Human and environmental impacts of nanoparticles: a scoping review of the current literature

1Nanoparticles are small particles ranging from 1 to 100 nm (nm) in size. They are used in a wide range of applications and can be grouped into four types: 1) inorganic-based nanoparticles, 2) carbon-based nanoparticles, 3) organic/polymer nanoparticles, and 4) composite-based nanoparticles. Inorganic-based nanoparticles are made up of different metal and metal oxides. Examples of metal-based inorganic nanoparticles include aluminium, silver, gold, zinc, lead, iron, cadmium, and copper, whereas examples of metal oxide-based inorganic nanoparticles include aluminium oxide, copper oxide, iron oxide, silica, zinc oxide, titanium oxide, and magnesium aluminium oxide. Carbon-based nanoparticles include fullerene, graphene, multi- and single-walled carbon nanotubes, carbon black, and carbon fibres. Organic-based nanoparticles are derived from organic materials without carbon, for example, liposome, dendrimers, cyclodextrin, and micelle, whereas composite nanoparticles are made from combinations of metal oxide-based, metal-based, organic-based, and/or carbon-based nanoparticles.

2In recent years, nanoparticles have gained increasing attention due to their use in consumer products, medicine, soil, and aquatic environments. For example, nanoparticles have been used for textiles, water treatment, environmental remediation, cancer therapy, radiology, and cosmetics. This growing attention and extensive usage of nanoparticles is due to specific novel characteristics exhibited by such particles, which results from their small size and large surface area. These unique qualities, while advantageous, pose certain risks to living organisms.

3The small sizes of nanoparticles give them the ability to permeate physiological barriers of living organisms, causing harmful biological reactions. Nanoparticles are known to enter the human body through the lung, intestinal tract, or skin, and can be toxic to the brain, cause lung inflammation and cardiac problems. In fact, certain nanoparticles have been found to cause permanent cell damage through organ injury and oxidative stress, due to their size and composition. In a study by Magrez et al. to assess the toxic effect of carbon-based nanoparticles on lung cancer cells, the authors reported findings suggesting that carbon-based nanoparticles cause size-dependent cytotoxicity. The level of toxicity of nanoparticles is suggested to be dependent on factors such as composition of the nanoparticle, size, surface functionality, crystallinity, and aggregation. Moreover, the toxicity of a nanoparticle in an individual is dependent on the genetic make-up of that individual, which is determined by the individual's ability to adapt and respond to toxic substances.

4There are growing concerns regarding the toxicologic effects of nanoparticles, and frequent exposure to nanoparticles is regarded as a public health threat. While there is extensive evidence about the benefits of nanoparticles, as well as the potential health and environmental risks associated with its production and use, current understanding of the impact of nanoparticles exposure to human health and the environment is limited. The current review seeks to explore, through a scoping review of the current literature, the effects of nanoparticles on human health and the environment. This review is unique as it adopts a systematic scoping approach to explore the current literature on the health risks posed by the manufacture, distribution, and use of nanoparticles. Published studies in this area have mainly used a narrative literature review approach.

5The objective of this review is to map the distribution of the current literature on the human and environmental impacts of nanotoxicity. Specifically, this scoping review will be guided by the following research questions:What is the relative distribution of the current literature on the human and environmental impact of nanotoxicity?Which exposure pathways and nanoparticles have been researched and which have not?What biomarkers have been used in assessing the human and environmental impact of exposure to nanoparticles?

6What is the relative distribution of the current literature on the human and environmental impact of nanotoxicity?

7Which exposure pathways and nanoparticles have been researched and which have not?

8What biomarkers have been used in assessing the human and environmental impact of exposure to nanoparticles?

