Disilver oxide

Endpoint summary

Description of key information

Reliable guideline conform in-vivo studies are available for skin and eye irritation of disilver oxide (OECD guidelines 404 and 405). Based on these studies, disilver oxide is not irritating to the skin but causes serious damage to the eyes. 

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:

1989-02-21 to 1989-02-24

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)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: white russian (albino)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG, Bielefeld
- Age at study initiation: 9 months (males) and 11 months (females)
- Weight at study initiation: 2.6 kg (males); 2.7 and 3.2 kg (females)
- Housing: stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH), individually housing
- Diet: approx. 120 g/day x animal (Standard diet, ssniff K, "Special Diet for Rabbits" supplied by ssniff Spezialfutter GmbH, D-4770 Soest)
- Water: ad libitum
- Acclimation period: 1 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22
- Humidity (%): 45 - 60
- Photoperiod: 12 hours dark/light

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

other: The opposite area of the treated dorsal skin was used as control site (no test material application).

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g of the test substance were moistened with demineralised water and placed on the shorn dorsal skin.

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.35 mL

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 hours after removal of the patches

Number of animals:

3 rabbits (1 male and 2 females)

Details on study design:

TEST SITE
- Area of exposure: The test material 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; 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 qualitatively (erythema/ eschar resp. edema) and quantitatively (values 0-4) assessed using the DRAIZE method. In addition, attention was paid to the occurrence of further reactions on the skin (e.g. corrosive effect) and to clinical symptoms (systemic toxic effects).

EVALUATION: The evaluation of the cutaneous irritation effect at observation times 1, 24, 48 and 72 hours p. appl. was expressed by an irritation index. A corresponding gradation was allocated to this index by the following scheme in a modified method according to Gilman et al. (1983):
0 - 0.5 = non irritant
0.6 - 3.0 = slightly irritant
3.1 - 5.0 = moderately irritant
5.1 - 8.0 = severly irritant

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

not specified

Irritant / corrosive response data:

The single application of 0.5 gram silver(I)-oxide to the intact skins of 3 rabbits caused no changes. During the observation period neither erythema nor edema could be detected.

Other effects:

The treated skin area was yellow to brown discoloured 24 hours after removal of the patch until the end of the 14-day observation period.
Systemic-toxic effects did not occur after dermal application of the test substance. The general condition of the test animals was not affected.

Interpretation of results:

GHS criteria not met

Remarks:

Silver(I)-oxide is not irritant to the skin

Conclusions:

The irritation index is 0.0.
Silver(I)-oxide therefore is a non-irritant in this test system.

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:

1989-04-10 to 1989-04-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: white russian (albino)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ASTA Pharma AG, Bielefeld
- Age at study initiation: 10 months (males); 10 and 11 months (females)
- Weight at study initiation: 2.53 kg (males); 2.78 and 2.94 kg (females)
- Housing: stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 cm (LxBxH), individually housing
- Diet: approx. 120 g/day x animal (Standard Diet, ssniff K, "Special diet for rabbits" supplied by ssniff Spezialfutter GmbH, D-4770 Soest)
- Water: ad libitum
- Acclimation period: 1 day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5 - 25.0
- Humidity (%): 40 - 60
- Photoperiod: 12 hours dark/light cycle

Vehicle:

not specified

Controls:

other: The right eye of each animal was not treated and was used as a control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.08 g (representing a volume of about 0.1 ml) of the test substance were applied into the conjunctival sac of the left eye. Then both lids were briefly closed by gentle finger pressure.

Duration of treatment / exposure:

"lids were briefly closed"

Observation period (in vivo):

1 hour post application

Number of animals or in vitro replicates:

3 rabbits (1 male and 2 females)

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 eyes (e.g. corrosive effect) and to clinical symptoms (systemic toxic effects).

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

EVALUATION: An irritation index was not determined because of the corrosive effects.

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

mean

Time point:

other: 1 hour after treatment

Score:

4

Max. score:

4

Reversibility:

other: animals were sacrificed

Irritation parameter:

cornea opacity score

Remarks:

(area of cornea involved)

Basis:

mean

Time point:

other: 1 hour after treatment

Score:

4

Max. score:

4

Reversibility:

other: animals were sacrificed

Remarks on result:

positive indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1 hour after treatment

Reversibility:

other: animals were sacrificed

Remarks on result:

other: evaluation not possible

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Time point:

other: 1 hour after treatment

Reversibility:

other: animals were sacrificed

Remarks on result:

other: evaluation not possible

Irritation parameter:

conjunctivae score

Remarks:

(discharge)

Basis:

mean

Time point:

other: 1 hour after treatment

Score:

2

Max. score:

3

Reversibility:

other: animals were sacrificed

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1 hour after treatment

Score:

1.33

Max. score:

4

Reversibility:

other: animals were sacrificed

Remarks on result:

positive indication of irritation

Irritant / corrosive response data:

The application of 0.08 g silver(I)-oxide into one conjunctival sac each of three rabbits caused severe changes. Because of the physical properties of the test substance the dose had to be limited to the a.m. level.
The cornea of all animals showed opacity of the whole corneal area (grade 4). The upper corneal area was olive-green discoloured.
An evaluation of the iris was impossible.
The conjunctiva of all animals was olive-green discoloured and the nictitating membrane of one animal parchment-like thinned. In addition, slight or obvious swelling with partial eversion of lids (grades 1 or 2) was observed.
Discharge with moistening of considerable parts around the eye (grade 3) was detected in two animals.

Other effects:

The animals were sacrificed painlessly for reasons of animal protection.
In general, identical histopathological findings were present in all three animals. Severe acute coagulation necrosis of the mucosa and submucosal tissue, incl. glandular tissue, with complete loss of the epithelium and moderate edema were observed in conjunctiva and nictitating membrane. In the cornea complete loss of the corneal epithelium and hyalinization of the superficial layers of the corneal stroma were found.

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

A full evaluation of iris anc conjunctivae score was not possible (due to the severity of the effects the animals had to be sacrificed before conclusion of the normal observation period).

Interpretation of results:

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

Remarks:

Silver(I)-oxide is corrosive to the eye.

Conclusions:

Silver(I)-oxide is corrosive in this test system.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Whereas classification for skin irritancy is not required, disilver oxide requires classification as "H318: Causes serious eye damage" (Category 1) in accordance with the criteria laid down in Regulation (EC) 1272/2008.

Justification for classification or non-classification

Reliable guideline conform in-vivo studies are available for skin and eye irritation of disilver oxide (OECD guidelines 404 and 405). Based on these studies, disilver oxide is not irritating to the skin but causes damage to the eyes. Whereas classification for skin irritancy is not required, disilver oxide requires classification as "H318: Causes serious eye damage" (Category 1) in accordance with the criteria laid down in Regulation (EC) 1272/2008. Regarding respiratory irritation, inhalation is not a relevant route of exposure for disilver oxide, based on particle properties (size, dustiness, density). Thus, no classification for respiratory irritation is required.