Nanotechnology/Health effects of nanoparticles

=Nanotoxicology: Health effects of nanotechnology=

The environmental impacts of nanotechnology have become an increasingly active area of research.

Until recently the potential negative impacts of nanomaterials on human health and the environment have been rather speculative and unsubstantiated.

However, within the past number of years several studies have indicated that exposure to specific nanomaterials, e.g. nanoparticles, can lead to a gamut of adverse effects in humans and animals, , .

This has made some people very concerned drawing specific parallels to past negative experiences with small particles ,.

Some types of nanoparticles are expected to be benign and are FDA approved and used for making paints and sunscreen lotion etc. However, there are also dangerous nanosized particles and chemicals that are known to accumulate in the food chain and have been known for many years:
 * Asbestos
 * Diesel particulate matter
 * ultra fine particles
 * DDT
 * lead

The problem is that it is difficult to extrapolate experience with bulk materials to nanoparticles because their chemical properties can be quite different. For instance, anti-bacterial silver nanoparticles dissolve in acids that would not dissolve bulk silver, which indicates their increased reactivity.

An overview of some exposure cases for humans and the environment shown in the table. For an overview of nanoproducts see the section Nanotech Products in this book.

The peer-reviewed journal Nanotoxicology is dedicated to Research relating to the potential for human and environmental exposure, hazard and risk associated with the use and development of nano-structured materials. Other journals also report on the research, for see the full Nano-journal list in this book.

Nanoecotoxicology
In response to the above concerns a new field of research has emergence termed “nano(eco-)toxiciolgoy” defined as the “science of engineered nanodevices and nanostructures that deals with their effects in living organisms” .

In the following we will first try to explain why some people are concerned about nanomaterials and especially nanoparticles. This will lead to a general presentation of what is known about the hazardous properties of nanoparticles in the field of the environment and nanoecotoxicology. This includes a discussion of the main areas of uncertainty and gaps of knowledge.

Human or ecotoxicology
The focus of this chapter is on the ecotoxicological - and environmental effects of nanomaterials, however references will be made to studies on human toxicology where it is assumed that such analogies are warranted or if studies have provided new insights that are relevant to the field of nanoecotoxicology as well. As further investigations are made, more knowledge will be gained about human toxicology of nanoparticles.

=Production and applications of nanotechnology=

At present the global production of nanomaterials is hard to estimate for three main reasons:
 * Firstly, the definition of when something is “nanotechnology” is not clear-cut.
 * Secondly, nanomaterials are used in a great diversity of products and industries and
 * Thirdly, there is a general lack of information about what and how much is being produced and by whom.

In 2001 the future global annual production of carbon-based nanomaterials was estimated to be several hundred tons, but already in 2003 the global production of nanotubes alone was estimated to be around 900 tons distributed between 16 manufacturers .

The Japanese company, Frontier Carbon Corp, plan to start an annual production of 40 tons of C60 .

It is estimated that the global annual production of nanotubes and fiber was 65 tons equal to €144 million worth and it is expected to surpass €3 billion by 2010 representing an annual growth rate of well over 60% .

Even though the information about the production of carbon-based nanomaterials is scarce, the annual production volumes of for instance quantum dots, nano-metals, and materials with nanostructured surfaces are completely unknown.

The development of nanotechnology is still in its infancy, and the current production and use of nanomaterials is most likely not representative for the future use and production. Some estimates for the future manufacturing of nanomaterials have been made. For instance the Royal Society and the Royal Academy of Engineering estimated that nanomaterials used in relation to environmental technology alone will increase from 10 tons per year in 2004 to between 1000-10.000 tons per year before 2020. However, the basis of many of these estimations is often highly unclear and the future production will depend on a number of things such as for instance:


 * 1) Whether the use of nanomaterials indeed entails the promised benefits in the long run;
 * 2) which and how many different applications and products will eventually be developed and implemented;
 * 3) And on how nanotechnology is perceived and embraced by the public?

With that said, the expectations are enormous. It is estimated that the global market value of nano-related products will be U.S. $1 trillion in 2015 and that potentially 7 million jobs will be created globally ,

=Exposure of environment and humans= Exposure of nanomaterials to workers, consumers, and the environment seems inevitable with the increasing production volumes and the increasing number of commercially available products containing nanomaterials or based on nanotechnology .

