Wearing Face Masks as a Potential Source for Inhalation and Oral Uptake of Inanimate Toxins: a Scoping Review

1. Introduction

Since 2020 until 2023, triggered by the SARS-CoV-2 pandemic and mandated by governments, wearing coverings of mouth and nose has become a new normal part of everyday life for many peoples around the world [1]. This is relevant, especially for health care professionals, who were mandated since the beginning of the pandemic based on WHO recommendations [2], laws [3,4] and institutional obligations in hospitals and healthcare-groups [5,6] to wear face masks. Furthermore, in many countries, children had been mandated to wear masks in schools for large proportions of the day [7,8]. The numerous commuters using public transport should also be mentioned [1].

Available characterizations of facemasks reveal the presence of chemicals like hydrocarbons, phthalates, organo phosphate ester compounds, amides, paraffins, olefins, polyethylene terephthalate oligomers and microplastics [9,10,11,12]. It is known from environmental research that the COVID-19 pandemic was exacerbated by environmental pollution, entailing (or bringing about) increased concerns. A recent comprehensive review on uptake, toxicity, and molecular targets of microplastics and nanoplastics impacting human health significantly mentioned face masks as a source of inhalation risk [13]. Also, numerous environmental toxicology reviews [14,15] derive an indirect (environmental) health risk from wearing face masks due to the release of chemical additives [16,17] and (micro)plastic fibers [18,19,20]. Face masks released contaminants (microplastics/fibers/chemical compounds) disturbing several ecosystems and affecting their biota [21,22].

However, so far direct risks associated with using face masks and their repercussions on human health had only been explored from a scientific and not from a holistic perspective [23]. Potentially, face masks, that come into close contact with the consumer can pose an immediate threat to human health due to the release of toxicologically relevant substances and continuous exposure to them [11,24]. Humans inhale emissions from a mask at nearly zero distance and swallow water droplets originating from the moist dead space enriched with mask ingredients. In this regard - theoretically - wearing a mask may exert a higher risk of exposure than many other environmental sources [25], keeping in mind the predominantly oral breathing while wearing a mask [26,27].

Chemical toxic additives used in the manufacturing processes of masks, including plasticizers, phthalates, UV stabilizers, and bisphenol A have already been shown to leach and cause adverse health effects in humans [28]. Children with less developed protective/conjugative pathways [29] are particularly vulnerable to many of face mask emissions. Some studies revealed no increased human health risk for skin [30], whereas other scientific publications were able to show nano- (<1 µm) and microplastics (<3 mm) in nasal mucosa after mask use and deduced a health risk to the wearer [31,32].

Interestingly, around the world, certain institutional regulatory actions were taken during the pandemic because face masks posed a considerable exposure risk [17,33,34,35,36,37,38,39,40,41,42].

By and large there is an increasing scientific interest focusing on the ingestion and inhalation risks from face masks, because of such an unprecedented use worldwide (2020–2023) implying long-term dermal contact, inhalation and ingestion exposure at population level. Nevertheless, overall knowledge on possible risks of wearing masks for humans is lacking. To our knowledge, since the beginning of the pandemic 2019, so far, no comprehensive scientific review on this complex topic has been realised.

Inspired by scientific reports and the undisputed fact that masks are capable of causing inhalation of potentially toxic substances [18,22,43,44] we decided to conduct a scoping review on this topic in order to evaluate reliable scientific data on toxic content and release from face masks. Moreover, we initially aimed for the assessment of the potential exceedances of toxin thresholds associated with face mask use.

2. Materials and Methods

2.1. Search and Retrieval Strategy

The PubMed/MEDLINE (NIH, national library of Medicine) database [45] was searched till 31st December 2022. The specific search terms according to the criteria defined in the PICO scheme [46] were: ((face mask) OR (facemask) OR (surgical mask) OR (FFP1) OR (FFP2) OR (FFP3) OR (N95) OR (KF94) OR (KN95)) AND ((toxicity) OR (toxic) OR (environmental health)). To expand the amount of published data we reviewed citations from included articles to locate additional research. Additional records identified through other sources were also taken into consideration, if applicable.

2.2. Inclusion and Exclusion Criteria

The aim was to study the potential of protective face masks for the maximum content and release of inanimate toxins that may be inhaled or ingested under use. Thus, popular cloth masks, surgical masks/FFP1, N95/KN95/KF94/FFP2 and FFP3 masks were the field of interest. Only manufactured content of the face mask was taken into account. Other substances like natural exhaled breath constituents including CO₂ were disregarded. The main findings considered were the quantifiable content and release of clinically relevant, potential toxins from face masks.

Assuming the worst case scenario in use with release of substances when the mask is drenched, bent, crumpled and by air currents passing through the mask during breathing, not only mask tissue analyses but also washout tests in water and similar test set-ups, e.g., with vacuuming or breathing simulation experiments were taken into account. This was intended to represent everyday use in the general population under worst-case scenarios as part of a simplified risk assessment. However, we excluded studies only aiming for release of toxins from masks after disposal, simulating decomposition, e.g., in salty sea water including washing, digestion experiments etc. Case reports, case series, expert opinions and preprints were also excluded.

The qualitative inclusion criteria for studies were: valid reproducible presentation of the outcomes, comprehensible recruitment of evaluated masks, credibility of the results, transferability to other mask studies and results, clear focus and comparability with existing evidence.

The quantitative inclusion criteria were: Appropriate and precise methods, valid processing, valid measurement of outcomes, representative selection of evaluated masks, and sufficiently reproducible analytical methods.

2.3. Data Extraction and Analysis

Two independent researchers identified and screened the eligible studies (Figure 1). The selected papers were checked by all authors for final eligibility. Study design, methodology, analytical and experimental method, primary and secondary outcomes and language have been evaluated. Exclusions and reasons have been documented. Concerning included studies the following data was extracted into tables: Author and year, method and type of study, sample size and mask types, outcomes/examined substances, content, release, main findings, and risks. Only the most relevant and toxic substances were included in the extraction tables. Studies on content and release have been presented in separate tables, respectively. Due to our toxicological approach, we focused on maximal content/release data on masks. Such approach is common in toxicological analyses with a worst case scenario. This enabled us to derive a risk estimation for members of the community. If not specified in the papers, the data representing exact maximal mask content/release of compounds was derived based on the data in the measurements of the original works and presented as the last column in the extraction tables. For example, on the basis of the data on leaching or exhaust vapour tests, etc.

2.4. Calculations and Exceedance Analysis

Due to the only basic arithmetic calculations in our study, the software Libre Office Calc [47] was used. If not realised in the included publications, we additionally performed a comparative analysis of the content and release of the toxic substances from the face masks with reference to (most appropriate) threshold limits. Such limits e.g., for the ambient air, are given by national or international institutions and organisations. For example, data from the United States Environmental Protection Agency (USEPA) [48], data from the WHO [49], as well as from the German Federal Environment Agency [50] and the European Union (EU) target limits [51] were taken into consideration. Similarly, textile content threshold values from international, high quality and standard organisations like the Oeko-Tex [52] were used. The calculated and extracted exceedance results were considered in the discussion section and were presented in separate tables. Text and tables were generated with Libre Office software [53].

For the purpose of data comparison the results of the included studies have been standardized and converted to values per mask, if not primarily reported. For those calculations data from the primary studies were gathered. If the necessary parameters were not exhaustively specified in the primary studies (e.g., mask surface or weight), we used valid values stated in previous scientific publications. Average mask weight was estimated from studies that give the specific mask weight within the scope of their measurements (average weight of the mask without rubber bands and nose clip, and if applicable also without valve) [54]. Thus, the disposable/textile/community mask was set at 2.5 g [55,56], the surgical mask was set at 3 g, the FFP2/KN95 at 4 g and the FFP3 mask at 5 g [54]. The average mask surface area was set at approximately 230 cm² (0.023 m²) [57], while we assuming the surface area of a standard N95 respirator to be 175 cm² (0.0175 m²) [58]. However, this assumption is not the worst case scenario, since some authors state larger surface areas in their primary evaluations [59]. For breathing calculations, we referred to the values from the USEPA calculating a breathing volume of 10 m³/12 h [60]. However, taking into account the high variability in breathing patterns, we assumed an adult at rest to breathe approximately 12–18 respirations per minute (mean 15), exchanging 0.5 litres - corresponding to approximately 0.5 m³/h, thus we rounded up for a simple calculation as 1 m³/2 h being in the normal range [61]. The exact calculation methods are mentioned continuously throughout our paper (e.g., by descriptions in the discussion, or as footnotes in the tables).

Figure 1. Flow diagram of the scoping review according to PRISMA. The selection was strictly based on the inclusion and exclusion criteria and the applied quality assessment (see methods section, inclusion and exclusion criteria).

Figure 1. Flow diagram of the scoping review according to PRISMA. The selection was strictly based on the inclusion and exclusion criteria and the applied quality assessment (see methods section, inclusion and exclusion criteria).

3. Results

3.1. General Findings

Of the original 1003 results, 24 studies (2.4%) were finally included (Figure 1). This is not an unusually low rate in reviews [62,63]. Moreover, our selection was strictly based on the inclusion and exclusion criteria and the quality assessment applied. Among the included papers eleven were published in 2021 and thirteen in 2022 representing very recent scientific interest in the mask toxin topic. The included papers, content/release was evaluated in 631 masks, among were 130 N95, 273 surgical, and 228 textile/disposable masks over an experimental period ranging from 17 minutes to 15 days. Altogether, among the included studies eleven measured the mask toxin content, twelve the mask toxin release and one both of them.

3.2. Analysed Substance Classes

Ten of the papers measured a microplastic (MP) release by face masks [12,32,59,64,65,66,67,68,69,70], representing 42% of the included papers. Also a nanoplastic (NP) release was documented by three of the included studies [32,65,70].

Among the included studies, five measured volatile organic compounds (VOCs) related to face masks, thereof three the emission [25,71,72] and two the content [24,56]. Two studies measured the organophosphate esters (OPE) content in face masks and did an intake estimation [54,56]. Only two studies measured the Polycyclic aromatic hydrocarbons (PAH) content in face masks [24,56]. We found eight studies that measured the phthalates and phthalate esters (PAE) emissions and content in face masks [24,54,55,59,68,73,74,75]. There was only one study that evaluated the UV-filter and organophosphate flame retardants (OPFR) content in face masks [56]. One study evaluated the per- and polyfluoroalkyl substances (PFAS) from masks and additionally did an exposure estimation [9]. Seven studies investigated trace elements and heavy metals, five predominantly release [65,68,69,70,71] and two the content [76,77] in face masks.

The evaluated toxic substances are summarised in Figure 2.

3.3. Special Findings

Interestingly, the N95 mask showed a higher content and release for MP/NP, OPEs, OPFRs, PAHs than other mask types.

