrap if used: 2.5 x 2.5 cm gauze patch, secured with paper tape and loosely overwrapped with Saran Wrap and fixed with Elastoplast

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm tapwater and paper towels
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize Scoring System

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No effects on skin were observed at any reading time point.

Other effects:

No other effects were observed.

Interpretation of results:

study cannot be used for classification

Conclusions:

In an skin irritation study in rabbits, performed equivalent or similar to OECD 404 test guidelines, no irritation was observed.

Executive summary:

Dermal irritation was tested using three rabbits exposed to the test substance, for 4 hours using a semiocclusive dressing, according to OECD 404 test guideline and according to GLP principles.

No effects on skin were observed at any reading time point. No other observations were recorded.

Based on the results, the test substance is not considered as irritating to skin and no classification for dermal irritation is needed according to EC regulation 1272/2008.

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:

29 Dec 1987 - 01 Jan 1988

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Comparable to guideline study with acceptable restrictions (purity of test substance not specified).

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 12. May 1981

Deviations:

yes

Remarks:

purity of test substance not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Denver, PA, USA
- Age at study initiation: young adult
- Weight at study initiation: 2320 to 2501 g
- Housing: individually in screen-bottom stainless stell cages (heavy gauge)
- Diet: measured amount of Purina High Fiber Rabbit Chow
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 39 - 41
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 Dec 1987 To: 01 Jan 1988

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.04 g (equivalent to 0.1 mL)

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

72 hours
reading time points: 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3 (1 male and 2 females)

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

Slight conjunctival redness and chemosis (Grade 1) was observed at 1 hour for all animals but was completely reversed in two animals within 24 hours and in the third animal within 48 hours.

Other effects:

No pain response was elicited from any animal following instillation of the test material. Blanching of the conjunctivae was observed in one animal at 1 hours.

Table1: Individual Eye Irritation Scores

	Cornea	Iritis	Conjunctivae Score
	Score	Score	Redness	Chemosis
Animal 1
1 hour	0	0	2	1
24 hour	0	0	1	1
48 hour	0	0	0	0
72 hour	0	0	0	0
Mean scores (24-72 h)	0	0	0,33	0,33
Animal 2
1 hour	0	0	1	1
24 hour	0	0	0	0
48 hour	0	0	0	0
72 hour	0	0	0	0
Mean Scores (24-72 h)	0	0	0	0
Animal 3
1 hour	0	0	1	1
24 hour	0	0	0	0
48 hour	0	0	0	0
72 hour	0	0	0	0
Mean scores (24-72 h)	0	0	0	0

Interpretation of results:

GHS criteria not met

Conclusions:

In an eye irritation study with rabbits, performed according to OECD 405 test guideline and GLP principles, no irritation effects on the eye were observed.

Executive summary:

An eye irritation study was performed according to OECD TG 405 and under GLP conditions. The test item was instillated in one eye of 3 rabbits. One eye remained untreated and served as a control. No irreversible effects were noted.

Based on the results above, the test material is not classified for eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) (CAS 107934-68-9) was tested for its skin irritation potential in a study according to OECD 404 (Glaza, 1988). The purity of the test substance was not specified and the first reading time point was after 30 min (60 min suggested in OECD 404, adopted 2002). The shaved skin of 2 male and 1 female rabbits was exposed to 0.5 g test material (moistened with 0.9% saline) for 4 hours under semi-occlusive conditions. No erythema and oedema reactions were observed 30 min, 24, 48, and 72 h after removal of the patch in any animal. In conclusion, the test substance was not skin irritating under the conditions of the study.

Eye irritation

4,4'-(9H-fluoren-9-ylidene)bis(2-chloroaniline) (CAS 107934-68-9) was tested for its eye irritation potential in a study according to OECD 405 (Glaza, 1988). The purity of the test substance was not specified. 0.04 g (equivalent to 0.1 mL) test substance was applied in the eye of 1 male and 2 female New Zealand White rabbits each. No washing was performed and the eyes were scored 1, 24, 48, and 72 h after instillation of the test substance. No effects on cornea and iris were observed in any animal at any reading time point. Slight redness and chemosis (score 1-2) were observed 1 h after instillation in all 3 animals. In 2 animals the effects on the conjunctivae were fully reversible within 24 h. In 1 animals redness and chemosis were also observed after 24 h (score 1), but it was fully reversible within 48 h. The mean values over 24, 48, and 72 h were 0 for cornea and iris in all animals. For redness and chemosis the mean values over 24, 48, and 72 h were 0 in 2 animals and 0.33 in 1 animal. The effects were fully reversible within 48 h. In conclusion, the test substance was not irritating to the eyes under the conditions of the study.

Justification for selection of skin irritation / corrosion endpoint:
There is only one study available.

Justification for selection of eye irritation endpoint:
There is only one study available.

Justification for classification or non-classification

The available data on skin and eye irritation of 4,4´-(9H-fluoren-9 -ylidene)bis(2 -chloroaniline) do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.