Registration Dossier

Administrative data

Description of key information

Skin irritation: 
Key study. Test procedure according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion). Not irritating to skin.
Eye irritation:
Key study. The test procedure used was OECD Guideline 405 (Acute Eye Irritation / Corrosion). Since the rabbit was killed two days after the treatment, it it not possible to confirm if the ocular lesions were still present at the end of the observation period. The substance is classified as "Irreversible effects on the eye, Cat 1" applying the precautionary principle.

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:
From November 26, 1900 to December 11, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: There are no deviations from the OECD Guideline 404 (Acute Dermal Irritation / Corrosion). No GLP.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms U.K. Ltd.
- Age at study initiation: 3.5 to 5.5 months
- Weight at study initiation: males: 3.74-4.01 kg; females: 3.55-4.10 kg
- Housing: Animals were singly housed in hanging, stainless steel cages with perforated dimple or wire-mesh flooring. Sawdust-filled undertrays for excreta were placed beneath each cage and changed twice weekly. Each cage measured 91 cm x 66 cm x 45 cm.
- Diet (e.g. ad libitum): Pelleted diet (Standard Rabbit Diet, S.Q.C. Special Diet Services Ltd. ), ad libitum.
- Water (e.g. ad libitum): From public supply, ad libitum.
- Acclimation period: two weeks.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-20 ºC.
- Humidity (%): Animal room humidity exceeded the target range of 30-70% for more than two consecutirve (four hourly) recordings on six days of the study. The raised humidity had no overt effect upon the health of the rabbits.
- Air changes (per hr): not documented.
- Photoperiod (hrs dark / hrs light): 12 hours day and 12 hours night.


IN-LIFE DATES: From November 26, 1900 to December 11, 1990
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
Duration of treatment / exposure:
The undiluted test material (0.5 ml) was applied to the skin on a 6 cm2 lint patch, covered with gauze and held in place by a semi-occlusive elactic adhesive bandage. After a 4 hour exposure the dresssings were removed, the skin washed with water and dried.
Observation period:
After treatment, animals were examined for erythema, oedema and other lesions at 24, 48 and 72 hours.
Number of animals:
Six rabbits (3 per sex)
Details on study design:
SCORING SYSTEM:
Erythema and oedema were scored on a five point scale (Study report - Attachment A).
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
1.44
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 h
Score:
0.7
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
The 4-hour semi-occluded topical application of 0.5 ml undiluted test substance to the clipped skin of six New Zealand White rabbits caused inflammatory reactions not exceeding well-defined erythema and very slight oedema. Maximum intensity of reaction occurred within 24 hours of treatment. Partial resolution of inflammation was first apparent 7 days after treatment but was commonly associated with desquamation of the treated skin. All dermal test sites were overtly normal two weeks after application.

Table 7.3.1: Dermal irritation scores

Erythema

Oedema

Animal No

1

2

3

4

5

6

1

2

3

4

5

6

after 24 h

2

2

1

1

2

1

1

1

0

1

1

0

after 48 h

2

1

1

2

2

1

1

1

0

1

1

0

after 72 h

2

1

1

2

1

1

1

1

0

1

1

0

Mean score 24 – 72 h

1.4

0.7

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
On the basis of reactions observed in this study and the criteria defined in Council Directive 67/548/EC and CLP Regulation, the test substance is not classified as irritant to skin.
Executive summary:

Six New Zealand White rabbits (3 per sex) were exposed via the dermal route to 0.5 mL of the test substance per animal. After a 4 hour exposure the dresssings were removed, the skin washed with water and dried. After treatment, animals were examined for erythema, oedema and other lesions at 24, 48 and 72 hours. On the basis of reactions observed in this study and the criteria defined in Council Directive 67/548/EC and CLP Regulation, the test substance is not classified as irritant to skin.

 

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:
From November 26, 1900 to November 29, 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The animal was killed before the end of the observation period. No GLP.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms U.K. Ltd.
- Age at study initiation: 3.5 to 5.5 months
- Weight at study initiation: male: 3.57 kg
- Housing: Animals were singly housed in hanging, stainless steel cages with perforated dimple or wire-mesh flooring. Sawdust-filled undertrays for excreta were placed beneath each cage and changed twice weekly. Each cage measured 91 cm x 66 cm x 45 cm.
- Diet (e.g. ad libitum): Pelleted diet (Standard Rabbit Diet, S.Q.C. Special Diet Services Ltd. ), ad libitum.
- Water (e.g. ad libitum): From public supply, ad libitum.
- Acclimation period: two weeks.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15-20 ºC.
- Humidity (%): Animal room humidity exceeded the target range of 30-70% for more than two consecutirve (four hourly) recordings on six days of the study. The raised humidity had no overt effect upon the health of the rabbits.
- Air changes (per hr): not documented.
- Photoperiod (hrs dark / hrs light): 12 hours day and 12 hours night.


