Pulmonary Toxicity of Single-Wall Carbon Nanotubes in Mice 7 and 90 Days After Intratracheal Instillation
TL;DR: Results show that, for the test conditions described here and on an equal-weight basis, if carbon nanotubes reach the lungs, they are much more toxic than carbon black and can be more Toxic than quartz, which is considered a serious occupational health hazard in chronic inhalation exposures.
About: This article is published in Toxicological Sciences.The article was published on 2003-09-26 and is currently open access. It has received 1954 citations till now. The article focuses on the topics: Carbon nanotubes in medicine & Carbon nanotube.
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TL;DR: The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.
Abstract: Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.
8,323 citations
TL;DR: Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices.
Abstract: Although humans have been exposed to airborne nanosized particles (NSPs; < 100 nm) throughout their evolutionary stages, such exposure has increased dramatically over the last century due to anthropogenic sources. The rapidly developing field of nanotechnology is likely to become yet another source through inhalation, ingestion, skin uptake, and injection of engineered nanomaterials. Information about safety and potential hazards is urgently needed. Results of older bio-kinetic studies with NSPs and newer epidemiologic and toxicologic studies with airborne ultrafine particles can be viewed as the basis for the expanding field of nanotoxicology, which can be defined as safety evaluation of engineered nanostructures and nanodevices. Collectively, some emerging concepts of nanotoxicology can be identified from the results of these studies. When inhaled, specific sizes of NSPs are efficiently deposited by diffusional mechanisms in all regions of the respiratory tract. The small size facilitates uptake into cells and transcytosis across epithelial and endothelial cells into the blood and lymph circulation to reach potentially sensitive target sites such as bone marrow, lymph nodes, spleen, and heart. Access to the central nervous system and ganglia via translocation along axons and dendrites of neurons has also been observed. NSPs penetrating the skin distribute via uptake into lymphatic channels. Endocytosis and biokinetics are largely dependent on NSP surface chemistry (coating) and in vivo surface modifications. The greater surface area per mass compared with larger-sized particles of the same chemistry renders NSPs more active biologically. This activity includes a potential for inflammatory and pro-oxidant, but also antioxidant, activity, which can explain early findings showing mixed results in terms of toxicity of NSPs to environmentally relevant species. Evidence of mitochondrial distribution and oxidative stress response after NSP endocytosis points to a need for basic research on their interactions with subcellular structures. Additional considerations for assessing safety of engineered NSPs include careful selections of appropriate and relevant doses/concentrations, the likelihood of increased effects in a compromised organism, and also the benefits of possible desirable effects. An interdisciplinary team approach (e.g., toxicology, materials science, medicine, molecular biology, and bioinformatics, to name a few) is mandatory for nanotoxicology research to arrive at an appropriate risk assessment.
7,092 citations
Cites background from "Pulmonary Toxicity of Single-Wall C..."
...In addition, as noted by Lecoanet et al. (2004), nanosized materials may not migrate through soils at rapid enough rates to be valuable in remediation....
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TL;DR: Probing the various interfaces of nanoparticle/biological interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings.
Abstract: Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.
6,075 citations
TL;DR: An overview on some of the currently used systems for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles is provided.
Abstract: The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation. This paper provides an overview on some of the currently used systems for drug delivery. Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.
3,140 citations
Cites background from "Pulmonary Toxicity of Single-Wall C..."
...In two in vivo studies SWCNTs were demonstrated to induce lung granulomas after intratracheal administration (Lam et al 2004; Warheit et al 2004) indicating that these nanotubes can not be classifi ed as a new form of graphite on material safety data sheets....
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...Carbon black, carbonyl iron and graphite produced no signifi cant adverse effects (Lam et al 2004; Warheit et al 2004)....
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Posted Content•
TL;DR: A review of the toxicity of nanoparticles is presented in this paper, with the goal of informing public health concerns related to nanoscience while raising awareness of nanomaterials toxicity among scientists and manufacturers handling them.
Abstract: This review is written with the goal of informing public health concerns related to nanoscience, while raising awareness of nanomaterials toxicity among scientists and manufacturers handling them. We show that humans have always been exposed to nanoparticles and dust from natural sources and human activities, the recent development of industry and combustion-based engine transportation profoundly increasing anthropogenic nanoparticulate pollution. The key to understanding the toxicity of nanoparticles is that their minute size, smaller than cells and cellular organelles, allows them to penetrate these basic biological structures, disrupting their normal function. Among diseases associated with nanoparticles are asthma, bronchitis, lung cancer, neurodegenerative diseases (such as Parkinson`s and Alzheimer`s diseases), Crohn`s disease, colon cancer. Nanoparticles that enter the circulatory system are related to occurrence of arteriosclerosis, and blood clots, arrhythmia, heart diseases, and ultimately cardiac death. We show that possible adverse effects of nanoparticles on human health depend on individual factors such as genetics and existing disease, as well as exposure, and nanoparticle chemistry, size, shape, and agglomeration state. The faster we will understand their causes and mechanisms, the more likely we are to find cures for diseases associated with nanoparticle exposure. We foresee a future with better-informed, and hopefully more cautious manipulation of engineered nanomaterials, as well as the development of laws and policies for safely managing all aspects of nanomaterial manufacturing, industrial and commercial use, and recycling.
