H112323

Endpoint summary

Description of key information

The available data suggest that test substance is non irritant to skin and 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:

Apr, 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted equivalent or similar to EU Method B.4. and OECD Guideline 404 in compliance with GLP

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Mellor Rabbits, Chadderton Heights, Chadderton, Nr Oldham, Greater Manchester, UK
- Age at study initiation: 15-24 wk
- Weight at study initiation: 3081-4125 g
- Housing: Housed individually in anodised aluminium sheet cages
- Diet (e.g. ad libitum): Labsure CRB Rabbit Diet, ad libitum
- Water (e.g. ad libitum): Water, ad libitum
- Acclimation period:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17±2 °C
- Humidity (%): 55±15 %
- Air changes (per hr): 25-30
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 g of test substance pasted with small amount of deion. water

Duration of treatment / exposure:

4 h

Observation period:

30-60 min, 24, 48 and 72 h after removal of the patches, additional readings were performed after 7 d

Number of animals:

Three

Details on study design:

TEST SITE
- Area of exposure: Left flank
- % coverage: 2.5 x2.5 cm
- Type of wrap if used: Yes, The treated areas were covered with pieces of surgical gauze (approximate size 2.5 cm x 2.5cm; 8 ply) each of which was secured by two crossed strips of surgical tape (approximate size 1cm x 8cm). These were covered by a piece of impermeable rubber sheeting (approximate size 35cm x 13cm) wrapped once around the trunk of the animal and secured with adhesive impermeable polyethylene tape (7.5cm wide).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gently cleansed free of any residual test sample using clean swabs of absorbent cotton wool soaked in clean warm water and were then dried gently with clean tissue paper.
- Time after start of exposure: 4 h

SCORING SYSTEM: Erythema, eschar formation and edema were evaluated numerically according to the DRAIZE scale

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: no erythema observed

Remarks on result:

other: -

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed

Remarks on result:

other: -

Irritant / corrosive response data:

- There were no signs of erythema in any animal.
- Very slight oedema was seen in two animals 30-60 min after decontamination. There were no additional signs of irritation.

Other effects:

None

None

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test substance was considered to be non-irritant to rabbit skin following a single 4-h application.

Executive summary:

A study was conducted to assess the skin irritation potential of test substance to the rabbit skin equivalent or similar to OECD Guideline 404 and EU Method B.4.

A group of three male rabbits each received a single four-hour application of test sample to the shorn flank. The animals were assessed for any signs of skin irritation 30-60 minutes after decontamination and then daily for 3 days.

Very slight oedema was observed in two animals 30-60 minutes after decontamination. There were no further signs of irritation. In conclusion, Substance H112323 was non-irritant to rabbit skin following a single four-hour application.

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:

Apr, 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted equivalent or similar to EU Method B.5. and OECD Guideline 405 in compliance with GLP

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Mellor Rabbits, Chadderton Heights, Chadderton, Nr Oldham, Greater Manchester, UK
- Age at study initiation: 15-24 wk
- Weight at study initiation: 4266-4412 g
- Housing: Housed individually in anodised aluminium sheet cages
- Diet (e.g. ad libitum): Labsure CRB Rabbit Diet, ad libitum
- Water (e.g. ad libitum): Water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17±2 °C
- Humidity (%): 55±15 %
- Air changes (per hr): 25-30
- Photoperiod (hrs dark / hrs light): 12 h dark/12 h light

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

1-2 h, Day 1, 2 , 3, 4, 6 and 7 of application

Number of animals or in vitro replicates:

Three

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, 24 h after administration the treated eyes were washed out thoroughly with isotonic saline at approx. 37 °C
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scale to assess the grade of ocular reaction and A modified form of the Kay and Calandra system was used to interpret and classify the numerical scores. As an aid in the assessment of corneal damage, fluorescein staining was used at the 1, 2 (2 animals), 3, 4, 6 and 7-d readings.

TOOL USED TO ASSESS SCORE: Fluorescein staining

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

3

Remarks on result:

other: Redness could not be fully assessed due to staining of the cornea but is unlikely to have occurred

Irritant / corrosive response data:

Application of the test sample into the conjunctival sac of the eye of one rabbit caused moderate initial pain (class 3 on a 0-5 scale). The eyes of the remaining rabbits were treated with a local anaesthetic prior to application and these animals showed no initial pain following application.
Apart from blue staining of the periorbital tissues by the test sample, there were no corneal or iridial effects. Blue staining of the conjunctiva by the test sample obscured any underlying redness which may have been present. However as the conjunctival effects were limited to a severe, but transient, discharge in one animal and an intermittent slight discharge in another animal, it is considered unlikely that significant redness was present in any of the animals.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the test substance was considered to be not irritant to the rabbit eye

Executive summary:

A study was conducted to assess the eye irritation potential of test substance to the rabbit eye equivalent or similar to EU Method B.5. and OECD Guideline 405 in compliance with GLP.

Instillation of the undiluted test sample into the conjunctival sac of the eye of one rabbit caused moderate initial pain (class 3 on a 0-5 scale). The eyes of the other two rabbits were therefore treated with a local anaesthetic prior to dosing and these animals showed no initial pain following application.

Apart from blue staining of the periorbital tissues by the test sample, there were no corneal or iridial effects. Blue staining of the conjunctiva by the test substance obscured any underlying redness that may have been present. However, as the observed ocular effects were limited to transient/intermittent conjunctival discharge it is considered unlikely that significant conjunctival redness was present in any of the animals.

As the staining is limited to the conjunctiva and no corneal effects occurred It is hence concluded that the test substance has no irritating effects on the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin Irritation

A study was conducted to assess the skin irritation potential of test substance to the rabbit skin equivalent or similar to OECD Guideline 404 and EU Method B.4.

A group of three male rabbits each received a single four-hour application of test sample to the shorn flank. The animals were assessed for any signs of skin irritation 30-60 minutes after decontamination and then daily for 3 days.

Very slight oedema was observed in two animals 30-60 minutes after decontamination. There were no further signs of irritation. In conclusion, Substance H112323 was non-irritant to rabbit skin following a single four-hour application.

Eye irritation

A study was conducted to assess the eye irritation potential of test substance to the rabbit eye equivalent or similar to EU Method B.5. and OECD Guideline 405 in compliance with GLP.

Instillation of the undiluted test sample into the conjunctival sac of the eye of one rabbit caused moderate initial pain (class 3 on a 0-5 scale). The eyes of the other two rabbits were therefore treated with a local anaesthetic prior to dosing and these animals showed no initial pain following application.

Apart from blue staining of the periorbital tissues by the test sample, there were no corneal or iridial effects. Blue staining of the conjunctiva by the test substance obscured any underlying redness that may have been present. However, as the observed ocular effects were limited to transient/intermittent conjunctival discharge it is considered unlikely that significant conjunctival redness was present in any of the animals.

As the staining is limited to the conjunctiva and no corneal effects occurred It is hence concluded that the test substance has no irritating effects on the rabbit eye.

 

Justification for classification or non-classification

Skin

Based on the available in vivo skin irritation study, test substance was found to be non-irritating to skin and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).

Eye

Based on the available in vivo eye irritation study, test substance was found to be non-irritating to the eye and does not meet the requirement for classification according to EC criteria (67/548/EEC) and according to CLP criteria (EC 1272/2008).