In contrast, regarding VOCs, PAEs and heavy metals the surgical masks are responsible for higher levels and releases than N95 masks. As far as this is concerned, the textile masks are comparable to the surgical masks.

All relevant results concerning the evaluated studies on toxins in face masks (study type, aim, mask types, outcomes, findings, special risks, maximal face mask content/ release), are summarised in the extraction Tables: Table 1 shows results on the face mask content and Table 2 on the release of toxins.

4. Discussion

The results of our review show that ingredients of mask manufacture/production play a key role in their potential toxic properties. We also found clear evidence that values of certain contents/emissions are alarmingly high in all scrutinized mask types (N95, surgical, textile) and may - in worst case scenarios - pose a health risk to the wearer, who inhales the toxic substances at nearly zero distance. In the following subheadings we discuss the origin, the release and risks of particular toxics and compare our results of the contents and releases from masks to the threshold limit values of air- or textile concentrations, if available, from international organisations and institutions.

4.1. Microfibers, Micro- and Nanoplastics (MPs and NPs)

4.1.1. MP and NP from Masks - Origin

Synthetic macromolecules with repeating units (plastic polymers) are the primary component of all types of face masks [13]. This fact is responsible for the mask being a significant source of plastic fiber and particle release [12,32,59,64,65,66,67,68,69,70]. Therefore, the mass consumption of face masks has generated a huge additional source of microplastics (MPs < 5 mm) or even nanoplastics (NPs < 1 μm) pollution [78,79,80,81,82]. Mask manufacturing materials consist of specific polymers with polypropylene (PP) being the most widely used [83], although polyethylene (PE), polyamide (PA), polystyrene (PS), and polyethylene terephthalate (PET), or polyester (PES) also are commonly used in synthetic textiles [23,32,59]. Especially, the nanofibers created from microfibers and fragments of melt-blown filters of facemasks (middle layers) contribute to the dust release and inhalation risk of MPs and NPs while wearing a mask [13]. When producing these non-woven fabrics, high-speed hot air is applied to blow the thermoplastic polymer to a conveyor collector [84]. NPs and MPs are generated during the production process of these fine fibers, giving face masks the potential to act as a primary source of MPs [68]. While the surgical mask usually consists of three layers with one melt-blown fiber layer [80], the FFP2/N95 mask has 5 layers, thereof two melt-blown fiber layers [59].

4.1.2. MP and NP from Masks - Release and Intake

Exposure to plastic particles has increased continuously in the modern world [85], but the obligations to wear masks around the world during the SARS-CoV-2 pandemic 2020–2023 [1] has increased this exposure even further [86]. Recent environmental studies have reported that plastic-based personal protective equipment (PPE) releases substantial amounts of NPs and MPs, to the environment [28,80,87]. The NPs and MPs released from face masks were detected even in marine organisms showing their broad distribution [13,64]. Once released, these MPs and NPs (MPs, <5 mm, NPs, <1 μm) originating from masks pose a delayed indirect environmental health risk to humans regarding oral uptake and inhalation [88].

But, according to the study results at hand, there exists also a significant direct immediate inhalation risk for the user, from the mask breathing zone into the airways [12,32,59,64,65,66,67,68,69,70], as already assumed by other papers [13,26,88,89]. The fact that MPs were also detected in the nasal mucus shortly after mask wearing [31,32] gives evidence that MPs can be directly inhaled while wearing a mask. This additional inhalation risk was also laboratory proven by breathing simulations with diverse mask types (N95, surgical and other) by Li et al. [12]. However, this study was not conducted in super-clean laboratory (no contamination control measures were applied) thus it is not clear whether the control air in the blank measurements (no mask) does not correspond to the air already contaminated by mask handling. Therefore, the control values (without mask) in this study should be interpreted with caution, as they probably provide additional evidence for the release of plastics from masks.

Interestingly, the release of MPs and NPs is predominantly higher for the N95 type when compared to the surgical mask [32,59,65,66,67,78]. This fact could be due to more layers including two melt-blown and thus higher overall plastic content and weight of the N95 mask. According to the literature, reusing a mask increases even the risk of microplastic release: regardless of whether a mask is new or used, the risk of inhaling spherical-type MPs and NPs released from the facemask remains significant [12,78]. Problematic is that mechanical stress, e.g., a beard under the mask or pulling the mask out of the pocket may contribute to mask’s physical abrasion of microplastics [13].

In the evaluated literature we found a possible maximal release of MPs up to 5390 particles per mask within 24 h [59] and a maximum mass loss of 0.831 mg/N95 mask (particles and fibers) during 24 h [67]. Depending on the filters and analytic methods used, the release experiments describe different sizes of the mask debris. For released fibers we found a size range of 25 µm to 2.5 mm [66,69,70] and an amount of 3152 fibers per surgical mask [69]. For released particles we found a size range of 89 nm [77] to 500 µm [70], among many other dimensions [12,32,59,64,65,67,68]. Noteworthy, a study with precise analysis on silicon wafers and using scanning electronic microscopy (SEM) for exploration describes most of the particles involved smaller than 1 µm [32].

Surgical and N95 masks have been designed to be worn for very specific purposes such as in hospital surroundings and for a short period of time [90]. If they are crumpled up in people’s pockets where the friction and damp environment promotes significant fiber abrasion and worn for longer periods of time, a high microplastic release is possible, as shown by included papers [12,64,67].

However, it is interesting to compare the plastic release of masks while wearing them for a period of time, e.g., 2 hours with average breathing of 1 m³ to known MP concentrations in ambient air given as n/m³. For example, the mask-independent average concentration of airborne MPs in the United States of America (USA) is being described in 2019 as high as 5.6 n/m³ (outdoor) and 12.6 n/m³ (indoor) and >59% were MPs with the size of <50 μm. [91] In Shanghai, China, the airborne MP concentration was maximum 4.18 and on average 1.42 ± 1.42 with a size range of 23–5000 μm [92]. An analytic study in Paris 2017 evaluated the indoor air concentrations of 0.4–59.4 n/m³ with 33.3% containing polymers. Outdoor fiber concentration was 0.3–1.5 n/m³ with presence of numerous inhalable MPs below 50 µm [93].

In contrast to MPs, to date, there is no information regarding the amount or concentration of airborne NPs [94].

According to the data in our extraction tables (Table 2) and assuming a case scenario with wearing a mask appropriately for 4 hours while breathing on average a total of 2 m³ air, the mentioned average concentration of airborne MP values (USA, China, France) would be highly exceeded during mask use and breathing through [32]. Under a worst case assumption, that the mask MP release during 4 hours would be as high as in the analytical experiments by Ma et al. [32], the subject wearing a mask 4 hours would inhale up to 2200 n/m³, exceeding the environmental airborne MP content of outdoor air in the USA by a factor of approximately 400 and in China and Paris even by a factor of approximately 1500. Regarding the MP concentrations in indoor air in Paris, the mask would be responsible for a 37-fold increase of the microplastic particles. Moreover, the mask release of microplastic would be shifted to extremely higher concentrations of smaller MP particles (and even NPs) than known in the environment [32,65,68].

Cox et al. have estimated that the intake of MPs by humans via food and inhalation ranges between 203 and 312 particles per day [95]. Our results indicate that wearing masks may substantially increase that daily inhalation of MPs by a factor of 10 to 22 (Table 2) under assumptions of release with wearing time between 1 h and 4 h [32,69]. But in other worst case release scenarios (wearing time for >4 h the daily inhalation of MPs would even increase by a higher factor (Table 2) [12,59].

Interestingly, the estimated daily intake (EDI) values of MPs via street dust ingestion ranges from 0.6 to 4.0 for children and from 0.3 to 2.0 particles per day for adults in Tehran, Iran [96]. Nevertheless, in some heavily polluted areas, such as Asaluyeh County, Iran, higher EDI values of MPs for children and adults were 0.7–103.3 and 0.3–51.7 particles/d, respectively [78,97].

Consequently, our results indicate that wearing masks may increase such values of inhalation of MPs by a high factor. With possible maximal mask MP release during breathing of 3090 particles/mask in only 2 h [12] and a maximal possible MP leaching of 5390 particles/mask in 24 h [59] (Table 2) the estimated daily intakes mentioned above (even those in heavily polluted regions) might be highly exceeded while wearing a mask by a factor of 30 or more, assuming a worst case scenario [12,69] (Table 2, Figure 3).

4.1.3. Limits for MPs (Nps)

A regulatory standard for MP and NP release from medical masks is not established so far. In contrast, efforts by major public health and environmental organizations around the world to reduce the dangers posed by particulate matter are intensifying [98].

MPs are categorized according to their diameter into particles > 10 μm, particles < 10 μm (PM₁₀), particles < 2.5 μm (PM_2.5), and ultra-fine particles < 0.1 μm [99]. The large particles > 10 μm are assumed to collide with the upper airways upon respiration, whereas PM₁₀ can enter the bronchioles, and PM_2.5 and ultra-fine particles can penetrate the alveoli [85,99,100]. The shape of MPs influence their toxicity by modifying interactions with cells and tissues (shape-specific toxicity) [100,101]. Moreover, the surface charge of micro-particles can affect their toxicity (particles potential, electrostatic interactions of MPs with cells and tissues including adhesion) [100,102,103].

MP adsorption of molecules, leaching of softeners and microorganisms can additionally modify their toxicity. The MPs may act as a carrier of adsorbed toxins or pathogenic bacteria and fungi [90] enlarging their potential to impact human health [100,104].

Concerning microplastic particles, being a relatively new and modern environmental harm, only few official limits exist [105]. For example, the updated WHO Air Quality Guidelines (AQG) state that annual average concentrations of PM_2.5 should not exceed 5 µg/m³, while 24-hour average exposures should not exceed 15 µg/m³ more than 3 to 4 days per year [106].

According to our data (Table 2) those thresholds appear to be exceeded while wearing a mask in a worst case scenario. A release of 34.63 µg MP per hour per mask (N95) may be possible [67]. Considering that only a few reliable studies with adequate fine particle filtering (e.g., silicon waver) and analytical methods (e.g., SEM) exist on mask-released particles [32], only these can be used to estimate the exact size of the released smaller particles. In fact, Ma et al. detected very small particles being predominantly <1 µm - equivalent to at least PM_2.5 [32,99]. Thus, we can assume for the worst case scenario, that wearing face masks, particularly N95 masks, may lead to highly exceeding the WHO PM_2.5 guidelines for 24-hour average exposure of 15 µg/m³ (Table 3A). Also the annual average concentrations of 5 µg/m³ PM_2.5 could have been exceeded, e.g., during mask wearing enforced by law during 2020–2023 with regular and/or daily use of masks in many countries [1]. None of the existing medical mask standards, including the ASTM standards (F1862, F2100, F2101, F2299) and NIOSH regulation (42 CFR 84), which are adopted by the FDA in regulating medical face masks and surgical respirators in the U.S. (FDA, 2020a), regulate respirable debris such as micro(nano)plastics that may be present in these products. ISO standards (ISO 22609, 16900), EU standards (EN 140, 143, 149, 14683) and Chinese standards (GB 19083, 2626; GB/T 32610, 38880; YY 0469; YY/T 0969) on masks and respirators give no information pertinent to the particular type of microplastic related hazard. However, according to our data those appeared necessary for many in their daily life and work, particularly during the pandemic. Thus, questions must be raised over this apparent regulatory gap concerning the long-term use safety of face masks [89].