2,652 citations
References
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TL;DR: Results from the lung histopathology component of the study indicated that pulmonary exposures to quartz particles produced dose-dependent inflammatory responses, concomitant with foamy alveolar macrophage accumulation and lung tissue thickening at the sites of normal particle deposition.
1,476 citations
TL;DR: A readily scalable purification process capable of handling single-wall carbon nanotube (SWNT) material in large batches, which should greatly facilitate investigation of material properties intrinsic to the nanotubes.
Abstract: We describe, in detail, a readily scalable purification process capable of handling single-wall carbon nanotube (SWNT) material in large batches. Characterization of the resulting material by SEM, TEM, XRD, Raman scattering, and TGA shows it to be highly pure. Resistivity measurements on freestanding mats of the purified tubes are also reported. We also report progress in scaling up SWNT production by the dual pulsed laser vaporization process. These successes enable the production of gram per day quantities of highly pure SWNT, which should greatly facilitate investigation of material properties intrinsic to the nanotubes.
1,400 citations
"Pulmonary Toxicity of Single-Wall C..." refers methods in this paper
...…NTs (PNTs), which were prepared by rigorous treatment (45-h reflux) with concentrated acids (2 M to 3 M nitric acid) to remove metal impurities (Rinzler et al., 1998), and contained only a small amount (2 % by weight) of residual iron, produced prominent granulomas, along with the fact that…...
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Journal Article•
841 citations
TL;DR: Although laboratory studies indicated that with sufficient agitation, unrefined SWCNT material can release fine particles into the air, concentrations generated while handling material in the field were very low, and estimates of the airborne concen-tration of nanotube material generated during handling suggest that concentrations were lower than 53μg/m3 in all cases.
Abstract: Carbon nanotubes represent a relatively recently discovered allotrope of carbon that exhibits unique properties. While commercial interest in the material is leading to the development of mass production and handling facilities, little is known of the risk associated with exposure. In a two-part study, preliminary investigations have been carried out into the potential exposure routes and toxicity of single-walled carbon nanotube material (SWCNT)--a specific form of the allotrope. The material is characterized by bundles of fibrous carbon molecules that may be a few nanometers in diameter, but micrometers in length. The two production processes investigated use-transition metal catalysts, leading to the inclusion of nanometer-scale metallic particles within unrefined SWCNT material. A laboratory-based study was undertaken to evaluate the physical nature of the aerosol formed from SWCNT during mechanical agitation. This was complemented by a field study in which airborne and dermal exposure to SWCNT was investigated while handling unrefined material. Although laboratory studies indicated that with sufficient agitation, unrefined SWCNT material can release fine particles into the air, concentrations generated while handling material in the field were very low. Estimates of the airborne concentration of nanotube material generated during handling suggest that concentrations were lower than 53 microg/m(3) in all cases. Glove deposits of SWCNT during handling were estimated at between 0.2 mg and 6 mg per hand.
767 citations
TL;DR: The HiPco process has been used to produce high-purity carbon single-walled nanotubes (SWNTs) using a gas-phase chemical-vapor-deposition process as mentioned in this paper.
Abstract: We have demonstrated large-scale production (10 g/day) of high-purity carbon single-walled nanotubes (SWNTs) using a gas-phase chemical-vapor-deposition process we call the HiPco process. SWNTs grow in high-pressure (30–50 atm), high-temperature (900–1100 °C) flowing CO on catalytic clusters of iron. The clusters are formed in situ: Fe is added to the gas flow in the form of Fe(CO)5. Upon heating, the Fe(CO)5 decomposes and the iron atoms condense into clusters. These clusters serve as catalytic particles upon which SWNT nucleate and grow (in the gas phase) via CO disproportionation: CO+CO⇒CO2+C(SWNT). SWNT material of up to 97 mol % purity has been produced at rates of up to 450 mg/h. The HiPco process has been studied and optimized with respect to a number of process parameters including temperature, pressure, and catalyst concentration. The behavior of the SWNT yield with respect to various parameters sheds light on the processes that currently limit SWNT production, and suggests ways that the producti...
704 citations
"Pulmonary Toxicity of Single-Wall C..." refers background or methods in this paper
...High-pressure CO conversion (HiPcoTM, Rice University, TX) is a CVD process and is a more advanced method that uses carbon monoxide as carbon source; up to 97% of the carbon in the HiPco product ends up in NTs (Bronikowski et al., 2001)....
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...High-pressure CO conversion (HiPco™, Rice University, TX) is a CVD process and is a more advanced method that uses carbon monoxide as carbon source; up to 97% of the carbon in the HiPco product ends up in NTs (Bronikowski et al., 2001)....
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...CNTs, which were made from graphite and may contain more graphite impurities than the CO-derived HiPco-NTs (Bronikowski et al., 2001), actually were less potent in producing granulomas....
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