Cobalt(2+) hydrogen citrate

Endpoint summary

Description of key information

Cobalt citrate
skin irritation: not irritating (according to OECD 404)
eye irritation: corrosive (according to OECD 405)

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:

30 Mar - 09 Apr 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministère de L'Economie de L'Industrie et de L'emploi

Species:

rabbit

Strain:

other: albino New Zealand

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste - F40260 Linxe)
- Age at study initiation: 11 or 12 weeks
- Weight at study initiation: between 2.43 kg and 2.68 kg
- Housing: individual box with suitable environmental enrichment
- Diet (e.g. ad libitum): SDS - C15 ad libitum
- Water (e.g. ad libitum): tap-water (from public distribution system - microbiological and chemical analyses of the water were carried out once every six months) ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light):12 hours light (07.00 to 19.00) and 12 hours darkness

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: on the opposite flank an untreated area served as the control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

Duration of treatment / exposure:

4 hours (as no tissue destruction was noted after a treatment during 3 minutes and 1 hour)

Observation period:

3 days: skin reactions were evaluated 1 hour and then 24, 48 and 72 hours after removal of the patch

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: back and flank
- % coverage: 6 cm2
- Type of wrap if used: strip of surgical adhesive tape under semi-occlusive dressing


REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsed with distilled water after the removal of the patch
- Time after start of exposure: 4 hours


SCORING SYSTEM: Grading scales 0 - 4 (erythema and eschar formation ; oedema)

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

other: not applicable

No cutaneous reactions (erythema and oedema) were observed on the treated area, whatever the examination time was (i.e. 1 hour, 24, 48 and 72 hours after the patch removal). The primary skin irritation index for cobalt citrate is 0.0.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

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:

06 Apr - 27 Apr 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministère de L'Économie de L'Industrie et de L'Emploi

Species:

rabbit

Strain:

other: albino New Zealand

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage de Gérome (Quartier Labaste -F40260 Linxe)
- Age at study initiation: 12 or 13 weeks
- Weight at study initiation: between 2.30 kg and 3.25 kg
- Housing: individual box
- Diet (e.g. ad libitum): SDS - C15 ad libitum
- Water (e.g. ad libitum): tap-water from public distribution system
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (07.00 to 19.00) and 12 hours darkness

Vehicle:

unchanged (no vehicle)

Controls:

other: The second eye of an animal remained untreated serving as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g

Duration of treatment / exposure:

the eye of one rabbit was unwashed, the eyes of two animals were rinsed (after one hour, as test item has not been removed)

Observation period (in vivo):

Ocular examinations were performed 1 hour, 24, 48 and 72 hours following treatment up to 21 days in order to determine the reversibility

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): unwashed (one rabbit)
- Washing (if done): rinsed (two animals)
- Time after start of exposure: one hour

SCORING SYSTEM: Chemosis 0 - 4; Discharge 0 - 3, Redness 0 - 3, Iris 0-2, Cornea: degree of opacity 0 - 4 and Cornea: extent of opacity 0 - 4.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 hours

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

other: Redness

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: relevant for classification

Irritation parameter:

other: Redness

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 9 days

Irritation parameter:

other: Redness

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 hours

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 2 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 hours

Score:

0

Max. score:

4

Table1: Individual and mean scores of conjunctivae, iris and cornea

Animal No.	Time after treatment	Conjunctivae Chemosis Redness		Iris Lesion	Cornea Opacity
A0115	24 hours	1	2	1	0
	48 hours	1	2	0	0
	72 hours	1	2	0	0
Total		3	6	1	0
Mean		1.0	2.0	0.3	0.0
A0110	24 hours	2	2	0	1
	48 hours	1	2	0	0
	72 hours	1	2	0	0
Total		4	6	0	1
Mean		1.3	2.0	0.0	0.3
A0117	24 hours	2	2	0	0
	48 hours	2	2	0	0
	72 hours	2	2	0	0
Total		6	6	0	0
Mean		2.0	2.0	0.0	0.0

The ocular reactions observed during the study have been slight to important and partially reversible: - at the conjunctivae level: a moderate redness associated with a moderate to important chemosis, noted 1 hour after the test item instillation. The redness was totally reversible in two animals between day 8 and day 9 and remained in the last one on day 21 (last day of the test, slight intensity). The chemosis was totally reversible between day 7 and day 10, - at the corneal level: a slight corneal opacity, noted 24 hours after the test item instillation in one animal and totally reversible on day 2, - at the iris level: a congestion, noted 24 hours after the test item instillation in one animal and totally reversible on day 2. In one animal, the presence of a white spot on the nictitating membrane was noted on day 2 and was associated with the presence of a white spot on the lower eyelid on day 6. These reactions remained on day 21 (last day of the test). In another animal, the presence of a white spot on the nictitating membrane was noted between day 2 and day 8 and on day 2 on the lower eyelid. This reaction was totally reversible on day 9.

Interpretation of results:

corrosive

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Eye damage 1, H318
DSD: Xi, R41

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation/corrosion study was performed in accordance with OECD 404 (Colas, 2010). The undiluted test substance was applied to the intact skin of rabbits and covered with a gauze patch. Under semi-occlusive conditions, the gauze patch was held in place with an adhesive tape for exposure periods of 3 min, 1 h or 4 h. After the respective exposure, the gauze patch was removed and the treated skin site was cleaned with distilled water. Evaluation of the treated skin sites was done 1, 24, 48 and 72 h after patch removal.

There were no signs of skin irritation at the treated skin sites. All scores at any observation time points were 0. Under the test conditions, the cobalt citrate was not irritating to the skin.

Eye irritation

The eye irritation potential of cobalt citrate was investigated according to OECD 405 under GLP conditions (Colas, 2010). After one hour, the eyes of two animals were rinsed, the treated eye of the third animal remained unwashed. The ocular reactions observed during the study have been slight to important and partially reversible. A moderate redness associated with a moderate to important chemosis was noted 1 hour after the test item instillation. The redness was totally reversible in two animals but persisted in the third animal on day 21 (last day of the test, slight intensity). The chemosis was totally reversible after 10 days. A slight and reversible corneal opacity was observed in one animal 24 hours after instillation. A congestion at the iris was noted 24 hours after the test item instillation in one animal which was totally reversible after 2 days. In one animal, the presence of a white spot on the nictitating membrane was noted on day 2 and was associated with a white spot on the lower eyelid on day 6. These reactions remained on day 21. In another animal, the presence of a white spot on the nictitating membrane was noted between day 2 and day 8 and on day 2 on the lower eyelid; this reaction was reversible. Under the conditions of the test, cobalt citrate had irreversible effects on the eye.

Justification for selection of skin irritation / corrosion endpoint:
There is only one study available.

Justification for selection of eye irritation endpoint:
There is only one study available.

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on eye irritation meet the criteria for classification as Category 1, H318 according to Regulation (EC) 1272/2008 and as Xi, R41 according to Directive 67/548/EEC.

The available data on skin irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.