AgNPs are among the most commonly used substances in consumer products, such as laundry machines, dusting cloths, and personal hygiene products. Hence, NPs contained in everyday household items are often discarded directly in sewage and can potentially be transported into waterways. They are mainly described to exhibit antibacterial properties ^{[28][29][30][31]}[28,29,30,31]. Typical AgNP applications include coatings of cloth and other textiles, food storage appliances, and cosmetics. They are also present in various applications used in the public health sector, and in medical products, such as disinfectants, wound dressings, central venous caterers, and surgical nettings. Furthermore, study results indicate that AgNPs may also exhibit cytotoxic properties, as they induce a typical cellular reaction of reactive oxygen species (ROS) formation ^{[12][16][32][33][34]}[12,16,32,33,34]. AgNPs have also shown antibacterial (against Staphylococcus aureus, Pseudomonas aeruginosa, Xanthomonas axonopodis pv. Citri), fungicidal (against Candida albicans, Candida parapsilosis), and antiviral properties, also affecting the SARS-CoV-2 virus ^[35][36][37][35,36,37]. In addition, the AgNPs toxic effect, in the range of 50% of lethal concentration (LC 50) on certain young and adult fish species (zebrafish), daphnia, and at least two algae species, has been described ^[38][39][38,39]. Silver in ionic form (Ag⁺) is also known to be toxic to aquatic organisms even at g/L concentrations by inhibiting the effects of ATPase Na⁺/K⁺ and causing ionic imbalance. These effects of AgNPs were similar in different marine animals, such as fish, daphnia, and crayfish ^[40][41][40,41].

AgNPs are easily assimilated by cells. Therefore, they are mainly applied in the biomedical industry due to their unique surface, electronic, and optical properties. They are also used as innovative tools in diagnostic research, e.g., the detection of heart disease or cancer biomarkers, and in drug delivery systems ^{[16][42][43][44][45][46][47]}[16,42,43,44,45,46,47]. Numerous reports have been published regarding the toxicity of gold nanoparticles depending on their size, shape, or structure of the coating and the spectrum of experimentally measured parameters. Toxicity depending on the size of gold nanoparticles in relation to different cell types has been described, demonstrating that smaller nanoparticles are generally more toxic ^[48][49][48,49].

In contrast, other teams of scientists have found no cytotoxic effects in cancerous cell lines treated with gold nanoparticles ^[25][50][51][25,50,51]. Subsequent works noted adverse effects on cytoskeleton components and a decrease in the growth of human cells exposed to AgNPs under culture conditions. Furthermore, increased levels of ROS were reported in aquatic organisms exposed to gold nanoparticles ^{[52][53][54][55][56]}[52,53,54,55,56].

3. Absorption of Silver Nanoparticles

Silver nanoparticles can be absorbed through the respiratory and digestive systems, and through the skin ^[33][57][33,57].

In Sprague–Dawley rats subject to inhalation exposure, silver nanoparticles were detected in the blood and lungs. In smaller amounts, they were also seen in other internal organs such as the liver, kidneys, spleen, heart, and brain. These experiments did not describe changes in body weight gain, internal organ weight, or biochemical parameters. However, there were some differences in respiratory parameters in rats, e.g., decreased respiratory volume and minute ventilation, and histopathological changes in the lungs at 90-day exposure to 20 nm silver nanoparticles at 49, 133, and 515 µg/m³ doses [55]. In Sprague–Dawley rats subjected to 28-day exposure to AgNP aerosol, the appearance of multinucleated macrophages was observed in the lungs, which indicates inflammation and active absorption of nanoparticles at the dose of 30.5 μg/m³ [58].

Spherical AgNP (20 nm) at doses of 50, 150, 300 mg/kg can be ingested orally, absorbed through the intestines into the bloodstream, and then accumulate in other organs such as the duodenum, liver, kidneys, and spleen. While this has been confirmed in mice, the authors of the study did not report any associated pathological changes [59]. Moreover, mice subjected to 14-day oral AgNP administration (dose: 1 mg/kg, size: 22, 42, 71, and 323 nm) also showed no histopathological changes in the liver, kidneys, testicles, or lungs. After 28 days and only in a dose of 1 mg/kg (size: 42 nm), only a small cellular infiltration was observed in the renal cortex. However, based on an increase in pro-inflammatory cytokines, induction of inflammation by AgNP incubation was confirmed. Furthermore, there was also an increase in liver enzymes [60].

In addition, Guinea pigs were found to accumulate free aggregate AgNP in the epidermis layers after 24 h of exposure at the highest dose used (100,000 ppm). However, microscopic evaluation did not reveal any abnormalities in the epidermis and skin layers in exposed areas of groups treated with colloidal AgNPs (spherical or polygonal shape, size: 10–20 nm) compared to controls [61]. The permeability of silver nanoparticles from textiles was also investigated. In the study by Bianco et al. (2016), volunteers wore an AgNP-containing sleeve on their forearm (average concentration 3.6 w/w), 8 h at night for five consecutive days. While the study confirmed the presence of AgNP aggregates in the skin, deeper layers there were less affected than those closer to the surface [62].