Exposure is a key element in risk assessment of nanomaterials since it is a precondition for the potential toxicological and ecotoxicological effects to take place. If there is no exposure – there is no risk. Nanoparticles are already being used in various products and the exposure can happen through multiple routes.

Human routes of exposure are:
 * dermal (for instance through the use of cosmetics containing nanoparticles);
 * inhalation (of nanoparticles for instance in the workplace);
 * ingestion (of for instance food products containing nanoparticles);
 * and injection (of for instance medicine based on nanotechnology).

Although there are many different kinds of nanomaterials, concerns have mainly been raised about free nanoparticles ,.

Free nanoparticles could either get into the environment through direct outlet to the environment or through the degradation of nanomaterials (such as surface bound nanoparticles or nanosized coatings).

Environmental routes of exposure are multiple.

One route is via the wastewater system. At the moment research laboratories and manufacturing companies must be assumed to be the main contributor of carbon-based nanoparticles to the wastewater outlet.

For other kinds of nanoparticles for instance titanium dioxide and silver, consumer products such as cosmetics, crèmes and detergents, is a key source already and discharges must be assumed to increase with the development of nanotechnology.

However, as development and applications of these materials increases this exposure pattern must be assumed to change dramatically. Traces of drugs and medicine based on nanoparticles can also be disposed of through the wastewater system into the environment.

Drugs are often coated, and studies have show that these coatings can be degraded through either metabolism inside the human body or transformation in environment due to UV-light . Which only emphasises the need to studying the many possible process that will alter the properties of nanoparticles once they are released in nature.

Another route of exposure to the into the environment is from wastewater overflow or if there is an outlet from the wastewater treatment plant where nanoparticles are not effectively held back or degraded.

Additional routes of environmental exposure are spills from production, transport, and disposal of nanomaterials or products .

While many of the potential routes of exposure are uncertain scenarios, which need confirmation, the direct application of nanoparticles, such as for instance nano zero valent iron for remediation of polluted areas or groundwater, is one route of exposure that will certainly lead to environmental exposure. Although, remediation with the help of free nanoparticles is one of the most promising environmental nanotechnologies, it might also be one the one raising the most concerns. The Royal Society and The Royal Academy of Engineering actually recommend that the use of free nanoparticles in environmental applications such as remediation should be prohibited until it has been shown that the benefits outweigh the risks.

The presence of manufactured nanomaterials in the environment is not widespread yet, it is important to remember that the concentration of xenobiotic organic chemicals in the environment in the past has increased proportionally with the application of these – meaning that it is only a question of time before we will find nanomaterials such as nanoparticles in the environment – if we have the means to detect them.

The size of nanoparticles and our current lack of metrological methods to detect them is a huge potential problem in relation to identification and remediation both in relation to their fate in the human body and in the environment.

Once there is a widespread environmental exposure human exposure through the environment seems almost inevitable since water- and sediment living organisms can take up nanoparticles from water or by ingestion of nanoparticles sorbed to the vegetation or sediment and thereby making transport of nanoparticles up through the food chain possible .

=Nanoecotoxicology= Despite the widespread development of nanotechnology and nanomaterials through the last 10-20 years, it is only recently that focus has been turned onto the potential toxicological effects on humans, animals, and the environment through the exposure of manufactured nanomaterials .

With that being said, it is a new development that potential negative health and environmental impacts of a technology or a material is given attention at the developing stage and not after years of application .

The term “nano(eco-)toxicology” has been developed on the request of a number of scientists and is now seen as a separate scientific discipline with the purpose of generating data and knowledge about nanomaterials effects on humans and the environment , . Toxicological information and data on nanomaterials is limited and ecotoxicological data is even more limited. Some toxicological studies have been done on biological systems with nanoparticles in the form of metals, metal oxides, selenium and carbon , however the majority of toxicological studies have been done with carbon fullerenes . Only a very limited number of ecotoxicological studies have been performed on the effects of nanoparticles on environmentally relevant species, and, as for the toxicological studies, most of the studies have been done on fullerenes. However, according to the European Scientific Committee on Emerging and Newly Identified Health Risks results from human toxicological studies on the cellular level can be assumed to be applicable for organisms in the environment, even though this of cause needs further verification. In the following a summary of the early findings from studies done on bacteria, crustaceans, fish, and plants will be given and discussed.

