A. Fucic,     Institute for Medical Research and Occupational Health, Croatia

1.1 Introduction

The outdoor and indoor living environment, occupational exposure and lifestyle may have diverse effects on human health depending on age and gender. Segments of living conditions may be modified on an indivdual basis, such as diet, smoking or drinking habits, while the major contaminants in air, food or water can only be improved through political will, economic conditions and public awareness which is largely based on the educational level of the parties involved. Development of sustainable buildings is a significant step forward, from both economic and ecological viewpoints, though the microenvironment created in such living surroundings may present a complex radiochemical setting that could pose a potential threat to the health of its occupants. As the modern lifestyle involves spending the majority of time indoors (70–80%) (Farrow et al., 1997), indoor air quality significantly contributes to overall public health.

The construction sector is rapidly developing and over the past two decades many new materials and technologies that improve the economy and energy efficiency of buildings have been introduced. Although reliable data on the health effects of volatile organic compounds, formaldehyde, asbestos and flame retardants have been collected, legislation and control of their application and emissions remain unsatisfactory. Small children and pregnant women deserve special concern, as foetuses and small children have specific metabolism, bioaccumulation and elimination of xenobiotics. Knowledge of the health effects of dangerous gases, particles and fibres that may be emitted at room temperature from certain building furnishing materials and construction products containing radionuclides that increase indoor exposure to ionizing radiation, has to be applied by all parties involved in construction of buildings and available to their occupants. Xenobiotics in indoor air may be irritants, immunodisturbing agents, endocrine disruptors and/or carcinogens. Their mechanisms interact and overlap, provoking various diseases based on genomic and non-genomic mechanisms which are both age-and gender-specific.

1.2 Radiation

Exposure to ionizing radiation is one of the basic mechanisms of evolution. However, the nuclear weapons industry and testing, nuclear war and nuclear accidents have increased ionizing radiation in the living environment to levels to which life on Earth has not adapted during evolution.

For decades, exposure to radiation was associated with genome damage and cancer development. Recent research on the mechanisms by which ionizing radiation may increase health risk has also been focused on cardiovascular diseases and immunological disturbances. There are special cases of very complex mechanisms involved in the biological effects of radioactive isotopes which may not only be a source of radiation but, as heavy metals, such as uranium, can express also hormonal, oestrogen-like activity.

In addition to naturally occurring radon, which may be present in high concentrations in some areas depending on geological characteristics and the soil, radioisotopes from fly ash, certain granites and zirconium minerals are major sources of exposure to ionizing radiation in the indoor environment.

Indoor exposure to radon is correlated with an increased risk of lung cancer, with an excess relative risk of 10% per 100 Bq m^− 3 (Fucic et al., 2010). Causality between radon exposure and lung cancer is known for uranium miners (Vacquier et al., 2011). Genome damage caused by densely ionizing radiation of radon represents a complex interaction of DNA damage and repair capacity that can be exhausted during tissue regeneration of lung cells. Such new mechanisms explain disturbance of cell division control beyond the threshold dose rate (Madas and Balásházy, 2011). Other biological mechanisms may also appear after exposure to radon (alpha particles), such as the bystander effect (in which unirradiated cells exhibit irradiated effects as a result of signals received from nearby irradiated cells) and adaptive response (when exposure to low doses of ionizing radiation can make cells more resistant to later radiation exposure). These mechanisms result in different lung cancer aetiology between uranium miners and residential, low-dose exposures (Balásházy et al., 2009). At the individual level, the risk of radon-induced lung cancer is much higher among current cigarette smokers than among lifelong non-smokers. This was illustrated in a pooled analysis of European residential radon studies (Darby et al., 2005). For lifelong non-smokers, it was estimated that living in a home with an indoor radon concentration of 0, 100 or 800 Bq m^− 3 was associated with a risk of lung cancer death (at the age of 75) of 4, 5 or 10 per 1000 persons, respectively. However, for cigarette smokers, each of these risks is substantially greater, namely 100, 120 and 220 per 1000 persons. For former smokers, the radon-related risks are substantially lower than for those who continue to smoke, though they remain considerably higher than the risks for lifelong non-smokers. This confirms the cost-effectiveness of indoor radon control of future policies, especially if complemented with policies for smoking reduction (Groves-Kirkby et al., 2011). It should be pointed out that cigarettes are not only a major source of numerous chemical agents, the majority of which are carcinogens, but also of radioactivity, as cigarettes also contain polonium and radioactive lead (Desideri et al., 2007). Additionally, the risk of combined exposure to smoking and indoor radon is gender-specific (Truta-Popa et al., 2010). There are also inter-individual differences in radiosensitivity to radon, since for carriers of certain types of the detoxification enzyme gluthatione-S-transferase, the risk of lung cancer is three times higher (Bonner et al., 2006).