9This scoping review was conducted and reported in accordance with the Joanna Briggs Institute Reviewers Manual. The following steps were followed:Defining and aligning the objectives and research questionsDeveloping and aligning the inclusion criteria with the objectives and research questionsDescribing the planned approach to evidence searching and selectionSearching for the evidenceExtracting the evidenceCharting the evidenceSummarising the evidence in relation to the objectives and research questions

10Defining and aligning the objectives and research questions

11Developing and aligning the inclusion criteria with the objectives and research questions

12Describing the planned approach to evidence searching and selection

13Searching for the evidence

14Extracting the evidence

15Charting the evidence

16Summarising the evidence in relation to the objectives and research questions

17The Preferred Reporting of Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used to summarise the screening process. The protocol of this review has been registered with the Open Science Framework.

18The aim of the search strategy was to find both published and unpublished studies that have examined the effect of nanotoxicity on human health and the environment. Search terms consisted of a combination of key terms and concepts in the objective and research questions, using the Boolean operators, 'AND', and 'OR' as follows:

19(nanomaterials OR nanoparticles OR nanostructures) AND (toxicity OR health) AND (“biomarker* of exposure” OR biomarker OR exposure) AND (human OR environment).

20The search was limited to peer-reviewed articles published from the year 2000. This was to enable us to study the current literature (research conducted over the last 2 decades). The search was limited to primary studies published in the English language due to difficulties with language translation.

21Table 1 below presents a list of the databases, grey literature, and search engines that were searched for eligible papers. The reference list of all included papers was also searched for additional papers on the subject matter.

22For the database searches, a master search strategy was first developed using the Medline database, this was then modified for the other databases. The supplementary material file presents the Medline search history. The literature search was conducted between 1st June 2021 and 31st July 2021.

23All search results were imported into an Endnote library to help manage references and to remove duplicate articles. Once duplicates were removed, the search results were exported from Endnote into Covidence (a web-based software platform that streamlines the production of scoping/systematic reviews) for screening. The Covidence software was also useful in identifying and deduplicating articles that could not be identified by Endnote.

24The following criteria were used to identify eligible articles for inclusion in the review.

25Studies that have assessed the human and environmental impacts of nanotoxicity were considered for inclusion in this review. Human participants included children and/or adults of any age, gender, or ethnicity. Studies involving the use of animals as biomarkers for assessing the environmental impact of nanotoxicity were also considered for inclusion.

26Studies that have examined the impacts of nanotoxicity as well as the biomarkers for assessing exposure to nanoparticles were eligible for inclusion in this review. While all types of nanoparticles were considered for inclusion, attention was given to studies involving metallic (oxides, pure metal) and carbonaceous (fullerenes, carbon nanotubes, and graphene) nanoparticles. This is mainly due to these particles being widely produced and used, therefore, they are considered the most relevant for public health.

27Studies from any geographical location aimed at assessing the human and/or environmental impact of nanotoxicity were considered eligible for inclusion. Studies whose full texts were in a language other than English were excluded because there were no available translators.

28We included all original primary research (both quantitative and qualitative), including, but not limited to randomised controlled studies, quasi-experimental studies, surveys, retrospective and prospective cohort studies, case studies, and phenomenological studies.

29The following exclusion criteria were applied to the title and abstract, as well as the full-text review stage:Irrelevant problem/focus: studies that have not examined the human and/or environmental impact of nanotoxicity, or the biomarkers for assessing exposure to nanoparticlesIrrelevant type of study: review reports or studies that did not contain any original research

30Irrelevant problem/focus: studies that have not examined the human and/or environmental impact of nanotoxicity, or the biomarkers for assessing exposure to nanoparticles

31Irrelevant type of study: review reports or studies that did not contain any original research

32We employed a two-step screening process to assess search results for eligible studies. The first level involved screening of the titles and abstracts and was done independently by two reviewers (EK and RF). The next step was carried out independently by three reviewers (EK, RF, and SH) and involved screening of the full-texts of potentially eligible papers. Disagreements between reviewers were resolved through discussions and consensus. Where disagreements persisted, a third reviewer (TP or FVZ) was consulted.

