Neodecanoic acid, cobalt salt

Endpoint summary

Description of key information

Skin irritation: not corrosive to the skin (OECD 431; GLP compliant)/not irritating to the skin (OECD 404; GLP compliant)
Eye irritation: not corrosive/not irritating (OECD 437 and OECD 405; GLP complaint)

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:

2013-11-12 to 2013-11-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The following deviations from the guideline OECD 404 (2002) occured, but they had no effect on the results of the study: - the animals were observed 4.5 hours after the removal of the test item instead of 60 minutes after test item removal - the animals were not observed for systemic adverse effects, but only for the skin irritation listed in the Draize scoring system

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002-04-24

Deviations:

yes

Remarks:

please refer to "Rationale for reliability incl. deficiencies" above

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kuiper Rabbitry, Gary, Indiana
- Age at study initiation: approximately ten to twelve weeks old
- Weight at study initiation: 2.45 to 2.67 kg
- Housing: the rabbits were individually housed in stainless steel cages.
- Diet (ad libitum): Purina Laboratory Rabbit Chow
- Water (ad libitum)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3° C
- Humidity: 30-70%
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL aliquot of the test material

Duration of treatment / exposure:

4 hours

Observation period:

approximately 4.5, 24, 48, 72 and 168 hours after treatment

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: 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 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.
- Type of wrap if used: the test substance was then covered with a 2.5 cm² - 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
- Time after start of exposure: at the end of the 4 hour contact period, excess material was removed from the site; the site being observed and scored.

SCORING SYSTEM: according to the Draize scale

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 168 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 168 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 168 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

There were moderate skin irritation reactions in all of the test subjects, which cleared by the 168 hour observation.
4.5 hour observation: test article adhered to skin & extremely difficult to remove.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item is not a 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

Study period:

2011-12-12 to 2011-12-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002-04-24

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2011-08-31

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: 2.58 or 2.65 kg
- Housing: the animals were individually housed in suspended cages.
- Diet (ad libitum): 2930 Teklad Global Certified Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

The 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 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

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 TEST
Initially, 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. Due to a technician error, the initial pain reaction was not recorded.

SCORING SYSTEM: according to the Draize scale
Any 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:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Initial pain reaction: slight initial pain

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

other: Blue coloured staining of the fur around treated eye throughout the observation period.

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: Blue coloured staining of the fur around treated eye throughout the observation period.

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Blue coloured staining of the fur was noted around both treated eyes throughout the study.
No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in both treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-hour observation. Minimal conjunctival redness was noted in one treated eye at the 48-hour observation.
Slight chemosis was observed a the 1-hour observation in both treated eyes and at the 24-hour observation in one treated eye.
Slight discharge was observed at the 1-hour observation in both treated eyes.
One treated eye appeared normal at the 48-hour observation and the other treated eye appeared normal at the 72-hour observation.

Other effects:

- Bodyweight: both animals showed expected gain in bodyweight during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material is non-irritating to the eyes.
According to the EC Regulation No. 1272/2008 and subsequent regulations, the substance is not classified as an eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

One reliable in vitro study described by Heppenheimer (2011) (OECD 431; GLP compliant) is considered to be reliable without restrictions. The substance was determined to be not corrosive to the skin.

One reliable in vitro study described by Heppenheimer (2011) (OECD 439; GLP compliant) is considered to be reliable without restrictions. The substance was determined to be a skin irritant.

One reliable in vivo study by Kukulinski (2013) is considered reliable without restrictions. The substance was determined to be not skin irritating.

Eye irritation

One reliable in vitro study described by Heppenheimer (2011)(OECD 437; GLP compliant) is considered to be reliable without restrictions. The substance is considered to be neither corrosive nor severely irritating to the eyes.

One reliable in vivo study described by Sanders (2012) (OECD 405; GLP complaint) is considered to be reliable without restrictions. The substance is not irritating to the eyes.

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

Justification for selection of eye irritation endpoint:
Key study.

Justification for classification or non-classification

Skin corrosion

Reference Heppenheimer (2011) is considered as the key study for skin corrosion and will be used for classification. 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: 108.1 %

Relative viability 60 min after treatment: 45.7 %

The classification criteria according to regulation (EC) 1272/2008 as corrosive to skin are not met since the relative viability after 3 and 60 minutes exposure was above 50 % and 15% respectively, hence neodecanoic acid, cobalt salt will not be classified as skin corrosive.

Reference Heppenheimer (2011), the mean relative absorbance (% of the negative control, correlating with mean tissue viability) after 15 minutes incubation in the in vitro human skin model test (EpiSkin, according to OECD 439) was as follows:

Heppenheimer (2011): relative viability = 11.7%

The classification criteria according to regulation (EC) 1272/2008 as skin irritant were met, since the mean tissue viability was below the threshold for skin irritants of 50.0%.

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 irritation

The reference Kukulinski (2013) is considered as the key studies for skin irritation and will be used for classification.

According to Kukulinski (2013) the overall irritation results 24, 48 and 72 hours after application per animal are as follows (according to OECD 404):

- erythema: 1, 2, 1.33

. oedema: 0.67 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 48 hours. No classification required.

Eye irritation

The reference Heppenheimer (2011) 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 0.00. 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.

The reference Sanders (2012) is also considered as the key study for eye irritation and will be used for classification. During the study the test item was applied to one eye of two animals each and the eye irritation was scored according to the Draize scale. The overall irritation results 24, 48 and 72 hours after application per animal are as follows:

-         Corneal opacity= 0 for both animals

-         Iris light reflex= 0 for both animals

-         Conjunctival redness=0.67 and 0.33

-         Conjunctival oedema (chemosis)= 0.33 and 0

The classification criteria acc. to regulation (EC) 1272/2008 as irritating to eyes are not met, since the values of conjunctival redness and chemosis were below the threshold of ≥ 2 as well as the effect was fully reversible within 48 hours and 72 hours, respectively. No classification required.