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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Substance considered to fall withing the scope of the read-across 'Nanosilver: Justification of a read-across approach for human health hazard endpoints' (document attached in IUCLID section 13 - "CSR Annex 11 - Weight of Evidence Justification for Silver metal - human health endpoints).
Reason / purpose for cross-reference:
read-across source
Positive control results:
Induction Phase:
Very faint to severe erythema (0.5-3) was noted
Challenge Phase:
Eight of ten positive control animals exhibited signs of a sensitization response (faint to moderate rythema [1-2] 24 and /or 48h after challenge
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50 % w/w
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
very faint erythema (0.5)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50 % w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: very faint erythema (0.5).
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 % w/w
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
very faint erythema (0.5)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 % w/w. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: very faint erythema (0.5).
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50 % w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
very faint erythema (0.5)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: naive control group (negative control). Dose level: 50 % w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: very faint erythema (0.5).
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50 % w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
very faint erythema (0.5)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: naive control group (negative control). Dose level: 50 % w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: very faint erythema (0.5).
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.04% DNCB in acetone
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
faint to moderate erythema (1-2)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.04% DNCB in acetone. No with. + reactions: 8.0. Total no. in groups: 10.0. Clinical observations: faint to moderate erythema (1-2).
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.04% DNCB in acetone
No. with + reactions:
7
Total no. in group:
10
Clinical observations:
faint to moderate erythema (1-2)
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.04% DNCB in acetone. No with. + reactions: 7.0. Total no. in groups: 10.0. Clinical observations: faint to moderate erythema (1-2).
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.04% DNCB in acetone
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
very faint erythema (0.5)
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: positive naive control group. Dose level: 0.04% DNCB in acetone. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: very faint erythema (0.5).
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.04% DNCB in acetone
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
no irritation
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: positive naive control group. Dose level: 0.04% DNCB in acetone. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: no irritation.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based on these findings and on the evaluation system used, Axenohl is not considered to be a contact sensitizer.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Substance considered to fall withing the scope of the read-across 'Nanosilver Justification of a read-across approach for human health hazard endpoints' (document attached in IUCLID section 13 - "CSR Annex 11 - Weight of Evidence Justification for Silver metal - human health endpoints).
Reason / purpose for cross-reference:
read-across source
Species:
guinea pig
Group:
positive control
Remarks on result:
not determinable because of methodological limitations
Group:
negative control
Remarks on result:
not determinable because of methodological limitations
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions were observed in test or control animals following the challenge application in the main study after 24 hours.

Range finding for intradermal induction: Three animals were intradermal treated with 100%, 30%, 10% and 3% concentrations of the test substance. Scores were obtained 24 hours after application. Slight to moderate irritation was observed in all concentrations tested. From the 30% concentration upward necrosis was observed as well. No irritation was observed after topical induction with 30% and 100% test substance concentrations in three animals. Challenge: No skin reactions were observed in test or control animals following the challenge application in the main study after 24 hours.

Interpretation of results:
not sensitising
Conclusions:
On the basis of the results obtained it was concluded that, under the conditions of this study and according to the EC-standards silver thiosulphate is not a sensitizer.
Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Introduction:


The hazard assessment for nanosilver is determined by the extent by which silver ions are released (as determined by in-vivo toxicokinetic data). In this respect, the key data for the hazard assessment of nanosilver is restricted to studies using nanosilver as test item.


The data used for the human health hazard assessment of nanosilver (‘target substances’) are not restricted to studies referring to only these substances as test item. Instead, a more generic approach for the toxicological assessment of “silver” in general is adopted by also including information/data generated with other inorganic silver substances (like silver nitrate or silver sulphate) or organic silver salts (such as silver acetate) that have the potential to release silver ions (‘source substances’) as supporting evidence.
The basic assumption for this is that the systemic toxicity is driven by the released silver ions (Ag+), which is considered the primary relevant species of silver for the hazard assessment. It is noted that many silver substances have a low to negligeable water solubility and are considered of low bioavailability in the body. Once dissolved, the counter-ions released from the silver salt (such as chloride or sulphate anions) are not considered further in the hazard assessment, since these are typically either ubiquitous ions in a physiological environment (like chloride) or generally known to be of no relevant toxicological (systemic) concern (like acetate or sulphate). Note that a different approach is applied if a substance is causing local effects, such as the soluble and corrosive silver nitrate. The read-across approach is used maximally to avoid unnecessary animal testing.


 


The approach and justification for the applied human health hazard assessment is detailed in the read-across justification document attached to the silver IUCLID file in section 13. The various human health endpoints of the silver REACH dossiers have been updated on an individual basis to reflect the approach that is described in the read-across justification document. 


 


Based on a weight-of-evidence assessment, it is concluded that silver substances do not elicit skin sensitising effects:


 


Human data:


Long term industrial experience does not raise any concern on skin sensitisation attributable to silver substances (personal communication, members of the Silver Work Group of the Precious Metals and Rhenium Consortium, 2010-07-27). Furthermore, a literature search has been conducted to check whether published literature is available which would provide further information on the potential occurrence or absence of skin sensitisation effects of silver substances, specifically in occupational settings. A report on this literature search is attached to the endpoint summary on sensitisation in the technical dossier. As a result, only a limited number of case reports dealing with skin sensitisation could initially be identified. However, upon close inspection, in several of these silver was not the potential cause. For example, one study investigated skin effects in workers with a range of precious metal compounds and found that silver compounds were not causing allergic skin reactions (Bruevich et al 1980). In other cases, “silver” was mentioned but not in the context of sensitisation by silver, but e. g. where thiourea contained in a silver polish was identified as a sensitiser (Dooms-Goossens, 1988).


Overall, very few publications are available and no specific concern for sensitising properties of silver (compounds) could be identified based on human data.


 


Animal data:


Two reliable studies on standard skin sensitisation tests are available with silver containing products/preparations:


Moore, G.E. (1999): Dermal sensitisation study (Buehler Method) in guinea pigs, with a biocidal product (aqueous solution) containing 2438 ppm Ag+ ions, besides other ingredients.


Prinsen, M.K. (1995): Sensitization study in guinea pigs (maximization test) with a liquid plant preservative preparation containing 18 g/L of silver thiosulfate in aqueous solution, besides other ingredients.


As a third source of information, the data published by Kim et al. (2012) on a guinea pig maximisation test are presented. Kim et al. studied the sensitising properties of a nano-silver product (in 1% citrate solution) in close agreement with OECD TG 406. Whereas this publication is of limited reliability since no test concentrations are stated and the use of a positive control is not reported, the clear negative outcome (no skin sensitisation) is in agreement with other information.


 


Conclusion:


Neither human nor animal data show any specific concern for skin sensitising properties of silver or silver substances. Based on a weight-of-evidence assessment it is concluded that classification for skin sensitisation is not required and that further experimental verification is not justified.



Migrated from Short description of key information:
Neither human nor animal data show any specific concern for skin sensitising properties of silver or silver substances. Based on this weight-of-evidence assessment, it is concluded that classification for skin sensitisation is not required and that further experimental verification is not justified (see discussion).

Justification for selection of skin sensitisation endpoint:
Weight-of-evidence assessment based on human and animal data.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Neither human nor animal data show any specific concern for skin sensitising properties of silver or silver substances. Based on this weight-of-evidence assessment, it is concluded that classification for skin sensitisation is not required and that further experimental verification is not justified. In consequence, classification for skin sensitisation is not required for silver substances.

Similarly, based on a complete absence of any indication of respiratory sensitisation in the public domain, classification is not required.