33We developed a standardised data extraction form in the Covidence software for data extraction. The form was designed to collect the following information from included studies: year of publication, aim/objective of study, study design, country, type of nanoparticle, application of the nanoparticle, major exposure route(s), biomarker/model used, how biomarker was obtained, and study outcome(s).

34The developed data extraction form was pilot-tested using 10% of the included articles before beginning the actual data extraction. Data extraction was done by one reviewer (PB, RF, or SH) and verified by another (EK, TP, or FVZ), using the Covidence software.

35The extracted data was first exported into Excel for editing and to check for accuracy. The edited data was then exported from Excel into SPSS (version 26) to aid with data synthesis. Descriptive statistics was used to report included studies by their characteristics and outcome measures, described below.

36Year of publication: studies were grouped based on their year of publication. As stated earlier, this included studies published from the year 2000 to July 2021 (the date of completion of literature searches).Country in which study was conducted: to assess the distribution of the current literature on human and environmental impact of nanotoxicity, the countries in which eligible studies were conducted were classified into six regions based on the World Bank’s classification of countries. This included: East Asia and Pacific, Europe and Central Asia, Latin America and Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa (World Bank Group, 2018).Study design: randomised controlled trial, non-randomised controlled trial, cohort study, experimental study, case control study, longitudinal study, uncontrolled before and after studies.Impact/effect assessed: human health and/or environment

37Year of publication: studies were grouped based on their year of publication. As stated earlier, this included studies published from the year 2000 to July 2021 (the date of completion of literature searches).

38Country in which study was conducted: to assess the distribution of the current literature on human and environmental impact of nanotoxicity, the countries in which eligible studies were conducted were classified into six regions based on the World Bank’s classification of countries. This included: East Asia and Pacific, Europe and Central Asia, Latin America and Caribbean, Middle East and North Africa, North America, South Asia, and Sub-Saharan Africa (World Bank Group, 2018).

39Study design: randomised controlled trial, non-randomised controlled trial, cohort study, experimental study, case control study, longitudinal study, uncontrolled before and after studies.

40Impact/effect assessed: human health and/or environment

41Type of nanoparticle: This was divided into four groups: 1) inorganic-based nanoparticles, 2) carbon-based nanoparticles, 3) organic nanoparticles, and 4) composite-based nanoparticles two groups, metallic (oxides, pure metal) and carbonaceous (fullerenes and carbon nanotubes) particles.Biomarker or model used in assessing human and/or environmental exposure: primary cell or immortalised cell lineEffect/impact on human health and/or the environment

42Type of nanoparticle: This was divided into four groups: 1) inorganic-based nanoparticles, 2) carbon-based nanoparticles, 3) organic nanoparticles, and 4) composite-based nanoparticles two groups, metallic (oxides, pure metal) and carbonaceous (fullerenes and carbon nanotubes) particles.

43Biomarker or model used in assessing human and/or environmental exposure: primary cell or immortalised cell line

44Effect/impact on human health and/or the environment

45A narrative synthesis was then used to further explore findings.

46The database searches resulted in 1553 papers (presented in Fig. 1): Medline (n = 1,381); ScienceDirect (n = 0); Sage Journals Online (n = 50); Campbell Collaboration (n = 0); Cochrane Collaboration (n = 0); Embase (n = 5); Scopus (n = 6); Web of Science (n = 50); CINAHL (n = 61). Google and Google Scholar searches yielded 100 results, and no article was obtained from grey literature searches. Following removal of duplicate articles, the titles and abstracts of 1495 articles were screened to assess their eligibility for inclusion, which resulted in the exclusion of a total of 1246 articles as they did not meet the inclusion criteria. As such, the full texts of 249 articles were assessed for eligibility. Following this stage, a total of 132 articles were excluded for several reasons (see Fig. 1), whereas 117 studies qualified for inclusion in the review.

