title: Deriving a provisional tolerable intake for intravenous exposure to silver nanoparticles released from medical devices.
abstract: 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.
authors.affiliation: Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Savery
authors.affiliation: Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: René
authors.initials: R
authors.lastname: Viñas
authors.affiliation: Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Amber M
authors.initials: AM
authors.lastname: Nagy
authors.affiliation: Department of Mathematics, Statistics, and Computer Science, Marquette University, P.O. Box 1881, Milwaukee, WI 53201, USA.
authors.forename: Prachi
authors.initials: P
authors.lastname: Pradeep
authors.affiliation: Department of Mathematics, Statistics, and Computer Science, Marquette University, P.O. Box 1881, Milwaukee, WI 53201, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Merrill
authors.affiliation: Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Hood
authors.affiliation: Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Subhas G
authors.initials: SG
authors.lastname: Malghan
authors.affiliation: Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: Peter.Goering@fda.hhs.gov.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Goering
authors.affiliation: Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Brown
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D004864:Equipment and Supplies; D005260:Female; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D011817:Rabbits; D051381:Rats; D018570:Risk Assessment; D012834:Silver / Q000008:administration & dosage / Q000633:toxicity*; D013045:Species Specificity; D035501:Uncertainty
chemical_list: D012834:Silver
keywords: Annapolis accords; Intravenous; Medical devices; Point of departure; Provisional tolerable intake; Safety assessment; Silver nanoparticles; ToxRTool; Uncertainty factors