Table 3A. Exemplary limit threshold exceedance for microplastics, MP (PM_2.5) in worst case scenario while wearing a mask.

Publication	Mask type	Outcome	Result *	AQG WHO [106] threshold value **	Factor of exceedance
Liang 2022 [67] (Ma 2022 [32])	N95	MP (PM2.5) release	41.55 µg/m3 (72 min use)	5 µg/m3 (PM2.5) annual average	8.31
Liang 2022 [67] (Ma 2022 [32])	surgical	MP (PM2.5) release	33.9 µg/m3 (72 min use)	5 µg/m3 (PM2.5) annual average	6.78
Liang 2022 [67] (Ma 2022 [32])	N95	MP (PM2.5) release	41.55 µg/m3 (72 min use)	15 µg/m3 (PM2.5) 3 to 4 days (24 h) per year	2.77
Liang 2022 [67] (Ma 2022 [32])	surgical	MP (PM2.5) release	33.9 µg/m3 (72 min use)	15 µg/m3 (PM2.5) 3 to 4 days (24 h) per year	2.26

Legend: MP = Microplastic, PM_2.5 = Particulate matter (≤2.5 µm), WHO = World Health Organisation. Footnotes: * calculated from 831 µg/24 h (N95) and 678 µm/24 h (surgical) [67]. Particles are assumed to be predominantly less or equal to 2.5 µm [32]. Breathing air is estimated to be 10 m³ in 12 h according to USEPA [60]. Particle release in the first 24 hours is estimated to be linear (34.63 µg/h and 28.25 µg/h for N95 and surgical mask, respectively) [67]. ** for further details see discussion section, limits for MP/NP.

Table 3A. Exemplary limit threshold exceedance for microplastics, MP (PM_2.5) in worst case scenario while wearing a mask.

Publication	Mask type	Outcome	Result *	AQG WHO [106] threshold value **	Factor of exceedance
Liang 2022 [67] (Ma 2022 [32])	N95	MP (PM2.5) release	41.55 µg/m3 (72 min use)	5 µg/m3 (PM2.5) annual average	8.31
Liang 2022 [67] (Ma 2022 [32])	surgical	MP (PM2.5) release	33.9 µg/m3 (72 min use)	5 µg/m3 (PM2.5) annual average	6.78
Liang 2022 [67] (Ma 2022 [32])	N95	MP (PM2.5) release	41.55 µg/m3 (72 min use)	15 µg/m3 (PM2.5) 3 to 4 days (24 h) per year	2.77
Liang 2022 [67] (Ma 2022 [32])	surgical	MP (PM2.5) release	33.9 µg/m3 (72 min use)	15 µg/m3 (PM2.5) 3 to 4 days (24 h) per year	2.26

Legend: MP = Microplastic, PM_2.5 = Particulate matter (≤2.5 µm), WHO = World Health Organisation. Footnotes: * calculated from 831 µg/24 h (N95) and 678 µm/24 h (surgical) [67]. Particles are assumed to be predominantly less or equal to 2.5 µm [32]. Breathing air is estimated to be 10 m³ in 12 h according to USEPA [60]. Particle release in the first 24 hours is estimated to be linear (34.63 µg/h and 28.25 µg/h for N95 and surgical mask, respectively) [67]. ** for further details see discussion section, limits for MP/NP.

4.1.4. MP and NP Risks

The toxicology of fibers and particles is becoming more and more important as the modern world contains ever more artificial objects [107,108]. Noteworthy is the fact that plastic particles released in the course of medical treatment and application of implants have been known since decades to be responsible for undesirable reactions in diverse tissues [109,110,111,112,113].

But above all, the breathing of microplastics has become more and more a health risk concern [114]. MPs found in nasal mucus following mask use [31,32] and complaints of throat irritation or discomfort in the respiratory tract by children, the elderly adult, or other sensitive individuals after using face masks are alerting signs of respectable amounts of respirable debris inhaled from masks and respirators [115,116]. There is very recent evidence of MPs isolated in lower airway of European citizens examined in 2021, a time with rigid mask mandates and a year after they had been introduced during the pandemic [117]. The involved subjects came from regions, where face mask mandates were enforced by law and widely followed [1]. Another scientist team could show resembling results in a similar investigation period with microplastic particles in all parts of the lungs containing predominantly polypropylene and polyethylene [118], which are the most common components of the face mask [59]. Thus, a correlation of mask wearing and the recently detected high amounts of MP in human lungs appears conclusive [13,31,32].

Generally, it can be concluded that face masks contribute to direct microplastic inhalation risk [13] and therefore expose the mask user immediately to health risks [114,119,120,121].

Special consideration must be given to the fact that due to increased breathing resistance wearing a mask can cause substantial damage to nasal airflow [26,122]. Due to the presence of the mask, people have a natural tendency to breathe through the open mouth which means less breathing resistance bypassing the nasal airflow [26,27]. Usually under natural nose breathing [123] particles impact further up the respiratory airways depositing in a size-dependent manner from the nasal passages to the larger bronchioles. The nose effectively filters foreign particles that enter the nasal cavity dependent on particle size and air flow rate with filtration efficiency decreasing with smaller particle size. Therefore, usually only smaller particles (<1–3 μm) diffuse deep into the lung tissue, depositing in the alveoli by a number of mechanisms including diffusion, sedimentation, and electrostatic effects. This relationship (particle size-depth of diffusion and deposition) is constant across humans [123,124]. Most humans incline to revert to oral breathing during mask wearing [26,27]. This significantly increases the amount and size of particles that may be directly inhaled into the bronchi and lungs due to bypassing the filtration of the nasal cavity [125]. In a human study using a radiolabelled aerosol, scientists found a huge increase in deposition in the lungs (+37%) when breathing through the mouth compared to the nose (75% vs. 38%) for particle diameters averaging 4.4 µm (range 3.8–5.1 µm) [126].

Thus, taking into account the nearly zero distance to the airways and the predominant mouth breathing, the particle release from masks and their appearance in the mask breathing zone, appear to be worse (predominant mouth breathing) than similar particle presence in normal air in the no mask condition (predominant nose breathing). This seems comparable to the difference between active and passive cigarette smoking, with higher risk for active smokers due to frequent inhalation of particles directly at nearly zero distance through mouth breathing [127].

In this respect, the use of room air limit values in the evaluation of (predominantly oral) respiration from the mask breathing zone (with the particles released there) does not seem entirely appropriate for comparison. Noteworthy is, that inhaled ultra-fine particles can penetrate the alveoli where they can enter the bloodstream [100]. In addition, scientific reports exist on microplastics in human blood with evidence of origin from masks used worldwide [128,129].

MPs exposure can cause toxicity through oxidative stress, inflammatory lesions and there is a potentiality of metabolic disturbances, neurotoxicity, and increased cancer risk in humans [105].

According to the WHO, air pollution (including MPs and NPs) is the second highest risk factor for noncommunicable diseases [130].

For the long term exposure, there is clear evidence that both PM_2.5 and PM₁₀ were associated with increased mortality from all causes: cardiovascular disease, respiratory disease and lung cancer. And the associations even remained below the former 2005 WHO guideline exposure level of 10 µg/m³ for PM_2.5 [131,132].

Moreover, even the short-term exposure to particulate matter with aerodynamic diameters less or equal than 10 and 2.5 µm (PM₁₀, PM_2.5) are positively associated with increased cardiovascular, respiratory, and cerebrovascular mortality [133].

The toxic effects of micro- and nanoplastics comprise inflammation with disruption of immune function (increased IL1-q, IL-1ß, IL-6, IL-8, IL-10) oxidative stress and apoptosis (increased ROS, ER stress), as well as disturbance of metabolic homeostasis (altered channel function of K⁺-channels, blocking of vesicle transport, dysbiosis, intestinal barrier function disturbance, absorption disturbance, impairment of energy metabolism), neurotoxicity (AChE activation), reproductive toxicity and DNA-damage (DNA breaks) [94,134,135].

The COVID-19 pandemic has increased face mask pollution, and the release of nanofibers from face masks has been reported to inhibit even reproduction and growth [136]. NP and MP exposure also damages the seminiferous tubules, causing apoptosis in spermatogenic cells and lowering sperm motility and concentration, increasing the frequency of sperm abnormalities [137].

But there exists even more harm due to inhaled mask debris: Face mask microfibers and particles may serve as an important vehicle for harmful contaminants [10,65,104]. The plastics usually contain chemicals from raw monomers and various types of additives to improve their properties. MP particles have been demonstrated to be very important carriers for the transformation and accumulation of the toxic PAHs (see referring section) [104]. In addition, plastics also absorb chemicals from their surroundings [94,104,138] including heavy metals [65] as well as microorganisms [134]. Moreover, a microorganism growth on and in masks is scientifically proven [90,139].

All these mechanisms can potentiate the adverse effects of MP and NP released from masks.

Finally, a significant role of MPs and NPs in exacerbating the COVID-19 pandemic has been discussed, as plastic particles that loaded the virus into the air increased the half-life of the virus and facilitated the transmission of the virus to humans through the Trojan horse effect: Increased transmission and, consequently, more cases of COVID-19 will lead to rising production and use of surgical masks, an acknowledged source of MPs and NPs [13]. The findings of Fögen 2022 [140] using data from the USA which show that mask use correlates with an increased mortality and case fatality rate of COVID-19 could be due to these processes. This phenomenon could also explain the elevated face mask related mortality found by Spira [141] in the EU. Possibly the respiratory overload with NPs and MPs due to N95 masks [12,32,59,64,65,66,67,68,69,70] could be responsible to the measured nasal blockage, postnasal discharge as well as to impairment in mucociliary clearance function while using a medical mask [142]. Thus, an impaired self-cleaning of the mucous membranes may favour infections and be responsible for the opposite effect - more rather than fewer respiratory infections - under face mask use at the population level [140,141]. Correspondingly, higher respiratory infection rates have been observed in Germany [143] and USA [144], where mask mandates for long periods were enforced by law [1]. Additionally, COVID-19 rates have been able to expand swiftly especially during Omicron [145] even in societies where mask use was assiduously followed - as in Korea, Taiwan, Hong Kong and Singapore [146].