IN-LIFE DATES: From November 26, 1900 to November 29, 1990
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
The undiluted test material (0.1 ml) was placed into the lower conjunctival sac of one eye. The treated eye was gently held closed for a few seconds to prevent loss of the test material. The eyes were not irrigated.
Observation period (in vivo):
The irritation scores were recorded at 1, 4, 24 and 48 h.
Number of animals or in vitro replicates:
One animal (male).
Details on study design:
SCORING SYSTEM:
The immediate reactions of the rabbit were scored as an initial pain response using a six point scale. Other ocular reactions to treatment were noted and scored using standard grades (Study report - Attachment A).
Irritant / corrosive response data:
The conjunctivae developed a crimson-red appearance, an ocular discharge and chemosis sufficient to cause partial eversion of the eyelids within one hour of ocular instillation. Intensification of the conjunctival responses caused a beefy-red appearance and chemosis obscuring part of the cornea within 4 hours of treatment.
Minor corneal opacity had developed on the day after ocular instillation and persisted at subsequent examination.
As the conditions of the conjunctivae showed very little improvement during the two days after treatment the rabbit was killed on humane grounds.
Other effects:
Installation of 0.1 ml undiluted test substance into one eye of a single rabbit resulted in a moderate initial pain response.

Table 7.3.2: Eye irritation scores

Redness

Chemosis

Opacity

Iris

1 hour

2

2a

0

0

4 hours

3

3a

0

0

24 hours

3

2b

1c

1

48 hours

3

2a

1d

1

a – Slight ocular discharge

b – Ocular discharge

c – Opacity affecting 25-50% of cornea

d – Opacity affecting < 25% of cornea

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Since the rabbit was killed two days after the treatment, it it not possible to confirm if the ocular lesions were still present at the end of the observation period.
The substance is classified as "Irreversible effects on the eye, Cat 1" applying the precautionary principle.
Executive summary:

The aim of the study was to investigate the eye irritation potential of the test material.

The test procedure used was OECD Guideline 405 (Acute Eye Irritation / Corrosion).

Instillation of the undiluted test material into the eye of a single rabbit caused severe conjunctival irritation reactions within four hours of treatment. As there was little improvement in the condition of the conjunctivae, the rabbit was killed two days later. No further rabbits were treated because it was considered that the marked irritancy had been adequately demonstrated. Since the rabbit was killed two days after the treatment, it it not possible to confirm if the ocular lesions were still present at the end of the observation period.

The substance is classified as "Irreversible effects on the eye, Cat 1" applying the precautionary principle.

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Key study. Test procedure according to OECD Guideline 404 (Acute Dermal Irritation / Corrosion).

Six New Zealand White rabbits (3 per sex) were exposed via the dermal route to 0.5 mL of the test substance per animal. After a 4 hour exposure the dresssings were removed, the skin washed with water and dried. After treatment, animals were examined for erythema, oedema and other lesions at 24, 48 and 72 hours. On the basis of reactions observed in this study and the criteria defined in Council Directive 67/548/EC and CLP Regulation, the test substance is not classified as irritant to skin.

 

Eye irritation:

Key study. The test procedure used was OECD Guideline 405 (Acute Eye Irritation / Corrosion).

Instillation of the undiluted test material into the eye of a single rabbit caused severe conjunctival irritation reactions within four hours of treatment. Since the rabbit was killed two days after the treatment, it it not possible to confirm if the ocular lesions were still present at the end of the observation period. The substance is classified as "Irreversible effects on the eye, Cat 1" applying the precautionary principle.


Justification for selection of skin irritation / corrosion endpoint:
Only one reliable study available.

Justification for selection of eye irritation endpoint:
Only one reliable study available. Klimisch 2. Non-GLP study.

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

On the basis of reactions observed in the available study and the criteria defined in Council Directive 67/548/EC and CLP Regulation, the test substance is not classified as irritant to skin.

Instillation of the undiluted test material into the eye of a single rabbit caused severe conjunctival irritation reactions within four hours of treatment. Since the rabbit was killed two days after the treatment, it it not possible to confirm if the ocular lesions were still present at the end of the observation period. The substance is classified as "Irreversible effects on the eye, Cat 1" applying the precautionary principle.