Exposure Route of TiO2 NPs from Industrial Applications to Wastewater Treatment and Their Impacts on the Agro-Environment

The tremendous increase in the production and consumption of titanium dioxide (TiO2) nanoparticles (NPs) in numerous industrial products and applications has augmented the need to understand their role in wastewater treatment technologies. Likewise, the deleterious effects of wastewater on the environment and natural resources have compelled researchers to find out most suitable, economical and environment friendly approaches for its treatment. In this context, the use of TiO2 NPs as the representative of photocatalytic technology for industrial wastewater treatment is coming to the horizon. For centuries, the use of industrial wastewater to feed agriculture land has been a common practice across the globe and the sewage sludge generated from wastewater treatment plants is also used as fertilizer in agricultural soils. Therefore, it is necessary to be aware of possible exposure pathways of these NPs, especially in the perspective of wastewater treatment and their impacts on the agro-environment. This review highlights the potential exposure route of TiO2 NPs from industrial applications to wastewater treatment and its impacts on the agro-environment. Key elements of the review present the recent developments of TiO2 NPs in two main sectors including wastewater treatment and the agro-environment along with their potential exposure pathways. Furthermore, the direct exposure routes of these NPs from production to end-user consumption until their end phase needs to be studied in detail and optimization of their suitable applications and controlled use to ensure environmental safety.


Introduction
Nanotechnology has touched every field by its scientific novelties. Although the use of nanotechnology is at the early stage, it appears to have significant effects in different areas. It offers great potential for the use of nanomaterials (NMs) in various fields related to all public and industrial sectors, including material, energy, agriculture, healthcare, communication, and information technologies. NMs are the materials that have at least one dimension on the nanoscale [1]. Titanium dioxide with formula TiO 2 is the most important binary metal oxide material which exists in three naturally occurring solid phases; anatase (3.2 eV), rutile (3.0 eV), and brookite (3.2 eV) [2]. Anatase is mostly used in photocatalysis and recognized as a major phase of commercial TiO 2 . Degussa P25 is widely used commercial TiO 2 nanoparticles (NPs) with an anatase to rutile phase ratio of 4:1. It has always been a

Wastewater Treatments
With the onset of industrialization, there has been a steady increase in the types and amount of pollutants released in the environment. These environmental problems have garnered much attention on the global scale, especially water scarcity. Global water scarcity is a temporal and graphical mismatch between freshwater resources and the world's water demand. The increasing world population and urban industrialization have made water scarcity more alarming as shown in Figure 2, predicting the gap between supply (4200 billion m 3 ) and demand (6900 billion m 3 ) of freshwater in 2030. A major proportion of this water is used for the agriculture sector and then for the industrial sector. With a growing world population, an ever-increasing demand for food production and potable water is questionable. The agriculture sector requires a surplus amount of water for irrigation. To avoid water scarcity issues, the reuse of wastewater is tremendously increasing across the planet.

Wastewater Treatments
With the onset of industrialization, there has been a steady increase in the types and amount of pollutants released in the environment. These environmental problems have garnered much attention on the global scale, especially water scarcity. Global water scarcity is a temporal and graphical mismatch between freshwater resources and the world's water demand. The increasing world population and urban industrialization have made water scarcity more alarming as shown in Figure 2, predicting the gap between supply (4200 billion m 3 ) and demand (6900 billion m 3 ) of freshwater in 2030. A major proportion of this water is used for the agriculture sector and then for the industrial sector. Nanomaterials 2020, 10, x 3 of 26 an overview of their possible exposure routes. As nanotechnology is still in its infancy, so it is timely to consider the potential future problems it could cause before large amounts of NMs/products reach the market, and inevitably reach the environment. In this way, we may prevent undesirable largescale effects through proactive approaches.

