Learning from Safe-by-Design for Safe-and-Sustainable-by-Design: Mapping the current landscape of Safe-by-Design reviews, case studies, and frameworks.

With the introduction of the European Commission's "Safe and Sustainable-by-Design" (SSbD) framework, the interest in understanding the implications of safety and sustainability assessments of chemicals, materials, and processes at early-innovation stages has skyrocketed. Our study focuses on the "Safe-by-Design" (SbD) approach from the nanomaterials sector, which predates the SSbD framework. In this assessment, SbD studies have been compiled and categorized into reviews, case studies, and frameworks. Reviews of SbD tools have been further classified as quantitative, qualitative, or toolboxes and repositories. We assessed the SbD case studies and classified them into three categories: safe(r)-by-modeling, safe(r)-by-selection, or safe(r)-by-redesign. This classification enabled us to understand past SbD work and subsequently use it to define future SSbD work so as to avoid confusion and possibilities of "SSbD-washing" (similar to greenwashing). Finally, the preexisting SbD frameworks have been studied and contextualized against the SSbD framework. Several key recommendations for SSbD based on our analysis can be made. Knowledge gained from existing approaches such as SbD, green and sustainable chemistry, and benign-by-design approaches needs to be preserved and effectively transferred to SSbD. Better incorporation of chemical and material functionality into the SSbD framework is required. The concept of lifecycle thinking and the stage-gate innovation model need to be reconciled for SSbD. The development of high-throughput screening models is critical for the operationalization of SSbD. We conclude that the rapid pace of both SbD and SSbD development necessitates a regular mapping of the newly published literature that is relevant to this field.

Analytical and toxicological aspects of nanomaterials in different product groups: Challenges and opportunities.

The widespread integration of engineered nanomaterials into consumer and industrial products creates new challenges and requires innovative approaches in terms of design, testing, reliability, and safety of nanotechnology. The aim of this review article is to give an overview of different product groups in which nanomaterials are present and outline their safety aspects for consumers. Here, release of nanomaterials and related analytical challenges and solutions as well as toxicological considerations, such as dose-metrics, are discussed. Additionally, the utilization of engineered nanomaterials as pharmaceuticals or nutraceuticals to deliver and release cargo molecules is covered. Furthermore, critical pathways for human exposure to nanomaterials, namely inhalation and ingestion, are discussed in the context of risk assessment. Analysis of NMs in food, innovative medicine or food contact materials is discussed. Specific focus is on the presence and release of nanomaterials, including whether nanomaterials can migrate from polymer nanocomposites used in food contact materials. With regard to the toxicology and toxicokinetics of nanomaterials, aspects of dose metrics of inhalation toxicity as well as ingestion toxicology and comparison between in vitro and in vivo conclusions are considered. The definition of dose descriptors to be applied in toxicological testing is emphasized. In relation to potential exposure from different products, opportunities arising from the use of advanced analytical techniques in more unique scenarios such as release of nanomaterials from medical devices such as orthopedic implants are addressed. Alongside higher product performance and complexity, further challenges regarding material characterization and safety, as well as acceptance by the general public are expected.

Human hazard potential of nanocellulose: quantitative insights from the literature.

This review aims to elucidate the current knowledge and future research needs regarding the hazard potential of nanocellulose to human health. Growing interest from research and industry alike has led to increasing likelihood of human contact to the material via various exposure routes. Although a number of comprehensive reviews on human health hazards of nanocellulose have been conducted, this paper brings new insights as it systematically analyzes and quantitatively assesses the results of in vivo and in vitro tests in terms of investigated endpoints, tested concentration ranges, physicochemical properties, surface modifications and source of the tested nanocellulose, exposure route, and cell lines used. The quality of the studies is further inspected based on various established criteria. Considering the rapid development of nanocellulose-based products and the novelty of the material, human health studies remain scarce. By assessing those that have been conducted, patterns and gaps were identified that will be helpful to guide future research. The results show that there are still significant uncertainties remaining, particularly regarding in vivo testing, with pulmonary exposure showing some cause for concern. Although a substantial number of in vitro studies have been undertaken, results are often conflicting. The detected effects could not be directly attributed to size of nanoparticles, cell lines, surface modifications or tested concentrations. This may also be linked to the varying quality of the studies. This review ends by identifying key gaps to help pave the way for future research and ensure the safe development and use of nanocellulose.

