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Description of key information

Supporting data of K4 are available on the skin and eye irritation of the test substance and K1 skin and eye irritation data on a structural analogue.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
20 - 27 January 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Good quality study data prepared according to international guidelines in accordance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Three New Zealand White rabbits supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.42 to 2.94 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 17 to 19" C and relative humidity of 46 to 59%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
A quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.
Duration of treatment / exposure:
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
Observation period:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H, (1 977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.
Number of animals:
3 animals
Details on study design:
The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.47
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
72 h
Score:
1.2
Max. score:
2
Reversibility:
fully reversible
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance produced a primary irritation index of 1.2 and was classified as MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
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 the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992).

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. All treated skin sites appeared normal at the 7-day observation.

The test material produced a primary irritation index of 1.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
10 - 15 February 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Good quality study data prepared according to international guidelines in accordance with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White rabbits, supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK, were used. At the start of the study the animals weighed 2.78 to 3.1 7 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 1 7 to 19 " C and relative humidity of 49 to 65%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eyes of test animals
Amount / concentration applied:
One rabbit was initially treated. A volume of 0.1 ml of the test material was instilled into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after instillation, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.

After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.
Duration of treatment / exposure:
Assessment of ocular damagehrritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation given in Appendix I, (from Draize J H (1 977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49).
Number of animals or in vitro replicates:
3 animals
Irritation parameter:
maximum mean total score (MMTS)
Basis:
mean
Time point:
24 h
Score:
9.3
Max. score:
10
Reversibility:
fully reversible
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance produced a maximum group mean score of 9.3 and is not irritating.
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 No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 671548lEEC).

A single instillation of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 48-hour observation.

The test material produced a maximum group mean score of 9.3 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as irritant according to EU labelling regulations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / Corrosion.

A single study was evaluated on this endpoint. In this the substance was tested for primary dermal irritation and corrosiveness. Mild reactions became apparent within the observation period of 3 days, however these were fully reversible within the period. Signs of toxicity were not observed. This evidence indicates no hazard potential to the skin and the test substance may therefore be regarded as 'not irritating to the skin’. It is not a dermal corrosive. No risk phrase or classification is required.

 

Eye irritation.

A single study was evaluated on this endpoint. In this the substance was tested for primary dermal irritation and corrosiveness.

In these the substance was tested for acute irritation. Test animals showed minor effects related to conjunctival irritation. Changes were fully reversible within 3 days. No classification is applicable.

Respiratory irritation

Respiratory irritation was not assessed; however no effects on the animals were noted in any associated studies.

 

The following information is taken into account for any hazard / risk assessment:

Skin and eye irritation are discussed.

Value used for CSA:

-         Skin irritation / corrosion: not irritating

-         Eye irritation: not irritating

Justification for classification or non-classification

The key studies available on a structural analogue have all been ranked reliability 1 according to the Klimish et al system. These data are supported by K4 data on the substance itself that agree with the results of the key studies.

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

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