Wastewater Treatments
With the onset of industrialization, there has been a steady increase in the types and amount of pollutants released in the environment. These environmental problems have garnered much attention on the global scale, especially water scarcity. Global water scarcity is a temporal and graphical mismatch between freshwater resources and the world's water demand. The increasing world population and urban industrialization have made water scarcity more alarming as shown in Figure 2, predicting the gap between supply (4200 billion m 3 ) and demand (6900 billion m 3 ) of freshwater in 2030. A major proportion of this water is used for the agriculture sector and then for the industrial sector. With a growing world population, an ever-increasing demand for food production and potable water is questionable. The agriculture sector requires a surplus amount of water for irrigation. To avoid water scarcity issues, the reuse of wastewater is tremendously increasing across the planet. With a growing world population, an ever-increasing demand for food production and potable water is questionable. The agriculture sector requires a surplus amount of water for irrigation. To avoid water scarcity issues, the reuse of wastewater is tremendously increasing across the planet. Reusing wastewater is a sustainable strategy to manage natural water resources [26]. However, the use of untreated wastewater for irrigation is a usual practice in developing countries causing serious threats to the ecosystem as well as human health. Specifically, carcinogenic pollutants pose a solemn threat to agricultural land, irrigated with industrial effluent without any treatment [27].
The whole world stands as a witness to unintended repercussions caused by rapid industrialization. The wastewater generated from industrial sectors has pronounced effects on humans as well as landmass fertility. Some industrial estates have operational wastewater treatment plants but unfortunately, they cannot handle a large proportion of industrial effluent. To meet the international standards of wastewater discharge, suitable technologies are required for wastewater treatment before discharging Nanomaterials 2020, 10, 1469 4 of 22 to streams. It could help to reduce the burden on freshwater resources by reusing treated water in various industrial processes. Due to the widely used application of nanotechnology, challenges, and opportunities of using engineered nanomaterials (ENMs) in wastewater treatment is a matter of endless concern. Based on the wastewater standards, a technique using TiO 2 NPs for resilient pollutants in the context of wastewater treatment has become popular in recent years. Up to date, TiO 2 NPs have drawn attention over other photocatalysts in every field of life. Over the last few decades, TiO 2 NPs with high photocatalytic efficacy has been tested to reduce the pollution load from various industrial units. The conventional wastewater treatment methods mostly come up with high costs as well as lower efficiencies. However, the advantages of the use of TiO 2 NPs (non-toxic, inexpensive, stable, and reusable NPs) appeared as a promising strategy to save the environment from pollution.

Slurry-Based Titanium Dioxide (TiO 2 ) System
To date, a widely used photocatalyst in wastewater treatment is Degussa-P25, a trademark used for commercial TiO 2 NPs. Very fine NPs of P25 TiO 2 have been used in the form of slurry as reference material for comparison of photocatalytic degradation under various conditions. This is because in slurry form, these commercial NPs are always linked with volumetric production of reactive oxygen species (ROS) relative to active surface sites. TiO 2 NPs have also played their role in the treatment of high strength industrial effluent (containing toxic organic and chlorinated compounds) generating from paper and pulp industries. In the pulp industry, the biodegradability index of effluent is 0.02-0.07 during bleaching of pulp which requires further treatment of the biological process for complete removal of these persistent pollutants [28]. Later in a study, where wastewater treatment was carried out using TiO 2 NPs, the biodegradability index increased from 0.16 to 0.35 indicating the use of TiO 2 NPs as an efficient pretreatment process before biological treatment step [29]. Some of the recent applications of TiO 2 NPs in the form of a slurry, for wastewater treatment, are listed in Table 1. 100% degradation in 120 min [39] Nanomaterials 2020, 10, 1469 5 of 22

TiO 2 -Based Photocatalytic Reactors
One of the essential aspects after the use of slurry-based TiO 2 NPs is regeneration, which is an important concern for the case of economically viable water-treatment technology. The regeneration capability of nanomaterials might be reflected as an additional benefit for their attractiveness in water-treatment technologies. Several techniques have been used to resolve the problem associated with the additional cost of separating NPs from water including immobilization of NMs on adequate substrates and the use of different separation methods. Regeneration of NPs can be achieved efficiently using various photocatalytic reactors. Photocatalytic reactors are classified into two main configurations based on the deployed state of TiO 2 NPs: (i) use of NPs in form of suspension and (ii) immobilization of NPs on inert carrier [40]. Downstream separation is required in the first type of configurations as compared to the other one which is a continuous operation. The various types of photoreactors, catalyst employed, and their mode of application are described in Table 2.