Previously, George et al. (2014) demonstrated the presence of clusters of silver in the stratum corneum and deeper layers of the epidermis after five days of skin exposure of healthy individuals to nanocrystal silver dressing (amount of silver released by dressing: 70 ppm of silver ions, size of particles: 10–40 nm). Thus, they confirmed the possibility of AgNP penetration through intact skin. However, despite the deposition of silver in the dermis, silver nanoparticles did not reach systemic circulation and should therefore not have systemic consequences [63].

4. Absorption of Gold Nanoparticles

Studies in rats show that gold nanoparticles can be absorbed through the respiratory and digestive systems ^[33][64][33,64].

In Sprague–Dawley rats subjected to spheroid AuNP (diameter under 6 nm) inhalation for 90 days, a decrease in respiratory parameters, i.e., lung function, respiratory volume, and minute volume, was observed compared to the control. Furthermore, histopathological examination demonstrated minimal alveoli, inflammatory infiltration of mixed cell type (lymphocytes/neutrophils/macrophages), and increased macrophage counts in rats receiving high doses of AuNP (20 μg/m³) [64].

Moreover, studies by Kreyling et al. (2018) also confirmed the absorption of “potato-shaped” gold nanoparticles (size: 20 nm, density: 19.5 g/cm³) by inhalation in rats. About 30% of AuNP accumulated in the epithelium of the respiratory tract, causing rapid mucociliary removal and swallowing into the gastrointestinal system. Long-term removal (after 28 days) of AuNP was dominated by macrophage-mediated transport through interstitial tissue to the larynx and gastrointestinal tract. Furthermore, AuNP retention has also been observed in the liver, spleen, kidneys, uterus, and brain [65].

In Wistar rats, ten days after intravenous administration of 25 nm colloidal AuNPs (0.3619 mg of particles/mL, per 1 kg), more than 50% of AuNP accumulated in the liver with smaller amounts in the lungs and spleen. This occurrence was associated with the collection of AuNPs from the circulation by the mononuclear phagocyte system. The total AuNP content of all organs represented 60% of the initial dose. In contrast, oral administration showed almost 50 times lower AuNP levels at the same amount (1.4% of the initial dose). Most AuNP was excreted in feces within four days after exposure. In turn, alterations in biochemical parameters were observed 72 h after intravenous AuNP administration. An increase in AST (aspartate aminotransferase) was observed, with a decrease in ALT (alanine aminotransferase), which affects the physiology of the liver. Furthermore, an increase in blood glucose has also been noted; thus, the effect of AuNP on pancreatic functions cannot be excluded [66].

The penetration of gold nanoparticles through the skin of the hind paw and the anterior abdominal wall of Sprague–Dawley rats was also confirmed by Raju et al. (2018), with smaller AuNPs (22 nm) showing higher penetration compared to larger nanoparticles (105 and 186 nm). The effect of 3-hour AuNP incubation on a fibroblast cell line (L929 mouse fibroblast cells) was also investigated, with no observed effect of AuNP on cell viability at any of the concentrations used (0.1, 1, and 10% v/v) [67].

In mice, the kidneys were the primary site of AuNP accumulation after oral administration for 8 days at 25, 22, 20, 18, and 15 μg gold/kg bodyweight concentrations, and subsequent intestinal absorption. AuNP can induce anti-inflammatory effects in macrophage RAW264.7 cells pretreated with 1/1000 OD of the AuNP for 5 h before stimulation with lipopolysaccharides (LPS) and incubation for another 20 h. AuNP reduce by reducing the lipopolysaccharide receptor expression on the cell surface, as well as catalytic detoxification of nitrite peroxide and hydrogen peroxide. The highest accumulation of gold nanoparticles was shown by those that were 5 nm in size and coated with PVP, compared to 5 nm AuNPs coated with citrate or tannic acid (TA) [68].

In other studies conducted in men subjected to nanoparticle inhalation for 2 h during intermittent exercise, AuNP was also confirmed to enter the lungs. Gold was detected in the urine after exposure to 4 nm AuNPs, but not in the urine of volunteers exposed to larger particles (34 nm). In mice, gold nanoparticles were also detected in urine only after exposure to particles ≤5 nm. AuNP found in human blood was usually at low levels after inhalation of AuNP, although the concentration of smaller particles was notably higher. This effect was also confirmed in mice, in which the incidence of detected gold and blood gold levels were significantly higher after exposure to smaller particles [69].

The possibility of absorption through human skin has been studied using surgically resected dermal fragments incubated for 24 h with AuNP. The permeability of spherical nanoparticles (15 and 100 nm) was confirmed by using a TEM (transmission electron microscope), with nanoparticles observed in the deeper stratum corneum, epidermis, and dermis [70].