Registration Dossier

Administrative data

Description of key information

Skin irritation: not irritating (OECD 404; GLP)
Eye irritation: irritating on the eye (OECD 405; GLP)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-10-19 to 2011-10-22
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
, 2002-04-24
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Kuiper Rabbitry, Gary, Indiana- Age at study initiation: approximately ten to twelve weeks old- Weight at study initiation: 2.42 to 2.67 kg- Housing: the rabbits were individually housed in stainless steel cages.- Diet (ad libitum): Purina Laboratory Rabbit Chow- Water (ad libitum): water- Acclimation period: at least five days prior to study initiationThe rabbits were maintained according to the recommendations contained in the National Academy Press 1996: "Guide for the Care and Use of Laboratory Animals".All animals used in this study were considered to be in good health at study initiation.ENVIRONMENTAL CONDITIONS- Temperature: 20 ± 3°C- Humidity: 30 - 70%- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 g aliquot of the test material, which was slightly warmed (34°C) in a water batch to facilitate application, was applied.
Duration of treatment / exposure:
4 hours
Observation period:
approximately 30 minutes after patches were removed, and 24, 48 and 72 and 168 hours after treatment
Number of animals:
3 female rabbits
Details on study design:
TEST SITE- Area of exposure and type of wrap if used: the day before study initiation, electric clippers were used to remove the hair from the left side of the trunk, from the midline of the back to the abdomen. The following day an aliquot of the test material, which was slightly warmed (34°C) in a water batch to facilitate application, was then applied to an area approximately 6 square centimeters on the side of the test animal. The application site is located approximately 5 - 7 centimeters down from the backbone. The test substance was then covered with a 2.5 cm^2 - 2 layer gauze patch held in place with non-irritating Kendall Curity Standard Porous Tape and the patch was then covered with a semi-occlusive plastic overwrap secured in place with Kendall Curity Standard Porous Tape for the duration of the exposure period. REMOVAL OF TEST SUBSTANCE- Washing (if done): excess material was removed from the site- Time after start of exposure: at the end of the 4 hour contact periodSCORING SYSTEM: the site was observed and scored according to the Draize scaleOther adverse changes at the skin sites will be recorded if present.
Irritation parameter:
erythema score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
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:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
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:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
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:
There were minimal irritation reactions (very slight erythema - grade 1) in two of the test subjects which cleared by the 168 hour observation.
Other effects:
There was slight mechanical damage to the skin when samples were removed, as the sticky material had adhered to the skin surface.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material is non-irritating to the skin of rabbits.According to 67/548/EC and subsequent regulations, cobalt borate neodecanoate is not classified as a skin irritant.According to the EC Regulation No. 1272/2008 and subsequent regulations, cobalt borate neodecanoate is not classified as a 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
Study period:
2012-10-01 to 2012-10-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study relibale without restrictions
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 2002-04-24
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspection date: 2012-07-10
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS - New Zealand White (Hsdlf:NZW) strain rabbits- Source: Harlan Laboratories UK Ltd., Leicestershire, UK- Age at study initiation: twelve to twenty weeks old- Weight at study initiation: 2.69 or 3.10 kg- Housing: the animals were individually housed in suspended cages.- Diet (ad libitum): 2930C Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK- Water (ad libitum): mains drinking water- Acclimation period: at least five daysThe animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.ENVIRONMENTAL CONDITIONS- Temperature: 17 to 23°C- Relative humidity: 30 to 70%- Air exchange: at least fifteen changes per hour- 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): a volume of 0.1 ml of the test item, which was found to weigh approximately 96 mg (as measured by gently compacting the required volume into an adapted syringe) was placed 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 treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes.
Duration of treatment / exposure:
not applicable
Observation period (in vivo):
approximately 1 hour and 24, 48 and 72 hours following treatment as well as on days 7 and 14
Number of animals or in vitro replicates:
2 male rabbits
Details on study design:
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.INITIAL AND CONFIRMATORY TESTInitially, a single rabbit was treated. Immediately after administration of the test item, an assessment of the initial pain reaction was made according to the six point scale (please refer to table 2 in the field "Any other information on materials and methods incl. tables" below).After consideration of the ocular responses produced in the first treated animal, a second animal was treated.SCORING SYSTEM: according to the Draize scaleAny other ocular effects were also noted.Any clinical signs of toxicity, if present, were also recorded.Individual bodyweights were recorded on Day 0 (the day of dosing) and at the end of the observation period.If evidence of irreversible ocular damage is noted, the test item will be classified as corrosive to the eye.TOOL USED TO ASSESS SCORE: examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Remarks on result:
other: Initial pain reaction: practically no initial pain; Slight to moderate discharge was observed at the 1, 24 and 48 hour observations.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight iridial inflammation was observed at the 1 hour observation.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Moderate conjunctivae redness was observed at the 1 hour observation.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Moderate chemosis was observed at the 1 hour observation.
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Initial pain reaction: slight initial pain; Moderate to severe discharge was observed at the 1, 24, 48 and 72 hour observations.
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Slight iridial inflammation was observed at the 1 hour observation.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Moderate conjunctivae redness was observed at the 1 hour observation.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Moderate chemosis was observed at the 1 hour observation.
Irritant / corrosive response data:
Scattered or diffuse corneal opacity was noted in one treated eye at the 24, 48 and 72-hour observations.Iridial inflammation was noted in both treated eyes one hour after treatment and at the 24 and 48-hour observations and persisted in one treated eye at the 72-hour observation.Moderate conjunctival irritation was noted in both treated eyes one hour after treatment and at the 24 and 48-hour observations. Moderate conjunctival irritation was noted in one treated eye with minimal conjunctival irritation noted in the other treated eye at the 72-hour observation. Minimal conjunctival irritation was noted in one treated eye at the 7-day observation.One treated eye appeared normal at the 7-day observation and the other treated eye appeared normal at the 14-day observation.
Other effects:
- Bodyweight: both animals showed expected gain in bodyweight during the study.
Interpretation of results:
Category II
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
The test material is irritating to the eyes.According to 67/548/EC and subsequent regulations, the substance is not classified as an eye irritant.According to the EC Regulation No. 1272/2008 and subsequent regulations, the substance is classified as Category 2.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation

