Silver carbonate

Endpoint summary

Description of key information

The skin irritation potential of silver carbonate has been investigated in two standardised studies (OECD 404 method). As result, silver carbonate does not required classification for skin irritation according to Regulation (EC) 1272/2008.
The eye irritation potential of silver carbonate has been investigated in two standardised studies (OECD 405 method).  According to the more recent key study (Allen, 1992), silver carbonate is considered to be at least a very severy irritant to the rabbit eye (class 7 on a 1-8 scale, according to a modified Kay and Calandra classification system. The test material produced positive criteria in the treated rabbit according to the EEC labelling regulations (EC-Commission directive 67/548/EEC) and was considered to be irritant to the rabbit eye. It is reasonable to assume the symbol "Xi" and highest risk phrase R41 "risk of serious damage to eyes" are required. According to the EC-Regulation 1272/2008 and subsequent regulations, this results in a preacuationary classification Category 1, "Irreversible effects on the eye", with the hazard statement "H318: Causes serious eye damage".

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:

1992-10-20 to 1992-10-27

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Guideline study, however no information on test item purity and stability was stated. Deviation from the guideline:- the weights of the rabbits at the conclusion of the test were missing- description of any other toxic effects was not given

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 1992-06-11

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.51 - 2.56 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet: ad libitum (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol, U.K)
- Water (ad libitum): mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 20
- Humidity (%): 39 - 55
- Air changes (per hr): approximately 15
- Photoperiod: 12 hours dark/light cycle

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A quantity of 0.5 g of the test material, moistened with distilled water immediately before application, was applied.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL of distilled water

Duration of treatment / exposure:

4 hours

Observation period:

approximately 1 hour following the removal of the patches, and 24,48 and 72 hours later and on day 7

Number of animals:

2 male rabbits / 1 female rabbit

Details on study design:

TEST SITE
- Area of exposure: on the day before the test each of a group of three rabbits was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with healthy intact epidermis by gross observation were selected for the study.
- Type of wrap if used: The test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.

SCORING SYSTEM: The test sites were examined for evidence of primary irritation and scored according to the Draize scale. Any other adverse skin reactions, if present, were also recorded.

Irritation parameter:

erythema 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:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

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:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

Faint yellow-coloured staining caused by the test material was noted at all treated skin sites following patch removal. This did not affect evaluation of skin responses. The faint yellow-coloured staining had disappeared by the end of the observation period.
Very slight erythema was noted at one treated skin site one hour after patch removal, at two treated skin sites at the 24 and 48-hour observations and at one treated skin site at the 72-hour observation. No adverse skin reactions were noted seven days after treatment.
No corrosive effects were noted.

Interpretation of results:

GHS criteria not met

Conclusions:

Silver carbonate 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 irritating to the skin.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is not classified as irritating to the skin.

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:

1992-11-02 to 1992-11-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Guideline study, however no information on test item purity and stability were stated. Minor deviation from the guideline: - a modified Draize scale was used. According to the Draize scale as stated in the guideline rating for conjunctival redness includes the cornea and iris. The cornea and iris were excluded in this study.

Qualifier:

according to guideline

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:

yes (incl. QA statement)

Remarks:

signed 1992-06-11

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: approximately 12 to 16 weeks
- Weight at study initiation: 3.10 kg
- Housing: the animal was individually housed in a suspended metal cage.
- Diet (ad libitum): Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol, U.K)
- Water(ad libitum): mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 20
- Humidity (%): 64 - 66
- Air changes (per hr): approximately 15
- Photoperiod: 12 hours dark/light cycle

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

For the purpose of this study the test material was used as supplied.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg test material 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 application, to prevent loss of the test material, 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 and 24 hours following treatment

Number of animals or in vitro replicates:

1 male rabbit

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbit were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope.

SCORING SYSTEM: Immediately after administration of the test material, an assessment of the initial pain reaction was made. Assessment of ocular damage/irritation was made according to the Draize scale. Any other adverse ocular effects were also noted.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Area of opacity: greater than three quarters, up to whole area; The effect was observed 1h after treatment.The animal was killed for humane reasons immediately after the 24-hour observation.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Area of opacity: greater than three quarters, up to whole area

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

not specified

Remarks on result:

other: Effects observed 1 hour after treatment

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

not specified

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: Grey-coloured staining over the nictitating and lower conjunctival membranes; petechial haemorrhage of the nictitating and conjunctival membranes. Effects observed 1 hour after treatment.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: White appearance of nictitating membrane. Haemorrhage of the nictitating membrane.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Discharge with moistening of the lids and hairs a considerable area around the eye. Residual test material around treated eye. Effects observed 1 hour after treatment.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Discharge with moistening of the lids and hairs a considerable area around the eye. Residual test material around treated eye.

Irritant / corrosive response data:

Residual test material was noted around the treated eye one and 24 hours after treatment.
Grey-coloured staining over the nictitating membrane and lower conjunctival membranes was noted in the treated eye one hour after treatment. This did not affect evaluation of ocular effects.
Areas of diffuse corneal opacity were noted in the treated eye one hour after treatment. Opaque corneal opacity over the lower half of the cornea with translucent to opalescent corneal opacity in the remaining area of the treated eye was noted at the 24-hour observation.
Iridial inflammation was noted in the treated eye one and 24 hours after treatment.
Moderate conjunctival irritation was noted in the treated eye one hour after treatment with severe conjunctival irritation at the 24-hour observation. Petechial haemorrhage of the nictitating and conjunctival membranes was noted in the treated eye one hour after treatment. Haemorrhage and white appearance of the nicititating membrane were noted in the treated eye at the 24-hour observation with haemorrhage of the conjunctival membrane also noted at this time.
There was an initial pain reaction of 2.
The animal was killed for humane reasons immediately after the 24-hour observation in accordance with current U.K. Home Office guidelines. No further animals were treated.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Silver carbonate is considered to be at least a very severy irritant to the rabbit eye (class 7 on a 1-8 scale, according to a modified Kay and Calandra classification system. The test material produced positive criteria in the treated rabbit according to the EEC labelling regulations (EC-Commission directive 67/548/EEC) and was considered to be irritant to the rabbit eye. It is reasonable to assume the symbol "Xi" and highest risk phrase R41 "risk of serious damage to eyes" are required.
According to the EC-Regulation 1272/2008 and subsequent regulations, this results in a preacuationary classification Category 1, "Irreversible effects on the eye", with the hazard statement "H318: Causes serious eye damage".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Additional information

Effects on eye irritation: highly irritating

Justification for classification or non-classification

The skin irritation potential of silver carbonate has been investigated in two standardised studies (OECD 404 method). As result, silver carbonate does not required classification for skin irritation according to Regulation (EC) 1272/2008.

The eye irritation potential of silver carbonate has been investigated in two standardised studies (OECD 405 method). According to the more recent key study (Allen, 1992), silver carbonate is considered to be at least a very severy irritant to the rabbit eye (class 7 on a 1-8 scale, according to a modified Kay and Calandra classification system. The test material produced positive criteria in the treated rabbit according to the EEC labelling regulations (EC-Commission directive 67/548/EEC) and was considered to be irritant to the rabbit eye. It is reasonable to assume the symbol "Xi" and highest risk phrase R41 "risk of serious damage to eyes" are required. According to the EC-Regulation 1272/2008 and subsequent regulations, this results in a preacuationary classification Category 1, "Irreversible effects on the eye", with the hazard statement "H318: Causes serious eye damage".