**6. Toxicological aspects of NPs**

According to Higashisaka et al. [213], NPs with diameters ≤100 nm are presently been used in various applications, including food production (e.g., to improve texture). An orally ingested NP can cross the gastrointestinal barrier, absorbed into the blood, and alter normal physiological functions, thus causing adverse health is to consumer(s) [213, 214]. Ezhkov and colleagues reported acute catarrhal inflammation on esophagus, stomach, and duodenum of mice fed with sapropel-NPs at a dose of 1.8 g/kg. However, 0.3 g/kg and 1.5 g/kg dose did not manifest any toxic effects [165].

A positive correlation was established between residues of Ag-NPs in rat organs and the NP suspension applied. NPs migrated from the luminal side to the intestinal epithelial cells via endocytosis or transcytosis, which are accumulated in the mentioned organs. However, all treated rats were able to excrete the NPs from most organs except the brain and testes [214–217]. Cellular uptake of NPs is similar to mechanism of the antimicrobial activity as its also depends on size, surface charge, and dispersion or aggregation state [218, 219]. Rhodamine B (RhB) labeled carboxymethyl chitosan grafted NPs (RhBCMCNP) and chitosan hydrochloride grafted NPs (RhB-CHNP) bearing positive or negative charges used as model chitosan to elucidate the effects of particle size and surface charge on the cellular uptake of NPs revealed that the surface charges were attracted to the macrophages, and could be attributed to the electrostatic interactions between particles and phagocytic cells. Besides, different cell lines, irrespective particle size, and surface charge difference influence the uptake of NPs [219]. Kim et al. [220] detected traces of Ag-NPs in blood, liver and other organs after they orally fed rats at a dose of 30, 125, or 500 mg/kg BW/day. A significant (p < 0.05)

*Mycotoxins and Food Safety*

▬COOH, and ▬NH2 improved the fungicidal activity (inhibition in spore elongation and germination) than the unmodified CNTs. It is hypothesized that modified CNTs formed a stable dispersions, which favoured interaction with spores, as a results enhanced antifungal activity. The authors observed a reduction in *F*. *graminearum* spore from 68.5, 54.5, 28.3, 27.4, and 29.5 μm, when 500 μg/mL MWCNTs (control), MWCNTs-COOH, MWCNTs-OH, and MWCNTs-NH2 were applied, respectively. Moreover, previous works [203, 204] documented that biological activity of nanotubes improved upon addition of functionalized aliphatic amide (covalent) and polyethylene glycol (PEG) and/or polyoxyethylene(40)nonylphenyl ether (IGPAL) (non-covalent) chemical groups [205]. Zare-Zardini et al. [206] conducted a covalent functionalization of MWCNTs with lysine and arginine under radiation. The modified MWCNTs exhibited potent biocidal activity against all test fungi (A*. niger*, *A. fumigatus, C. albicans, P. chrysogenum, S. cerevisiae, F. culmorum, Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum, and P. lilacinum*) compared unmodified MWCNTs. Surprisingly, the fungicidal activity of MWCNTs-arginine against all the test fungi was slightly higher than MWCNTs-lysine. The authors hypothesized that the positive charge on arginine might have enhanced the binding of NPs on the fungal membrane and altered the genetic makeup (DNA). Thus, lysine and arginine could be utilized to improve the fungicidal activity of CTNs. Recently, Katerine et al. [207] reported the fungicidal activity of cotton fabric silica-silver carbon-based hybrid NPs against *A*. sp., *Cladosporium* sp. and *Chaetomium globosum*. The fabrics with high number carbon exerted the most increased biocidal activity

The ability of CNPs to interact and integrate into fungi cells determines their fungicidal activities. Wang et al. [201] reported the importance of surface contact

**148**

**Figure 3.**

*Various carbon-based NPs [208].*

on *C. globosum* and *Aspergillus* sp.

