CURRENT INTELLIGENCE BULLETIN 70 Health Effects of Occupational Exposure to Silver Nanomaterials Centers for Disease Control and Prevention National Institute for Occupational Safety and Health On the cover: Silver nanomaterials and products or processes using silver nanomaterials. Clockwise from top left and ending with center: Composite image of cells 24 hours post-exposure to silver nanoparticles coated with polyvinylpyrrolidone. Nanoparticles, endoplasmic reticulum, nuclei, and mitochondria shown in white, red, blue, and green, respectively. Photo by Robert M. Zucker, U.S. EPA. Silver metal (Ag), crystal structure. Photo by ©Molekuul/Getty Images. Printed circuit boards and components, which frequently use silver. Photo by ©Isti2/Getty Images. Silver nanoparticles within macrophages in lung tissue. Photo by NIOSH. Silver nanoparticles imaged by scanning electron microscope. Photo by NIOSH. Sock fabric, which is among textiles that frequently contain silver as an antimicrobial agent. Photo by ©Gojak/Getty Images. A tradesperson uses an airless sprayer to apply paint containing silver biocide. Photo by Bruce Lippy, CPWR. Current Intelligence Bulletin 70 Health Effects of Occupational Exposure to Silver Nanomaterials DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Institute for Occupational Safety and Health This document is in the public domain and may be freely copied or reprinted. Disclaimer Mention of any company or product does not constitute endorsement by the National Insti- tute for Occupational Safety and Health (NIOSH), Centers for Disease Control and Preven- tion (CDC). In addition, citations of websites external to CDC/NIOSH do not constitute CDC/NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, CDC/NIOSH is not responsible for the content of these websites. All web ad- dresses referenced in this document were accessible as of the publication date. Get More Information Find NIOSH products and get answers to workplace safety and health questions: 1-800-CDC-INFO (1-800-232-4636) | TTY: 1-888-232-6348 CDC/NIOSH INFO: cdc.gov/info | cdc.gov/niosh Monthly NIOSH eNews: cdc.gov/niosh/eNews Suggested Citation NIOSH [2021]. Current Intelligence Bulletin 70: health effects of occupational exposure to silver nanomaterials. By Kuempel E, Roberts JR, Roth G, Dunn KL, Zumwalde R, Drew N, Hubbs A, Trout D, and Holdsworth G. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2021-112, https://doi. org/10.26616/NIOSHPUB2021112. DHHS (NIOSH) Publication No. 2021–112 DOI: https://doi.org/10.26616/NIOSHPUB2021112 May 2021 ii NIOSH CIB 70 • Health Effects of Occupational Exposure to Silver Nanomaterials Foreword When the U.S. Congress passed the Occupational Safety and Health Act of 1970 (Public Law 91‒596), it established the National Institute for Occupational Safety and Health (NIOSH). Through the Act, Congress charged NIOSH with recommending occupational safety and health standards and describing exposure limits that are safe for various periods of employ- ment. These recommendations include but are not limited to the exposures at which no workers will suffer diminished health, functional capacity, or life expectancy because of their work experience. The growing use in commerce of nanomaterials (materials with one or more dimension smaller than about 100 nm) has resulted in increased awareness and understanding of the associated potential hazards. Since the early 2000s, NIOSH has been assessing and address- ing the potential occupational safety and health effects of high-volume nanomaterials, in- cluding silver nanomaterials. Elemental silver has been in commerce for centuries. In 1988 NIOSH adopted a recommended exposure limit (REL) for total silver of 10 micrograms per cubic meter (µg/m3) as an 8-hour time-weighted average (TWA) concentration to protect workers from developing argyria (bluish-gray pigmentation to the skin and mucous mem- branes) and argyrosis (bluish-gray pigmentation to the eyes). The previous authoritative assessments of occupational exposure to silver did not account for particle size. Recent studies in animals have demonstrated that biologic activity and potential adverse health effects are related to particle size. Adverse health effects of nanoscale silver particles, such as early stage lung inflammation and liver hyperplasia, have been observed in rats fol- lowing inhalation exposure. NIOSH considers these responses of pulmonary inflammation and liver hyperplasia to be relevant to workers and estimated the risks to workers based on these animal data. This led NIOSH to determine that it is reasonable and prudent to estab- lish a REL for nanoscale silver. The NIOSH REL for