47The studies included in this review originated from 23 countries across several continents, with the majority of the studies originating from Europe and Central Asia (n = 50). Nevertheless, the United Sates recorded the highest number of publications (n = 30), followed by China, India, and Saudi Arabia recording the same number of publications (n = 8). The lowest number of studies (n = 1 each) originated from Argentina, Czech Republic, Egypt, Mexico, Pakistan, Poland, and Russia. There were no studies recorded from Sub-Saharan Africa. Figure 2 presents a classification of the included studies by region.

48Included studies were published between the year 2006 and 2021, with a high proportion of the articles (95.75%) published from the year 2009. However, the year 2020 recorded the highest number of publications (n = 15; 12.82%), followed by 2016 (n = 14; 11.97%). Table 2 below presents the number of publications per year.

49The majority of the studies used an experimental study design (n = 112, 95.7%), with only 5 (4.3%) studies employing a cross-sectional design. Regarding the type of impact/effect of nanoparticle assessed, a vast majority of the studies assessed impact on human health (n = 109), 5 of the studies assessed effects on the environment, with only 3 studies assessing both human and environmental health impact (Fig. 3).

50Just over 65% (n = 77) of the included studies investigated the human and/or environmental effect of inorganic-based nanoparticles. The inorganic-based nanoparticles that were investigated include, but not limited to, bismuth oxide (Bi2O3), silicon dioxide (SiO2), copper oxide (CuO), zinc oxide (ZnO), titanium dioxide (TiO2), silver (Ag), gold (Au), platinum (Pt), iron oxide (Fe2O3), cerium oxide (CeO2), cobalt oxide (Co3O4), aluminium oxide (Al2O3), molybdenum trioxide (MoO3), magnesium oxide (MgO), nickel oxide (NiO), chromium oxide (Cr2O3), tungsten oxide (WO3), yttrium oxide (Y2O3), and manganese oxide (Mn2O3).

51Thirty-five (29.9%) studies reported on carbon-based nanoparticles (including single and multi-walled carbon nanotubes (SWCNTs/MWCNTs), graphene oxide (GO), and graphene nanoplatelets, GNP). Three studies reported on both inorganic- and carbon-based nanoparticles; one study reported on both inorganic-based and polymer nanoparticles (i.e., Titanium dioxide, terbium-doped gadolinium, and polylactic-co-glycolic acid, PLGA), whereas another study investigated the effect of Poly lactic-co-glycolic acid (a polymer) nanoparticle on the environment.

52The most investigated nanoparticles were ZnO (n = 25), followed by MWCNTs (n = 20), TiO2 (n = 16), CeO (n = 15), SWCNTs and Fe2O3 (n = 14), and SiO2 (n = 12). The least studied nanoparticles include Pt, Au, MgO, MoO3, WO3, Carbon Black (CB), and GNP with only one report available.

53A significant number (n = 90, 76.9%) of the included studies used immortalised cell lines as the biomarker for assessing the human health effect of nanoparticles. Examples of the immortalised cell lines that were used include the human hepatocarcinoma cell line (HepG2), human (alveolar) epithelial A549 cell line with human monocyte-derived dendritic cells (MDDCs) and macrophages (MDMs), Melanoma cells and human foreskin fibroblasts, human airway epithelial (BEAS-2B) cells, human bronchial epithelium (BEAS-2B) cells, human neuroblastoma SHSY5Y cell line, human keratinocyte (HaCaT) cell line, and MCF-7 cell line, which is a human breast cancer cell line with oestrogen, progesterone and glucocorticoid receptors. Immortalised cell lines were mostly purchased/obtained from organisations such as the American Type Culture Collection (ATCC, Manassas, VA, USA).

