Nanomaterials are generally defined as engineered structures having at least one dimension in the nanoscale size range of 1–100 nm (nm) [1]. For reference, the width of a piece of paper or human hair is about 100,000 nm. Nanotechnology is often touted as one of the next industrial revolutions and an increasing number of products are being created and brought to market with a wide range of applications. For example, in consumer products: nanosilver in bedsheets and sports clothing to make them resistant to bad odors from bacteria and fungi; silica nanoparticles in rubber tires for reducing rolling resistance and in personal care products such as toothpaste for abrasiveness; carbon nanotubes add strength and decrease weight in golf clubs, kayaks, and archery arrows; nanoclays increase the bounce of tennis and golf balls; and, carbon nanotubes decrease resistance and increase grip on road racing tires [2, 3]. Nanosilver is the most common nanomaterial in consumer products, including toothpaste, faces creams, cosmetics, medical bandages, disinfectants, kids' plush toys, baby blankets, towels, socks, kitchen utensils and insecticides [2, 4]. There is awareness and concern among consumers, retailers, manufacturers, researchers and regulators about the sustainability of nanomaterials used in consumer products including potential ecological and human health risks [5, 6].
Despite the prevalence of nanomaterials in consumer products, the nanomaterials going into the products that we wear, play with, store our food in, and apply as cosmetics and skin creams have undergone only limited testing for potential adverse human health or ecosystem effects. In most cases no tests have been conducted for chronic health endpoints such as cancer or neurodevelopmental effects [7]. Consumers want to make informed purchasing decisions and many are seeking greater levels of transparency about the potential health and environmental impacts of chemicals added to products. In order to do so, information is needed about what is in these products, whether it is hazardous, and how it compares to ingredients in other similar products. In response, retailers and manufacturers are increasingly turning to their supply chain for this information [8].
Chemical hazard assessment is a powerful tool to support informed decision making for product design, development and procurement [9, 10]. It is being incorporated into corporate policies, internal product design and development protocols and ecolabels and standards. The systematic gathering, classification and visual communication of hazard information helps to communicate quickly what is known and not known about the hazards associated with a particular substance and its potential transformation products.
Here, we demonstrate the use of an existing transparent and systematic method for chemical hazard assessment – GreenScreen® for Safer Chemicals (GreenScreen) - to assess and communicate hazard information and identify critical data gaps to help manufacturers and their supply chain make informed decisions when selecting materials that are non-hazardous or less hazardous than ones being replaced. This report is the first known application of GreenScreen for assessing the inherent hazards of nanomaterials.
This project provides support for the use of an existing method for chemical hazard assessment and communication – with minor adaptations described in this paper – to compare hazards across conventional silver and two kinds of nanosilver. Nanosilver forms used in textiles were considered to be well-suited to these first nanomaterial GreenScreen assessments because of the relatively robust hazard data set available in the public literature, and their widespread use in consumer clothing and other textiles that can lead to direct human exposures and environmental releases. We did not generate any new data, but relied on publicly available existing data.
While conducting chemical hazard assessments can be a complicated process for all chemicals, it can be particularly difficult for nanomaterials. Nanomaterials have the same chemical composition as their conventionally-sized counterparts, but can exhibit unique and commercially desirable properties, as well as unique and sometimes unwelcome hazards, at the nanoscale [11–13]. As the size of a particle decreases, there is a corresponding increase in the surface area per mass [12]. A material that is chemically or electrically inert at conventional scale may be more reactive at nanoscale on a per mass basis, due to the increased surface area available for chemical interactions [12]. All these size-dependent characteristics may influence the risk associated with the material [13]. In addition to enhanced reactivity, certain nanomaterials may be able to more easily penetrate bodily tissues including organs such as the brain and fetal circulation [11, 14]. Beyond differences in potential human health hazards, these size-dependent properties of nanomaterials may also affect aquatic and terrestrial ecosystems differently than conventional chemicals.
Surface coatings and other modifications can further affect the potential hazard of a nanomaterial in different media, such as soil or water [11]. So while the hazard endpoints associated with the conventional bulk chemical form remain relevant (i.e. carcinogenicity, developmental toxicity, acute toxicity), nanomaterials present challenges to existing toxicity prediction methods that are solely based on chemical composition and mass. This has stimulated governments to tackle the problem, notably the Organisation for Economic Co-operation and Development (OECD)’s Working Party on Manufactured Nanomaterials, which hosts an international body of experts focused on the human health and environmental safety implications of engineered nanoscale chemicals, including toxicity testing methods and risk assessment approaches [15].
Both conventional silver and nanosilver are approved by the U.S. Environmental Protection Agency (US EPA) Office of Pesticide Products (OPP) for use as antibacterial agents. They can both effectively kill harmful or odor-causing bacteria and appear in products including “antibacterial sheets and pillowcases” that kill bacteria and fungi, “antibacterial tableware and kitchen tools” that prevent diseases including dysentery and hepatitis, and a baby plush toy “with the additive of silver nanoparticles … to fight against harmful bacteria, molds and mites”[16–18]. Their non-specific antimicrobial properties inhibit the growth of microbes, thought to be due to a steady release of toxic silver ions (Ag+) or nanosilver from the surface of the molecule [14, 19]. Some low-soluble forms of nanoscale silver can be incorporated into textiles, plastics, and other materials as a polymer coating or directly imbedded into synthetic polymer fibers.
Colloidal silver is a suspension of intentionally produced nanosilver particles ranging in size from 10 to 1000 nm. It has been used for about a century by people claiming it has health benefits, despite a 1999 the U.S. Food and Drug Administration determination that colloidal silver products were neither safe nor effective [20]. Colloidal silver products marketed with medical or health benefits are now considered “misbranded” under the law, although they are still sold as homeopathic remedies and dietary supplements [20].
