Disilver(1+) sulphate

Endpoint summary

Description of key information

Reliable guideline conform in-vivo studies are available for skin and eye irritation of silver(I)sulfate (OECD guidelines 404 and 405). Based on these studies, silver(I)sulfate is not irritating to the skin. According to the study results, silver(I)sulfate is corrosive to the eye and classification as "Eye Damage 1, H318" is proposed.

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:

1990-10-09 to 1990-10-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study. At the time of the study conduct, GLP was not compulsory . However, the study was conducted in accordance with the principles of GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1981-05-12

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: white russian (albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-9 months
- Weight at study initiation: 2.54-2.80 kg
- Housing: stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH), supplied by ASTA Pharma AG, 4800 Bielefeld, Germany; individually housing
- Diet: approx. 120 g/day x animal standard diet, ssniff K, special diet for rabbits, supplied ny ssniff Spezialfutter GmbH, 4770 Soest, Germany
- Water: ad lipidium; drinking water quality from the Stadtwerke Bielefeld
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 - 24.0
- Humidity (%): 40 - 70
- Photoperiod: 12 hours dark/light cycle

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g test item was given to the dorsal skin area.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.14 mL demineralised water per 0.5 g test material.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after removal of the patches, thereafter once daily: 2 animals were observed for 3 days after application and in 1 animal for 5 days after application.

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: the application sites were clipped free of hair one day before treatment.Test substance was placed on the shorn dorsal skin area between shoulder and sacrum.
- Type of wrap if used: The site of application was covered with a linen cloth (approx. 6.25 cm2) which adhered to a synthetic film glue. A bandage
wrapped several times around the trunk (Acrylastic, No. 2408, width 8 cm; supplied by P. Beiersdorf and Co. AG, Hamburg) provided a complete occlusion.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the end of the exposition time remaining test material was gently washed off as far as possible.

SCORING SYSTEM: The treated skin area was assessed qualitatively (erythema/eschar resp. edema) and quantitatively (values 0-4) using the DRAIZE scale. In addition, attention was paid to the occurrence of further reactions on the skin (e.g. corrosive effects) and to clinical symptoms (systemic toxic effects).

Irritation parameter:

erythema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #1

Time point:

24/48/72 h

Score:

0.33

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:

0

Max. score:

4

Reversibility:

not specified

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:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

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:

The single application of 0.5 g silver(I) sulphate to the intact skin of three rabbits each caused only very slight changes.
A very slight erythema (grade 1) occurred in one animal only 48 hours after application and in another animal from 24 hours after application until day 4.
A very slight oedema (grade 1) was observed in one animal only 2 days after application, 24 hours later the finding had completely disappeared.
In addition, the treated skin areas of all three animals were brownish discoloured during the whole observation period.
The control sites did not show any reactions.

Other effects:

Systemic toxic effects did not occur after dermal application of the test substance. The general conditions of the test animals was not affected.

Interpretation of results:

GHS criteria not met

Conclusions:

Silver (I) sulphate is not irritating to the skin, according to EC-Regulation 1272/2008.

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:

1990-10-22 to 1990-10-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study. At the time of the study conduct, GLP was not compulsory . However, the study was conducted in accordance with the principles of GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 1987-02-24

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: white russian (albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 months
- Weight at study initiation: 2.63 kg
- Housing: stainless steel cage with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH) supplied by ASTA Pharma AG, D- 4800 Bielefeld 14, Germany; individually housed
- Diet: approx. 120 g/day x animal standard diet, ssniff K, special diet for rabbits supplied by ssniff Spezialfutter GmbH, D- 4770 Soest, germany
- Water (ad libitum): drinking water quality from the Stadtwerke Bielefeld
- Acclimation period: 1 day under test conditions before application of the test substance. Veterinary supervision of the animal ws done before start of the study.

Preliminary inspection of the eyes: before application of the test substance.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 - 22.5
- Humidity (%): 40 - 70
- Photoperiod: 12 hours dark/light cycle

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.18 g (representing a volume of about 0.1 mL) of the test substance were applied into the conjunctival sac of the right eye. Then both lids were briefly closed by gentle finger pressure. The other eye of the animal was not treated and acted as control.

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

1 hour after application

Number of animals or in vitro replicates:

1 male rabbit

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated eye was not rinsed.

SCORING SYSTEM: Signs of irritation on the cornea, iris, and conjunctiva were assessed quantitatively and qualitatively using the Draize scale. In addition, attention was paid to the occurrence of further reactions on the eye (e.g. corrosive effects) and to clinical symptoms (systemic toxic effects).

TOOL USED TO ASSESS SCORE: The treated eye was examined using a Cliptrix pencil light (supplied by Varta, Hannover, No. 645).

SACRIFICE
2 hours after removal of the patch the animal was sacrificed with T 61(R) (supplied by Hoechst Veterinär GmbH, D-8044 Unterschleißheim).

PATHOLOGY
The treated eye as well as eye lids and nictitating membrane were removed, fixed (in SUSA fixative according to HEIDENHAIN for approximately 24 hours, thereafter in 4 % formaldehyde solution according to LILLIE), trimmed, embedded in paraffin wax, sectioned at approximately 4 µm, and stained with hematoxylin and eosin (H&E). The slides were examined microscopically.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hour after exposure

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks:

animals were sacrificed

Remarks on result:

other: 1-h observation: Iris: evaluation impossible; Conjunctiva redness: white-green discolouration of the conjunctiva; Discharge: moistening of the lids and hairs, and considerable areas around the eye; 2 h after removal of the patch the animal was sacrificed.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour after exposure

Score:

2

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

The single application of 0.18 g (representing a volume of about 0.1 mL) silver(I)-sulphate into one conjunctival sac of one rabbit caused severe changes.
1 hour after application the cornea was opaque and the iris was not discernible through the opacity (grade 4). The whole corneal area was involved. In addition, the whole corneal area was grey-green discoloured.
An evaluation of the iris was impossible because of the opaque cornea.
The conjunctiva was white-green discoloured one hour after application. In addition, obvious swelling with partial eversion of the lid (grade 2) occurred.
Discharge moistened lids and hair just adjacent to lids (grade 2).
At microscopical examination of the treated eye the conjunctiva and the nictitating membrane showed acute coagulation necrosis of the epithelium and beginning granulocytic cell infiltration. The surface was covered with brown-black material (test material). In addition, focal loss of the corneal epithelium as well as acute coagulation necrosis of the corneal epithelium which was brown-black discoloured by the test material were found. The anterior eye chamber was filled with granular eosinophilic material.
The untreated eye did not show any changes.

Other effects:

There were no systemic toxic effects after conjunctival application of the test substance.

Interpretation of results:

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

Conclusions:

Silver (I) sulphate is corrosive to the eyes.
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is classified as risk of serious damage to eyes.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 1.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Justification for classification or non-classification

Reliable guideline conform in-vivo studies are available for skin and eye irritation of silver (OECD guidelines 404 and 405). Based on these studies, silver(I)sulfate is not irritating to the skin. According to the study results, silver(I)sulfate is corrosive to the eye and classification as "Eye Damage 1, H318" is proposed.