A Methodological Safe-by-Design Approach for the Development of Nanomedicines.

Safe-by-Design (SbD) concepts foresee the risk identification and reduction as well as uncertainties regarding human health and environmental safety in early stages of product development. The EU's NANoREG project and further on the H2020 ProSafe initiative, NanoReg2, and CALIBRATE projects have developed a general SbD approach for nanotechnologies (e.g., paints, textiles, etc.). Based on it, the GoNanoBioMat project elaborated a methodological SbD approach (GoNanoBioMat SbD approach) for nanomedicines with a focus on polymeric nanobiomaterials (NBMs) used for drug delivery. NBMs have various advantages such as the potential to increase drug efficacy and bioavailability. However, the nanoscale brings new challenges to product design, manufacturing, and handling. Nanomedicines are costly and require the combination of knowledge from several fields. In this paper, we present the GoNanoBioMat SbD approach, which allows identifying and addressing the relevant safety aspects to address when developing polymeric NBMs during design, characterization, assessment of human health and environmental risk, manufacturing and handling, and combines the nanoscale and medicine field under one approach. Furthermore, regulatory requirements are integrated into the innovation process.

Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility.

Nanoparticles (NPs) assumed an important role in the area of drug delivery. Despite the number of studies including NPs are growing over the last years, their side effects on the immune system are often ignored or omitted. One of the most studied polymers in the nano based drug delivery system field is chitosan (Chit). In the scientific literature, although the physicochemical properties [molecular weight (MW) or deacetylation degree (DDA)] of the chitosan, endotoxin contamination and appropriate testing controls are rarely reported, they can strongly influence immunotoxicity results. The present work aimed to study the immunotoxicity of NPs produced with different DDA and MW Chit polymers and to benchmark it against the polymer itself. Chit NPs were prepared based on the ionic gelation of Chit with sodium tripolyphosphate (TPP). This method allowed the production of two different NPs: Chit 80% NPs (80% DDA) and Chit 93% NPs (93% DDA). In general, we found greater reduction in cell viability induced by Chit NPs than the respective Chit polymers when tested in vitro using human peripheral blood monocytes (PBMCs) or RAW 264.7 cell line. In addition, Chit 80% NPs were more cytotoxic for PBMCs, increased reactive oxygen species (ROS) production (above 156 µg/mL) in the RAW 264.7 cell line and interfered with the intrinsic pathway of coagulation (at 1 mg/mL) when compared to Chit 93% NPs. On the other hand, only Chit 93% NPs induced platelet aggregation (at 2 mg/mL). Although Chit NPs and Chit polymers did not stimulate the nitric oxide (NO) production in RAW 264.7 cells, they induced a decrease in lipopolysaccharide (LPS)-induced NO production at all tested concentrations. None of Chit NPs and polymers caused hemolysis, nor induced PBMCs to secrete TNF-α and IL-6 cytokines. From the obtained results we concluded that the DDA of the Chit polymer and the size of Chit NPs influence the in vitro immunotoxicity results. As the NPs are more cytotoxic than the corresponding polymers, one should be careful in the extrapolation of trends from the polymer to the NPs, and in the comparisons among delivery systems prepared with different DDA chitosans.

How the Lack of Chitosan Characterization Precludes Implementation of the Safe-by-Design Concept.

Efficacy and safety of nanomedicines based on polymeric (bio)materials will benefit from a rational implementation of a Safe-by-Design (SbD) approach throughout their development. In order to achieve this goal, however, a standardization of preparation and characterization methods and their accurate reporting is needed. Focusing on the example of chitosan, a biopolymer derived from chitin and frequently used in drug and vaccine delivery vector preparation, this review discusses the challenges still to be met and overcome prior to a successful implementation of the SbD approach to the preparation of chitosan-based protein drug delivery systems.

