Silver

Carcinogenicity

Description of key information

In accordance with Regulation (EC) No 1907/2006 ("REACH"), Annex X, 8.9.1, column 2, a carcinogenicity study for silver substances is NOT proposed by the registrant (see discussion).

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Silver or inorganic silver substances are not classified for mutagenicity, nor are there any indications of hyperplasia and/or pre-neoplastic lesions in the available toxicological studies involving repeated exposure of experimental animals (i. e. the conditions cited in accordance with Regulation (EC) No 1907/2006 ("REACH"), Annex X, 8.9.1, column 2). In addition, despite a long history of use of silver and silver substances, there is no reliable human data indicating any concern for carcinogenicity. Animal toxicity and human occupational studies using normal routes of exposure (i. e. excluding implantation studies) have not provided evidence of carcinogenicity, and silver is not expected to pose a carcinogenic hazard to humans.

In consequence, hazard classification for carcinogenicity is NOT required, based on the criteria of Regulation (EC) No. 1272/2008 ("CLP"), Annex I, Part 3.6.

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. 

 

 

A carcinogenicity study for silver substances is not proposed by the registrant. Silver or inorganic silver substances are not classified for mutagenicity, nor are there any indications of hyperplasia and/or pre-neoplastic lesions in the available toxicological studies involving repeated exposure of experimental animals (i. e. the conditions cited in accordance with Regulation (EC) No 1907/2006 ("REACH"), Annex X, 8.9.1, column 2). In addition, despite a long history of use of silver and silver substances, there is no reliable human data indicating any concern for carcinogenicity. Animal toxicity and human occupational studies using normal routes of exposure (i. e. excluding implantation studies) have not provided evidence of carcinogenicity, and silver is not expected to pose a carcinogenic hazard to humans.

Justification for selection of carcinogenicity via oral route endpoint:
Waiving.

Justification for selection of carcinogenicity via inhalation route endpoint:
Waiving.

Justification for selection of carcinogenicity via dermal route endpoint:
Waiving.