Editorial Feature

Nanotoxicology: An Overview

Nanotoxicology is a specialized branch of nanotechnology focused on assessing the harmful effects of nanoparticles (NPs) on human health and the environment.1 NPs exhibit unique properties compared to their bulk counterparts due to their quantum size effects and high surface-to-volume ratio, which affect their toxicity.

Nanotoxicology: An Overview

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As nanotechnology becomes increasingly popular in biomedicine and related areas, it is crucial to study the toxic effects of NPs comprehensively to establish advanced safety guidelines. Nanotoxicology research is necessary to ensure that progress in nanotechnology does not pose environmental or societal threats.

Common Uses of NPs

NPs, typically of size ranging between 1 and 100 nm, have transformed numerous industries thanks to their distinctive optical, physiochemical, and biological characteristics. In the pharmaceutical field, NPs advance drug delivery by targeting specific diseased cells, boosting the efficacy of treatments, and reducing the side effects.2

Diagnostics and molecular detection have also benefited, with magnetic NPs and gold NPs used in medical diagnostics for detecting pathogens and genetic defects. NPs are also employed in pregnancy tests and allergy diagnostics due to their optical properties and stability.2

In textiles, incorporating NPs can enhance properties such as stain resistance, antimicrobial activity, and durability. In the food packaging industry, NPs form barriers against gases and moisture and provide antibacterial and antioxidant effects, extending the shelf life of food products.2 Nanofluids and nanocrystals are used in photovoltaic devices to increase the efficiency of solar energy harvesting.

In water purification, iron NPs enriched with palladium can remove organic chlorine contaminants from water and soil.2 Agriculture has adopted NPs, such as copper hydroxide NPs, for biofortification and as environmentally friendly pesticides.

NPs are also employed in bone reconstruction, car tire reinforcement, and heat transfer in speakers, demonstrating their broad applicability.

Health and Environmental Risks of NPs

While NPs offer numerous benefits, their small size and unique properties also pose potential health and environmental risks. NPs can cross cellular barriers of skin and enter the body through inhalation or food, causing serious effects on the brain, lungs, and heart.3 Further, certain NPs can cause permanent cell damage through oxidative stress and organ injury.

Toxicity varies based on the composition, size, surface properties, crystallinity, synthesis route, and tendency to aggregate.1 Studies have shown that the cytotoxicity of carbon-based NPs that can lead to lung cancer is majorly size-dependent.3

Additionally, chemically synthesized NPs often display higher toxicity due to synthetic surface functional and capping agents than biosynthesized NPs, which tend to be more biocompatible.4 Needle-shaped NPs tend to be more toxic than spherical ones, as they can penetrate cell membranes easily, have higher internalization rates, and have greater adhesiveness to the surfaces of the cells.4

Once released into the environment, NPs can agglomerate spontaneously, potentially harming various organisms. This is a significant concern as manufactured NPs, unlike naturally occurring ones, tend to persist due to surfactants and stabilizers.2

NPs permeating through the physiological barriers of living organisms can also have harmful environmental effects. Certain NPs, such as zinc oxide, exhibit antibacterial properties, which can disrupt microbial communities and impact processes like nutrient cycling and decomposition, essentials of a self-sustaining ecosystem.

Current Research and Methodologies in Nanotoxicology

The rapid increase in the use of NPs necessitates thorough assessment and regulation to mitigate these risks. Unlike bulk materials, the hazardous properties of NPs do not correlate directly with concentration or chemical composition. Toxicity is calculated when there is a chance for the NPs to reach a biologically effective concentration, which can cause severe damage.5

Hence, studying the toxicity of NPs based on various properties, from size to agglomeration and environmental factors such as pH and temperature, is essential.1 Understanding the interaction of NPs with biological systems is also crucial for employing safer nanotechnology applications.

Given the complexity of NP risk assessment, two main strategies are employed in toxicological evaluation: testing each type of NP individually and predicting their behavior based on structural and compositional features. Toxicological and ecotoxicological bioassays are crucial in assessing the risks of NPs.6

Research data from numerous comprehensive in vitro (in culture dish) and in vivo (within a living organism) studies provide the basis for an initial understanding of the toxic mode of action of NPs.7 Investigating time-dependent effects is crucial, particularly for stable NPs.

However, testing every single type of NP is expensive, time-consuming, and inefficient. Consequently, computational methods that offer statistically reliable, accessible, and comprehensive predictions of the harmful influences of NPs are becoming popular.6 Computational models can simulate NP interactions with biological systems, forecast their behavior and potential toxicity, and thus guide experimental research more effectively.

Safety and Regulatory Considerations

A key strategy in developing and using NPs is the "Safety-by-Design" (SbD) approach, which integrates safety considerations into the engineering of NPs from the outset.8 SbD aims to eliminate unwanted effects by incorporating knowledge of potential adverse impacts during the design phase.