Molecular Modeling for Nanomaterial-Biology Interactions: Opportunities, Challenges, and Perspectives.

Injection of nanoparticles (NP) into the bloodstream leads to the formation of a so-called "nano-bio" interface where dynamic interactions between nanoparticle surfaces and blood components take place. A common consequence is the formation of the protein corona, that is, a network of adsorbed proteins that can strongly alter the surface properties of the nanoparticle. The protein corona and the resulting structural changes experienced by adsorbed proteins can lead to substantial deviations from the expected cellular uptake as well as biological responses such as NP aggregation and NP-induced protein fibrillation, NP interference with enzymatic activity, or the exposure of new antigenic epitopes. Achieving a detailed understanding of the nano-bio interface is still challenging due to the synergistic effects of several influencing factors like pH, ionic strength, and hydrophobic effects, to name just a few. Because of the multiscale complexity of the system, modeling approaches at a molecular level represent the ideal choice for a detailed understanding of the driving forces and, in particular, the early events at the nano-bio interface. This review aims at exploring and discussing the opportunities and perspectives offered by molecular modeling in this field through selected examples from literature.

Hazard Assessment of Polymeric Nanobiomaterials for Drug Delivery: What Can We Learn From Literature So Far.

The physicochemical properties of nanobiomaterials, such as their small size and high surface area ratio, make them attractive, novel drug-carriers, with increased cellular interaction and increased permeation through several biological barriers. However, these same properties hinder any extrapolation of knowledge from the toxicity of their raw material. Though, as suggested by the Safe-by-Design (SbD) concept, the hazard assessment should be the starting point for the formulation development. This may enable us to select the most promising candidates of polymeric nanobiomaterials for safe drug-delivery in an early phase of innovation. Nowadays the majority of reports on polymeric nanomaterials are focused in optimizing the nanocarrier features, such as size, physical stability and drug loading efficacy, and in performing preliminary cytocompatibility testing and proving effectiveness of the drug loaded formulation, using the most diverse cell lines. Toxicological studies exploring the biological effects of the polymeric nanomaterials, particularly regarding immune system interaction are often disregarded. The objective of this review is to illustrate what is known about the biological effects of polymeric nanomaterials and to see if trends in toxicity and general links between physicochemical properties of nanobiomaterials and their effects may be derived. For that, data on chitosan, polylactic acid (PLA), polyhydroxyalkanoate (PHA), poly(lactic-co-glycolic acid) (PLGA) and policaprolactone (PCL) nanomaterials will be evaluated regarding acute and repeated dose toxicity, inflammation, oxidative stress, genotoxicity, toxicity on reproduction and hemocompatibility. We further intend to identify the analytical and biological tests described in the literature used to assess polymeric nanomaterials toxicity, to evaluate and interpret the available results and to expose the obstacles and challenges related to the nanomaterial testing. At the present time, considering all the information collected, the hazard assessment and thus also the SbD of polymeric nanomaterials is still dependent on a case-by-case evaluation. The identified obstacles prevent the identification of toxicity trends and the generation of an assertive toxicity database. In the future, in vitro and in vivo harmonized toxicity studies using unloaded polymeric nanomaterials, extensively characterized regarding their intrinsic and extrinsic properties should allow to generate such database. Such a database would enable us to apply the SbD approach more efficiently.

Computational Assessment of the Pharmacological Profiles of Degradation Products of Chitosan.