Bacteria
The effect of nanoparticles on bacteria is very important since bacteria constitute the lowest level and hence the entrance to the food chain in many ecosystems .

The effects of C60 aggregates on two common soil bacteria E. coli (gram negative) and B. subtilis (gram positive) was investigated by Fortner et al. on rich and minimal media, respectively, under aerobe and anaerobe conditions. At concentrations above 0.4 mg/L growth was completely inhibited in both cultures exposed with and without oxygen and light. No inhibition was observed on rich media in concentration up to 2.5 mg/L, which could be due to that C60 precipitates or gets coated by proteins in the media. The importance of surface chemistry is highlighted by the observation that hydroxylated C60 did not give any response, which is in agreement with the results obtained by Sayes et al. who investigated the toxicity on human dermal- and liver cells. The antibacterial effects of C60 has furthermore been observed by Oberdorster , who observed remarkably clearer water during experiments with fish in the aquarium with 0.5 mg/L compared to control.

Lyon et al. explored the influence of four different preparation methods of C60 (stirred C60, THF-C60, toluene-C60, and PVP-C60) on Bacillus subtilis and found that all four suspensions exhibited relatively strong antibacterial activity ranging from 0.09 ± 0.01 mg/L- 0.7 ± 0.3 mg/L, and although fractions containing smaller aggregates had greater antibacterial activity, the increase in toxicity was disproportionately higher than the associated increase in surface area.

Silver nanoparticles are increasingly used as antibacterial agent

Crustacean
A number of studies have been performed with the freshwater crustacean Daphnia magna, which is an important ecological important species that furthermore is the most commonly used organisms in regulatory testing of chemicals.

The organism can filter up to 16 ml an hour, which entails contact with large amounts of water in its surroundings. Nanoparticles can be taken up via the filtration and hence could lead to potential toxic effects . Lovern and Klaper , observed some mortality after 48 hours of exposure to 35 mg/L C60 (produced by stirring and also known as “nanoC60” or “nC60”), however 50% mortality was not achieved, and hence an LC50 could not be determined . A considerable higher toxicity of LC50 = 0.8 mg/L is obtained when using nC60 put into solution via the solvent tetrahydrofuran (THF) – which might indicate that residues of THF is bound to or within the C60-aggreggates, however whether this is the case in unclear at the moment. The solubility of C60 using sonication has also been found to increase toxicity , whereas unfiltered C60 dissolved by sonication has been found to cause less toxicity (LC50 = 8 mg/L). This is attributed to the formation of aggregates, which causes a variation of the bioavailability to the different concentrations. Besides mortality, deviating behavior was observed in the exposed Daphnia magna in the form of repeated collisions with the glass beakers and swimming in circles at the surface of the water . Changes in the number of hops, heart rate, and appendage movement after subtoxic levels of exposure to C60 and other C60-derivatives . However, Titanium dioxide (TiO2) dissolved via THF has been observed to cause increased mortality in Daphania magna within 48 hours (LC50= 5.5 mg/L), but to a lesser extent than fullerenes, while unfiltered TiO2 dissolved by sonication did not results in a increasing dose-response relationship, but rather a variation response . Lovern and Klaper have furthermore investigated whether THF contributed to the toxicity by comparing TiO2 manufactured with and without THF and found no difference in toxicity and hence concluded that THF did not contribute to neither the toxicity of TiO2 or fullerenes.

Experiments with the marine species Acartia tonsa exposed to 22.5 mg/L stirred nC60 have been found to cause up to 23% mortality after 96 hours, however mortality was not significantly different from control25. And exposure of Hyella azteca by 7 mg/L stirred nC60 in 96 hours did not lead to any visible toxic effects – not even by administration of C60 through the feed .

Only a limited number of studies have investigated long-term exposure of nanoparticles to crustaceans. Chronic exposure of Daphnia magna with 2.5 mg/L stirred nC60 was observed to cause 40% mortality besides causing sub-lethal effects in the form of reduced reproducibility (fewer offspring) and delayed shift of shield . Templeton et al. observed an average cumulative life-cycle mortality of 13 ± 4% in an Estuarine Meiobenthic Copepod Amphiascus tenuiremis after being exposed to SWCNT, while mean life-cycle mortalities of 12 ± 3, 19 ± 2, 21 ± 3, and 36 ± 11 % were observed for 0.58, 0.97, 1.6, and 10 mg/L.