Regulation and control of radon levels in occupational and living environments has been ongoing for several decades and reflects the knowledge to date. The current opinion given by international bodies such as ICRP, WHO and IAEA agrees on an upper limit for residential indoor radon of 200–300 Bq m^− 3, which will be incorporated in their new documents in a short time (Bochicchio, 2011). However, the control of indoor radon levels and recommended remediation pertain to naturally occurring indoor radon, while there is no regulation that would control the incorporation of fly ash in concrete which may also significantly increase indoor radon levels.

Children are of special concern (Fucic et al., 2008; Holland et al., 2011) as they are more radiosensitive due to the higher cell division rate and underdeveloped xenobiotic elimination system. For this reason, radon-caused genome damage is especially dangerous in children (Bilban and Vaupotič, 2001). As radon is nine times heavier than air, small children who breathe air closer to the floor and at a higher frequency per body mass than adults (Gratas-Delamarche et al., 1993) are more exposed than adults. It could be thus suggested that recommendations for radon level in kindergartens and schools should be lower than in other buildings and the general population should be educated in how to protect children at home.

Fly ash as a by-product of thermal plants concentrates radionuclides such as uranium (²³⁵U, ²³⁸U), radium (²²⁶Ra), thorium (²³²Th), lead (²¹⁰Pb), polonium (²¹⁰Po) and potassium (⁴⁰ K) by a factor of 20 to 25 compared to levels in the original peat (European Commission, RP-112, 1999). Globally, about 280 million tonnes of coal ash is produced annually, of which 40 million tonnes is used in the production of bricks, cement, road stabilizers, road fill, and asphalt mix (UNSCEAR, 2006). From such sources, individual doses of radiation exposure to the general public can be about 100 μSv per year (Menon et al., 2003). Cement is successfully replaced with fly ash in concrete in the range from 10% to 80%. As fly ash is a hazardous waste containing toxic metals and radionuclides, its use as a construction material is encouraged as a form of waste management. Thus, fly ash has become a zero-cost raw building material that would otherwise require special waste management (Nisnevich et al., 2008) due to its physical and chemical characteristics. Similarly, the use of red mud, bauxite and clay additives should be strictly controlled from a radiation protection aspect due to the possible ²²⁶Ra and ²³²Th activity, especially when applied in the brick industry (Somlai et al., 2008).

Health effects related to exposure to uranium and thorium from fly ash are much more complex than in the case of indoor radon. As a heavy metal, uranium is a source of ionizing radiation, is highly toxic, teratogenic and embryotoxic, and has affinity to oestrogen receptors (endocrine disruption) (Bosque et al., 1993; Raymond-Whish et al., 2007).

Exposure to thorium is associated with pancreatic and lung cancer and respiratory diseases (Polednak et al., 1983). As it is a heavy metal, it can accumulate in bones and may cause bone cancer (Rosemann et al., 2006; Ottaviani and Jaffe, 2009). Like uranium, thorium probably has affinity for oestrogen receptors, although this biological mechanism has not been investigated. However, as both lung and pancreatic cancer are oestrogen related (Fucic et al., 2010) such mechanism could be involved.

The emission of radionuclides from concrete depends on its ageing; however, studies have not been conducted regarding the emission of their decay products, especially thoron in concretes where 70% of cement is replaced with fly ash (Chambers et al., 2011; Ramachandran, 2010).

A special concern is building waste which in the future will contain more radionuclides than ever before. It must also be stressed that in addition to radioactive isotopes, fly ash contains a number of other contaminants, mostly heavy metals. Emissions from ageing and microcracking concrete containing radioactive fly ash represent a mixture of radioisotopes, meaning that their biological effects also depend on their interaction. Current knowledge on the emissions of radionuclides from concrete is available from monitoring and experiments on concrete materials in nuclear facilities (Deissmann et al., 2006).