Noteworthy is also the problem regarding nanoparticles: Females are particularly more vulnerable to NP toxicity, and this may affect reproductivity and fetal development [147]. Additionally, various types of NPs have negative impacts on male germ cells [147]. Moreover, NPs as an environmental hazard are able to cause allergic asthma, pleural, interstitial lung disease and even sarcoma [148,149].

4.2. Organic Compounds and Organic Contaminants: Volatile Organic Compounds (VOCs) in General, Including total VOCs (TVOCs)

4.2.1. VOCs from Masks - Origin

Volatile organic compounds (VOCs) are relatively small organic compounds, usually containing five to 20 carbon atoms, showing generally a molecular weight in the range of 50 to 200 Dalton [150]. In conjunction with face masks, they are regarded as residues, probably originating from the fossil fuel-based petrochemicals used in the manufacturing of the plastic polymer filtering material [24,56]. The long-chain organic molecules contained in the face mask polymers can liberate the VOCs when in use [71]. Since face masks’ inner layers are mostly polypropylene and polyethylene polymers, aliphatic compounds are produced when they degrade due to oxidation reactions [71]. Studies have shown that the degradation of e.g., polyethylene (one of the main mask contents) liberates several VOCs (e.g., the aliphatic compounds 4-methylheptane, octadecane, tetracosane and 2,4-dimethylhept-1-ene) [71]. The solvent spinning process of the face mask fiber polymer uses a large amount of organic solvents and e.g., methanol is the dominant organic solvent currently used in the commercial production of cellulose acetate and triacetate fibers, which are widely used as the particle-retentive filters of a N95 mask. Thus, methanol accounts for 52% of total VOC emissions in N95 respirators [25]. Examples for commonly detected other VOCs in face masks are butene, pentene, propene and propyne [25], acrolein, glyoxal and decanal [24], xylene, toluene, benzene, caprolactam and aldehydes [72] as well as methylheptane [71].

4.2.2. VOCs - Release/Intake

Results from the included studies show that VOC concentrations in the mask breathing zone were positively correlated with the levels of VOC residues in the masks [24]. VOCs are divided in very volatile organic compounds (VVOCs) and semi-volatile organic compounds (SVOC) with different release characteristics [151]. According to the available data, the amount of possible intake of VOCs by inhalation while wearing masks is alarming. The total VOC release in the first minutes of mask use can go up to concentrations of 403 mg/m³ for N95 masks during the first 17 minutes [72]. Total face mask VOC emission exceeds concentrations of 1000 µg/m³ in the first hour and reaches on average 445 µg/m³ in a surgical mask and 406 µg/m³ in a N95 respirator during the following 6 hours [25]. In children face masks these values are much higher, even 836 µg/m³ [25], which is alarming compared to usual levels known from indoor air. Total VOC concentrations observed in indoor environments in diverse countries (including Europe, Japan, Australia, China) range on average between 44.3 and 415 µg/m³ with maximal values of 3.36 mg/m³ [151]. Interestingly, according to our data, face mask wearing of N95/FFP may exceed those indoor air concentration values by a factor of 971, and even compared to the maximum indoor air concentrations by a factor of 120 [72].

4.2.3. Limits for VOCs

A regulatory standard for chemical residues in face masks is not established [24]. However, VOC emissions from consumer products are regulated in many countries around the world [152,153]. Textile standards like the Standard 100 by Oeko-Tex defines accurate steps in the production and delivering of textiles which are not harmful to the health for consumers and include also limits for VOCs [154]. Standard definitions of VOCs in the air are determined even in European buildings [151]. There is mentioning of VOC in a guideline for air quality [155] and concerning selected VOC-pollutants in an additional guide from the WHO [156]. Some countries present their indoor air quality (IAQ) values for VOCs as regulations [157]. For the European Union (EU), the European Community has prepared a target guideline value for TVOCs of 0.3 mg/m³, where no individual VOC should exceed 10% of this target guideline [157,158,159,160,161,162]. However, the total VOC (TVOC) concept has evolved from the need to study mixtures and represents only a summation of individual VOCs [163]. Thus, TVOC as a measure reveals little regarding the nature of the individual compounds, their concentrations and possible toxicity [151]. Therefore, TVOC is not a toxicologically based parameter and only suitable for a limited number of screening purposes [153].

For example, the German hygienic Indoor Guide Value for total VOC regards rates >1 mg/m³ as suspicious, >3 mg/m³ as questionable and >10 mg/m³ as unacceptable from a hygienic perspective due to health risks [164,165]. It has been agreed upon that TVOC levels in indoor air should be kept as low as reasonably achievable, which is in accordance with the so-called ALARA-principle [153,162]. Regarding the fact that inhalation of total VOCs (TVOCs) from the mask breathing zone may be very high in comparison to the environmental exposition [72], it is interesting to compare maximal outcomes documented in the included studies with recommendations from those institutions [164,165].

Disturbingly, in some of the included studies, TVOC-concentrations are exceeded by all N95 masks and being partially more than 40-fold (concentrations of 403 mg/m³ for N95 masks during the first 17 minutes) [72] than the unacceptable limit for hygienic air quality (>10 mg/m³) [164,165]. The Oeko-Tex Standard 100 limit of 0.5 mg/m³ TVOCs may be exceeded 806-fold in the initial 17 minutes of N95 mask wearing [72]. With increasing mask wearing time, these concentrations decrease, but still exceed the Oeko-Tex concentration limits by a factor of 2 in the first hour under surgical masks and by a factor of 1.7 under children’s masks up to the sixth hour of wearing time [25].

Also, in the experiments the mask released xylene concentrations were exceeded as well [72], entered values which require immediate action according to, e.g., the German Federal Environmental Agency [164,165]. Additionally, by using a mask under rest conditions, for 17 minutes with average breathing of 0.236 m³ according to data from Kerkeling et al. (maximal xylene concentrations of 12 mg/m³ with arithmetic average of 529 µg/m³) [72] the xylene concentration in mg/kg (calculation with assuming the mask weighing 4 g) would be on average 3 times higher (and in the worst case 70.8 times higher than the Oeko-Tex Standard 100 limit value for textiles (10 mg/kg)) [154] Another particular VOC, acrolein, increased during the first 30 min of mask wearing to over 0.049 μg/m³ in the behind-mask breathing zone of all tested masks [24], exceeding the inhalation reference concentration (RfC; a daily inhalation exposure concentration below which yields no appreciable risk) for acrolein (0.02 μg/m³) set by EPA [166,167]. Furthermore, wearing the mask containing the highest level of acrolein residues (0.64 μg/mask) increased acrolein concentrations in the behind-mask breathing zone to over 0.5 μg/m³ and remained above the RfC for 1 h [24]. Moreover, in evaluations with diverse face masks including N95 and textile masks, Xie et al. reported 73.6% of all mask samples exceeding a calculated cumulative carcinogenic risk (CCR) for semi-VOCs [56].

4.2.4. VOCs - Risks

VOCs are respiratory irritants and suspected or known carcinogens [24]. There is evidence that an average daily (8 h) TVOC exposure above 300 µg/m³ range is associated with acute perceived discomfort as well as temporary symptoms of irritation in eyes and the respiratory system [162]. When the average TVOC concentration exceeds 3000 µg/m³ the number of complaints rises, while an average concentration above 25 mg/m³ leads to an increase in the prevalence of irritating symptoms in eyes and the respiratory tract [162]. Additionally, according to the WHO, health effects reported for VOC range from sensory irritation to behavioural, neurotoxic, hepatotoxic and genotoxic effects [155]. An exposure to a mixture of VOC as shown for face masks according to our results (TVOC, Table 2) [24,25,56,71,72] may be an important trigger of the so-called Sick Building Syndrome (SBS) [155]. SBS-like symptoms have been linked to mask use in recent comprehensive reviews on adverse face mask effects [26,62,63]. Possibly, some of the symptoms immediately occurring while wearing a mask may be caused by toxic chemicals released by the face mask.

According to a WHO paper, neurotoxicity, genotoxicity and carcinogenicity are expressed a long time after exposure to VOCs and it is assumed that there is no threshold concentration for an effect, therefore risk estimation is extended to very low concentrations [163] requiring the ALARA principle [153].

The US Environmental Protection Agency and Public Health England list the potential health effects of VOCs including irritation of the eyes and respiratory tract, allergies and asthma, central nervous system symptoms, liver and kidney damage, as well as cancer risks [151]. Some VOCs emitted from face masks have metabolic toxic properties (e.g., methanol with predominant toxic effects of its metabolites) with short-term exposure resulting in dizziness, blurred vision, and headache [25]. Unfortunately, children in schools that are particularly vulnerable to many classes of such VOCs [168] have been mandated to wear face masks for long periods during the SARS-CoV-2 pandemic [7,8].

4.3. Specific Organic Compounds: Organophosphate Esters (OPEs) and Organophosphate Flame Retardants (OPFRs)

4.3.1. OPEs and OPFRs from Masks - Origin

Organophosphorus esters (OPEs) are a class of organic compounds containing phosphate conjugated to oxygen [169]. OPEs, often used as plasticizers, are added to make the mask material softer and more flexible, while organophosphorus flame retardants (OPFRs a special kind of OPEs) are chemical additives to facemask components designed to prevent ignition [54,56]. Face masks are produced with flame retardant properties and OPFRs are usually applied as such flame retardants during the mask tissue manufacturing process [55]. More OPFRs are involved in the production of the N95 masks than other medical masks [56]. The most common OPEs detected in medical masks are triethyl phosphate (TEP), triphenyl phosphate (TPHP), Tri-n-butyl phosphate (TNBP), tris(2-ethylhexyl) phosphate (TEHP), tris(1,3-dichloro-2-propyl) phosphate (TDClPP) and tris(2-chloroisopropyl) phosphate (TCIPP) [54,56].

4.3.2. OPEs and OPFRs from Masks - Release/Intake

Up to 92.5% of the mask samples contain OPFRs [56]. The median values of total concentrations of the OPFRs in the KN95 masks were 224 ng/g [56]. All masks analysed in the included studies presented an OPE contamination, with maximal values up to 27.7 µg/mask in the FFP3. The maximal OPE values for N95 masks was 20.4 µg and for surgical masks 0.717 µg [54]. Interestingly, the higher OPE levels were found in N95 masks, while the lowest values were those of surgical masks. The estimated OPE inhalation percentages during the use of masks was around 10% according to Fernandes-Arribas et al., but the experimental tests did not consider the humidity present between the mask and the face when inhaling, and the higher exposure temperatures during summer-time or exercise (real world scenario). As these factors can affect a higher emission of plasticizers from the mask, those results could underestimate the real amounts of plasticizers that can be inhaled [54].