Exposure to 10 mg/L showed: Templeton also observed that exposure to 1.6 mg/L caused a significantly increase in development rate of 1 day faster, whereas a 6 day significant delay was seen for 10 mg/L.
 * 1) significantly increased mortalities for the naupliar stage and cumulative life-cycle;
 * 2) a dramatically reduced development success to 51% for the nauplius to copepodite window, 89% for the copepodite to adult window, and 34% overall for the nauplius to adult period;
 * 3) a significantly depressed fertilization rate averaging only 64 ± 13%.

Fish
A limited number of studies have been done with fish as test species. In a highly cited study Oberdorster found that 0.5 mg/L C60 dissolved in THF caused increased lipid peroxidation in the brain of largemouth bass (Mikropterus salmoides). Lipid peroxidation was found to be decreased in the gills and the liver, which was attributed to reparation enzymes. No protein oxidation was observed in any of the mentioned tissue, however a discharge of the antioxidant glutathione occurred in the liver possibility due to large amount of reactive oxygen molecules stemming from oxidative stress caused by C60 .

For Pimephales promelas exposured to 1 mg/L THF-dissolved C60, 100 % mortality was obtained within 18 hours, whereas 1 mg/L C60 stirred in water did not lead to any mortality within 96 hours. However, at this concentration inhibition of a gene which regulates fat metabolism was observed. No effect was observed in the species Oryzia latipes at 1 mg/L stirred C60, which indicates different inter-species sensitivity toward C60 ,.

Smith et al. observed a dose-dependent rise in ventilation rate, gill pathologies (oedema, altered mucocytes, hyperplasia), and mucus secretion with SWCNT precipitation on the gill mucus in juvenile rainbow trout.

Smith et al. also observed:
 * dose-dependent changes in brain and gill Zn or Cu, partly attributed to the solvent;
 * a significant increases in Na+K+ATPase activity in the gills and intestine;
 * a significant dose-dependent decreases in TBARS especially in the gill, brain and liver;
 * and a significant increases in the total glutathione levels in the gills (28 %) and livers (18 %), compared to the solvent control (15 mg/l SDS).
 * Finally, they observed increasing aggressive behavior; possible aneurisms or swellings on the ventral surface of the cerebellum in the brain and apoptotic bodies and cells in abnormal nuclear division in liver cells.

Recently Kashiwada 29 reported observing 35.6% lethal effect in embryos of the medaka Oryzias latipes (ST II strain) exposed to 39.4 nm polystyrene nanoparticles at 30 mg/L, but no mortality was observed during the exposure and postexposure to hatch periods at exposure to 1 mg/L. The lethal effect was observed to increase proportionally with the salinity, and 100% complete lethality occurred at 5 time higher concentrated embryo rearing medium. Kashwada also found that 474 nm particles showed the highest bioavailability to eggs, and 39.4 nm particles were confirmed to shift into the yolk and gallbladder along with embryonic development. High levels of particles were found in the gills and intestine for adult medaka exposed to 39.4 nm nanoparticles at 10 mg/L, and it is hypothesized that particles pass through the membranes of the gills and/or intestine and enter the circulation.

Plants
To our knowledge only one study has been performed on phytotoxicity, and it indicates that aluminum nanoparticles become less toxic when coated with phenatrene, which again underlines the importance to surface treatments in relation to the toxicity of nanoparticles .

=Identification of key hazard properties= Size is the general reason why nanoparticles have become a matter of discussion and concern.

The very small dimensions of nanoparticles increases the specific surface area in relation to mass, which again means that even small amounts of nanoparticles have a great surface area on which reactions could happen.

If a reaction with chemical or biological components of an organism leads to a toxic response, this response would be enhanced for nanoparticles. This enhancement of the inherent toxicity is seen as the main reason why smaller particles are generally more biologically active and toxic that larger particles of the same material .

Size can cause specific toxic response if for instance nanoparticles will bind to proteins and thereby change their form and activity, leading to inhibition or change in one or more specific reactions in the body .

Besides the increased reactivity, the small size of the nanoparticles also means that they can easier be taken up by cells and that they are taken up and distributed faster in organism compared to their larger counterparts ,.

Due to physical and chemical surface properties all nanoparticles are expected to absorb to larger molecules after uptake in an organism via a given route of uptake .