Zircon (zirconium silicate) is a mineral often used as an opacifier and pigment in the production of ceramic tiles. Its high level of radioactivity is due to its specific crystal structure, which incorporates radium (²²⁶Ra and ²²⁸Ra), uranium and thorium. Radiation emissions from ceramic tiles are specific, as radon is locked up in the tile by a glass-like matrix during the vitrification process (Xinwei, 2004), making gammaradiation the basic radiation type. Fashion and floor heating systems have increased the coverage of floors in living rooms with tiles and granite, which can significantly increase exposure to ionizing radiation compared with just decades ago when tiles were typically applied only in kitchens and bathrooms. As the radioactivity of zircon and granite vary according to geological origin, in order to control levels of exposure, activities in the future should be focused on control of their radiation emissions and limitation of the upper mass of zircon in porcelain/ceramics and granite used in indoor ambient (Selby, 2007). As in the case of indoor radon, small children and toddlers are more exposed to radiation from tiles and granite by playing on the floor.

The biological effects of radiation, like other xenobiotics, should never be estimated alone without investigating their possible interaction at the level of different biological pathways. Of course, it is also important to stress that in indoor environments sources of non-ionizing radiation are also present, such as microwave ovens, cellphones and computers, whose effects should not be neglected.

1.3 Chemical carcinogens and endocrine disruptors

Humans are exposed to hundreds of chemicals in food, water and air. Some of these chemicals are transplacental and may cause significant health risks which can be expressed later in life. Indoor air, especially in new buildings due to emissions from walls and floors, may represent a mixture of chemicals. Risk assessment of possible health effects of such mixtures is required and should include assessment of their mechanisms as toxic, carcinogenic and endocrinic either individually or as a consequence of their interactions. The majority of cancer types are related to the levels of oestrogen receptor disturbances, and thus the biological effects of chemical agents are gender-related. As lung cancer is the most frequent cancer type that could be expected from indoor air exposure, it is important to know that lung cancer differs between women and men in levels of oestrogen receptors, and this also has an impact on therapy selection and the survival prognosis (Fucic et al., 2010).

Chemical compounds in indoor air differ in the range of their preferential biological effects. New methods in xenobiotics reserch have dramatically changed our insight into the pathways involved in carcinogenesis. For example, formaldehyde was long described as a chemical that could cause irritation and nasopharyngeal cancer by inducing cell division. However, it was recently shown that formaldehyde also has an impact on signalling pathways related to cancer, inflammatory response and endocrine system regulation (Rager et al., 2011; Goldstein, 2011; Nielsen and Wolkoff, 2010). This also indicates that age differences in the biological response could be expected, as disturbance of the immunological system of an adult man could significantly differ from that in a small child whose immunological system is underdeveloped. Similar differences can be expected at the excretion level due to differences in metabolism and the rate of elimination between adults and children in whom, up to two years of age, the kidneys do not have the same clearance as in adults.

Volatile organic compounds (VOC) are a large group of chemicals used in finishing and furnishing. This is also a group of chemicals which is supported by the largest number of investigations on health effects. The highest levels of VOCs are present in new buildings and those with poor ventilation (Nielsen et al., 2007). The timing of measurements of VOCs in buildings is of major significance, as the highest levels of emissions are present during the first few months after finishing and furnishing, though this can exceed more than a year (Xu et al., 2009). As new flats and buildings are expected to be occupied by young couples, the most exposed subpopulation is therefore at the same time the most susceptible, i.e. pregnant women and children.

According to estimations the VOCs with highest indoor concentrations are toluene, xylene, styrene and 1,2,4-trimethylbenzene (Delgado-Saborit et al., 2011). Despite general awareness of the need for efficient control of indoor air emissions, the unstandardized approach to their measurements and the fact that health effects have to be interpreted as a consequence of complex radiochemical exposure and not based solely on summarizing the causality of health effects of each agent make legislation articulation difficult. This indicates the need for serious remodelling of the current evaluation system. An additional problem is that the available data on health risks concerning exposure to the majority of VOCs are related to occupational exposure and experimental models with substantially higher concentrations than in the case of indoor air in residential buildings. It can be hypothesized that lower doses may cause different health effects than those described for high doses.