Chitosan is a natural polymer revealing an increased potential to be used in different biomedical applications, including drug delivery systems, and tissue engineering. It implies the evaluation of the organism response to the biomaterial implantation. Low-molecular degradation products, the chito-oligomers, are resulting mainly from the influence of enzymes, which are found in the organism fluids. Within this study, we have performed the computational assessment of pharmacological profiles and toxicological effects on human health of small chito-oligomers with distinct molecular weights, deacetylation degrees, and acetylation patterns. Our approach is based on the fact that regulatory agencies and researchers in the drug development field rely on the use of modeling to predict biological effects and to guide decision making. To be considered as valid for regulatory purposes, every model that is used for predictions should be associated with a defined toxicological endpoint and has appropriate robustness and predictivity. Within this context, we have used FAF-Drugs4, SwissADME, and PreADMET tools to predict the oral bioavailability of chito-oligomers and SwissADME, PreADMET, and admetSAR2.0 tools to predict their pharmacokinetic profiles. The organs and genomic toxicities have been assessed using admetSAR2.0 and PreADMET tools but specific computational facilities have been also used for predicting different toxicological endpoints: Pred-Skin for skin sensitization, CarcinoPred-EL for carcinogenicity, Pred-hERG for cardiotoxicity, ENDOCRINE DISRUPTOME for endocrine disruption potential and Toxtree for carcinogenicity and mutagenicity. Our computational assessment showed that investigated chito-oligomers reflect promising pharmacological profiles and limited toxicological effects on humans, regardless of molecular weight, deacetylation degree, and acetylation pattern. According to our results, there is a possible inhibition of the organic anion transporting peptides OATP1B1 and/or OATP1B3, a weak potential of cardiotoxicity, a minor probability of affecting the androgen receptor, and phospholipidosis. Consequently, these results may be used to guide or to complement the existing in vitro and in vivo toxicity tests, to optimize biomaterials properties and to contribute to the selection of prototypes for nanocarriers.

Eco-Efficient Process Improvement at the Early Development Stage: Identifying Environmental and Economic Process Hotspots for Synergetic Improvement Potential.

We present here a new eco-efficiency process-improvement method to highlight combined environmental and costs hotspots of the production process of new material at a very early development stage. Production-specific and scaled-up results for life cycle assessment (LCA) and production costs are combined in a new analysis to identify synergetic improvement potentials and trade-offs, setting goals for the eco-design of new processes. The identified hotspots and bottlenecks will help users to focus on the relevant steps for improvements from an eco-efficiency perspective and potentially reduce their associated environmental impacts and production costs. Our method is illustrated with a case study of nanocellulose. The results indicate that the production route should start with carrot pomace, use heat and solvent recovery, and deactivate the enzymes with bleach instead of heat. To further improve the process, the results show that focus should be laid on the carrier polymer, sodium alginate, and the production of the GripX coating. Overall, the method shows that the underlying LCA scale-up framework is valuable for purposes beyond conventional LCA studies and is applicable at a very early stage to provide researchers with a better understanding of their production process.

LICARA nanoSCAN - A tool for the self-assessment of benefits and risks of nanoproducts.

The fast penetration of nanoproducts on the market under conditions of significant uncertainty of their environmental properties and risks to humans creates a need for companies to assess sustainability of their products. Evaluation of the potential benefits and risks to build a coherent story for communication with clients, authorities, consumers, and other stakeholders is getting to be increasingly important, but SMEs often lack the knowledge and expertise to assess risks and communicate them appropriately. This paper introduces LICARA nanoSCAN, a modular web based tool that supports SMEs in assessing benefits and risks associated with new or existing nanoproducts. This tool is unique because it is scanning both the benefits and risks over the nanoproducts life cycle in comparison to a reference product with a similar functionality in order to enable the development of sustainable and competitive nanoproducts. SMEs can use data and expert judgment to answer mainly qualitative and semi-quantitative questions as a part of tool application. Risks to public, workers and consumers are assessed, while the benefits are evaluated for economic, environmental and societal opportunities associated with the product use. The tool provides an easy way to visualize results as well as to identify gaps, missing data and associated uncertainties. The LICARA nanoSCAN has been positively evaluated by several companies and was tested in a number of case studies. The tool helps to develop a consistent and comprehensive argument on the weaknesses and strengths of a nanoproduct that may be valuable for the communication with authorities, clients and among stakeholders in the value chain. LICARA nanoSCAN identifies areas for more detailed assessments, product design improvement or application of risk mitigation measures.