silver nanomaterials (≤100 nm primary particle size) is 0.9 μg/m3 as an airborne respirable 8-hour TWA concentration. In addition, NIOSH continues to recommend a REL of 10 μg/m3 as an 8-hour TWA concentration for to- tal silver (metal dust, fume, and soluble compounds) as Ag. NIOSH further recommends the use of workplace exposure assessments, engineering controls, safe work procedures, training and education, and established medical surveillance approaches to protect workers. NIOSH recommends that employers disseminate this information to workers and customers and requests that professional and trade associations and labor organizations inform their members about the potential hazards of occupational exposure to silver nanomaterials. NIOSH appreciates the time and effort of the expert peer, stakeholder, and public reviewers whose comments and input strengthened this document. John Howard, M.D. Director, National Institute for Occupational Safety and Health Centers for Disease Control and Prevention NIOSH CIB 70 • Health Effects of Occupational Exposure to Silver Nanomaterials iii Abstract Nanoscale silver particles are some of the most widely used nanomaterials in commerce, with numerous uses in consumer and medical products. Workers who produce or use silver nanomaterials are potentially exposed to those materials in the workplace. Previous author- itative assessments of occupational exposure to silver did not account for particle size. The National Institute for Occupational Safety and Health (NIOSH) assessed potential health risk from exposure to silver nanomaterials by evaluating more than 100 studies of silver nanomaterials in animals or cells. In studies that involved human cells, silver nanomaterials were associated with toxicity (cell death and DNA damage) that varied according to the size of the particles. In animals exposed to silver nanomaterials by inhalation or other routes of exposure, silver tissue concentrations were elevated in all organs tested. Exposure to silver nanomaterials in animals was associated with decreased lung function, inflamed lung tis- sue, and histopathological (microscopic tissue) changes in the liver and kidney. In the rela- tively few studies that compared the effects of exposure to nanoscale or microscale silver, nanoscale particles had greater uptake and toxicity than did microscale particles. To date, researchers have not reported health effects in workers exposed to silver nanomaterials. To assess the risk of health effects from exposure to silver nanoparticles quantitatively, NIOSH evaluated the data from two published subchronic (intermediate duration) inhala- tion studies in rats. These studies revealed lung and liver effects that included early-stage lung inflammation and liver bile duct hyperplasia. NIOSH researchers used the data from these studies to estimate the dose of silver nanoparticles that caused these effects in rats. They then calculated the corresponding dose that would be expected to cause a similar response in humans, accounting for uncertainties in those estimates. From this evaluation, NIOSH derived a recommended exposure limit (REL) for silver nanomaterials (<100 nm primary particle size) of 0.9 micrograms per cubic meter (µg/m3) as an airborne respi- rable 8-hour time-weighted average (TWA) concentration. In addition, NIOSH continues to recommend a REL of 10 µg/m3 as an 8-hour TWA for total silver (metal dust, fume, and soluble compounds, as Ag). NIOSH further recommends the use of workplace exposure assessments, engineering controls, safe work procedures, training and education, and es- tablished medical surveillance approaches to protect workers. iv NIOSH CIB 70 • Health Effects of Occupational Exposure to Silver Nanomaterials Executive Summary Introduction Nanotechnology is an enabling technology involving structures generally defined as having one, two, or three external dimensions in the range of approximately 1 to 100 nanometers (nm) [ISO 2008]. Nanoscale substances may have physical (including morphological) and chemical properties that differ from those of the same substances as larger particles or in bulk [Wijnhoven et al. 2009]; such useful properties may be exploited by manufacturers. One prominent example of these substances is silver nanomaterials, which are used in the manufacture of electronics and textiles and have been used as pigments, catalysts, and an- timicrobials [Wijnhoven et al. 2009; Nowack et al. 2011]. The United States produced an estimated 20 tons of silver nanomaterials in 2010 [Hendren et al. 2011], and an estimated 450–542 tons were produced worldwide in 2014 [Future Markets, Inc. 2013]. A more re- cent study by