**5.1 Mechanistic action of CNPs fungicidal activity**

dose-related decrease in the bodyweight of high-dose male rats at the fourth, fifth, and seventh weeks was observed; however, no significant dose-dependent changes in the female rats. Further hematological assays showed a significant increase (p < 0.01) in cholesterol in the both high-dose male and female rats. A significant increase (p < 0.01) in alkine phosphotase (ALP) was also indicated for the high-dose female rats. The authors reported no-observed-adverse-effect level (NOAEL) and lowestobserved-adverse-effect level (LOAEL) as 30 mg/kg BW/day and 125 mg/kg BW/ day, respectively. Treatment with NPs of diameters ranging from 25 to 80 nm at a dose of 5000 mg/kg body weight altered the levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, and lactate dehydrogenase, along with lesions on the liver and kidneys of female mice. Myocardial damage associated with groups showing a notable changes in serum LDH and alpha-HBDH levels compared to the control experiment. Also, a biodistribution test disclosed that TiO2 was predominantly retained in the liver, spleen, kidneys, and lung tissues, indicating TiO2-NPs were transported via endocytosis to other tissues and organs after their uptake by the gastrointestinal tract [221]. Contradictory finding was reported by Warheit et al. [222] where no adverse effects were manifested after orally fed rats with TiO2-NPs. However, the NOAEL on rats exposed for 90 days was >1000 mg/kg BW/day. In a similar study, Sharma et al. [223] divided male Swiss albino mice into three groups (group 1—vehicle control (water); group 2—ZnO nanoparticles (300 mg/kg body weight); group 3— ZnO nanoparticles (50 mg/kg)) and fed them with 50 and 300 mg/kg b.wt. ZnO-NPs for 14 consecutive days. ZnO-NPs induced oxidative stress, which damage the DNA and apoptosis in the mouse liver. Additionally, elevated levels of ALT and ALP serum and subsequent pathological lesions were observed in the treated mice. Lastly, at a higher dose (300 mg/kg) of ZnO-NPs, a significant (p < 0.05) induction of lipid peroxidation was observed in the liver, brain, and kidney (**Figure 4**) of the treated mice in comparison with the control test. Cho et al. [224] discovered ZnO-NPs had a higher absorption efficiency than TiO2-NPs in rats. ZnO-NP concentrations in the liver and kidney were significantly higher compared to the control, whereas with TiO2- NPs, no dramatic increase was detected in the sampled organs. In the feces, very high and low concentrations of Ti and Zn were detected, respectively. The concentration of ZnO in the spleen and brain was minimally elevated. Similarly, Ti concentrations were not drastically increased in urine; in contrast, it was Zn levels, that remarkably

#### **Figure 4.**

*Zinc content in selected tissue of the mice (n = 5) after oral administration of ZnO nanoparticles (NPs) (300 mg/kg) for 14 consecutive days. Data represent mean±S.E.M. of three animals. \**p *< 0.05, compared to control. Modified with permission from ref 4495441125809.*

**151**

*The Potential Application of Nanoparticles on Grains during Storage: Part 2 – An Overview…*

changed. Therefore, the absorption of various NPs could be attributed to the higher dissolution rate in the acidic gastric fluid; however, this might not be applicable when NPs are utilized during grain storage. When a stored grain undergoes sun drying, milling, etc., the levels of NPs may decrease to a level that could not affect the consumer health. Moreover, many NPs have received approval for application in many fields. Nevertheless, rigorous studies are warranted to expound on any risks or the safety of NPs use in grain storage. According to Zare-Zardini et al. [206], CNPs appeared less toxic to humans and animals compared to metal NPs and are therefore the better alternative and a novel method for reducing mycotoxin biosynthesis in grains.

1.The first method is direct processing of grains with solutions of the required concentration of NPs. To achieve this, biocompatible NPs in an aqueous disper-

2.Treatment with aerosols NPs could also be used if the NPs are dispersed evenly over the granary or silos. The aerosols to apply should be modified to prevent aggregation on grains. Using aerosols saves time and labor since additional

3.The use of packages made from NPs during storage, transportation, and sale will extend the shelf life of grains. Alternatively, NPs formulated cubes could be place in jute bags with grains; however, periodic mixing is required to dis-

4.In our opinion, one of the most inexpensive methods is the use NPs in the production of materials for granaries, as well as treating interior and exterior

The ability of NPs to suppress the synthesis of mycotoxins in fungi and other microorganisms could be a breakthrough to curbe the issue of aflatoxin prevalence worldwide. NPs displayed excellent antifungal activity against important fungal species which contaminate grains with toxins during storage. The concentration, volume, type, and illumination (sunlight) significantly influenced the biostatic activity of NPs. Hence, these factors should carefully be considered when applying NPs in grain storage. The proposed NPs are environmentally friendly and pose no threat to consumer compared to some conventional methods of grain preservation. Several ex vivo, in vivo, and in vitro studies supports these claims. Moreover, NPs are biocompatible to the human system hence their usage in the food industry. Despite safety of NPs guaranteed by international safety organizations such as the Food Safety Authority, routine testing is required to understand the impact it has on

This work was supported by the Ministry of Science and Higher Education of

grain nutritional, sensory, and other physicochemical parameters.

**7. Proposed methods of applying NPs during grain storage**

sion medium with pH values close to neutral should be used.

*DOI: http://dx.doi.org/10.5772/intechopen.93213*

drying is not required.

surfaces of the storage facilities.

tribute the NPs.

**8. Conclusions**

**Acknowledgments**

Russia (Project No.075-15-2019-1896).

*The Potential Application of Nanoparticles on Grains during Storage: Part 2 – An Overview… DOI: http://dx.doi.org/10.5772/intechopen.93213*

changed. Therefore, the absorption of various NPs could be attributed to the higher dissolution rate in the acidic gastric fluid; however, this might not be applicable when NPs are utilized during grain storage. When a stored grain undergoes sun drying, milling, etc., the levels of NPs may decrease to a level that could not affect the consumer health. Moreover, many NPs have received approval for application in many fields. Nevertheless, rigorous studies are warranted to expound on any risks or the safety of NPs use in grain storage. According to Zare-Zardini et al. [206], CNPs appeared less toxic to humans and animals compared to metal NPs and are therefore the better alternative and a novel method for reducing mycotoxin biosynthesis in grains.