Probabilistic environmental risk assessment of five nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes).

The environmental risks of five engineered nanomaterials (nano-TiO2, nano-Ag, nano-ZnO, CNT, and fullerenes) were quantified in water, soils, and sediments using probabilistic Species Sensitivity Distributions (pSSDs) and probabilistic predicted environmental concentrations (PECs). For water and soil, enough ecotoxicological endpoints were found for a full risk characterization (between 17 and 73 data points per nanomaterial for water and between 4 and 20 for soil) whereas for sediments, the data availability was not sufficient. Predicted No Effect Concentrations (PNECs) were obtained from the pSSD and used to calculate risk characterization ratios (PEC/PNEC). For most materials and environmental compartments, exposure and effect concentrations were separated by several orders of magnitude. Nano-ZnO in freshwaters and nano-TiO2 in soils were the combinations where the risk characterization ratio was closest to one, meaning that these are compartment/ENM combinations to be studied in more depth with the highest priority. The probabilistic risk quantification allows us to consider the large variability of observed effects in different ecotoxicological studies and the uncertainty in modeled exposure concentrations. The risk characterization results presented in this work allows for a more focused investigation of environmental risks of nanomaterials by consideration of material/compartment combinations where the highest probability for effects with predicted environmental concentrations is likely.

Toward the development of decision supporting tools that can be used for safe production and use of nanomaterials.

Although researchers have intentionally produced and used nanomaterials for more than a century, nanotechnology has made its mark in most areas of daily life in the past 20 years. Now thousands of products contain nanoparticles, nanofibers, or nanostructured parts. Because some chemical products have caused severe problems to human health and to the environment, we should consider the overall biological and toxicological effects of nanomaterials as we decide whether to use them in various products. We should also reflect on the mechanisms for making these decisions, which may greatly influence the development, production, and use of such products. The preselection of appropriate materials during the early product design state should allow industry and applied researchers to mitigate the risks of these new materials. However, currently the human and ecological risks of the applied nanomaterials during their life cycle are unknown. A large set of physicochemical characteristics can determine the potential human and environmental exposure to and hazards from nanomaterials. Thus, researchers will need many years to gather and analyze all the data to perform a comprehensive risk assessment for engineered nanomaterials and to develop a sound decision making process. The ideal risk assessment approach would include cost-effective screening processes to target resources toward the risks of greatest concern. The outcome of the risk assessment is only as good as the quality of the data used. Unfortunately, the actual review process of most journals that publish on nanotoxicology focuses on "mechanistic studies and results" rather than a toxicologically relevant outcome. For example, journals often do not include studies that show no effect as worthy of publication ("no-effect-studies" dilemma), which can lead to misleading interpretations of toxicological data for hazard identification. However, even with insufficient data sets, researchers can produce a preliminary comparable risk assessment ("approximate" risk assessment). Researchers have already performed risk-based evaluations of nanomaterials grounded on the comparison of exposure concentrations with no-effect levels (as required for chemical risk assessment), examining generic nanomaterials such as "nano-TiO2" but not specific forms or modifications. Even though these data sets on hazard and exposure are incomplete, they already provide the basis to illustrate the current state of knowledge and uncertainties. Therefore industry and applied researchers can calculate the probability that an adverse effect might occur and begin to balance the benefits and potential risks of an innovation. Based on the increasing numbers of nanotoxicology publications and funding programs, this Account reviews the decision support approaches that already exist to safely implement engineered nanomaterials during an early phase of innovation.

Environmental and health effects of nanomaterials in nanotextiles and façade coatings.