4.3.3. Limits for OPEs and OPFRs

There is no specific regulation for organic additives in face masks [54].

However, the United States Environmental Protection Agency (USEPA) updates regularly the oral reference dose (RfD) and oral cancer slope factors (SFO) of some OPEs [170]. Similarly, the European Union (EU) introduced regulations and criteria for the hazard classification and labelling of certain OPEs (Regulation (EC) No 12/72/2008) [171].

For textiles the Oeko-Tex norm Standard 100 set limits for flame retardants content [154].

Xie et al. and Fernandes-Arribas deduced no obvious risk for OPEs and OPFRS from face masks [54,56]. However, it is important to note that OPE exposure also occur by other routes, such as indoor/outdoor inhalation, dust ingestion, dermal absorption, dietary intake and the sum of all these exposures (including mask use) can bring the values closer to (or even above) the established safety limits [54].

4.3.4. OPEs and OPFRs - Risks

OPEs are associated with asthma and allergies, some harbour cancer risks [170]. OPFRS as well as as OPEs are predominantly metabolised to diaryl and dialkyl phosphate esters (DAPs) in the human body [169] and there are many reported health risks associated with DAPs including infertility, DNA oxidative stress, kidney disease and in the case of pregnant women, behavioural developmental deficits comprising depression, attention problems, withdrawal from the offspring [169]. Special OPEs, e.g., tri-n-butyl phosphate (TNBP) have been observed to disrupt endocrine and reproductive functions and nervous system development [172]. Epidemiological studies have reported that exposure to tris(1,3-dichloro-2-propyl) phosphate (TDClPP) is associated with decline of semen quality [172]. Therefore, Fernandez-Arribas et al. suggest that N95 masks are the least recommended to be used by the population when considering exposure to OPEs [54].

4.4. Specific Organic Compounds: UV-filters

4.4.1. UV-Filters from Masks - Origin

Organic UV filters are a group of chemicals that due to their chemical structure are capable to absorb UV irradiation by their high degree of conjugation [173]. UV-filters are not only components in sunscreen products, but are also widely used in other products, e.g., plastics, textiles and also face masks in order to protect these from UV triggered photodegradation [173]. Examples for some simple popular UV-filters detected in face masks are: benzothiazole, oxybenzone, octocrylene, benzophenone, octyl salicylate, octyl methoxycinnamate and octocrylene [56].

4.4.2. UV-Filters from Masks - Release/Intake

UV-filters contribute most significantly the SVOCs exposure accounting for 40% (mean value) and have been detected in 96.2% of the mask samples [56]. For the UV-filters content, no significant difference was found between different types of masks [56]. The median value of the total levels of UV-filters in diverse masks calculated with data from an included study [56] is around 3.43 µg/mask (average mask weight 3.15 g) and the median calculated daily exposure dose for the UV-filters from face masks is 0.99 ng/kg bodyweight/day [56].

4.4.3. Limits for UV-Filters

A regulatory standard for chemical residues in face masks is not established, however, around the world a total of 45 organic UV-filters are only permitted as additives in cosmetics with limits ranging from 2 to 20% [173]. For textiles the Oeko-Tex norm Standard 100 set limits for UV-filter content as well, being 0.1% [154]. In indoor dust samples from eastern China, the total concentration of four UV-filters ranged from 66.6 to 56,123 ng/g [173]. Regarding the concentration of UV-filters in face masks from the included studies (Table 2) [56], the exposure while wearing a mask appears not significantly higher than from other high exposure sources like indoor dust [173]. However, the maximum concentrations of UV filters in masks of about 3.43 µg/g [56] should be viewed critically, particularly with regard to the Oeko-Tex limits of less than 0.1% [154]. Additionally, regarding the fact that masks harbour the risk of inhaling a lot of microplastics originating from the mask tissue itself (37-fold increase of the microplastic particles inhaled compared to indoor air, see microplastic section above and Table 2, Figure 3), face masks are undoubtedly able to enlarge the total daily exposure to UV-filters.

4.4.4. UV-Filters - Risks

UV-filters, being highly lipophilic tend to accumulate after dermal absorption, oral intake or inhalation in fatty tissues [173]. It is known from studies that UV-filters harbour potential endocrine disruption with negative effects on placenta, human embryos and human sperm. The possible toxic effects comprise men’s infertility and sulphonated compounds of UV-filters have been reported to act as DNA alkylating agents (mutagens) and as genotoxic agents [174]. Additionally, there are reports of association of organic UV-filters with oxidative stress, obesity, including several diseases like diabetes, osteoarthritis, respiratory/allergic disease, breast cancer, polycystic ovary syndrome, decreased testosterone in adolescent boys and reduced estradiol, follicle-stimulating hormone and luteinizing hormone in healthy women and in pregnant women even effects on the next generation [173].

4.5. Specific Organic Compounds: Phthalates and Phthalate esters (PAEs)

4.5.1. Phthalates and PAEs from Masks - Origin

Phthalates and Phthalate esters (PAEs) are low-molecular-weight organic compounds and commonly used as plasticizers, added to give the mask plastic material more softness, flexibility and durability [24,59,73].

4.5.2. Phthalates and PAEs from Masks - Release/Intake

Since PAEs are not covalently bonded to the polymer and only combined with the plastic matrix by hydrogen bonds or van der Waals forces, PAEs can easily leak from the masks’ material [73]. Interestingly, the surgical masks are responsible for higher levels and releases than N95 masks.

Xie et al. 2022 measured the total concentrations of the phthalates ranging up to a maximum of 37.7 µg/g contributing to 191.64 µg/mask [55]. In their analytical study, Min et al. found some PAEs such as dihexyl phthalate (DHXP) more than 0.9 μg/g or 200 μg/m² [73]. The most frequent phthalates detected were DEXP, DEHP, DAP and BBP [73].

According to our calculations based on the data of Vimalkumar et al. (Table 1), the maximum levels of known PAEs in textile masks were 5.85 µg for DEP, 6.325 µg for di-iso-butyl phthalate (DiBP), 5.025 µg for DBP, 19.175 µg for DEHP and 13.75 µg for butyl benzyl phthalate (BBzP) [75].

4.5.3. Limits for Phthalates and PAEs

No regulations exist concerning Phthalates and PAES in face masks [11,24,54,55,56,59,73,74]. The EU has prohibited placing goods with phthalate contents of more than 0.1% by weight of the material (sum of DEHP, DBP, BBP and DiBP) [175]. Several included studies point at possible exceedances of this limit in masks [55,59,73,75]. Accordingly, Zuri et al. 2022 found total concentrations for phthalates of 35 µg/mask for FFP (N95) and 25.3 g/mask for the surgical mask [59].

In the analytical study by Xie et al. 2022, the total concentrations of the phthalates for a textile mask with 50 mask samples showed potential carcinogenic risks in the cumulated risk calculations [55]. The maximum disposable textile mask concentration of DEHP (36.73 µg/g) in the mentioned study would exceed even the threshold limit for phthalate/plasticizer established by Oeko-Tex Standard 100 (0.01% of weight) by factor 367; for the N95 mask (6.3 µg /g), the exceedance would be a factor of 63 [55,154].

4.5.4. Phthalates and PAEs - Risks

Phthalate exposure is associated with asthma, obesity, impaired reproductive development, endocrine disruption, and infertility [24,176]. Additionally, phthalates and PAEs are known as endocrine disruptors that can have adverse effects on human hormonal balance and development and harbour also a carcinogenic potential [73,176]. Thus, also the PAEs belong to the “three-causing” substances, being carcinogenic, teratogenic and mutagenic [59].

Alarmingly, DEHP, which is a known androgen antagonist and has been demonstrated to have a lasting effect on male reproductive function and carcinogenicity was detected in one-third of the tested mask samples at concentrations as high as 1450 ng/mask by Jin et al. [24]. Phthalates, as endocrine-disrupting chemicals are detrimental to the reproductive, neurological, and developmental systems and children are at a higher level of exposure and more vulnerable to phthalates than adults [176].

4.6. Specific Organic Compounds: Polycyclic Aromatic Hydrocarbons (PAHs)

4.6.1. PAHs from Masks - Origin

Polycyclic aromatic hydrocarbons (PAHs) belong to a class of hazardous organic substances that contain two or more fused aromatic hydrocarbon rings [104]. In general, the PAHs are not intentionally added into the masks, but are existent in the raw materials commonly used as plasticizers or fillers [56]. Thus, PAHs are ubiquitous in plastic ware manufactured from petroleum-derived materials and can remain in polymer-based plastics like face masks [24].

Examples for PAHs found in face masks are: naphthalene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo(a)anthracene, chrysene, benzo(a)pyrene [56].

4.6.2. PAHs from Masks - Release/Intake

In his analytical study Xie et al. detected the PAHs in 90.6% of the mask samples [56]. Naphthalene was the most abundant mask-borne PAH (5296 ng/surgical mask), accounting for over 80% of total PAH levels (5563 ng/surgical mask) [24].

4.6.3. Limits for PAHs

Already in 2011, the Occupational Safety and Health Administration (OSHA) in 2011 set an 8–hour time-weighted average (TWA) limit of PAHs of 0.2 mg/m³ in the air [177]. The ECHA CMRD Directive 2004/37/EC list and gives the advice on limiting the exposure to several PAHs that are cancerogenic as far as possible [178].

However, the Oeko-Tex norm allows up to 10mg/kg PAHs in textiles with plastic and synthetic fibers [154].

4.6.4. PAHs - Risks

Regarding PAHs, the unprecedented use of face masks worldwide during the SARS-CoV-2-pandemic by nearly all parts of the population (long-term exposure at the population level) [1] could have pose a health risk.

PAHs are a typical class of “three-causing” substances (carcinogenic, teratogenic and mutagenic). As the number of rings in the molecular structure increases, the toxicity of PAHs becomes stronger [104]. Evidence exists regarding adverse effects of PAHs, including carcinogenicity and teratogenicity, genotoxicity, reproductive- and endocrine-disrupting effects, immunotoxicity and neurotoxicity [104].

Benzo[a]pyrene is a well-known and extensively studied carcinogen, primarily responsible for lung cancer caused by cigarette smoke. It’s also the leading cause of chimney sweep cancer, a tumor of the testicular membrane resulting from soot irritation containing benzo[a]pyrene [104,179]. Therefore, is noteworthy, that Xie et al. detected benzo[a]pyrene several times in substantial concentrations, even in masks for infants [56]. Xie et al. summarized, that more than 70 % of the masks tested “exceeded the safe level for the carcinogenic risks”.