Some nanoparticles such as fullerene derivates are developed specifically with the intention of pharmacological applications because of their ability of being taken up and distributed fast in the human body, even in areas which are normally hard to reach – such as the brain tissue . Fast uptake and distribution can also be interpreted as a warning about possible toxicity, however this need not always be the case . Some nanoparticles are developed with the intension of being toxic for instance with the purpose of killing bacteria or cancer cells , and in such cases toxicity can unintentionally lead to adverse effects on humans or the environment.

Due to the lack of knowledge and lack of studies, the toxicity of nanoparticles is often discussed on the basis of ultra fine particles (UFPs), asbestos, and quartz, which due to their size could in theory fall under the definition of nanotechnology ,.

An estimation of the toxicity of nanoparticles could also be made on the basis of the chemical composition, which is done for instance in the USA, where safety data sheets for the most nanomaterials report the properties and precautions related to the bulk material .

Within such an approach lies the assumption that it is either the chemical composition or the size that is determining for the toxicity. However, many scientific experts agree that that the toxicity of nanoparticles cannot and should not be predicted on the basis of the toxicity of the bulk material alone ,.

The increased surface area-to-mass ratio means that nanoparticles could potentially be more toxic per mass than larger particles (assuming that we are talking about bulk material and not suspensions), which means that the dose-response relationship will be different for nanoparticles compared to their larger counterparts for the same material. This aspect is especially problematic in connection with toxicological and ecotoxicological experiments, since conventional toxicology correlates effects with the given mass of a substance ,.

Inhalation studies on rodents have found that ultrafine particles of titanium dioxide causes larger lung damage in rodents compared to larger fine particles for the same amount of the substance. However, it turned out that ultra fine- and fine particles cause the same response, if the dose was estimated as surface area instead of as mass .

This indicates that surface area might be a better parameter for estimating toxicity than concentration, when comparing different sizes of nanoparticles with the same chemical composition5. Besides surface area, the number of particles has been pointed out as a key parameter that should be used instead of concentration . Although comparison of ultrafine particles, fine particles, and even nanoparticles of the same substance in a laboratory setting might be relevant, it is questionable whether or not general analogies can be made between the toxicity of ultrafine particles from anthropogenic sources (such as cooking, combustion, wood-burning stoves, etc.) and nanoparticles, since the chemical composition and structure of ultrafine particles is very heterogeneous when compared to nanoparticles which will often consists of specific homogeneous particles . From a chemical viewpoint nanoparticles can consist of transition metals, metal oxides, carbon structures and in principle any other material, and hence the toxicity is bound to vary as a results of that, which again makes in impossible to classify nanoparticles according to their toxicity based on size alone .

Finally, the structure of nanoparticles has been shown to have a profound influence on the toxicity of nanoparticles. In a study comparing the cytotoxicity of different kinds of carbon-based nanomaterials concluded that single walled carbon nanotubes was more toxic that multi walled carbon nanotubes which again was more toxic than C60 .

=Hazard identification=

In order to complete a hazard identification of nanomaterials, the following is ideally required
 * ecotoxicological studies
 * data about toxic effects
 * information on physical-chemical properties
 * Solubility
 * Sorption
 * biodegradability
 * accumulation
 * and all likely depending on the specific size and detailed composition of the nanoparticles

In addition to the physical-chemical properties normally considered in relation to chemical substances, the physical-chemical properties of nanomaterials is dependent on a number of additional factors such as size, structure, shape, and surface area. Opinions on, which of these factors are important differ among scientists, and the identification of key properties is a key gap of our current knowledge ,, . There is little doubt that the physical-chemical properties normally required when doing a hazard identification of chemical substances are not representative for nanomaterials, however there is at current no alternative methods. In the following key issues in regards to determining the destiny and distribution of nanoparticles in the environment will be discussed, however the focus will primarily be on fullerenes such as C60.

Solubility
Solubility in water is a key factor in the estimation of the environmental effects of a given substance since it is often via contact with water that effects-, or transformation, and distribution processes occur such as for instance bioaccumulation.

