Synthetic resin, a reaction product of 4,4'-bis(N-maleimido)diphenylmethane with 3-aminobenzoic acid hydrazide

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-11-02 to 1989-12-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted February 24, 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1,1'-(methylenedi-p-phenylene)bismaleimide

EC Number:

237-163-4

EC Name:

1,1'-(methylenedi-p-phenylene)bismaleimide

Cas Number:

13676-54-5

Molecular formula:

C21H14N2O4

IUPAC Name:

1,1'-[methylenedi(4,1-phenylene)]di(1H-pyrrole-2,5-dione)

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: males 14 weeks, female 15 weeks
- Weight at study initiation: males 2.5-2.6 kg, female 2.4 kg
- Housing: individually in stainless steel cages equipped with an automatic cleaning and drinking system (Dipl. Ing WE. Ehret GmbH, Versuchstiertechnik, D-7830 Emmendingen)
- Diet: ad libitum, pelleted Kliba 341, Batch 48/89 and 49/89 rabbit maintenance diet ("Kliba", Kingenmuehle AG, CH-4303 Kaiseraugst)
- Water: ad libitum, community tap water from Itingen
- Acclimation period: 4 days under laboratory conditions after veterinary examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g of the test substance was instilled into the conjunctival sac of the left eye
- Concentration: undiluted

Duration of treatment / exposure:

7 days, single exposure, no washing

Observation period (in vivo):

7 days, Reading points: 1, 24, 48 and 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

The test article (0.1 g per animal) was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test article. The right eye remained untreated and served as the reference control.

REMOVAL OF TEST SUBSTANCE
- Washing : No

SCORING SYSTEM: According to OECD guideline 405 (Draize et al.)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Corrosion: Corneal opacity was observed in one animal (no.71, female) from 1 to 72 hours after treatment. No opacity was observed in any other animal.

Other effects:

Clinical symptoms / Mortality: No acute clinical symptoms were observed in the animals during the test period, and no mortality occurred.
Coloration: No staining of the cornea and conjunctivae of the treated eyes by pigment or coloring of the test article was observed.
Body weights: The body weight gain of all rabbits was similar.
Necropsy: No necropsy was performed. All animals were killed and discarded.

Any other information on results incl. tables

Table 1: Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test

Score at time point / Reversibility	Cornea	Iris	Conjunctivae	Chemosis
	Max. score: 4	Max. score: 2	Max. score: 3	Max. score: 4
24 h	0/0/1	0/0/1	2/2/2	1/1/2
48 h	0/0/1	0/0/0	2/2/2	0/0/1
72 h	0/0/1	0/0/0	1/1/1	0/0/0
Average 24h, 48h, 72h	0/0/1	0/0/0.33	1.67/1.67/1.67	0.33/0.33/1
Reversibility*)	c.	c.	c.	c.
Average time for reversion	72h	72h	7days	72h

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In the present study conducted according to OECD guideline 405 (adopted February 24, 1987) 0.5 g Compimide MDAB were instilled into the conjuctival sac of three New Zealand White rabbits (two male and one female animal). The treated eyes were not rinsed and the effects of the test item were recorded at 1h, 24h, 48h and 72h after application. After another 21 days observation period the animals were sacrificed and discarded. In all three animals a slight conjunctival redness was detected at the 72h reading (score 1) but the redness was fully reversible within 7 days, thus, the test item does not need to be classified according to Regulation (EC) No 1272/2008 (CLP) and the globally harmonized system of classification and labelling of chemicals (GHS).