For centuries, silver and silver salts have been used in many different products such as jewelry, cosmetics, food, textiles, medicine, medical devices, biocidal products, electronics etc.
Although systemic uptake of silver has been reported, this has generally been considered to have no adverse consequences for human health. Until now, the US EPA, FDA and WHO have considered the critical effect to be a blue-greyish discoloration of the skin and eyes (known as argyria) observed after long-term exposure because of the accumulation of insoluble silver selenide and silver sulfide in the skin and eyes.
To protect against lifelong exposure leading to such accumulation and discoloration, the US EPA set an oral reference dose of 0.005 mg/kg bw/day back in 1991. At the time, the US EPA noted that this was to protect against a cosmetic effect and not an adverse effect and indicated that the reference value should be considered to have low reliability due to poor data quality.
New data support new classification
In recent evaluations of silver-containing biocidal substances in the EU, the Swedish biocides authority considered a body of new data on silver which further led to an EU classification proposal for metallic silver in 2020 and for silver nitrate in 2023. While the classification proposal for silver has been concluded by ECHA’s Committee for Risk Assessment (RAC), the proposal for silver nitrate is currently under discussion.
Information supporting the classification proposals contains data from several recent high-quality experimental animal studies and is considered highly relevant for a renewed evaluation regarding the toxicity of silver. Silver Ag+ ions may be released from various articles such as consumer products and medical devices and consequently impact human health.
Classification proposals
For metallic silver the classification proposal has been concluded, and the following classification was adopted:
Repr. 2, H361f
STOT RE 2 H373 (nervous system)
Aquatic Acute 1 H400
Aquatic Chronic 1 H410
The discussion of a new classification of silver nitrate is currently ongoing, but the following classification is proposed:
Ox. Sol. 1 H271
Repr. 1B H360FD
STOT RE 2 H373
Acute Tox 2 H300
Skin Corr. 1A H314
Skin sens. 1 H317
Muta. 2 H341
Aquatic Acute 1 H400
Aquatic Chronic 1 H410
Need for revision of tolerable exposure levels
New oral rat studies in the classification documents show signs of neurotoxicity and adverse effects on fertility and development.
Data from a reproductive one-generation study in rats indicate a NOAEL* of 2.5 mg Ag+/kg bw/day for effects on fertility. This value may be considered a new relevant starting point for calculations of a new tolerable exposure level, for instance in connection with risk assessment under the REACH regulation (DNEL value) or for safety assessment of medical devices (TI value according to the new ISO 10993-13:2023 Standard).
An abstract and a poster of the above was presented at the 58th Congress of the European Societies of Toxicology (EUROTOX 2024) in Copenhagen in September 2024.
For more information on silver substances and calculation of exposure levels, please contact:
Poul Bo Larsen
pbl@ dhigroup. com
Tel +45 4516 9478
* The no-observed-adverse-effect-level