Solubility of a given substance can be estimated from its structure and reactive groups. For instance, Fullerenes consist of carbon atoms, which results in a very hydrophobic molecule, which cannot easily be dissolved in water. Fortner et al. have estimated the solubility of individual C60 in polar solvents such as water to be 10-9 mg/L. When C60 gets in contact with water, aggregates are formed in the size range between 5-500 nm with a greater solubility of up to 100 mg/L, which is 11 orders of magnitude greater than the estimated molecular solubility. This can, however, only be obtained by fast and long-term stirring in up to two months. Aggregates of C60 can be formed at pH between 3.75 and 10.25 and hence also by pH-values relevant to the environment . As mentioned the solubility is affected by the formation of C60 aggregates, which can lead to changes in toxicity .

Aggregates form reactive free radicals, which can cause harm to cell membranes, while free C60 kept from aggregation by coatings do not form free radical . Gharbi et al. point to the accessibility of double bonds in the C60 molecule as an important precondition for its interactions with other biological molecules.

The solubility of C60 is less in salt water, and according to Zhu et al. only 22.5 mg/L can be dissolved in 35 ‰ sea water. Fortner et al. have found that aggregate precipitates from the solution in both salt water and groundwater with an ionic strength above 0.1 I, but aggregates would be stable in surface- and groundwater, which typically have an ionic strength below 0.5 I. The solubility of C60 can be increased to about 13,000-100,000 mg/L by chemically modifying the C60–molecule with polar functional groups such as hydroxyl . The solubility can furthermore be increased by the use of sonication or the use of none-polar solvents.

C60 will neither behave as molecules nor as colloids in aqueous systems, but rather as a mixture of the two ,.

The chemical properties of individual C60 such as the log octanol-water partitioning coefficient (log Kow) and solubility are not appropriate in regard to estimating the behavior of aggregates of C60. Instead properties such as size and surface chemistry should be applied a key parameters 18.

Just as the number of nanomaterials and the number of nanoparticles differ greatly so does the solubility of the nanoparticles. For instance carbon nanotubes have been reported to completely insoluble in water . It should be underlined that which method is used to solute nanoparticles is vital when performing and interpreting environmental and toxicological tests.

Evaporation
Information about evaporation of C60 from aqueous suspensions has so far not been reported in the literature and since the same goes for vapor pressure and Henry’s constant, evaporation cannot be estimated for the time being. Fullerenes are not considered to evaporate – neither from aqueous suspension or solvents – since the suspension of C60 using solvents still entails C60 after evaporation of the solvent ,.

Sorption
According to Oberdorster et al. nanoparticles will have a tendency to sorb to sediments and soil particles and hence be immobile because of the great surface area when compared to mass. Size alone will furthermore have the effect that the transport of nanoparticles will be dominated by diffusion rather than van der Waal forces and London forces, which increases transport to surfaces, but it is not always that collision with surfaces will lead to sorption . For C60 and carbon nanotubes the chemical structure will furthermore result in great sorption to organic matter and hence little mobility since these substances consists of carbon. However, a study by Lecoanet et al. 45 found that both C60 and carbon nanotubes are able to migrate through porous medium analogous to a sandy groundwater aquifer and that C60 in general is transported with lower velocity when compared to single walled carbon nanotubes, fullerol, and surface modified C60. The study further illustrates that modification of C60 on the way to - or after - the outlet into the environment can profoundly influence mobility. Reactions with naturally occurring enzymes , electrolytes or humid acid can for instance bind to the surface and make thereby increase mobility , just as degradation by UV-light or microorganisms could potentially results in modified C60 with increased mobility 45.

Degradability
Most nanomaterials are likely to be inert , which could be due to the applications of nanomaterials and products, which is often manufactured with the purpose of being durable and hard-wearing. Investigations made so far have however showed that fullerene might be biological degradable whereas carbon nanotubes are consider biologically non-degradable , . According to the structure of fullerenes, which consists of carbon only, it is possible that microorganisms can use carbon as an energy source, such as it happens for instance with other carbonaceous substances.

Fullerenes have been found to inhibit the growth of commonly occurring soil- and water bacteria ,, which indicates that toxicity can hinder degradability. It is, however, possible that biodegradation can be performed by microorganisms other than the tested microorganisms, or that the microorganism adapt after long-term exposure. Besides that C60 can be degraded by UV-light and O. UV-radiation of C60 dissolved in hexane, lead to a partly or complete split-up of the fullerene structure depending on concentration .