TiO 2 -Based Electrospun Nanofibers
Nowadays, TiO 2 assisted photoreactors have become unfavorable, owing to the proper configuration and artificial light source which is associated with surplus use of electric power as well as treatment costs. The limitations associated with the use of TiO 2 NPs in conventional ways paved a path for the synthesis of TiO 2 -based nanofibers (a one-dimensional form of nanomaterial) by electrospinning. One dimensional nanofibers are superior to NPs owing to intriguing characteristics such as; excellent charge carrier mobility, larger surface area, electrode availability to hole-transporting Nanomaterials 2020, 10, 1469 6 of 22 materials due to pores, improved charge collection as well as transport, and capability to assemble as free stand-alone membrane [51]. They can be synthesized in the form of thin mats and films with a fixed substrate with no need to recover the NPs after treatment.
With the entry of nanotechnology in every field of science, functional NPs can be easily immobilized/impregnated into polymer matrix for avoiding the costly downstream separation step. Furthermore, it also offers an opportunity to fetch priority contaminants that come close to the photocatalytic active sites for efficient utilization of short-lived reactive oxygen species (ROS), commonly known as "bait-hook and destroy strategy" [52]. Polymeric nanofibers can serve as a competent carrier of photocatalytic NPs for efficient industrial wastewater treatment. Photocatalytic degradation of organic contaminants using nanofibers has garnered much attention in recent years.
In the past few decades, several researchers have been devoted to the fabrication and characterization of electrospun TiO 2 nanofibers where the precursor solution (polymeric solution) contains amorphous TiO 2 followed by calcination at 500 • C. After calcination, obtained TiO 2 nanofibers are transformed into crystallized forms (rutile and anatase) for efficient photocatalytic activity. TiO 2 nanofibers were also synthesized using titanium-tetraisopropoxide (TTIP) and tetrabutyl titanate (Ti(OBu) 4 ) as TiO 2 precursors [53,54]. The commercial-grade TiO 2 NPs Degussa (P25) has been used directly with a polymer blend for the fabrication of TiO 2 nanofibers which did not require a calcination step afterward [55]. TiO 2 NPs can easily be immobilized/supported on polymer nanofibers (either directly in polymer solution or decorated on the surface of nanofibers) with the advantage of efficient recovery after complete mineralization of pollutants [56,57]. Some of the studies on industrial wastewater treatment using TiO 2 nanofibers are summarized in Table 3. Heterogeneous photocatalytic degradation using TiO 2 NPs has gained popularity as an effective alternative environment-friendly water treatment approach for a variety of water pollutants including organic and inorganic impurities in industrial effluent. Besides the tremendous use of TiO 2 NPs in wastewater treatment, the inhibitory and biocidal effects of these NPs have been well known. In this context, they have exhibited an excellent broad-spectrum antibacterial activity against various microorganisms especially the pathogenic bacteria [62]. Before discharging industrial effluent into the agro-environment, TiO 2 NPs-based treatment technique can be used that could help to completely mineralize water contaminants and eradicate the major concerns of the industrial wastewater treatment. Subsequently, the use of TiO 2 NPs is highly anticipated for future studies owing to their effective photocatalytic property, and photo-stability. According to a modeling approach, among the ENMs released from wastewater treatment plants; the concentrations of TiO 2 NPs in biosolids constitute about 263-367 mg kg −1 , 273-342 mg kg −1 , and 70-120 mg kg −1 in London, New York City, and Shanghai [63]. The biosolids produced during wastewater treatment are utilized as fertilizers in agriculture [64]. The application of biosolids to agricultural land leads to an increase in the release of TiO 2 NPs in the soil [65]. In this context, the potential impacts, fate, and behavior of these NPs need to be investigated in the agro-environment.