4.7. Specific Organic Compounds: Per- and Polyfluoroalkyl Substances (PFAS)

4.7.1. PFAS from Masks - Origin

Poly- and perfluoroalkyl substances (PFASs) are a family of highly fluorinated organic compounds [180]. Face masks are designed to not only prevent inhalation of particles or pathogens (bacteria, fungi) but also to repel fluids (e.g., bodily) and in many water-repellant fabrics the repellency factor indicates the potential presence of PFAS, which are known components also of speciality gear [9,180]. Additionally, their abundance in facemasks could originate from sources such as PFAS-impacted water used in manufacturing and PFAS in components to maintain or operate machinery. The carbon–fluorine bonds (extremely strong), along with other special chemical properties, are responsible for the fact that many PFAS are not appreciably degraded under environmental conditions [180].

4.7.2. PFASs from Masks - Release/Intake

Of the nonvolatile PFAS in masks, perfluoroalkyl carboxylates (PFCAs) showed the highest abundance, followed by fluorotelomer-based PFAS, and perfluoroalkyl sulfonates (PFSAs) [9]. Nonvolatile PFAS were found in all facemasks, and volatile PFAS were found in five of nine (55.5%) evaluated facemasks [9]. Total fluorine was quantifiable in most face masks and ranged up to 40,000 nmol F/cm². The summed PFAS concentrations ranged up to 2900 µg/m² [9]. In the estimates of human exposure wearing masks treated with high levels of PFAS for extended periods of time can be a notable source of exposure: High physical activity increased inhalation exposure estimates to over 70% (children), 700% (women), and 400% (men) more than the summed ingestion and dermal exposure routes [9].

4.7.3. Limits for PFAS

A regulatory standard for PFAS in face masks is not established. Our calculations show disturbing values of PFAS concentrations in masks. In contrast, the US Environmental Protection Agency (EPA) wants the limits for individual PFAS in drinking water to be as close as possible to zero with concentrations in parts-per-trillion (10⁻¹²), e.g., 0.004 ppt for PFOA and 0.02 ppt for PFOS [181,182]. Similarly, the European Commission in the long term aims to ban all PFAS, but its Drinking Water Directive, which took effect in January 2021, includes a limit of 0.5 µg/l for all PFAS (Directive (EU) 2020/2184 on the quality of water intended for human consumption (recast) [182,183]. Alarmingly, Muensterman et al. estimated exposure via inhalation to children wearing a PFAS-rich mask at moderate physical activity level being 7.04 µg/kg bodyweight/day, exceeding the reference dose for 6:2 fluorotelomer alcohol (FTOH) of 5 µg/kg bodyweight per day based on data from the Danish Ministry of Environment [9,184]. Moreover, calculating with an average weight of 2.5 g for cloth masks and 3 g for surgical masks [54,55] and an average mask surface of 0.023 m² [57] according to data from Muensterman et al. the mask PFAS content would exceed the Oeko-Tex norm concentration of 250µg/kg [154]: for surgical masks by a factor of 1.4 (352.7 µg/kg) and for cloth masks by a factor of 33.5 (8372 µg/kg) [9].

4.7.4. PFAS - Risks

For PFAS an evidence for increased cancer risk exists [180]. There is also solid data indicating immunosuppression and increased infection susceptibility related to PFAS exposure, as well as metabolic diseases such as diabetes, overweight, obesity, and heart diseases [180]. And regarding pregnant women, there are neurodevelopmental effects of PFAS to the offspring including attention-deficit/hyperactivity disorder (ADHD) and disturbed behaviours in childhood, and neuropsychological functions such as IQ decline [180]. These risks explain why the EPA wants the limits for PFAS to be as close as possible to zero [181].

4.8. Trace Elements and (Heavy) Metals Including TiO₂

4.8.1. Trace Elements and Heavy Metals from Masks - Origin

In particular, both surgical and KN95 masks, are composed of synthetic thermoplastic carbon polymers which are synthesized by a variety of chemical processes, which require a range of heavy metal catalysts (Sb, Ti, Zr and Sn) [76].

In addition, to the catalytic function, metals and heavy metals are involved in several other stages of polymer manufacturing such as: additives for flame retardants (Sb and Al), pigments (Pb, Cd, Cr, Cu) and stabilizers (Pb and Cd) [76]. Some masks have intentionally titanium dioxide nanoparticles bound within the fibers, as this compound exhibits antimicrobial properties [65]. In addition, TiO₂ particles are applied as a white colourant or as a matting agent, or to assure durability reducing polymer breakdown by ultraviolet light [77]. Moreover, Cu nanoparticles incorporated into polymer matrices are used to develop polymer nanocomposites with antibacterial properties [76]. Additionally, since face masks are manufactured of several filter layers and a nose wire metal frame, some of the detected trace elements and heavy metals might have their origin from the nose wire made of stainless steel. Stainless steel is produced by galvanization and, e.g., zinc used in galvanized steel, as well as trace amounts of lead can contaminate it [71]. However, also metals accumulated from the environment, metals from additives such as the dye applied to the masks, as well as metals from other sources in a particulate or non-particulate form are assumed to be detected in mask samples [69].

4.8.2. Trace Elements and Heavy Metals from Masks - Release/Intake

Trace elements and heavy metals in a mask can reach the mask wearer via the moist breath and saliva. The exposure could occur in people who extensively use contaminated masks or to children who may chew/play with the mask material. It is also important to point out, that human saliva contains a multitude of enzymes that could enhance metal leaching [76].

In their saliva experiments Bussan et al. could demonstrate there is a high possibility for trace elements to leach out of a mask that contains them. Specifically, Pb leached out close to 60% after a 6-h exposure to a saline solution [76].

Fittingly, besides release of other toxins, Li et al. could prove that surgical masks contain several types of potentially toxic metals such as Cd, Cr, and Pb and leached them in the following order of concentration: Pb > Cr > Cd [71].

In their experimental study, Verleysen et al. described the total TiO₂ mass up to 152,345 μg per reusable textile mask [77]. The estimated TiO₂ mass at the inhalable fiber surface ranged from 17 to 4394 μg, and systematically exceeded 1220-fold the acceptable exposure level to TiO₂ by inhalation (3.6 μg, calculated by Verelysen et al.) in a scenario where face masks are worn intensively [77].

4.8.3. Limits for Trace Elements and Heavy Metals

Standards for face mask do not exist regarding trace elements and heavy metals to our knowledge. Textile standards like the Standard 100 by Oeko-Tex defines contents of toxins in textiles which are not harmful to the health for consumers and include also limits for trace elements and metals [154]. According to our calculations based on the data of Sullivan et al. (Table 1), these threshold values set by Oeko-Tex standard would be exceeded in a worst case scenario for Pb, Cd and Sb by a factor of 3.4, 1.92 and 1.31 respectively [70,154].

Similarly, a calculation with data from Bussan et al. showed also an exceeding of the limit values for Pb (surgical), Cu (surgical) and Sb (KN95) by a factor of 66.5, 8.2 and 3, respectively [76,154]. Also, regarding the maximum results reported by Z. Liu et al. for Cd, Pb and Co the Oeko-Tex Standard 100 levels would be exceeded 2.2-, 1.1- and 1.3-fold, respectively [68,154].

4.8.4. Trace Elements and Heavy Metals - Risks

Heavy metals can have several different effects, depending on the specific metal and its concentration, including neurological disorders and muscular diseases [65]. TiO₂-nanoparticles can cause oxidative stress and have a genotoxic effect [65]. Moreover, when inhaled, TiO₂ is a suspected human carcinogen [77]. Similarly, ingesting Cd, Co, Cr and Pb was reported to have potential carcinogenic risk to both children and adults [68]. Even low exposures to Pb can lead to neurological damage and be detrimental to foetal development [70]. Inhaled and ingested Pb can cause severe brain damage, reproductive system damage and in higher concentrations death [76]. Sb is a possible carcinogen and it can cause pneumoconiosis, also chronic bronchitis, chronic emphysema, pleural adhesions, and respiratory irritation [76]. As such, contact allergy to Cr, Ni and Co are the most common metal allergies and approximately 1–3% of the adult general population are affected [68]. Additionally, multiple metal–metal interactions, e.g., Cd, Cu, Ni, and Zn, may contribute to a higher toxicity in a mixture [68].

4.9. Consequences for Science and Supervisory Authorities

Currently, the quality control of face masks is only focused on their physical and biological properties, that is, the filtration efficiency, e.g., ASTM F2101 and EN 14683 [57,185] BS EN 14683:2019 [24] and microbial populations, e.g., ISO 11737-1 [24] but does not address the levels of hazardous chemicals contained in them. This fact needs to be reconsidered, as our scoping review revealed the repeated detection of several hazardous ingredients in face masks and also their calculated emissions and contents of concern with exceeding institutional limit thresholds of WHO, EPA, European Union (EU) and German Federal Environmental Agency (see Tables 3A–3C). In addition, the masks have higher content of certain substances than the health maintaining Oeko-Tex Standard 100 label allows. Thus, health concerns for some masks and individual mask wearing conditions cannot be excluded (skin contact, inhalation at nearly zero distance, oral intake). In this regard, mask wearing may exert a higher risk of exposure than many environmental sources. Thus, a special, customized risk assessment for individual toxins in masks appears necessary. The evidence we have found for toxins in masks is more than troubling, especially given the worldwide use by diverse even susceptible portions of the population (e.g., children, pregnant women, adolescents).

Researchers have shown with their calculations that the special mask situation also requires a different evaluation without simple recourse to room air or product standards [24,56,77].

Fifteen of the 24 face mask studies included (63%) indicated high or excessive concentrations of inanimate toxins (institutional and organizational limits) (Tables 3A–3C). Thereof, five studies on MP an NP showed highly elevated levels [12,32,59,67,69] with possible exceedances for both surgical and N95 masks (Table 3A). Six papers indicated levels that are above institutional and organisational limits for organic compounds (Table 3B) including TVOC, VOCs, phthalates, acrolein, DEHP and PFAs in all types of masks (textile, surgical and N95 masks) [9,24,25,55,56,68,72].

As can be seen from Table 3C four studies revealed exceedances for trace elements and heavy metals including Pb, Cd, Co, Cu, Sb and TiO₂ in textile, surgical and N95 masks [68,70,76,77].

Table 3B. Exemplary limit threshold exceedance of organic compounds in a worst case scenario while wearing a mask).