These antimicrobial properties also make nanosilver highly toxic to beneficial organisms, including fish and other aquatic life. Nanosilver indiscriminately kills beneficial fungi, algae, and many aquatic organisms along with the undesirable bacteria and fungi. The OECD assessed relevant studies of nanosilver, and based on the Globally Harmonized System (GHS), assigned a Category 1 toxicity score for daphnia and algae, and a Category 2 for fish (see nanosilver GreenScreen in Additional file 2). This was based on an average 96 h median lethal concentration (LC50) for nanosilver in fish (Oryzias latipes) of 1.8 mg/L, in Daphnia a median effective concentrations (EC50s) of 0.012 mg/L and in algae (Raphidocelis subcapitata) a 72 h EC50 (concentration at which a 50 % inhibition of the growth rate is observed) of 0.74 mg/L (Additional file 2, GreenScreen for nanosilver). The very high aquatic toxicity of nanosilver has raised concern about nanosilver entering the wastewater stream during washing and laundering of treated textiles, with some studies showing that as much as half of imbedded nanosilver can be lost from treated textiles during a single wash cycle [21, 22]. Toxicity to indicator species such as Daphnia suggests the possibility of adverse impacts to related aquatic organisms that comprise a healthy aquatic ecosystem, and to beneficial bacteria required to treat sewage sludge in wastewater treatment facilities. Widespread use of products containing nanosilver in homes could also lead to the proliferation of resistant microbes [23].
Human health concerns regarding ingestion, dermal contact, and especially inhalation of nanosilver particles are based on results of laboratory studies in cells and whole animals (reviewed in [24]). Whole animal studies of rats exposed to nanosilver via inhalation for 9 days reported compromised lung function and lung inflammation, as well as cellular changes in the kidney and liver [24–30]. The inhaled nanosilver released silver ions that entered the bloodstream and was then distributed to all major organs and tissues including the kidney, liver, and brain [24, 27, 31, 32]. Once in organs and tissues, in vitro cellular studies report that nanosilver causes DNA damage, genotoxicity and oxidative stress leading to apoptotic cell death [24, 33, 34]. Scientists have also identified adverse impacts to the beneficial human skin microbiome as a potential concern [35].
Because of the health concerns associated with uses of nanosilver with direct human contact, the U.S. National Institutes of Health has initiated a clinical trial to examine the potential impacts of nanosilver inhalation on human lung function [36]. The study is designed to address cleaning products and clothing that contain nanosilver, as well as solutions marketed specifically to be inhaled as purported immune system boosters. Laboratory analyses will include measuring penetration of silver nanoparticles into the blood stream, circulation through the body, and potential changes to the lung microbiome.
A draft National Institute for Occupational Safety and Health (NIOSH) Current Intelligence Bulletin on the Health Effects of Occupational Exposure to Silver Nanomaterials, which is a comprehensive review of all available published studies, concludes that there are risks of lung and liver effects including lung inflammation associated with exposure silver nanoparticles in the range of 15–20 nm [24]. NIOSH used results from rodent subchronic inhalation studies to model an estimated range of exposures from 0.19 to 195 micrograms per cubic meter (μg/m3) over a 45-year working lifetime. NIOSH estimated that these exposure are low enough that they would not be expected to result in adverse lung or liver effects [24, 28, 29]. The current workplace NIOSH recommended exposure limit (REL) and the enforceable Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for silver metal dust and soluble silver are both 10 μg/m3 as an 8-h time-weighted average airborne concentration [24]. While this value is expected to be protective, NIOSH has also noted that the currently available data specific to nanoscale silver are too limited to develop an REL with confidence, and thus effective workplace controls to avoid exposures and minimize risks should be put into place, along with medical monitoring of workers.
US EPA has approved two nanosilver pesticide active ingredients – both as antimicrobials for use on textiles – one called AGS-20 that is included the GreenScreen evaluation and subsequently a second called Nanosilva. There are other products on the market with nanosilver, but they have not gone through the legally-required registration and approval process. AGS-20 is a silica-silver nanocomposite. HeiQ, the registrant for AGS-20, submitted toxicity information for the oral, dermal, and inhalation route of exposure as well as eye irritation data to US EPA as part of the registration process. Due to challenges such as material characterization, data gaps, and relevancy of current toxicity testing methods for nanomaterials, US EPA sought advice from its independent Scientific Advisory Panel [14]. The Panel advised US EPA against extrapolation from silver or other forms of nanosilver, such as using read-across information from ionic and metallic silver to inform its nanosilver assessment. Disregarding the Panel’s recommendations, US EPA approved AGS-20 and subsequently Nanosilva by filling data gaps with hazard data from other nanosilver materials [37, 38]. The US EPA risk assessment relied on a 90-day rat inhalation study of uncoated nanosilver particles with an average diameter of 18 nm and immunotoxicity effects reported in a 28-day mouse oral study with uncoated nanosilver particles with an average diameter of 42 nm [28, 39]. No studies longer than 90 days (i.e. no chronic toxicity studies) were available; US EPA identified data gaps or data deficiencies for neurotoxicity, developmental and reproductive toxicity, and mutagenicity endpoints. The US EPA risk assessment applied a 10-fold uncertainty factor to adjust for these data gaps and deficiencies, resulting in a conclusion of ‘no risk’ for consumers and workers [35]. US EPA granted the nanosilver products a conditional registration approval, permitting market access immediately on the condition that registrants submit additional data over several years. The information that US EPA requested included a study of leaching from textiles, a 90-day inhalation study, a dermal toxicity study, a reproductive/developmental toxicity test, and an in vitro micronucleus assay [35].
