Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (equivalent or similar to OECD 404; Non-GLP compliant)
Eye irritation: not irritating (equivalent or similar to OECD 405; Non-GLP compliant)

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study reliable without restrictions Minor deviations from the guideline: - physical nature and batch/lot no. were not stated. - the relative humidity in the animal room should be 30 - 70 %. In this study the humidity was slightly higher (55% +/- 25 %). - approx. 24 h before the test the fur should be removed by clipping or shaving. In this study the time of removal of the fur was not stated. - the type of vehicle used for moistening the solid test substance was not clearly stated. It was only stated that either water or an appropriate fluid was used to moisten the test substance. - the age, source, and the weight of the animals at the conclusion of the test were missing.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted 199207-17
Deviations:
yes
Remarks:
, please refer to "Rationale for reliability incl. deficiencies" above
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2501 - 2654 grams
- Housing: individual stainless steel cages, brand Tecniplast; cleaning: automatic
- Diet (daily dose of 150 g): special diet for experimental rabbits, provided by an authorized provider
- Drink: automatic ad libitum, treated and filtered at 5 µm
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 2 °C
- Relative humidity: 55 % +/- 25 %
- Air: renewed 15 times per hour and prefiltered at 5 µm
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
other: water or appropriate fluid
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of a solid sample moistened with water (or appropriate fluid) was applied.
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after removal of the bandages
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure and type of wrap used: the skin at the back (scapular area) close to the vertebral column was shaved (20 cm long, 13 cm wide rectangle). Once the rabbit had been shaved, the sample is applied directly onto the skin, covering a surface of approximately 6 cm^2. It was covered with a bandage, held with a plaster and covered with a hypoallergenic plaster bandage.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: once the period of exposure as ended
- Washing: the sample was softly removed with water or appropriate solvent.

SCORING SYSTEM: according to the Draize scale
Also, observations of corrosion were made (if there was a destruction of tissue in all the thickness of the skin)

OBSERVATIONS:
- Weight control: it was performed at the beginning of the study
- General examination: the general condition of the animal was observed, as well as the condition of the skin. Special attention was given to the apparition of modifications on the treated area, like corrosion, irritation, erythema, scarification, oedema or any other alteration.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight erythema (hardly perceptibel) was observed in all animals at the 1 hour observation.
Very slight erythema (hardly perceptibel) was observed in two animals at the 24 hour observation, which was still observed in one animal at the 48 hour observation.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
MARRÓN-B5 is not irritating to the skin.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is not classified as skin irritant.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as skin 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study reliable without restrictions Minor deviations from the guideline: - the batch/lot no. of the test substance was missing. - the relative humidity is slightly higher than 70 % (55 % +/- 25 %). - it was not stated, if the eyelids were held together after application of the test substance.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 1987-02-24
Deviations:
yes
Remarks:
, please refer to "Rationale for reliability incl. deficiencies" above
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2030 grams - 2288 kg
- Housing: individual stainless steel cages, brand Tecniplast; cleaning: automatic
- Diet (daily dose of 150 g): special diet for experimental rabbits, provided by an authorized provider
- Drink: automatic ad libitum, treated and filtered at 5 µm
- Acclimation period: 7 days

At arrival at the Unit, rabbits went through a health control.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 2 °C
- Relative humidity: 55 % +/- 25 %
- Air: renewed 15 times per hour and prefiltered at 5 µm
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g of the solid test item (grinded to fine dust) was administered into the conjunctival bag of one eye by separating the lower eyelid.The untreated eye was used as control.
Observation period (in vivo):
1, 24, 48 and 72 hours as well as 7 days after administration of the test substance
Number of animals or in vitro replicates:
3 males
Details on study design:
The rabbits were fixed in an immobilization trap during test item administration.

REMOVAL OF TEST SUBSTANCE
not stated

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: in order to facilitate the evaluation of the reactions, light from a manual lamp was used and 24 hours after administration of the test item, fluorescein was used to check for injuries of the cornea.

OBSERVATIONS:
- Weight control: it was performed at the beginning of the study
- General examination: the general condition of the animal was observed, as well as the conditions of the eyes. Special attention was given to the apparition of modifications on the treated eye: cornea, iris, conjunctiva, as well as any other injury observed.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 adn 72 hours
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritant / corrosive response data:
Opacity of the cornea of grade 1 affecting 1/4 of the eyeball was observed in all animals at the 1 hour and 24 hour observations.
Injury of the iris of grade 1 was observed in all animals at the 1 hour observation.
Erythema of the conjunctiva of grade 2 was observed in one animal at the 1 hour and 24 hour observations, which then lessened to grade 1 at the 48 observation and had disappeared at the 72 hour observation.
Erythema of the conjunctiva of grade 2 was observed in the remaining two animals at the 1 hour, 24 hour and 48 hour observation, which then lessened to grade 1 at the 72 hour observation and had disappeared at the 7 day observation.
Oedema of the conjunctiva of grade 1 was observed in one animal at the 1 hour observation.
Oedema of the conjunctiva of grade 2 was observed in the remaining two animals at the 1 hour observation, which then lessend to grade 1 at the 24 hour observation and had disappeared at the 48 hour observation.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
MARRÓN-B5 is not irritating to the eye.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is not classified as eye irritant.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item is not classified as eye irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation

One reliable in vivo study described by Alvarez Genoher (2000) (equivalent or similar to OECD 404; Non-GLP compliant) is considered to be reliable without restrictions. The substance was determined to be not irritating to the skin.

Eye irritation

One reliable in vivo study described by Alvarez Genoher (2000) (equivalent or similar to OECD 405; Non-GLP compliant) is considered to be reliable without restrictions. The substance was determined to be not irritating to the eyes.


Justification for selection of skin irritation / corrosion endpoint:
One reliable in vivo study described by Alvarez Genoher (2000) (equivalent or similar to OECD 404; Non-GLP compliant) is considered to be reliable without restrictions. The substance was determined to be not irritating to the skin.

Justification for selection of eye irritation endpoint:
One reliable in vivo study described by Alvarez Genoher (2000) (equivalent or similar to OECD 405; Non-GLP compliant) is considered to be reliable without restrictions. The substance was determined to be not irritating to the eyes.

Justification for classification or non-classification

Skin irritation

Reference Alvarez Genoher (2000) is considered as the key study for in vivo skin irritation and will be used for classification. The skin irritation was scored according to the Draize scale. The mean score (24, 48, 72h) for oedema was 0 for all animals. The mean score for erythema for the three animals was 0.33, 0, and 0.67, repsectively. The study was terminated after the 72 hour observation. According to regulation (EC) 1272/2008 and subsequent amendments the substance will not be classified as skin irritant.

Eye irritation

Reference Alvarez Genoher (2000) is considered as the key study for in vivo eye irritation and will be used for classification. During the study the test item was applied to one eye of three animals each and the eye irritation was scored according to the Draize scale. The following mean scores (24, 48 and 72 hours) were observed for the three animals:

cornea: 0.33 for all animals

iris: 0 for all animals

conjunctivae score: 1, 1.67, and 1.67

chemosis score: 0, 0.33 and 0.33

The ocular effects were fully reversible within 7 days. Thus, according to Regulation (EC) 1272/2008 and subsequent amendments the substance will not be classified as irritating to the eyes.

Respiratory irritation

The classification as respiratory irritant is normally covered under the endpoint specific target organ toxicity- single exposure and repeated exposure. Please refer to the endpoint summaries on acute toxicity (endpoint 7.2) for further information.