Publication	Mask type	Outcome	Result *	Threshold value Institution/Organisation **	Factor of exceedance
Kerkeling 2021 [72]	N95	TVOC release	403 mg/m3 (17 min)	0.3 mg/m3 target guideline European Community [157,161,162,164] German Federal Environment Agency [158,159,160,164,165]	1343
Kerkeling 2021 [72]	N95	TVOC release	403 mg/m3 (17 min)	0.5 mg/m3 Oeko-Tex [154]	806
Xie 2022 [55]	textile	DEHP content	36.7 µg/g	0.01% of weight Oeko-Tex [154]	367
Xie 2021 [56]	textile	SVOC carcinogenic risk (CR)	2.27 × 10−4	≤1 × 10−6 US EPA [186,187]	227
Xie 2022 [55]	textile	Phthalates content	37.7 µg/g	0.025% of weight Oeko-Tex [154]	150.8
Muensterman 2022 [9]	textile (coated)	PFAS content	2900 µg/m2	250 µg/kg Oeko-Tex [154]	107
Kerkeling 2021 [72]	N95	Xylene release	12 mg/m3 (17 min)	10 mg/kg Oeko-Tex [154]	70.8
Xie 2022 [55]	N95	DEHP content	6.3 µg/g	0.01% of weight Oeko-Tex [154]	63
Muensterman 2022 [9]	textile (coated)	FTOH content	1200 µg/m2	250 µg/kg Oeko-Tex [154]	44.2
Xie 2022 [55]	textile (for children)	Phthalate carcinogenic risk (CR)	4.26 × 10−5	≤1 × 10−6 US EPA [186,187]	42.6
Kerkeling 2021 [72]	N95	TVOC release	403 mg/m3 (17 min)	10 mg/m3 AgBB, German Federal Environment Agency [164,165]	40
Muensterman 2022 [9]	textile	PFAS content	910 µg/m2	250 µg/kg Oeko-Tex [154]	33.5
Zuri 2022 [59]	N95	phthalates content/release	8.16 µg/g	0.025% of weight Oeko-Tex [154]	32
Zuri 2022 [59]	surgical	phthalates content/release	7.56 µg/g	0.025% of weight Oeko-Tex [154]	30
Jin 2021 [24]	surgical	Acrolein release	0.5 μg/m3 (30 min)	0.02 μg/m3 US EPA [166,167]	25
Xie 2021 [56]	N95 (for children)	SVOC carcinogenic risk (CR)	2.5 × 10−5	≤1 × 10−6 US EPA [186,187]	25
Kerkeling 2021 [72]	N95	Xylene release	12 mg/m3 (17 min)	500 µg/m3 AgBB, German Federal Environment Agency [158,159,160,164,165]	24
Xie 2021 [56]	N95	SVOC carcinogenic risk (CR)	1.59 × 10−5	≤1 × 10−6 US EPA [186,187]	15.9
Xie 2022 [55]	textile	Phthalate carcinogenic risk (CR)	1.45 × 10−5	≤1 × 10−6 US EPA [186,187]	14.5
Chang 2022 [25]	surgical	TVOC release	>1 mg/m3 (1 h)	0.3 mg/m3 target guideline European Community, [157,161,162,164] German Federal Environment Agency [158,159,160,164,165]	>3
Chang 2022 [25]	surgical	TVOC release	>1 mg/m3 (1 h)	0.5 mg/m3 Oeko-Tex [154]	>2
Muensterman 2022 [9]	surgical	PFAS content	46 µg/m2	250 µg/kg Oeko-Tex [154]	1.4
Muensterman 2022 [9]	textile	FTOH intake estimation 10 h mask use	7.04 µg/kg-bw/day	5 µg/kg-bw/day Danish Ministry of Environment [184]	1.4
Xie 2021 [56]	N95	Naphthalene content	2.43 µg/g	2 mg/kg Oeko-Tex [154]	1.2

Legend: AgBB = Ausschuss zur gesundheitlichen Bewertung von Bauprodukten (Committee for the Health Evaluation of Building Products, Federal Environment Agency Germany), DEHP = di(2-ethylhexyl) phthalate, FTOH = 6:2 fluorotelomer alcohol, kg-bw = kilogram per bodyweight, PFAS = Poly- and perfluoroalkyl substances, SVOC = semi volatile organic compounds, TVOC = Total Volatile Organic Compounds, US EPA = United States Environmental Protection Agency, VOC = Volatile Organic Compounds. Footnotes: * If necessary, the units had to be converted, with the surface area of the N95 respirator being 175 cm² (0.0175 m²) [58] and the surface area of the surgical/textile mask being 230 cm² (0.023 m²) [57]. If not given in the studies the average weight was set at 2.5g for cloth masks [55,56], 3g for surgical masks and 4g for N95 mask [54]. Breathing air was estimated to be 10 m³ in 12 h according to USEPA [60]. Please note: VOCs release in the first hours is known to decrease exponentially [25]. ** for further details see discussion section, limits for VOCs, PFAS, phthalates.

Table 3B. Exemplary limit threshold exceedance of organic compounds in a worst case scenario while wearing a mask).

Publication	Mask type	Outcome	Result *	Threshold value Institution/Organisation **	Factor of exceedance
Kerkeling 2021 [72]	N95	TVOC release	403 mg/m3 (17 min)	0.3 mg/m3 target guideline European Community [157,161,162,164] German Federal Environment Agency [158,159,160,164,165]	1343
Kerkeling 2021 [72]	N95	TVOC release	403 mg/m3 (17 min)	0.5 mg/m3 Oeko-Tex [154]	806
Xie 2022 [55]	textile	DEHP content	36.7 µg/g	0.01% of weight Oeko-Tex [154]	367
Xie 2021 [56]	textile	SVOC carcinogenic risk (CR)	2.27 × 10−4	≤1 × 10−6 US EPA [186,187]	227
Xie 2022 [55]	textile	Phthalates content	37.7 µg/g	0.025% of weight Oeko-Tex [154]	150.8
Muensterman 2022 [9]	textile (coated)	PFAS content	2900 µg/m2	250 µg/kg Oeko-Tex [154]	107
Kerkeling 2021 [72]	N95	Xylene release	12 mg/m3 (17 min)	10 mg/kg Oeko-Tex [154]	70.8
Xie 2022 [55]	N95	DEHP content	6.3 µg/g	0.01% of weight Oeko-Tex [154]	63
Muensterman 2022 [9]	textile (coated)	FTOH content	1200 µg/m2	250 µg/kg Oeko-Tex [154]	44.2
Xie 2022 [55]	textile (for children)	Phthalate carcinogenic risk (CR)	4.26 × 10−5	≤1 × 10−6 US EPA [186,187]	42.6
Kerkeling 2021 [72]	N95	TVOC release	403 mg/m3 (17 min)	10 mg/m3 AgBB, German Federal Environment Agency [164,165]	40
Muensterman 2022 [9]	textile	PFAS content	910 µg/m2	250 µg/kg Oeko-Tex [154]	33.5
Zuri 2022 [59]	N95	phthalates content/release	8.16 µg/g	0.025% of weight Oeko-Tex [154]	32
Zuri 2022 [59]	surgical	phthalates content/release	7.56 µg/g	0.025% of weight Oeko-Tex [154]	30
Jin 2021 [24]	surgical	Acrolein release	0.5 μg/m3 (30 min)	0.02 μg/m3 US EPA [166,167]	25
Xie 2021 [56]	N95 (for children)	SVOC carcinogenic risk (CR)	2.5 × 10−5	≤1 × 10−6 US EPA [186,187]	25
Kerkeling 2021 [72]	N95	Xylene release	12 mg/m3 (17 min)	500 µg/m3 AgBB, German Federal Environment Agency [158,159,160,164,165]	24
Xie 2021 [56]	N95	SVOC carcinogenic risk (CR)	1.59 × 10−5	≤1 × 10−6 US EPA [186,187]	15.9
Xie 2022 [55]	textile	Phthalate carcinogenic risk (CR)	1.45 × 10−5	≤1 × 10−6 US EPA [186,187]	14.5
Chang 2022 [25]	surgical	TVOC release	>1 mg/m3 (1 h)	0.3 mg/m3 target guideline European Community, [157,161,162,164] German Federal Environment Agency [158,159,160,164,165]	>3
Chang 2022 [25]	surgical	TVOC release	>1 mg/m3 (1 h)	0.5 mg/m3 Oeko-Tex [154]	>2
Muensterman 2022 [9]	surgical	PFAS content	46 µg/m2	250 µg/kg Oeko-Tex [154]	1.4
Muensterman 2022 [9]	textile	FTOH intake estimation 10 h mask use	7.04 µg/kg-bw/day	5 µg/kg-bw/day Danish Ministry of Environment [184]	1.4
Xie 2021 [56]	N95	Naphthalene content	2.43 µg/g	2 mg/kg Oeko-Tex [154]	1.2

Legend: AgBB = Ausschuss zur gesundheitlichen Bewertung von Bauprodukten (Committee for the Health Evaluation of Building Products, Federal Environment Agency Germany), DEHP = di(2-ethylhexyl) phthalate, FTOH = 6:2 fluorotelomer alcohol, kg-bw = kilogram per bodyweight, PFAS = Poly- and perfluoroalkyl substances, SVOC = semi volatile organic compounds, TVOC = Total Volatile Organic Compounds, US EPA = United States Environmental Protection Agency, VOC = Volatile Organic Compounds. Footnotes: * If necessary, the units had to be converted, with the surface area of the N95 respirator being 175 cm² (0.0175 m²) [58] and the surface area of the surgical/textile mask being 230 cm² (0.023 m²) [57]. If not given in the studies the average weight was set at 2.5g for cloth masks [55,56], 3g for surgical masks and 4g for N95 mask [54]. Breathing air was estimated to be 10 m³ in 12 h according to USEPA [60]. Please note: VOCs release in the first hours is known to decrease exponentially [25]. ** for further details see discussion section, limits for VOCs, PFAS, phthalates.

Table 3C. Exemplary limit threshold exceedance of anorganic toxins and compounds in a worst case scenario while wearing a mask.

Publication	Mask type	Outcome	Result *	Threshold value Institution/Organisation **	Factor of exceedance
Verleysen 2022 [77]	textile, reusable	TiO2 exposure Adverse effect level (AELmask) two mask per day, 8h	4394 μg	3.6 µg ANSES, France [188,189,190]	1220
Bussan 2022 [76]	surgical	Pb content	13.3 µg/g	0.2 mg/kg Oeko-Tex [154]	66.5
Bussan 2022 [76]	surgical	Cu content	410 µg/g	50 mg/kg Oeko-Tex [154]	8.2
Sullivan 2021 [70]	textile	Pb content	0.68 µg/g	0.2 mg/kg Oeko-Tex [154]	3.4
Bussan 2022 [76]	N95	Sb content	90.18 µg/g	30 mg/kg Oeko-Tex [154]	3
Z. Liu 2022 [68]	surgical	Cd content	0.22 µg/g	0.1 mg/kg Oeko-Tex [154]	2.2
Sullivan 2021 [70]	textile	Cd content	0.19 µg/g	0.1 mg/kg Oeko-Tex [154]	1.9
Z. Liu 2022 [68]	surgical	Co content	1.33 µg/g	1 mg/kg Oeko-Tex [154]	1.33
Sullivan 2021 [70]	textile	Sb content	39.3 µg/g	30 mg/kg Oeko-Tex [154]	1.3
Z. Liu 2022 [68]	surgical	Pb content	0.22 µg/g	0.2 mg/kg Oeko-Tex [154]	1.1

Legend: Cd = Cadmiun, Co = Cobalt, Cu = Copper, Pb = Plumbum (Lead), Sb = Stibium (Antimon), TiO₂ = Titandioxide. Footnotes: * If not given in the studies the average weight was set at 2.5g for cloth masks [55,56], 3g for surgical masks and 4g for N95 mask [54]. ** for further details see discussion section, limits for trace elements and heavy metals.

