Deriving a provisional tolerable intake for intravenous exposure to silver nanoparticles released from medical devices.
Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i. v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool). The point of departure (POD) was based on an i. v. 28-day repeated AgNP (20 nm) dose toxicity study reporting an increase in relative spleen weight in rats with a 5% lower confidence bound of the benchmark dose (BMDL05) of 0.14 mg/kg bw/day. The POD was extrapolated to humans by a modifying factor of 1,000 to account for intraspecies variability, interspecies differences and lack of long-term toxicity data. The pTI for long-term i. v. exposure to 20 nm AgNPs released from blood-contacting medical devices was 0.14 μg/kg bw/day. This pTI may not be appropriate for nanoparticles of other physicochemical properties or routes of administration. The methodology is appropriate for deriving pTIs for nanoparticles in general.
['Savery|Laura C|LC|', 'Viñas|René|R|', 'Nagy|Amber M|AM|', 'Pradeep|Prachi|P|', 'Merrill|Stephen J|SJ|', 'Hood|Alan M|AM|', 'Malghan|Subhas G|SG|', 'Goering|Peter L|PL|', 'Brown|Ronald P|RP|']
D061605:Administration, Intravenous D000818:Animals D004864:Equipment and Supplies D005260:Female D006801:Humans D008297:Male D053768:Metal Nanoparticles D051379:Mice D019055:No-Observed-Adverse-Effect Level D011817:Rabbits D051381:Rats D018570:Risk Assessment D012834:Silver D013045:Species Specificity D035501:Uncertainty
Provisional tolerable intake Intravenous Silver nanoparticles Medical devices Safety assessment Annapolis accords ToxRTool Point of departure Uncertainty factors