Registration Dossier

Administrative data

Description of key information

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 is not irritating to skin or eyes when tested either in nanoform or not. Two acute inhalation toxicity studies failed to demonstrate any test-item related effects characteristic of respiratory irritation when tested either in nanoform or not. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-07-29 to 1993-08-01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: In principle well documented GLP-study, but no information on test item purity was provided.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
, no initial test was performed
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.09 - 2.52 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet: ad libitum (RABMA Rabbit Diet, Special Diet Services Ltd., Witham, Essex, U.K.)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 62 - 75
- Air changes (per hr): 15
- Photoperiod: 12 hours dark/light cycle
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free of fur from the dorsal flank area
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 0.5 mL of distilled water, was applied.
Duration of treatment / exposure:
4 hours
Observation period:
Approximately 1 hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined.
Number of animals:
3 rabbits (2 females an 1 male animal)
Details on study design:
TEST SITE
- Area of exposure: On the day of the test a suitable test site was selected on the back of each rabbit.
- Type of wrap if used: Test material was introduced under a 2.5 x 2.5 cm gauze patch placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tabe. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 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 diethyl ether.

SCORING SYSTEM: After removal of the patches, the test sites were examined for evidence of primary irritation and scored according to the scale from DRAIZE (1959).
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours after removal of the patch
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours after removal of the patches
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours after removal of the patch
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 72 hours after removal of the patches
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours after removal of the patch
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours after removal of the patch, respectively
Score:
0
Max. score:
4
Irritant / corrosive response data:
Very slight erythema was noted at two treated skin sites 1 hour after patch removal and persisted at one treated skin site at the 24 and 48 hours observations. All treated skin sites appeared normal at the 72-hour observation.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as non-irritant to rabbit skin.
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-08-04 to 1993-08-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: In principle well documented GLP-study, but no information on test item purity was provided.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12 - 16 weeks
- Weight at study initiation: 2.2 - 2.52 kg
- Housing: The animals were individually housed in suspended metal cages.
- Diet: ad libitum (RABMA Rabbit Diet, Special Diet Services Ltd., Witham, Essex, U.K.)
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23
- Humidity (%): 62 - 68
- Air changes (per hr): 15
- Photoperiod: 12 hours dark/light cycle
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg of the test material was placed into the conjunctival sac of the right eye.
Duration of treatment / exposure:
1 second
Observation period (in vivo):
Immediately after administartion of the test material, an assessment of the initial pain reaction was made.
Number of animals or in vitro replicates:
3 rabbits: After consideration of the ocular response produced in the first treated animal, two additional animals were treated.
Details on study design:
REMOVAL OF TEST SUBSTANCE
no data

SCORING SYSTEM: Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from DRAIZE 1959.

TOOL USED TO ASSESS SCORE: Examination of the eye was facilitated by use of the light source from a standard opthalmoscope.
Irritation parameter:
cornea opacity score
Remarks:
, opacity
Basis:
mean
Time point:
other: up to 72 hours after treatment
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: up to 72 hours after treatment
Score:
0
Max. score:
1
Irritation parameter:
conjunctivae score
Remarks:
chemosis
Basis:
mean
Time point:
other: up to 72 hours after treatment
Score:
0
Max. score:
0
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.
No ocular effects were noted 24, 48 or 72 hours after treatment.
Other effects:
Residual test material was noted around the treated eye of all animals during the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material was classified as non-irritant according to EEC labelling regulations.
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

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 is neither irritating to the skin and no irritating to eyes, regardless of whether the test material was in nanoform or not.

With regards to respiratory irritation, an acute inhalation toxicity study is available, which was extended with a satellite group of animals subject to detailed histopathology of the respiratory tract (Haferkorn, 2012). For technical reasons, a summary on this study is presented in the technical IUCLID dossier in section 7.9.3 (“Specific investigations: other studies”) and a tabular summary appears in the CSR in chapter 5.10.1.3. The mass median aerodynamic diameter of inhaled silver particlesas determined in the inhalation chamber during the study was MMAD = 2.3 µm. There were no clinical signs indicating respiratory irritation. Also, with respect to the results of the histopathological and macroscopic investigations on lung tissues, silver is not considered to represent a respiratory irritant. This conclusion is supported by findings by Sung et al. (2011) who reported an absence of statistically significant effects on lung function tests when the material was administered as nanomaterial.Asummary on this study by Sung et al. (2011) is presented in the technical IUCLID dossier in section 7.2.2 (“Acute toxicity: inhalation”) and a tabular summary appears in the CSR in chapter 5.2.1.2.

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 is not irritating to skin or eyes when tested either in nanoform or not. Two acute inhalation toxicity studies failed to demonstrate any test-item related effects characteristic of respiratory irritation when tested either in nanoform or not. In consequence, no classification is required.