Environmental

Nanotechnology
Fundamentals Towards Interactions,
Implications, and Applications
Module 9
Dr. Tanushree Parsai
Assistant Professor, Department of Civil Engineering
IIT Madras

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Nanotoxicology
• Nanotoxicology is study of toxicity of nanomaterials
• Nanotoxicology is defined as the study of the nature and mechanism
of toxic effects of nanoscale materials/particles on living organisms
and other biological systems

How could NM hurt us?

How do we come into contact with it?
How does it affect us?
How far can NM affect us?
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 Biointerphases, Vol. 2 (4), 2007; Buzea
[6, 35] , C., Pacheco, I.I., Robbie, K.
Nanomaterials and nanoparticles:
Sources and toxicity, 17-71.

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Nanoparticles in our day to day life

UV-blockers
nTiO2, Textiles (TiO2 and
nSiO2
ZnO)
Cosmet
Food nAg ics

Carbon
Medicin
Electro Black e Drug
nAu nics delivery
Inks

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Exposure pathways
• Inhalation: Through Lungs
The quantity of nanoparticles that reach the bloodstream through inhalation amounts to only a
fraction (<0.05 %) of the quantity administered
Olfactory nerve
• Dermal route: through skin
• Through Ingestion: gastrointestinal tract
• Injection: directly to bloodstream
Ingestion Contaminant concentration in the ingested media,
amount of ingested material, bioavailability to
gastrointestinal system

Inhalation Concentration in the year and dust, particle size

distribution, bioavailability to pulmonary system,
rate of respiration
Dermal contact Concentration in soil and dust, rate of deposition
of dust from air, direct contact with Soil,
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bioavailability, amount of skin exposed
Toxicological targets

Molecular Level Cell Level Organ level

• ROS • Inflammation
• Mechanical • Kidney
Formation
disturbance • Lung
• Metal binding
• Macrophage • Heart
• Protein
overload • Brain
Binding

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Nanotoxicology Principles

Transport-principle
• Phagocytosis
• vesicle transport pathway
• “diffusion” through the
plasma membranes

Krug and Wick, 2011

Angew. Chem. Int. Ed. 2011, 50, 1260 – 1278

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Surface principle
Reduction in particle size can improve and accelerate reactions in the
case of catalysis or other chemical processes; it increases the reactivity
with cells or their components in the biological system.
surface properties enhance the possible interaction with biological
molecules such as lipids, proteins, or nucleic acids and may induce
adverse effects in cells and tissues

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Material Principle
Variations in ENM composition (either bulk
or surface) lead to differences in their
reactivity and behaviour in biological
systems . Gold or silver metal particles;
metal oxides, such as SiO2, TiO2, ZnO,
FexOy, and CeO2; and carbon-based
materials, all have different binding
capacities for biological molecules, different
reactivity towards biological molecules such
as proteins, lipids, or DNA, and different
distribution patterns

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Toxicokinetics
• absorption
• distribution
• degradation
• elimination

Krug and Wick, 2011

Angew. Chem. Int. Ed. 2011, 50, 1260 – 1278
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Testing

In-Vitro methods In-Vivo methods Ex-Vivo methods In-Silico methods

Cell culture
Stem-cell
Tissue Animal Molecular
Dissected organs
engineering Insects docking
Post surgical
Microfluidics Embroyos QSAR Assay
materials
Larvae MD simulations
Inflammatory
Response (ELISA)

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Cytotoxicity

DOI: 10.1039/D2NA00534D (Review Article) Nanoscale Adv., 2023, 5, 2674-2723

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Factors affecting nanotoxicology

size,
surface area,
shape,
aspect ratio,
surface coating,
crystallinity,
dissolution, and
agglomeration.

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• Du et al. 2013 investigated cardiovascular toxicity of different sizes of
amorphous silica NPs (90, 60, and 30 nm) and 600 nm of fine silica
NPs after intratracheal instillation in rats.
• Blood levels of inflammation-related proteins, cytokines, and tumor
necrosis factor were found higher in rats administered fine silica
particles.

Du, Z., Zhao, D., Jing, L. et al. Cardiovascular Toxicity of Different Sizes Amorphous Silica Nanoparticles in Rats After
01-07-2024 Intratracheal Instillation. Cardiovasc Toxicol 13, 194–207 (2013). https://doi.org/10.1007/s12012-013-9198-y 14
• Silver nanoplates were found to be more harmful than silver
nanospheres in zebrafish (Danio rerio) embryos

Abramenko, Natalia B., et al. "Ecotoxicity of different-shaped silver nanoparticles: Case of

zebrafish embryos." Journal of hazardous materials 347 (2018): 89-94.