54Twenty-two studies used primary cells obtained from study participants/volunteers. Examples of the primary cells that were used as biomarkers by included studies are human bone marrow mesenchymal stem cells (hBMMSCs) taken from the iliac crest of human donors, human lymphocytes (blood), and human dermal fibroblasts which were isolated by the outgrowth method using infant foreskins obtained after circumcision. Workplace air samples have also been used to investigate workplace exposures to graphene nanoplatelets. Five studies that reported on the environmental effect of nanoparticles used a variety of biomarkers, including soil samples and soybean seeds, Allium cepa bulbs, zebrafish larvae, seedlings of buckwheat, Nitrosomonas europaea KCTC 12270 bacterium (an ammonia-oxidizing bacterium) and Nitrospira moscoviensis (a nitrite-oxidizing bacterium), as well as aquatic species including Daphnia magna neonates, fish, and Carp (Cyprius carpio). The studies included in this review reported several toxicities associated with the production and application of nanoparticles. The most reported health impact of nanoparticles was found to be decreased cell viability and/or cell death (observed by twenty-nine studies). Twenty-eight studies also noted reactive oxygen species generation as a result of exposure to nanoparticles, especially to CNT (n = 7), ZnO (n = 7), SiO2 (n = 5), and TiO2 (n = 4). The third commonly observed health impact was dose-dependent oxidative stress in the biomarkers (n = 25), particularly, in cases of exposure to SiO2 (n = 5), ZnO (n = 5), Fe3O4 (n = 4), CeO2 (n = 3), and CuO (n = 3). In addition, there were sixteen reports regarding DNA damage after exposure to nanoparticles, mainly for ZnO (n = 4) and MWCNTs (n = 3). Table 3 presents a comprehensive outline of the effects (human health and the environment) reported by each of the included studies. These are further explored in the ensuing section.

55The objective of this scoping review was to ascertain the distribution of the current literature on the human and environmental impacts of nanoparticles. Specifically, in this review, we synthesised evidence regarding the exposure pathways and types of nanoparticles that have been researched and the ones that have not, as well as the biomarkers that have been used in assessing human and environmental impact of exposure to nanoparticles.

56While the majority of studies originated from Europe and Central Asia, the United States of America (USA) alone recorded the highest number of publications. This finding is not surprising, as the USA has continuously fostered the development of nanotechnology through significant investments in research and development in this area. In 2016, the USA was projected to account for almost one-third of total global nanotechnology research funding. Moreover, the USA and the European Union have over the years taken a committed approach towards enhancing the health and safety of nanoparticles. As part of this commitment, annual meetings are held, where researchers discuss topics relating to nano-safety, as well as funding priorities and research needs.

57While there have been some investments in nanotechnology research in African countries (including Egypt and South Africa), a recent publication by the United Nations Economic Commission for Africa (UNECA) indicates that the African continent, relative to other continents, is lagging behind with regards to nanotechnology research. This assertion is consistent with the findings of this review, which found only one study originating from North Africa (Egypt), with no study conducted in Sub-Saharan Africa.

58Over the past two decades, there have been increasing public awareness of nanotechnology and a growing concern about its commercial applications. This has led to rapidly increasing scientific publications in this field, especially from early 2000s. It is, therefore, not surprising that the studies included in this scoping review were published from the year 2006. Indeed, a literature search of nanotechnology publications by Huang et al. revealed over 50,000 publications for the year 2006.

59Although the included studies investigated a wide range of nanoparticles, most of them focused on inorganic-based nanoparticles (e.g., zinc oxide, titanium dioxide, copper oxide, and silica), followed by carbon-based nanoparticles (e.g., carbon-nanotubes, fullerenes, and graphene) (Table 3). This finding is consistent with previous reviews that have reported extensive investigation into the impact of inorganic-based and/or carbon-based nanoparticles. These nanoparticles may have gained attention due to their extensive production and usage. In addition to their use for cancer treatment, inorganic and carbon-based nanoparticles provide significant benefits in photothermal therapy, diagnosis, tissue engineering, imaging contrast agents, and sensing applications. This is due to their unique physical and chemical properties (such as electrical, thermal, structural, mechanical, and optical diversity), which make them stronger, flexible, and more electrically conductible towards several biological entities. The advantages of, for example inorganic-based nanoparticles, including their high reactivity, small size and good capacity have been found to induce adverse harmful effects in both humans and the environment.