One reliable in vivo study described by Kukulinski (2011) (OECD 404; GLP compliant) is considered to be reliable without restrictions. The substance was not determined to be a skin irritant.

Eye irritation

One reliable in vivo study described by Sanders (2013) (OECD 405; GLP compliant) is considered to be reliable without restrictions. The substance was determined to cause irritating effects on the eye.

Furthermore, a reliable in vitro study described by Heppenheimer (2012) (OECD 437; GLP compliant) is considered to be reliable without restrictions. The substance was determined to be neither corrosive nor severely irritating to the eye.


Justification for selection of skin irritation / corrosion endpoint:
Key study

Justification for selection of eye irritation endpoint:
Key study

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin corrosion

Reference Heppenheimer (2010) is considered as disregarded study for skin corrosion, since an in vivo skin irritation test is available. The overall irritation results in an in vitro human skin model test (according to OECD 431) are as follows:

Relative viability 3 min after treatment: 20.7 %

Relative viability 60 min after treatment: 20.5 %

Testing requirements in other international schemes necessitated an in vivo test. Since in vivo test results should take precedence over in vitro test results, the results received from this in vivo test are taken forward for the chemical hazard assessment.

Skin corrosion/irritation

The reference Kukulinski (2011) is considered as the key studies for skin irritation and will be used for classification.

According to Kukulinski (2011) the overall irritation results 24, 48 and 72 hours after application per animal are as follows (according to OECD 404):

- erythema: 0, 1, 1

- oedema: 0 for all three animals

The classification criteria acc. to regulation (EC) 1272/2008 as irritating to skin are not met, since the values of erythema and oedema were below the threshold of ≥2.3 as well as the effects were fully reversible within 7 days. No classification required.

Eye irritation

Reference Heppenheimer (2012) is considered as the key study for severe eye irritation and will be used for classification. The mean in vitro score after 240 minutes incubation results of the in vitro bovine corneal opacity and permeability assay (BCOP, according to OECD TG 437) was 1.04. The value was below the threshold for severe eye irritants of 55.1. The classification criteria according to regulation (EC) 1272/2008 as severe eye irritation are not met, hence no classification required.

Reference Sanders (2013) is considered as key study for eye irritation and will be used for classification. According to the reference the overall irritation results 24, 48 and 72 hours after application per animal are as follows:

- Corneal opacity = 0 and 1

- Iris light reflex = 0.67 and 1

- Conjunctival redness = 2 for both animals

- Conjunctival oedema = 2 and 1.67

The classification criteria acc. to regulation (EC) 1272/2008 as irritating to eyes are met, since conjunctival redness was at the threshold of ≥ 2 as well as the effect were fully reversible within 14 days.Thus, cobalt borate neodecanoate will be classified as eye irritant category 2 (H319).

Respiratory irritation

The justification for classification as respiratory irritant is covered under the endpoint specific target organ toxicity- single exposure: inhalation as given in the acute toxicity section.