Engineered nanomaterials (ENM) are expected to hold considerable potential for products that offer improved or novel functionalities. For example, nanotechnologies could open the way for the use of textile products outside their traditional fields of applications, for example, in the construction, medical, automobile, environmental and safety technology sectors. Consequently, nanotextiles could become ubiquitous in industrial and consumer products in future. Another ubiquitous field of application for ENM is façade coatings. The environment and human health could be affected by unintended release of ENM from these products. The product life cycle and the product design determine the various environmental and health exposure situations. For example, ENM unintentionally released from geotextiles will probably end up in soils, whereas ENM unintentionally released from T-shirts may come into direct contact with humans and end up in wastewater. In this paper we have assessed the state of the art of ENM effects on the environment and human health on the basis of selected environmental and nanotoxicological studies and on our own environmental exposure modeling studies. Here, we focused on ENM that are already applied or may be applied in future to textile products and façade coatings. These ENM's are mainly nanosilver (nano-Ag), nano titanium dioxide (nano-TiO(2)), nano silica (nano-SiO(2)), nano zinc oxide (nano-ZnO), nano alumina (nano-Al(2)O(3)), layered silica (e.g. montmorillonite, Al(2)[(OH)(2)/Si(4)O(10)]nH(2)O), carbon black, and carbon nanotubes (CNT). Knowing full well that innovators have to take decisions today, we have presented some criteria that should be useful in systematically analyzing and interpreting the state of the art on the effects of ENM. For the environment we established the following criteria: (1) the indication for hazardous effects, (2) dissolution in water increases/decreases toxic effects, (3) tendency for agglomeration or sedimentation, (4) fate during waste water treatment, and (5) stability during incineration. For human health the following criteria were defined: (1) acute toxicity, (2) chronic toxicity, (3) impairment of DNA, (4) crossing and damaging of tissue barriers, (5) brain damage and translocation and effects of ENM in the (6) skin, (7) gastrointestinal or (8) respiratory tract. Interestingly, some ENM might affect the environment less severely than they might affect human health, whereas the case for others is vice versa. This is especially true for CNT. The assessment of the environmental risks is highly dependent on the respective product life cycles and on the amounts of ENM produced globally.

The importance of life cycle concepts for the development of safe nanoproducts.

Whilst the global players in industry are rapidly moving forward to take advantage of the new opportunities and prospects offered by nanotechnologies, it is imperative that such developments take place in a safe and sustainable manner. The increasing use of engineered nanomaterials (ENMs) in consumer products has raised certain concerns over their safety to human health and the environment. There are currently a number of major uncertainties and knowledge gaps in regard to behavior, chemical and biological interactions and toxicological properties of ENMs. As dealing with these uncertainties will require the generation of new basic knowledge, it is unlikely that they will be resolved in the immediate future. One has to consider the whole life cycle of nanoproducts to ensure that possible impacts can be systematically discovered. For example, life cycle assessment (LCA) - a formalized life cycle concept - may be used to assess the relative environmental sustainability performance of nanoproducts in comparison with their conventional equivalents. Other less formalized life cycle concepts in the framework of prospective technology assessment may uncover further detailed and prospective knowledge for human and environmental exposure to ENMs during the life cycle of nanoproducts. They systematically reveal impacts such as cross product contamination or dissipation of scarce materials among others. The combination of different life cycle concepts with the evolving knowledge from toxicology and risk assessment can mitigate uncertainties and can provide an early basis for informed decision making by the industry and regulators.

Reviewing the environmental and human health knowledge base of carbon nanotubes.

Carbon nanotubes (CNTs) are one of the most promising materials in nanotechnology. The various synthesis, purification and postprocessing methods produce CNTs with diverse physical characteristics, appliable in many fields. Their extensive projected use makes it important to understand their potential harmful effects. Besides showing a notable range of results of some toxicology studies, this review concluded that: a) there are different types of CNTs; thus, they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. Their properties suggest a possible accumulation along the food chain and high persistence. In organisms, CNT absorption, distribution, metabolism, excretion and toxicity depend on the inherent physical and chemical characteristics (e.g., functionalization, coating, length and agglomeration state), influenced by external environmental conditions during CNT production, use, and disposal. Thus, characterized exposure scenarios could be useful in toxicology studies. However, upon reaching the lungs in enough quantity, CNTs produce a toxic response (time and dose-dependent). The risks to human health and environment should be identified for a successful introduction of CNTs in future applications.