Bioaccumulation
Carbon based nanoparticles are lipophilic which means that they can react with and penetrate different kinds of cell membranes . Nanomaterials with low solubility (such as C60) could potentially accumulate in biological organisms , however to the best of our knowledge no studies have been performed investigating this in the environment. Biokinetic studies with C60 in rats result in very little excretion which indicates an accumulation in the organisms . Fortner et al. estimates that it is likely that nanoparticles can move up through the food chain via sediment consuming organisms, which is confirmed by unpublished studies performed at Rice University, U.S. Uptake in bacteria, which form the basis for many ecosystems, is also seen as a potential entrance to whole food chains .

=Surface chemistry and coatings= In addition to the physical and chemical composition of the nanoparticles, it is important to consider any coatings or modifications of a given nanoparticles .

A study by Sayes et al. found that the cytotoxicity of different kinds of C60-derivatives varied by seven orders of magnitude, and that the toxicity decreased with increasing number of hydroxyl- and carbonyl groups attached to the surface. According to Gharbi et al. , it is in contradiction to previous studies, which is supported by Bottini et al. who found an increased toxicity of oxidized carbon nanotubes in immune cells when compared to pristine carbon nanotubes.

The chemical composition of the surface of a given nanoparticle influences both the bioavailability and the surface charge of the particle, both of which are important factors for toxicology and ecotoxicology. The negative charge on the surface of C60 is suspected to be able to explain these particles ability to induce oxidative stress in cells .

The chemical composition also influences properties such as lipophilicity, which is important in relation to uptake through cells membranes in addition to distribution and transport to tissue and organs in the organisms5. Coatings can furthermore be designed so that they are transported to specific organs or cells, which has great importance for toxicity .

It is unknown, however, for how long nanoparticles stay coated especially inside the human body and/or in the environment, since the surface can be affected by for instance light if they get into the environment. Experiments with non-toxic coated nanoparticles, turned out to be very cell toxic after 30 min. exposure to UV-light or oxygen in air .

=Interactions in the Environment= Nanoparticles can be used to enhance the bioavailability of other chemical substances so that they are easily degradable or harmful substances can be transported to vulnerable ecosystems .

Besides the toxicity of the nanoparticles itself, it is furthermore unclear whether nanoparticles increases the bioavailability or toxicity of other xenobiotics in the environment or other substances in the human body. Nanoparticles such as C60 have many potential uses in for instance in medicine because of their ability to transport drugs to parts of the body which are normally hard to reach. However, this property is exactly what also may be the source to adverse toxic effects . Furthermore research is being done into the application of nanoparticles for spreading of contaminants already in the environment. This is being pursued in order to increase the bioavailability for degradation of microorganisms 54, however it may also lead to increase uptake and increased toxicity of contaminants in plants and animals, but to the best of our knowledge, no scientific information is available that supports this ,.

=Conclusion= It is still too early to determine whether nanomaterials or nanoparticles are harmful or not, however the effects observed lately have made many public and governmental institutions aware of , .
 * 1) the lack of knowledge concerning the properties of nanoparticles
 * 2) the urgent need for a systematic evaluation of the potential adverse effect of Nanotechnology

Furthermore, some guidance is needed as to which precautionary measures are warranted in order to encourage the development of “green nanotechnologies” and other future innovative technologies, while at the same time minimizing the potential for negative surprises in the form of adverse effects on human health and/or the environment.

It is important to understand that there are many different nanomaterials and that the risk they pose will differ substantially depending on their properties. At the moment it is not possible to identify which properties or combination of properties make some nanomaterials harmful and which make them harmless, and properly it will depend on the nanomaterial is question. This makes it is extremely difficult to do risk assessments and life-cycle assessment of nanomaterials because, in theory, you would have to do a risk assessment for each of the specific variation of nanomaterial – a daunting task!

=Contributors to this page= This material is based on notes by
 * Steffen Foss Hansen, Rikke Friis Rasmussen, Sara Nørgaard Sørensen, Anders Baun. Institute of Environment & Resources, Building 113, NanoDTU Environment, Technical University of Denmark
 * Stig Irving Olsen, Institute of Manufacturing Engineering and Management, Building 424, NanoDTU Environment, Technical University of Denmark
 * Kristian Mølhave, Dept. of Micro and Nanotechnology - DTU - www.mic.dtu.dk

=References=

See also notes on editing this book about how to add references Nanotechnology/About.