The SbD approach has been adopted in various industries, including construction and green chemistry, to modify initial designs and reduce product toxicity. Europe-based projects like NANoREG and NANoREG II have implemented SbD principles, focusing on the safe design, production, and application of nanomaterials.8

Regulatory frameworks such as the REACH (Registration, Evaluation, Authorization, and Restriction of Chemical Substances) emphasize toxicity testing once a product enters the market, as the toxicity of NPs varies due to the design and environment of the final product.8

However, SbD advocates early in vitro and computational screenings to identify potential toxicities before extensive product development. This approach aims to minimize future losses and ensure safety, although unforeseen adverse events can still emerge post-market. Despite substantial data being produced, inconsistencies in sampling, methodologies, analyses, and lab practices have hindered their utility in regulatory decision-making.

Future Directions

NPs are increasingly used in various fields due to their distinctive physicochemical, biological, optical, and other properties. However, their potential toxic effects on health and the environment have raised significant concerns.

An article in the Journal of Toxicology highlights the necessity of considering a wide range of NP properties and their toxic effects, which can be influenced by even minor changes in particle characteristics.4 The toxic effects of NPs depend on various factors, including their type, size, surface area, shape, aspect ratio, surface coating, crystallinity, solubility, and agglomeration.

In biomedicine, studying the interaction of NPs with cells and tissues (including mechanisms such as the creation of reactive oxygen species, cellular toxicity, and possible genotoxic or neurotoxic effects) is extremely important.4 An article in Current Opinion in Toxicology emphasizes the advantages of using both experimental and computational methods simultaneously for a more accurate risk assessment.

Ensuring the safety of NPs involves adopting SbD principles, employing rigorous risk assessment methods, and developing robust regulatory frameworks.8 Questions about dependable testing parameters and translating scientific knowledge into regulatory requirements must be addressed to avoid false positives, negatives, and misrepresentations of NP safety data.

Further research to understand the mechanisms and design advanced methodologies in nanotoxicology is essential to keep pace with the rapid advancements in nanotechnology.

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References and Further Reading

  1. Walters, C., Pool, E., Somerset, V. (2016). Nanotoxicology: a review. Toxicology-new aspects to this scientific conundrum. DOI: 10.5772/64754. https://www.intechopen.com/chapters/51876
  2. Martínez, G., et al. (2020). Environmental impact of nanoparticles’ application as an emerging technology: A review. Materials. DOI: 10.3390/ma14010166, https://www.mdpi.com/1996-1944/14/1/166
  3. Kumah, EA., Fopa, RD., Harati, S., Boadu, P., Zohoori, FV., Pak, T. (2023). Human and environmental impacts of nanoparticles: a scoping review of the current literature. BMC Public Health. DOI: 10.1186/s12889-023-15958-4, https://link.springer.com/article/10.1186/s12889-023-15958-4
  4. Egbuna, C., et al., (2021). Toxicity of nanoparticles in biomedical application: nanotoxicology. Journal of Toxicology. DOI: 10.1155/2021/9954443, https://onlinelibrary.wiley.com/doi/full/10.1155/2021/9954443
  5. Krug, HF., Wick, P. (2011). Nanotoxicology: an interdisciplinary challenge. Angewandte Chemie International Edition. DOI: 10.1002/anie.201001037, https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.201001037
  6. Pikula, K., Zakharenko, A., Chaika, V., Kirichenko, K., Tsatsakis, A., Golokhvast, K. (2020). Risk assessments in nanotoxicology: Bioinformatics and computational approaches. Current Opinion in Toxicology. DOI: 10.1016/j.cotox.2019.08.006, https://www.sciencedirect.com/science/article/abs/pii/S2468202019300646
  7. Ahmad, A., Imran, M., Sharma, N. (2022). Precision nanotoxicology in drug development: Current trends and challenges in safety and toxicity implications of customized multifunctional nanocarriers for drug-delivery applications. Pharmaceutics. DOI: 10.3390/pharmaceutics14112463, https://www.mdpi.com/1999-4923/14/11/2463
  8. Zielińska, A., et al. (2020). Nanotoxicology and nanosafety: Safety-by-design and testing at a glance. International Journal of Environmental Research and Public Health. DOI: 10.3390/ijerph17134657, https://www.mdpi.com/1660-4601/17/13/4657

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Janaky

Written by

Janaky

Janaky holds a Ph.D. in Material Science from Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) in Bangalore, where she used Raman spectroscopy to study phase transitions in various novel materials. Her research involved chalcogenides, orthoferrites, vanthoffites, eutectics, and metal-organic frameworks, providing her with extensive experience in proposal writing, manuscript preparation, and scientific review.    

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