Registration Dossier

Skin irritation/corrosion: Based on the results the test material was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Eye irritation: It is considered reasonable to assume that the test material is irritant according to EEC labelling regulations.

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

No further details specified in the study report.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Not specified in the summary report.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

As per the guideline -0.5ml

Duration of treatment / exposure:

4 hour

Observation period:

72 hour

Number of animals:

Six animals (sex not specified).

Details on study design:

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits.
An additional group of three rabbits was also treated.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 72 hours

Score:

3.8

Reversibility:

not fully reversible within: 72 hours. Study terminated due to toxicity.

Remarks on result:

other: Study terminated due to toxicity.

Irritant / corrosive response data:

Surviving animals showed very slight to well-defined erythema and very slight to moderate oedema at the treatment sites during the study. Incidents of crust formation were also noted.
No corrosive effects were noted.

Other effects:

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits resulted in the death of one animal one day after treatment. It also became necessary to kill one animal for humane reasons later the same day owing to the development of severe respiratory problems. The surviving animal showed very slight to well-defined erythema and slight oedema at the treatment site during the study. The study was terminated after the 72-hour observation. At the time it was thought that the deaths may not have been treatment-related. An additional group of three rabbits was therefore treated. One rabbit in this group was also found dead two days after treatment. The two surviving animals showed very slight to well-defined erythema and very slight to moderate oedema at the treatment sites during the study. Incidents of crust formation were also noted. It was concluded that the deaths seen during this study were due to the toxicity of the test material. No further animals were treated.
Based on the results of the surviving animals the test material produced a primary irritation index of 3.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Based on these results the test material was classified as irritant according to EEC labelling regulations.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as abasicforclassificationand labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 91/325/EEC).

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits resulted in the death of one animal one day after treatment. It also became necessary to kill one animal for humane reasons later the same day owing to the development of severe respiratory problems. The surviving animal showed very slight to well-defined erythema and slight oedema at the treatment site during the study. The study was terminated after the 72-hour observation. At the time it was thought that the deaths may not have been treatment-related. An additional group of three rabbits was therefore treated. One rabbit in this group was also found dead two days after treatment. The two surviving animals showed very slight to well-defined erythema and very slight to moderate oedema at the treatment sites during the study. Incidents of crust formation were also noted. It was concluded that the deaths seen during this study were due to the toxicity of the test material. No further animals were treated.

Based on the results of the surviving animals the test material produced a primary irritation index of 3.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The above results triggered classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). The following classification for irritant effects is therefore required:

Category 2 Skin Irritant

H315: Causes skin irritation

R 38- Irritating to skin

Endpoint conclusion:

adverse effect observed (irritating)

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not specified

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

See "Principles of Method if other than guideline"

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

See "Principles of Method if other than guideline"

Principles of method if other than guideline:

A single instillation of the test material to the non-irrigated eye of one rabbit produced areas of diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Other adverse ocular effects noted were a dulling of the normal lustre of the corneal surface and petechial haemorrhage of the nictitating membrane. Two days after treatment the animal showed signs of respiratory problems which were thought to be treatment-related. The animal was therefore killed for humane reasons in accordance with current U.K. Home Office guidelines and no further animals were treated.

GLP compliance:

yes

Specific details on test material used for the study:

No further details specified in the study report.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Not specified in the report.

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

Not specified

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

Two days

Number of animals or in vitro replicates:

One animal (sex not specified)

Details on study design:

A single instillation of the test material to the non-irrigated eye of one rabbit.

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 48 hour

Score:

39

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

Areas of diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation.

Other effects:

Other adverse ocular effects noted were a dulling of the normal lustre of the corneal surface and petechial haemorrhage of the nictitating membrane. Two days after treatment the animal showed signs of respiratory problems which were thought to be treatment-related. Two days after treatment the animal showed signs of respiratory problems which were thought to be treatment-related. The animal was therefore killed for humane reasons in accordance with current U.K. Home Office guidelines and no further animals were treated.

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

It is considered reasonable to assume that the test material is irritant according to EEC labelling regulations.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method B5 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 91/325/EEC).

A single instillation of the test material to the non-irrigated eye of one rabbit produced areas of diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Other adverse ocular effects noted were a dulling of the normal lustre of the corneal surface and petechial haemorrhage of the nictitating membrane. Two days after treatment the animal showed signs of respiratory problems which were thought to be treatment-related. The animal was therefore killed for humane reasons in accordance with current U.K. Home Office guideline and no further animals were treated.

The test material produced a maximum total score of 39.0 and was considered to be at least a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on one rabbit only).

It is considered reasonable to assume that the test material is irritant according to EEC labelling regulations. As such, the results triggered classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008). The following classification for irritant effects is therefore required:

Category 2 Eye Irritant

H319: Causes serious eye irritation

R 36- Irritating to the eyes

Endpoint conclusion:

adverse effect observed (irritating)

Endpoint conclusion:

no study available

Skin Irritation/Corrosion

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits resulted in the death of one animal one day after treatment. It also became necessary to kill one animal for humane reasons later the same day owing to the development of severe respiratory problems. The surviving animal showed very slight to well-defined erythema and slight oedema at the treatment site during the study. The study was terminated after the 72-hour observation. At the time it was thought that the deaths may not have been treatment-related. An additional group of three rabbits was therefore treated. One rabbit in this group was also found dead two days after treatment. The two surviving animals showed very slight to well-defined erythema and very slight to moderate oedema at the treatment sites during the study. Incidents of crust formation were also noted. It was concluded that the deaths seen during this study were due to the toxicity of the test material. No further animals were treated.

Based on the results of the surviving animals the test material produced a primary irritation index of 3.8 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Eye Irritation

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. A single instillation of the test material to the non-irrigated eye of one rabbit produced areas of diffuse corneal opacity, iridial inflammation and moderate conjunctival irritation. Other adverse ocular effects noted were a dulling of the normal lustre of the corneal surface and petechial haemorrhage of the nictitating membrane. Two days after treatment the animal showed signs of respiratory problems which were thought to be treatment-related. The animal was therefore killed for humane reasons in accordance with current U.K. Home Office guideline and no further animals were treated.

The test material produced a maximum total score of 39.0 and was considered to be at least a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on one rabbit only).

It is considered reasonable to assume that the test material is irritant according to EEC labelling regulations.

Justification for selection of skin irritation / corrosion endpoint:

Effect level derived using EU Method B4 and OECD guideline 404.

Justification for selection of eye irritation endpoint:

Effect level derived using EU Method B5 and OECD guideline 405.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

The above studies have all been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted to GLP and the results are well documented. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

The above results triggered classification under the the CLP Regulation (EC No 1272/2008). The following classification for irritant effects is therefore required:

Category 2 Skin Irritant

H315: Causes skin irritation

Category 2 Eye Irritant

H319: Causes serious eye irritation