Reviewing the environmental and human health knowledge base of carbon nanotubes / Revisão sobre a base de conhecimento de saúde ambiental e humana dos nanotubos de carbono

Carbon nanotubes (CNTs) are one of the most promising materials in nanotechnology. The various synthesis, purification and postprocessing methods produce CNTs with diverse physical characteristics, appliable in many fields. Their extensive projected use makes it important to understand their potential harmful effects. Besides showing a notable range of results of some toxicology studies, this review concluded that: a) there are different types of CNTs; thus, they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. Their properties suggest a possible accumulation along the food chain and high persistence. In organisms, CNT absorption, distribution, metabolism, excretion and toxicity depend on the inherent physical and chemical characteristics (e.g., functionalization, coating, length and agglomeration state), influenced by external environmental conditions during CNT production, use, and disposal. Thus, characterized exposure scenarios could be useful in toxicology studies. However, upon reaching the lungs in enough quantity, CNTs produce a toxic response (time and dose-dependent). The risks to human health and environment should be identified for a successful introduction of CNTs in future applications.

Os nanotubos de carbono(CNT)são um dos materiais mais promissores da nanotecnologia. Os métodos de síntese, purificação e pós-processamento produzem CNT com diversas características físicas e uso em várias áreas. A projeção de uso abrangente do CNT urge a compreensão de seus possíveis efeitos nocivos. Essa revisão mostra um leque de resultados de estudos toxicológicos e concluiu que: a) há diferentes tipos de CNT; portanto, não pode ser considerado um grupo uniforme de substâncias; e b) em compartimentos ambientais,o CNT pode ser biodisponível aos organismos. Suas propriedades sugerem possível acúmulo na cadeia alimentar e alta persistência. Em organismos, sua absorção, distribuição, metabolismo, excreção e toxicidade do dependem de características físicas e químicas inerentes (e.g., funcionalização, revestimento, comprimento e estado de aglomeração), influenciadas por condições ambientais externas durante a produção, uso e eliminação de CNT. Portanto, os cenários de exposição caracterizados podem ser úteis em estudos toxicológicos. Contudo, quando chega aos pulmões em quantidade suficiente, o CNT produz uma resposta tóxica (tempo e dose dependente). Os riscos à saúde humana e meio ambiente devem ser identificados para que o CNT possa ser usado com sucesso em futuras aplicações.

Reviewing the environmental and human health knowledge base of carbon nanotubes.

Carbon nanotubes (CNTs) are considered one of the most promising materials in nanotechnology, with attractive properties for many technologic applications. The different synthesis, purification, and postprocessing methods produce CNTs with different physical characteristics, which can be applied in different fields ranging from composite materials, medical applications, and electronics to energy storage. The widespread projected use of CNTs makes it important to understand their potential harmful effects. In this environmental health review we observed a remarkable range of results of some of the toxicology studies. The comparability should be improved by further standardization and introduction of reference materials. However, at present the findings of this review suggest several key points: a) there are different types of CNTs, and therefore they cannot be considered a uniform group of substances; and b) in environmental compartments, CNTs can be bioavailable to organisms. The properties of CNTs suggest a possible accumulation along the food chain and high persistence. In organisms the absorption, distribution, metabolism, excretion, and toxicity of CNTs depend on the inherent physical and chemical characteristics such as CNT functionalization, coating, length, and agglomeration state that are influenced by the external environmental conditions during CNT production, use, and disposal stages. Characterized exposure scenarios could therefore be useful when conducting toxicologic studies. However, CNTs produce a toxic response upon reaching the lungs in sufficient quantity; this reaction is produced in a time-and dose-dependent manner. The identification of possible risks to human health and environment is a prerequisite for a successful introduction of CNTs in future applications.