60In this review, a number of approaches were used by included studies to assess the toxicity of nanoparticles. However, the majority of the studies applied the in vitro method, perhaps because in vitro studies are time saving and cost-effective. Nonetheless, the in vitro approach has been criticised by researchers (e.g., Bahadar et al.) for producing varying results in different laboratories.

61The included studies used differing methods in assessing cytotoxicity and genotoxicity: cell membrane integrity was assessed with Lactate dehydrogenase (LDH) assays; cell viability was assessed using tetrazolium reduction assays; apoptosis was assessed using immunohistochemistry biomarkers; electron microscopy was used to assess intracellular localisation of nanoparticles; and cell inflammation was estimated using chemokines biomarkers (i.e., IL-8, TNF- α, and IL-6). Compounds such as MTT, XTT, MTS, and WST-1 are used to detect viable cells. However, in the current review, most of the studies employed MTT tetrazolium assays for investigating cell toxicity. Similar findings have been reported by Bahadar et al. who conducted a review on the toxicity of nanoparticles.

62Most of the studies in this review focused on assessing the characteristics of nanoparticles, as well as the impact of nanoparticles on, particularly, human health. In recent years, there have been promising results from the application of nanoparticles to human health, especially in cancer treatment. This is due to the potential of nanoparticles to provide innovative solutions to curb the limitations of traditional treatment methods, including radiotherapy and chemotherapy. Relative to conventional cancer treatment methods, nanoparticle-based drug delivery systems have been shown to have significant advantages in a) drug resistance, b) correctly targeting tumour cells, c) having good pharmacokinetics, and d) reduction of treatment side effects. Notwithstanding these benefits, however, nanoparticles have potential harmful effects, and there are controversies about their safe use in humans. This has undoubtedly led to the rapidly growing number of studies investigating the human health impact of nanoparticles, as was revealed in this review.

63The majority of the studies (n = 90) in this review used immortalised cell lines as the biomarker for assessing human health impact of nanoparticles, and only 22 studies used primary cells as biomarkers. Immortalised cell lines have mostly been used for nano-safety studies because, relative to primary cells, they are generally less expensive, readily accessible, and easier to cultivate. However, the type of cell that is used as biomarker for nano-safety studies is of great importance since this may have an impact on the general outcome of studies. Cancer cell lines, for example, have a disturbed anti-apoptotic balance, and have undergone transformation in metabolism, which impacts their ability to sustain their high rate of proliferation. As such, using these cells may have an impact on study findings. Nonetheless, the use of primary cells in nano-safety studies, are not without limitations. Primary cells have limited lifespan in vitro and can suffer from clonal changes.

64In using immortalised cell lines, several studies) have reported variations in findings regarding nanoparticle-induced effects in cell lines obtained from different species or tissues. For example, Zhang et al. and Mukherjee et al. investigated the effect of exposure to silver nanoparticle on mammalian cells. Zhang et al. used epithelial cells and microphages, and Mukherjee et al. used the human dermal and cervical cell lines as biomarkers. Mukherjee et al. reported nanoparticle-induced cytotoxicity such as elevated levels of oxidative stress, cell membrane damage, and glutathione depletion, whereas Zhang et al. reported effects including changes in antioxidant defence and metallothionein. Moreover, while Ekstrand-Hammarstrom et al. and Kermanizadeh et al. have compared the effect of nanoparticles on immortalised cell lines versus primary cells of the same species and tissues, available data regarding the relative effectiveness of these two types of cells are unclear. Therefore, it is difficult to make explicit conclusions as to which of these two types of cells can be used as a reliable biomarker for nano-safety studies.