Impacts of TiO 2 Nanoparticles (NPs) in the Agro-Environment
In agro-environment, soil is the main and complex matrix in which analyzing the fate of TiO 2 NPs is a challenging task. Furthermore, the impacts of TiO 2 NPs are difficult to measure in the soil due to the high geogenic background of Ti (≈0.6% of the terrestrial crust). Up until now, modeling studies had helped to estimate the approximate amount of TiO 2 NPs that is accumulating in the environment. According to recent forecasts, TiO 2 NPs sludge treated soils (with 45,000 tons) were observed to be the largest sink for NPs release among different environmental compartments [16]. The crop plants served as an entry route for NPs' uptake into the food chain. Presently, there are limited data available about these NPs interactions within the soil matrix. As nanotechnology is emerging in the field of agriculture sector in terms of growing global food production, nutritional contents, quality, food safety, and security [66]. Besides all these aspects, there are several other applications of NPs in agro-environments as shown in Figure 3, such as food processing and production, nano-fertilizer, nano-pesticides, etc. but the important concern arises here is the fate of these NPs.  Scientists have investigated the effects of TiO2 NPs on the soil-plant continuum and have observed diverse impacts based on different characteristics of NPs, plant species, experimental conditions, and exposure period. For example, Figure 4, shows the TiO2 NPs effects on plants with respect to different stages, concentration range, and exposure time. In a recent study, experiments were conducted on growth-promoting rhizobacteria (PGPR) inoculation with and without TiO2 NPs in peat soil under the three stress situations. TiO2 NPs were reported to enhance the performance of growth-promoting rhizobacteria which further promotes the solubilization of insoluble phosphates [67]. A grassland soil was treated with TiO2 NPs at the rate of 0, 500, 1000, and 2000 mg kg −1 of soil. These NPs were observed to negatively affect the soil bacterial communities after 60 days of exposure [68]. TiO2 NPs effects on several bacterial taxa were also studied using incubated soil microcosms having concentrations range of TiO2 NPs 0, 0.5, 1.0, and 2.0 mg g −1 soil. Of the identified taxa that exist in all samples, 9 taxa were found to be positively correlated with TiO2 NPs, 25 taxa were Scientists have investigated the effects of TiO 2 NPs on the soil-plant continuum and have observed diverse impacts based on different characteristics of NPs, plant species, experimental conditions, and exposure period. For example, Figure 4, shows the TiO 2 NPs effects on plants with respect to different stages, concentration range, and exposure time. In a recent study, experiments were conducted on growth-promoting rhizobacteria (PGPR) inoculation with and without TiO 2 NPs in peat soil under the three stress situations. TiO 2 NPs were reported to enhance the performance of growth-promoting rhizobacteria which further promotes the solubilization of insoluble phosphates [67]. A grassland soil was treated with TiO 2 NPs at the rate of 0, 500, 1000, and 2000 mg kg −1 of soil. These NPs were observed to negatively affect the soil bacterial communities after 60 days of exposure [68]. TiO 2 NPs effects on several bacterial taxa were also studied using incubated soil microcosms having concentrations range of TiO 2 NPs 0, 0.5, 1.0, and 2.0 mg g −1 soil. Of the identified taxa that exist in all samples, 9 taxa were found to be positively correlated with TiO 2 NPs, 25 taxa were negatively correlated whereas 135 taxa were not affected by TiO 2 NPs [69]. In another study, TiO 2 NPs effects were investigated at concentrations ranging from 0.05 to 500 mg kg −1 dry soil on different bacterial communities. The abundance of ammonia-oxidizing archaea was reported to decrease by 40% in response to TiO 2 NPs whereas Nitrospira was not affected at all. Furthermore, the abundance of ammonia-oxidizing bacteria and Nitrobacter were also reported to reduce due to TiO 2 NPs treatments [70].