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• The greater the NPs' aspect ratio, the higher the toxicity of the NPs
• The type of crystalline structure may affect the toxicity of
nanomaterials. Polymorphs, the different crystalline structures of the
same chemical composition showed different chemical and physical
properties
• The dissolution ability of nanoparticles is a significant property that
determines safety, uptakes, and associated toxic mechanism.
• The agglomeration of nanoparticles could be a potential inducer of
inflammatory lung conditions in humans
• NPs surface passivation reduces the oxidative stress and alteration of
iron homeostasis and, consequently, the overall toxicity(Malvindi et
al.,2014)

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 Biocidal properties of nanoparticles

Siddiqi, K.S., Husen, A. & Rao, R.A.K. A review on biosynthesis of silver nanoparticles and their biocidal properties. J Nanobiotechnol 16, 14 (2018).
https://doi.org/10.1186/s12951-018-0334-5

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Environmental Factors Affecting Nanotoxicity
NOM, temperature, medium, chemical surface modifications and ionic
strength
Surface Modification
Sulfidization of Ag NPs significantly mitigates nanotoxicity, mainly because the formation of Ag2S
with extremely low solubility dramatically precipitated and reduced the bioavailability of Ag+

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Biomedium
Proteins, serum, and other biomedium are often used to enhance the dispersion and stabilization of
NPs. It is believed that NPs are covered by proteins or amino acids to form a corona once NPs are in
contact with biological fluids, such as the cell serum, that mediate the interactions with cells in situ.
The biological corona will change the dispersion, stability, biocompatibility, translocation and
transformation processes of NPs

Temperature
It was observed that the toxicity of zero-valent copper nanoparticles (ZVCN) toward E. coli increased
with the increase in the temperature of the environment (Rispoli et al., 2010).

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Ionic strength
As ionic strength increased, Ag+ in solution increased thus, E. coli demonstrated a low
tolerance to Ag NP exposure (e.g., toxicity increases) (Chambers et al.,2014)
NOM
NOM can deliver negative surface charges to NPs and inhibit the adhesion of NPs to the
cells, thereby alleviating the oxidative stress on the cells. NOM may also directly scavenge
NP-produced ROS and thus mitigate the nanotoxicity
Light
The properties of NPs can be changed by light irradiation. Some nanomaterials are
photoactive and Produce reactive oxygen species (ROS) or promote the release of metal
ions when exposed to sunlight
Example) It was found that the acute toxicity of S-TiO2 nanoparticles (S-TiO2 NPs) was
enhanced by simulated sunlight irradiation(He et al.,2014)

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Nanoparticle risk and regulation

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 Step1 Step2 Exposure Assessment(Ingestion route)
Hazard
Average Daily Dose Estimation
Identification
Aquatic Total Concentration of % of NPs
Matrices ZnO and CuO BAF(ZnO/CuONPs) Ingestion rate
NPs remaining/ % ion
(Nanopart NPs: sources,
icles effect, harm to
human health? Body Weight(Child/Adult)
Mixture)

Step4 Human health

Human Health Risk Step5 Risk
Step3 Dose Response Assessment Characterization Management

Toxicity Data Modified weight of Evidence(USEPA) • Max

ZnONP, CuO NP, Zn Allowable
(Literature
ion, Cu ion n n
concentrati
Compilation) HIint = (HQi ×
B θ ij
fij Mij ij )
i=1 j≠i
on posing
no human
Scenarios health risk
ZnO Alone, CuO Alone, ZnO+CuO ,ZnO+Ext Cu,
• Target Organ : Whole RfD= CuO+ExtZn, ZnO+ CuO+Ext Zn, ZnO+CuO+Ext Cu,
i.e HIint<1
digestive system 𝑃𝑜𝑖𝑛𝑡 𝑜𝑓 𝐷𝑒𝑝𝑎𝑟𝑡𝑢𝑟𝑒
ZnO+CuO+ExtZn+Ext Cu • Uncertainty
𝑈𝑛𝑐𝑒𝑟𝑡𝑎𝑖𝑛𝑖𝑡𝑦 𝐹𝑎𝑐𝑡𝑜𝑟
• RfD Animal to RfD characteriz
Human No ation
HI<1 HI>1 Risk
Risk
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Nanoparticle standard

• Risk management for the protection of human health and the environment
is presently in a difficult situation due to often incomplete information

• No standard guidelines for nanoparticles usage and limit available

• A larger number of studies from multi-laboratory consortia, where all

participants use the same materials and procedures, would lead to a more
systematic understanding of the biological, toxicological, and
immunological effects of ENM

Important websites for Nanomaterial Information

Nanotrust, safenano, ICON, OECD, IANH, CEINT, IRIS
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 Thank You

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