65This review has revealed that humans are exposed to nanoparticles through inhalation, ingestion, or dermal route. After their exposure, nanoparticles induce toxic effects such as production of oxidative stress at the exposure site, inflammation, DNA damage, and cell death. For instance, exposure of human neuroblastoma (Sh-sy5y) cells to inorganic nanoparticles, such as titanium dioxide, silica dioxide, and silver are associated with induction of neurotoxicity, membrane damage, reaction oxygen specie formation, decrease in cell viability, and autophagy dysfunction. Similarly, exposure to carbon-based nanoparticles such as single and multi-walled carbon nanotubes reduce cell viability, as well as induce changes in cell structure, cell cycle, and cell-to-cell interactions in human lung epithelial cells (BEAS-2B).

66The findings of this scoping review indicate a gap in the literature regarding environmental impact of nanoparticles. Out of the 117 included studies, only 5 had assessed the environmental impact of exposure to nanoparticles. This significant gap in the scientific literature has been highlighted by authors such as Bundschuh et al.. The growing production and usage of nanoparticles has undoubtedly led to a diversification of emission sources into both the aquatic and soil environment. Nanoparticles enter the environment mainly through three emission scenarios: a) released during production of nano-enabled products and raw materials, b) during application, and c) following disposal of products containing nanoparticles. These emissions occur either indirectly through systems such as landfills or wastewater treatment plants, or directly to the environment. Nonetheless, nanoparticles are mostly released during the application phase and following disposal. Indeed, during production, only about 2% of the production volume is emitted. The studies in this review used biomarkers such as soil samples and soybean seeds, zebrafish larvae, fish, and Daphnia magna neonates. This finding is in line with a previous review by Bundschuh et al., which explored the effects of nanoparticles on the environment.

67In this review, every effort was made to reduce bias. The search strategy was developed by experts of the review team with many years of experience in conducting systematic/scoping reviews. A comprehensive search of multiple relevant databases and other resources was conducted by one review author (EAK) and a rerun of the searches was done after 4 weeks of the initial search. Two authors (EAK and RF or PB and SH) independently screened the search results, and disagreements between reviewers were resolved by FVZ or TP.

68The main limitation of this review is that the searches were limited to studies published in the English language. This may have led to the exclusion of potentially relevant papers published in other languages. Also, searches were restricted to studies published from the year 2000, which may have led to the omission of potentially relevant papers.

69This review has provided an extensive synthesis of the current literature on the effects of nanoparticles on human health and the environment. The review has shown that while nanoparticles are beneficial in a range of applications, they pose significant threats to humans and the environment. Through the use of several biological models and biomarkers (e.g., human bronchial epithelial cells (Beas-2), soil samples, and soybean seeds), the included studies revealed the toxic effects of nanoparticles, with the most investigated nanoparticles being Zinc Oxide, MWCNTs, Titanium Dioxide, Cerium Oxide, SWCNTs, Ferric Oxide, and Silicon Dioxide. The main health impacts of nanoparticles identified in this review are decreased cell viability, cell death, reactive oxygen species generation, production of oxidative stress (dose-dependent), DNA damage, apoptosis, and induction of inflammatory responses.

70This review has revealed a significant gap in the scientific literature regarding environmental impact of nanoparticles of all types. Future studies should be directed at investigating the impact of the various types of nanoparticles on the aquatic, terrestrial, and soil environment. The findings from this review have also shown limited data regarding the relative effectiveness of immortalised cell lines and primary cells as biomarkers in nano-safety studies. Future research should focus on evaluating the effectiveness of these two types of cells, in order to determine the cell that can be used as a reliable biomarker for nano-safety studies. There is also the need for future studies in this area to focus on exploring the toxic effects of Platinum, Gold, Magnesium Oxide, Molybdenum Trioxide, Tungsten trioxide, and Carbon Black nanoparticles, as findings from this review has shown that these nanoparticles are least researched. The findings of this review will be useful to policy makers and stakeholders in assessing the potential effects of nanoparticles.