1 Figure 4. Effects of TiO 2 NPs on plants with respect to different stages, concentration range, and exposure time. (a) represents the effects of TiO 2 NPs on germination % of fennel seeds after short term exposure in a petri dish, the lowercase letters show the level of significance such as 'a' represent significant increase in germination percentage at Nano 60 treatment compared to control group. Adapted with permission from [71], published by ELSEVIER, 2013, (b) shows the effects of TiO 2 NPs on plant length after short-term exposure in soil Adapted with permission from [72], published by Society for the Advancement of Agricultural Sciences Pakistan, 2015, (c) shows the effects of these NPs on lettuce plants after long term exposure of 90 days in soil, Adapted with permission from [73], published by American Chemical Society, 2015.
TiO 2 NPs (0, 5, 20, 40, 60, and 80 mg/kg) were used to study phytotoxicity and stimulatory impacts on fennel after 14 days of exposure. The mean germination percentage was increased by 76% at 60 mg L −1 , while the mean germination time was decreased by 31% at 40 mg L −1 [71]. Similarly, in another study, plant shoot-root length was increased by 49% and 62%, respectively at 100 mg kg −1 of NPs treatment in lettuce after 14 days exposure in soil medium [72]. Another study was performed using TiO 2 NPs treatments (0, 50-250 mg kg −1 ) in soil medium for a period of 90 days. The total dry biomass was observed to increase 1.4-fold and phyto-available phosphorus (P) in soil by 2.2-fold, respectively [73]. Table 4 enlists the recent studies conducted for the investigation of TiO 2 NPs effects on different plants. The germination of cabbage significantly increased. In cucumber and onion, significant root elongation was observed.
[85] Based on the characteristics of size and shape, TiO 2 NPs can induce different levels of toxicity in terms of seed vigor index, aberration index and oxidative stress in plants. [96] Studies have shown the positive effects of TiO 2 NPs on the physiology of red bean plants, leaving no negative biochemical impacts in plants [97]. Low concentrations of TiO 2 NPs were reported with their positive effects on chickpea cells especially when they were exposed to cold stress. However, TiO 2 NPs especially at 5 mg kg −1 concentration level was reported to reduce cold-induced damages in sensitive and resistant chickpea genotypes. Such domino effects raised key questions regarding the potential mechanisms. It was supposed that the activation of the defensive mechanisms in chickpea seedlings after the absorption of TiO 2 NPs support the plants in cold stress. These results are quite interesting for further practice in cases of environmentally stressed conditions. These new findings could pave the way to increase the use of NPs especially to improve the cold stress tolerance in major crops [98]. Furthermore, in future studies, TiO 2 NPs application in combination with fertilizers could be an effective option to search out a way for better application of these agrochemicals in a sustainable way. We further need to explore the potential of nanotechnology by upscaling the present studies by investigating the effects of NPs at different stages in the life cycle of plant species and understand their mechanism of environmental exposure.

