Deriving a Provisional Tolerable Intake for Intravenous Exposure to Silver Nanoparticles Released from Medical Devices

Authors

Laura C. Savery, U.S. Food and Drug Administration
Rene Vinas, U.S. Food and Drug Administration
Amber M. Nagy, U.S. Food and Drug Administration
Prachi Pradeep, Marquette UniversityFollow
Stephen Merrill, Marquette UniversityFollow
Subhas G. Malghan, U.S. Food and Drug Administration
Peter L. Goering, U.S. Food and Drug Administration
Ronald P. Brown, U.S. Food and Drug Administration

Document Type

Article

Language

eng

Publication Date

4-2017

Publisher

Elsevier

Source Publication

Regulatory Toxicology and Pharmacology

Source ISSN

0273-2300

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.

Comments

Accepted version. Regulatory Toxicology and Pharmacology, Vol. 85 (April 2017): 108-118. DOI. © 2018 Elsevier B.V. Used with permission.

Recommended Citation

Savery, Laura C.; Vinas, Rene; Nagy, Amber M.; Pradeep, Prachi; Merrill, Stephen; Malghan, Subhas G.; Goering, Peter L.; and Brown, Ronald P., "Deriving a Provisional Tolerable Intake for Intravenous Exposure to Silver Nanoparticles Released from Medical Devices" (2017). Mathematics, Statistics and Computer Science Faculty Research and Publications. 556.
https://epublications.marquette.edu/mscs_fac/556