Table 3C. Exemplary limit threshold exceedance of anorganic toxins and compounds in a worst case scenario while wearing a mask.

Publication	Mask type	Outcome	Result *	Threshold value Institution/Organisation **	Factor of exceedance
Verleysen 2022 [77]	textile, reusable	TiO2 exposure Adverse effect level (AELmask) two mask per day, 8h	4394 μg	3.6 µg ANSES, France [188,189,190]	1220
Bussan 2022 [76]	surgical	Pb content	13.3 µg/g	0.2 mg/kg Oeko-Tex [154]	66.5
Bussan 2022 [76]	surgical	Cu content	410 µg/g	50 mg/kg Oeko-Tex [154]	8.2
Sullivan 2021 [70]	textile	Pb content	0.68 µg/g	0.2 mg/kg Oeko-Tex [154]	3.4
Bussan 2022 [76]	N95	Sb content	90.18 µg/g	30 mg/kg Oeko-Tex [154]	3
Z. Liu 2022 [68]	surgical	Cd content	0.22 µg/g	0.1 mg/kg Oeko-Tex [154]	2.2
Sullivan 2021 [70]	textile	Cd content	0.19 µg/g	0.1 mg/kg Oeko-Tex [154]	1.9
Z. Liu 2022 [68]	surgical	Co content	1.33 µg/g	1 mg/kg Oeko-Tex [154]	1.33
Sullivan 2021 [70]	textile	Sb content	39.3 µg/g	30 mg/kg Oeko-Tex [154]	1.3
Z. Liu 2022 [68]	surgical	Pb content	0.22 µg/g	0.2 mg/kg Oeko-Tex [154]	1.1

Legend: Cd = Cadmiun, Co = Cobalt, Cu = Copper, Pb = Plumbum (Lead), Sb = Stibium (Antimon), TiO₂ = Titandioxide. Footnotes: * If not given in the studies the average weight was set at 2.5g for cloth masks [55,56], 3g for surgical masks and 4g for N95 mask [54]. ** for further details see discussion section, limits for trace elements and heavy metals.

Figure 4 summarises the toxic substances and classes that may be responsible for limit value exceedances with resulting potential life-shortening effects.

Moreover, there are possible chemical reactions of all the reported chemicals with each other and with the exhaled compounds resulting from human metabolism [191] in the mask breathing zone (mask dead space), e.g., oxidation. For this reason, the mask breathing zone could act as a “chemical reactor” at the entrance of the airways. This phenomenon could lead to further toxic compounds with a new kind of threat to human health. One has to consider that the mask dead space does not only have a higher temperature, but is more humid [26,63], which facilitates many chemical reactions. It should not go unmentioned, that there is an additional possibility of amplifying toxic effects, resulting from the mixture of toxins.

Mask use may additionally - even if not exceeding threshold values - increase the burden of the airways and lungs and organs with chemical compounds, heavy metals, micro-and nanoplastics. And there could be a cumulative effect concerning indoor use of masks (which was recommended by the WHO during the pandemic) [192], because indoor air exposition to several toxic compounds (e.g., VOCs, MPs and NPs) is per se higher than outdoors [72]. Some of the substances are ultrafine (e.g., TiO₂, NPs) and require another risk and toxicological evaluation [32,77,147,148]. Interestingly, face masks have no toxicological regulations so far.

Despite a broad narrative during the SARS-CoV-2 pandemic supporting the efficacy of face masks against virus transmission [62,63] there is only weak evidence for the effectiveness against respiratory viral infections even from the highest evidence-based institutions [193]. Regarding our results of multiple toxic substances released by face masks that can be ingested and inhaled (Table 1, Table 2 and Table 3), the introduction of mask mandates by law for the general population in many countries during the SARS-CoV-2-pandemic 2020-2023 appears questionable from an empirical and scientific perspective.

Considering the weak antiviral effectiveness [62,63] and the lack of medium or strong empirical evidence for face mask effectiveness in preventing respiratory virus infections [26,62,63], wearing face mask frequently during the SARS-CoV-2 pandemic - according to our results - may have led to negative health and possible life shortening effects. From environmental science a lot of chronic subthreshold toxic effects have been evaluated and described and have been named “silent killer effects” [63,194,195,196,197,198,199]. As the mask wearing may be linked to toxin exposure and an unprecedented use worldwide occurred, a toxic influence related to the general population could contribute to a similar effect [26,63,194,195,196,197,198,199,200]. Thus, without a thorough risk-benefit analysis enforced mask obligations by law as happened in the SARS-CoV-2-pandemic, acting against the evidence of science (regarding mask effectiveness and mask hazardous substance content standardization), should not be repeated in the future.

5. Limitations

This review does not claim to be exhaustive, especially with regard to the evaluation of the results. This is because inhalation toxicology is a very complex field, and combined exposure in particular must be considered separately, since the toxic effects can reinforce each other.

In our tables, we quote maximum values; if these are not available, we quote mean values. In this way, we ensure a worst-case consideration [201], which is quite common in toxicology. Since we do not perform any precise toxicological evaluation to ensure human safety, this worst case consideration is not only legitimate, but necessary.

Most of the studies included in our review are in vitro studies and give only estimation data for an in vivo human exposure to diverse toxins which may be different under real world conditions. Our estimated and discussed exposition might be different than in real life, due to the fact that masks may be crumpled up in pockets etc. or changed frequently during a day as it has been recommended [64,202]. Moreover, we have taken average physiological variables for our tentative preliminary calculations, e.g., respiratory rate, tidal volume, however, the diversity and individuality of the breathing pattern [61] is worth being taken into account as there could be more harm for one subject and less for the other. Correspondingly, some authors could show higher toxin exposure in physical activity [9] respectively under rapid breathing [32].

The release of microplastics was assessed in a worst-case scenario (liquid extractions etc.) [32,64,65,66,67,69]. However, a more realistic air-based scenario using breathing models (e.g., Sheffield heads) could show different outcomes [69]. Unfortunately, too few such studies having been carried out so far, further evaluations regarding more realistic microplastic inhalation risk assessment could not be performed. Nevertheless, studies with breathing simulations show a significant inhalation risk, e.g., for microplastics [12]. In the above estimations we applied WHO limits in our calculations [131]. However, slightly different regulations exist in many countries, e.g., Germany [203] and are also regulated in the European Union [204]. Moreover, the limit thresholds, e.g., like the WHO Air Quality Guidelines (AQG) for particulate matter in ambient air cannot be transferred one-to-one to the mask wearing situation. Thus, our comparisons and calculations should only act as a preliminary exploratory analysis, since the particle inhalation at nearly zero distance predominantly with oral breathing (less nasal filtration) while using a mask may represent a different condition than inhaling ambient air with predominantly nose breathing.

As we concentrated on the direct human health risks resulting from direct absorption of possible toxins from the mask while wearing it, the environmental effects including pollution and damage of the animate ecosystem could not be taken entirely into account. However, these consequences also may have indirect health threatening repercussions on humans [22] (e.g., via the nutrition circle).

We did not address the risks of the inhalable living organisms in our review, although there is also a large body of scientific evidence on this issue, describing the health risk for humans from animate toxins [139,205,206,207,208,209].

We regarded the toxins separately, however their mixture and interaction can contribute to a higher toxicity than each substance on its own. Additionally, we could not evaluate further risks of chemical reactions in the mask breathing zone [191] which we assume to be a “chemical reactor“ at the entrance of the airways.

We also did not address the toxicological risks of inhaled CO₂ from the mask dead space, as it is not a manufactured content of the face mask, and moreover has been extensively evaluated in a recent review by Kisielinski et al. [62].

6. Conclusions

Of course, masks filter bacteria, dirt and plastic particles and fibers from the air we breathe, but according to our data, they also carry the risk of inhalation of microplastic and nanoplastic particles and potentially toxic substances originating from the mask material itself.

Therefore, the benefits (depending on the application situation and application-related efficacy) and the risks of use must be carefully weighed.

Undoubtedly, our results show, that the mask mandates around the world during the SARS-CoV-2 pandemic have generated an additional source of potentially harmful exposition to toxins at the population level from nearly zero distance to the airways (predominantly oral inhalation route) and to the gastrointestinal tract. Among the 24 included studies, 63% showed strikingly high values and possible exceedances for substances such as micro- and nanoplastics (MPs and NPs), volatile organic compounds (VOCs), xylene, acrolein, Per- and polyfluoroalkyl substances (PFAS), phthalates including DEHP, as well as heavy metals like Pb, Cd, Co, Cu, Sb and TiO₂ (Tables 3A, 3B and 3C). For the N95 mask, MP release was 831 µg in 24 h and up to 4400 particles within 4 h (with predominant size < 1 µm) and up to 6 × 10⁹ NP in 4 h. Surgical masks released up to 3152 microfibers in <1 hour. Our worst-case estimations show breathing, that may exceed the WHO Air Quality Guideline (AQG) limits. Also, we found exceedances of total VOCs (TVOCc) with 403 mg/m³ within 17 min for the N95 mask, and >1000 µg within the first hour for the surgical mask, being over the threshold limits of EU target guideline, German Federal Environmental Agency and the Oeko-Tex Standard 100. The textile norms were also exceeded for PFAS (N95, surgical, textile mask), DEHP, phthalates, flurotelomer-alcohol, FTOH (textile masks each), naphthalene (N95), Pb (surgical, textile), Cu (surgical), Sb (N95, textile), Cd and Co (each surgical). Additionally, acrolein (surgical) and xylene (N95) were above the USA and German environmental protection agency levels, respectively.

Regarding the potential negative short- and long-term effects of the aforementioned toxins, some of the immediate discomforts while wearing a mask (headaches, dry cough, rhinitis, and skin irritation) could be related to this. In this way, the toxic substances of face masks could also contribute to the symptoms already described, known as mask-induced exhaustion syndrome (MIES).

Moreover, from a toxicological point of view, concerning their potential risks of use, face mask obligations enforced by law 2020-2023 have been introduced without preceding comprehensive risk analyses and without regulatory provisions (as is common for various products). On top of that, there was [210] and still is no empirical evidence for the effectiveness of the masks in limiting the spread of viruses in the general populace [193].

Regarding the numerous toxic face mask contents, further reappraisal, research and normative acts are imperative.