Understanding the Mechanism of Environmental Exposure of NPs
The increased use of NPs in different fields has raised a worldwide concern regarding their release and impact on human health and the environment. For this reason, in the recent decade, toxicological effects of NPs on human health and the environment also gained attention. The potential for exposure to these NPs begins with the production of these materials until their associated life cycle completion and release into the air, soil, and water [99] as shown in Figure 5.
TiO2 NPs especially at 5 mg kg −1 concentration level was reported to reduce cold-induced damages in sensitive and resistant chickpea genotypes. Such domino effects raised key questions regarding the potential mechanisms. It was supposed that the activation of the defensive mechanisms in chickpea seedlings after the absorption of TiO2 NPs support the plants in cold stress. These results are quite interesting for further practice in cases of environmentally stressed conditions. These new findings could pave the way to increase the use of NPs especially to improve the cold stress tolerance in major crops [98]. Furthermore, in future studies, TiO2 NPs application in combination with fertilizers could be an effective option to search out a way for better application of these agrochemicals in a sustainable way. We further need to explore the potential of nanotechnology by upscaling the present studies by investigating the effects of NPs at different stages in the life cycle of plant species and understand their mechanism of environmental exposure.

Understanding the Mechanism of Environmental Exposure of NPs
The increased use of NPs in different fields has raised a worldwide concern regarding their release and impact on human health and the environment. For this reason, in the recent decade, toxicological effects of NPs on human health and the environment also gained attention. The potential for exposure to these NPs begins with the production of these materials until their associated life cycle completion and release into the air, soil, and water [99] as shown in Figure 5. Among possible exposure routes of TiO2 NPs, there are three major exposure routes including occupational exposure, consumer exposure and environmental exposure.

Occupational Exposure via Industries
According to a Swiss survey report, the usage of TiO2 NPs increased in amounts of approximately more than 1000 kg per company annually [100]. Occupational exposure to NPs may occur through dermal contact and dust inhalation at workplaces or industries; where these NPs are used or manufactured. The National Institute for Occupational Safety and Health (NIOSH) reported that the workers over the industrial units are at high risk of exposure to NPs due to unintentional hand-to-mouth touch [101]. Usually, the materials at microscale levels are considered to be harmless, however recent studies suggested that frequent inhalation of NPs could be dangerous [102]. The impact of NPs on humans has been investigated using various rodent models through various exposure routes and conditions. For example, inhalation of TiO2 NPs was reported to cause lung damage in mice due to inflammation, pulmonary fibrosis, and initiation of lung tumors [103]. In the human body, the liver is the most susceptible organ targeted by NPs [104]. TiO2 NPs have been Among possible exposure routes of TiO 2 NPs, there are three major exposure routes including occupational exposure, consumer exposure and environmental exposure.

Occupational Exposure via Industries
According to a Swiss survey report, the usage of TiO 2 NPs increased in amounts of approximately more than 1000 kg per company annually [100]. Occupational exposure to NPs may occur through dermal contact and dust inhalation at workplaces or industries; where these NPs are used or manufactured. The National Institute for Occupational Safety and Health (NIOSH) reported that the workers over the industrial units are at high risk of exposure to NPs due to unintentional hand-to-mouth touch [101]. Usually, the materials at microscale levels are considered to be harmless, however recent studies suggested that frequent inhalation of NPs could be dangerous [102]. The impact of NPs on humans has been investigated using various rodent models through various exposure routes and conditions. For example, inhalation of TiO 2 NPs was reported to cause lung damage in mice due to inflammation, pulmonary fibrosis, and initiation of lung tumors [103]. In the human body, the liver is the most susceptible organ targeted by NPs [104]. TiO 2 NPs have been reported to induce toxic effects on the liver affecting its functions [105]. In China, a study regarding occupational exposure to TiO 2 NPs was conducted in a packaging workshop. Workers were selected on the basis of age (20 years or more) and employment (at least one year). Cardiopulmonary effects through possible biomarkers and physical experiments were conducted to reveal TiO 2 NPs exposure. A pattern having time (dose)-response was observed in exposed workers, suggesting that long-term exposure to TiO 2 NPs cause serious threats through occupational exposure [106].
TiO 2 NPs have the ability to generate reactive oxidative species and oxidative stress even at lower NPs concentration. In a recent study, an acute exposure of TiO 2 NPs to human lungs resulted in substantial modifications in gene expression along with long-term effects on progeny cells even after multiple generations via transcriptional changes [107]. Similarly, genotoxicity and cytotoxicity of TiO 2 NPs (having different shapes) in bronchial epithelial cells were studied. Genotoxicity was determined on the basis of cellular-uptake as well as the ability of NPs to aggregate, whereas lesser cytotoxicity of NPs was observed to be significantly influenced by irradiation time and the shape of TiO 2 NPs [108]. Another study reported that in case of acute exposure conditions, TiO 2 NPs did not cause cytotoxicity in human alveolar A549 cells [109], but there is a lack of information related to the magnitude of NPs released and exposed to organisms, which can be better interpreted in future studies [110].

