Registration Dossier

Administrative data

Description of key information

No irritating effects observed.

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:
10 January 1995 to 24 January 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU and OECD test guidance. GLP is assumed, given the references and QA procedures, although is not specifically mentioned.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4470 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Remarks:
GLP is assumed, given the references and QA procedures, although is not specifically mentioned.
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Ltd
- Age at study initiation: Adult
- Weight at study initiation: Average 3.9 kg
- Housing: Individually housed in stainless steel cages
- Diet (e.g. ad libitum): Standard diet, approx 100 - 200g per animal/day; once per day in the monring
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50 - 70
- Air changes (per hr): 12 - 15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours, artificial illumination from 6 am to 6 pm

Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500mg moistened with deionised water.


Duration of treatment / exposure:
Exposure 4 hours
Observation period:
14 days
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: hypoallergenic Hansamed patch

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With water
- Time after start of exposure: 4 hours

SCORING SYSTEM: DRAIZE
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible
Remarks on result:
other: due to staining of the skin was erythema evaluation not possible between day 1 and day 7
Irritant / corrosive response data:
Evaluation of skin erythema was not possible in all three animals due to the intense colouration by the test substance. Nevertheless, no other inflammatory signs (eschar or oedema formation) became apparent within the observation period of 7 days. 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’.
Other effects:
Areas of exposed skin were stained the colour of the test sample.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Substance not irritant.
Executive summary:

Study conducted to recent EU test guidance 92/69/EEC B4 and OECD Guideline 404.

Test substance was found not to be irritant.

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:
10 January 1995 to 24 January 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to recent EU and OECD test guidance. GLP is assumed, given the references and QA procedures, although is not specifically mentioned.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.4500 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Remarks:
GLP is assumed, given the references and QA procedures, although is not specifically mentioned.
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Ltd
- Age at study initiation: Adult
- Weight at study initiation: Average weight 3.8 kg
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): Standard diet, approx 100-120g per animal/day; once per day in the morning
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50 - 70
- Air changes (per hr): 12 -15 times per hour
- Photoperiod (hrs dark / hrs light): 12 hours, artifical illumination from 6am to 6pm

Vehicle:
not specified
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx 67mg (equivalent to 100 ul test substance)

Duration of treatment / exposure:
24 hours exposure
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
three
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Normal saline
- Time after start of exposure: 24 hoours

SCORING SYSTEM: DRAIZE

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: overall at 24, 48 72 hours
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: All animals showed mild effects up to 72 hours. No effects were noted at the end of the exposure period.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: overall at 24, 48 and 72 hours.
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72
Remarks on result:
other: All animals showed mild effects up to 72 hours. No effects were noted at the end of the exposure period.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: overall at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: overall at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritant / corrosive response data:
Exposure of the test substance to the eye resulted in all three animals in transient slight conjunctival redness and discharge, and in one animal a very slight oedema was observed too (1 hour after the application). These signs of irritation had subsided in all animals by 72 hours. Cornea and iris showed no lesions or other signs of irritation. No ocular lesions and other signs of toxicity were not observed. This evidence indicates that the product may be considered as 'not irritating to the eye'.
Other effects:
Some discolouration occured in conjunctiva of all animals but not sufficient to affect the readings of reactions. Conjunctival swelling was noted in one animal and discharge from the eyes of all animals at the 1 hour reading. These were not noted in remaining assessments.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Substance is not irritating to the eye
Executive summary:

Study conducted to recent EU test guidance 92/69/EEC B5 & OECD 405.

The substance was found not irritating to the eye.

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

Respiratory irritation

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

Additional information

Skin irritation / Corrosion.

A single study was evaluated on this endpoint. In these the substance was tested for primary dermal irritation and corrosiveness. Due to staining of the skin, redness etc could not be evaluated, nevertheless, no other inflammatory signs (eschar or oedema formation) became apparent within the observation period of 7 days. 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 these the substance was tested for acute irritation and was found not to be an irritant to the rabbit eye. Effects were noted in all animals assessed; however these were fully reversible within 72 hours. 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 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 an in compliance with agreed protocols. Sufficient dose ranges and numbers are detailed; hence it is appropriate for use based on reliability and animal welfare grounds.

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 irritation effects is therefore required.