4,4'-Methylene-bis-(3-chloro-2,6-diethylaniline)

Endpoint summary

Description of key information

Skin irritation in vivo:

The study was performed 1988 as GLP-test following OECD-method 404. The used species were New Zealand White rabbits; 3 females were treated with 500 mg test item, moistened with water. No effects were observed throughout the study period, all irritation scores were 0. In conclusion, the test item is not irritant to rabbit skin.

Skin irritation in-vitro:

The test item was found to be non-irritating in an in vivo skin irritation study on rabbits performed for new substance notification (ELINCS). Therefore, an in vitro skin irritation study does not need to be conducted.

Eye irritation in vivo:

The study was performed 1986 as GLP-test following EC-test method B.5. The used species were New Zealand White rabbits; 100 mg test item was instilled in the conjunctival sac of two males and one female. Conjunctival irritation was limited to slight redness and chemosis (score 1) in 1/3 rabbits and moderate redness, chemosis and discharge (score 2) in 2/3 rabbits at 1 h post instillation. After 24 h, slight redness persisted in 2/3 rabbits. By 48 h all treated eyes were normal. In conclusion, P5367 is not irritant to rabbit eyes.

Eye irritation in vitro:

The test item was found to be non-irritating in an in vivo eye irritation study on rabbits performed for new substance notification (ELINCS). Therefore, an in vitro eye irritation study does not need to be conducted.

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:

key study

Study period:

April 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: stable

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: female
- Source: Ranch Rabbits, Crowley
- Age: at least 12 weeks
- Weight at study initiation: 2.10 - 4.05 kg
- Housing: individually in grid floor cages
- Diet: Standard Rabbit Diet, Special Diets Services Ltd., Stepfield
- Water: Mains water was provided at all times and dispensed from glass water bottles
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature: 16 - 22°C
- Humidity: 40 - 70%
- Air changes: 10 changes /hour; single air-conditioned room
- Photoperiod: 14 hours darkness; 10 hours fluorescent lightning

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

500 mg

Duration of treatment / exposure:

4 hours

Observation period:

observations were done 1, 24, 48 and 72 hours after treatment

Number of animals:

3

Details on study design:

TREATMENT:
The back of each animal was clipped free of hair the day prior to treatment using electric veterinary clippers. A portion of test article (500 mg, moistened with water) was applied to an area of skin approximately 6 cm2 on each animal and covered with a gauze patch. The patch was occluded and secured using a strip of impermeable adhesive tape. A plastic collar was placed around the neck of each animal to prevent premature removal of the wrappings and ingestion of the test article. Four hours after application the patches were removed and the skin wiped with a disposable paper towel moistened with water to remove any test article still remaining.

EVALUATION OF EFFECTS:
One hour after removal of the wrappings the skin reactions were scored using the scale below.* The evaluation was repeated 24, 48 and 72 hours after removal of the patches. No irritation was noted at the 72 hour observation and the study was terminated.

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

Irritant / corrosive response data:

No adverse skin reactions were noted up to 72 hours post-administration, when the study was terminated.

Other effects:

No adverse skin reactions were noted up to 72 hours post-administration, when the study was terminated.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was found to be non-irritating to rabbit skin.

Executive summary:

The study was performed 1988 as GLP-test following OECD-method 404. The used species were New Zealand White rabbits; 3 females were treated with 500 mg test item, moistened with water. No effects were observed throughout the study period, all irritation scores were 0. In conclusion, the test item is not irritant to rabbit skin.

Reference 2

Endpoint:

skin irritation: 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

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
The test item was found to be non-irritating in an in-vivo skin irritation study on rabbits performed for new substance notification (ELINCS). Therefore, an in-vitro skin irritation study does not need to be conducted.

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:

key study

Study period:

September 1986

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: stable

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Sex: Two males and one female
- Source: Cheshire Rabbit Farms Ltd.
- Weight at study initiation: 2.5 - 3 kg
- Housing: individually in aluminium cages
- Diet: Special Diet Services Expanded Rabbit Diet
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 17 - 21°C
- Humidity: mean 58%

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

The rabbit was held firmly but gently and the test material placed into the right eye by gently pulling the lower eyelid away from the eyeball to form a sac into which the test material was dropped. The lids were then gently held together for one or 2 s. The other eye remained untreated to serve as a control.

Observation period (in vivo):

Observations were done 1, 24, 48 and 72 hours after treatment

Number of animals or in vitro replicates:

3 (2 males & 1 female)

Details on study design:

Approximately 24 h before test commencement, both eyes of each rabbit were examined for defects. The quantity of material instilled into each treated eye was 100 mg. Instillation of the test material was by the following technique: The rabbit was held firmly but gently and the test material placed into the right eye by gently pulling the lower eyelid away from the eyeball to form a sac into which the test material was dropped. The lids were then gently held together for one or 2 s. The other eye remained untreated to serve as a control.The eyes were examined for irritation using standard illumination. The ocular reaction was recorded at 1, 24, 48 and 72 h after
instillation.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

24/48/72 h

Score:

0.23

Max. score:

1

Reversibility:

fully reversible within: 48 h

Remarks:

score 1 observed in two animals at 24h observation time

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24 h

Remarks:

score 1 observed in one animal one hour after treatment

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

Reversibility of any observed effect: Changes fully reversible within 2 days

Other effects:

Conjunctival redness, chemosis and discharge were recorded at 1 hour (maximum score was 2 in two animals). By 48 hours all treated eyes were normal.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was found to be non-irritating to rabbit seyes.

Executive summary:

The study was performed 1986 as GLP-test following EC-test method B.5. The used species were New Zealand White rabbits; 100 mg test item was instilled in the conjunctival sac of two males and one female. Conjunctival irritation was limited to slight redness and chemosis (score 1) in 1/3 rabbits and moderate redness, chemosis and discharge (score 2) in 2/3 rabbits at 1 h post instillation. After 24 h, slight redness persisted in 2/3 rabbits. By 48 h all treated eyes were normal. In conclusion, P5367 is not irritant to rabbit eyes.

Reference 2

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

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
The test item was found to be non-irritating in an in-vivo eye irritation study on rabbits performed for new substance notification (ELINCS). Therefore, an in-vitro eye irritation study does not need to be conducted.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the data available the substance is not classified or labelled according to Regulation 1272/2008/EC (CLP).