Consumer Exposure
Consumer products available in markets including i.e., cosmetics, beverages and food, appliances, health and fitness, gardens and homes, etc., contain NPs and are expected to have direct consumer exposure [111]. TiO 2 NPs having different sizes were used to investigate their effects on a human keratinocyte cell line (HaCaT) and reported that all the tested types of TiO 2 NPs increased the superoxide production, and apoptosis in a dose-dependent manner [112]. Another study reported that TiO 2 NPs at the half maximal effective concentration (EC 50 ) ranges from 10 −4 to 10 −5 mol L −1 induced cytotoxic effects on HaCaT cells [113]. Recently, in another study the authors investigated the TiO 2 NPs in combination with the ingredients from modern lifestyle products like cosmetics, skin-care products, and Henna tattoos. TiO 2 NPs alone were not reported to induce any damage in cell viability upon application of 100 µg mL −1 up to 24 h [114]. Recently a social survey was conducted in USA regarding the individual exposure to TiO 2 NPs used in personal care products. From these results, toothpaste and sunscreen were considered as the major source of dermal exposure depending on their usage pattern and amount of TiO 2 NPs in these products. It is estimated that a person can exposed to 2.8 to 21.4 mg TiO 2 per day through dermal exposure. Per day oral exposure is estimated from 0.15 to 3.9 mg TiO 2 via toothpaste [115].
Over the course of history, TiO 2 has been considered to pose low toxicity both for humans and the environment. Since ancient times, it has been the most widely used material as a coloring agent [116]. However, in 2018 the French national assembly revised the guidelines with the amendment to ban the use, import, and sale of nano-scale TiO 2 as a food additive in any kind of food by 2020 [117]. Because of the fact that limited information is available on the safe usage of these NPs in consumer products, their potential hazards for their users need to be assessed. There are several factors involved in the assessment of the consumer exposure to these NPs that constrained due to the limited access of information; (a) list of commercial products containing NPs, (b) amount of NPs used in such products, and (c) behavior of the consumer towards them [118]. Most of the commercial products containing these NPs do not enlist this information on their ingredient lists. Moreover, the number of consumers of such products and industry-derived data are kept hidden from all stakeholders including the governments, public, and private sectors which makes the consumer exposure situation more alarming [119].

Environmental Exposure
The term environmental exposure is based on the extent of NPs taken up by biota, either in metabolized or degraded form, and their rates of excretion. This is where the least amount of data is available, and particularly data that consider the modifying effects of the environments where organisms live while they are exposed to NPs. In the product life cycle starting from manufacturing until consumer usage, each stage for NPs could result in their release into the environment. The tendency for physicochemical properties varies as these NPs move from different environmental compartments such as water, soil, and air. Understanding the importance, their fate, transport, and transformation need to be emphasized. However, little is known about what governs these processes for NPs in general. So, we tried to summarize what is known about the environmental behavior of these NPs which is as follows.
Upon release into the environment, NPs usually act in one or more of the following ways: (1) stay suspended as an individual particle; (2) form agglomerates (and potentially sorbed onto some surface or experience facilitated transport); (3) dissolve in a liquid; and (4) transform chemically by reacting with organic matter or other natural particles. The extent to which NPs' behavior follows any of the aforementioned patterns depends on their surrounding environment, and several biological, chemical, and physical processes. Nanosize TiO 2 made them extremely mobile in the soil system, but their larger surface areas (compared to their size) enhance their tendency to sorb onto the soil, which restricts their movement or makes them immobile. For example, TiO 2 NPs considered as having low solubility, remained in the soil for long periods which might create potential environmental risks for deeper soil layers. Small-sized TiO 2 NPs (20 nm) were able to penetrate the plant cell wall and have been reported to reduce wheat's biomass [120]. Plants offered a potential route for the transmission of NPs to the environment and ultimately paved the way for their bioaccumulation into the food chain. Different studies have determined the response of NPs to plants growth and their possible mechanism. Plant cell walls do not allow the smooth entrance of any external agent as well as NPs into the plant cells. The screening property of the cell wall depends on the diameter of pores present in the cell wall that mostly ranges from 5 to 20 nm [121]. Therefore, NPs and their accumulates within the stated range could simply cross the cell membrane and transfer to the plant's aerial parts. NPs might generate various morphological changes in the root structures, which increases pore sizes or generates new pores in the cell wall, which further enhances the uptake of NPs and their aggregates [122]. A recent study reported that TiO 2 NPs from the environment undergoes the size selection process during the foliar and root uptake mechanism in Dittrichia viscosa wild plants. The study reported that the TiO 2 NPs having a size less than 50 nm were accumulated in plant's leaves (53%), stems (90%), and roots (88.5%) [123]. In another study, TiO 2 NPs of size 4 and 150 nm were reported to be internalized through foliar uptake in lettuce plant leaves via stomata [124]. Another report stated that NPs accumulated on photosynthetic surface-induced foliar heating that can alter the gaseous exchange due to stomatal disturbance. Consequently, altering the different molecular and physiological functions of plants [125]. Therefore, the influence and translocation of different NPs within plants need to be investigated further to understand the whole mechanism and their behavior in plants [126]. As the human food chain instigated with plants, so it is critically important to understand how plants respond differently to these NPs which are frequently concentrating in our ecosystem through various routes.
Aquatic systems are usually considered as the main recipient of NPs. As in the terrestrial environment, transformation in the aquatic system includes several, physical (aggregation/agglomeration and deposition), biological (interaction with macromolecules including polysaccharides, proteins, and surfactants) and chemical processes (dissolution, sorption, and redox reactions). Aside from the intrinsic properties, transformation, and toxicity of TiO 2 NPs also rely on various environmental factors such as temperature, pH, light, and presence of natural organic matter [127]. In natural aquatic systems, many organisms are sensitive to NPs' exposure and exhibit pronounced toxic effects during their transport and transformation. This might be because NPs have surface coatings that help to improve their solubility and suspension and made them more mobile than the other large-sized particles. TiO 2 NPs have been reported to induce a significant decrease in growth parameters of an aquatic plant Spirodela polyrrhiza, whereas the increased concentration of TiO 2 NPs was observed to increase the photosynthetic pigmentation and the peroxidase activity [128]. Overall, the negative effects of nanoparticles must not be ignored, especially on human health and the environment, and must be studied in detail to make their use controlled and safe. Table 5 below briefly enlists some studies of TiO 2 NPs on terrestrial and aquatic organisms. The mortality rate was observed to be 0, 3.3, and 10% in response to 25, 125, and 250/mg L −1 of TiO 2 NPs, respectively. Mortality rate of 5, 20, 20, 53, and 57% was observed in response to 0, 500, 1000, 1500, and 2000 mg L −1 TiO 2 NPs, respectively. [138]

Conclusions and Future Perspectives
This review briefly discussed the recent developments of TiO 2 NPs in wastewater treatment technologies and the agro-environment. The potential exposure pathways of these NPs and their associated environmental risks were also highlighted. In fact, the use of TiO 2 NPs will further increase for promising applications in the near future. In wastewater treatment technologies, downstream separation of these NPs after photocatalytic degradation is still a matter of concern which can be minimized by using TiO 2 in photocatalytic reactors either in slurry form or immobilized on a solid substrate. Immobilization might result in loss of potential active sites which could be minimized by adding NMs into the polymeric substrate. The polymer can provide firm anchoring to TiO 2 NPs, however, there is still a chance of NPs leaching into the treated water and reaching the agricultural soils via irrigation. Since the agriculture sector is the backbone of the economy in most countries, studies based on crop improvement using TiO 2 NPs could help to overcome the burden of nutrient deficit in soils providing better crop yield. Apart from the potential benefits of TiO 2 NPs there are also some limitations that we could not ignore. At this stage, we could not claim with surety that the use of NPs is fully safe for human health and the environment or if it is harmful. Risks associated with chronic exposure of these NPs, interaction with flora and fauna, and their possible bioaccumulation effects have not been fully considered yet. The other limitations include the lack of information about a safe range of NPs' concentration, scalability of research and development for prototypes, industrial production, and public concern about health and safety issues. Detailed investigations are necessarily required to resolve these concerns and provide conclusive statements. We need to optimize the useful concentration levels of TiO 2 NPs for various applications and limit their usage for environmental safety.