Toluene, benzene and xylene exposures have been associated with asthma, especially in children (Hulin et al., 2010; Arif and Shah, 2007). In animal models toluene in low concentrations causes very complex airway inflammatory responses by modulating neuroimmune crosstalk (Shwe et al., 2007). Toluene and benzene are usually present in indoor air as a mixture. Investigation of their effect showed that they act synergistically. After in vitro exposure to toluene the induced DNA damage was repaired within 24 h after the treatment; however, after exposure to a mixture of toluene and benzene an increase in the cytotoxic effect and DNA damage was detected without any further repair (Pariselli et al., 2009). Benzene, as a known hematotoxicant and carcinogen, is shown to have more severe effects on those subjects with certain polymorphisms of immune genes (Shen et al., 2011). However, it is interesting that as a transplacental agent it causes gender-related differences in liver metabolism in animal models (Badham et al., 2010).

Styrene levels in indoor air, similar to benzene, toluene, ethylbenzene and xylenes, can originate from building material emissions and from cigarette smoke (Chambers et al., 2011). As for other VOCs, the majority of data on styrene is available for males, due to the fact that most studies are performed on workers in industry. Therefore, there are insufficient data on effects of styrene on women, pregnant women and children. According to the Final Report on the Carcinogens Background Document for Styrene of the National Toxicology Program (2008), lymphohematopoietic and pancreatic cancers are associated with exposure to styrene. The same report summarizes a large number of studies on animal and cell models showing that styrene metabolites (styrene-7,8-oxide and 4-vinylphenol) are genotoxic. In experiments much higher doses are applied than those to which occupants can be exposed in buildings. Such high doses of styrene vapours can cause also eye and respiratory tract irritation and CNS depression. Sublethal doses are associated with maternal toxicity, foetotoxicity, skeletal and kidney abnormalities, decreases in birth weight and developmental delays. There are also studies outlining endocrine effects of styrene. In animal models styrene significantly decreases testosterone levels in male mice, thus pointing out the importance of investigating its possible effects on boys during prepuberty and puberty (Takao et al., 2000).

It is also important to incorporate calculations of the transgenerational effects of VOCs in risk assessment. Very commonly glycol ether, 1-methoxy-2-propanol is shown in animal models to have an impact on three subsequent generations with regard to sex ratio, foetal loss and birth weight reduction after parental exposure (Lemazurier et al., 2005).

The constant increase in respiratory problems such as asthma, allergy and rhinitis cannot be explained only by the genetic predisposition of sensitive subpopulations (Pearce and Douwes, 2006). According to recent findings, oestrogen seems to have a strong promoting effect on asthma, which explains its higher prevalence in adult women (Tantisira et al., 2008; Shah et al., 2010; Chen et al., 2008). As a large number of VOCs are xenoestrogens, this may explain the described mechanisms in asthma etiology relating to exposure to VOCs.

Increased interest in the use of wood as a building material basically will not reduce indoor exposure to different chemicals. On the contrary, since current agents for wood preservation are characterized by much deeper penetration into the wood structure than preceding compounds, they cause emissions over longer periods of time. An example is chromated copper arsenate (CCA) which is used as a potent wood preserver. Its application enables wood to last up to 40 years, making wood building material a new item of special waste if specific procedures for its detoxification are not conducted (McLean and Beveridge, 2001). This chemical agent represents a health risk, especially for small children and pregnant women, as the chromate VI present in CCA is toxic for the foetus, while arsenic has a strong impact on oestrogen receptors (Danielsson et al., 1982; Apostoli and Catalani, 2011; Chatterjee and Chatterji, 2010; Bae-Jump et al., 2008). Despite the fact that the US EPA prohibited its application for residential uses in 2003, due to the longevity of wood preserved with this chemical it will be present in living environments for decades. The US EPA has proposed alternatives for CCA such as copper azole, cyproconazole or crioiconazole; however, all these compounds contain azoles which are aromatase inhibitors, i.e. endocrine disruptors that decrease the levels of oestrogen in living organisms and which are already in use as fungicides and in the treatment of breast cancer (Furet et al., 1993; Trosken et al., 2004).

Tight-fitting windows and doors made of plastics may increase indoor humidity, creating excellent conditions for mould growth. In addition to causing respiratory problems, exposure to moulds should be evaluated with regard to its complex impact on endocrine imbalance. Mould produces various mycotoxins, some of which are also endocrine disruptors such as ochratoxin, zearalenone and aflatoxin (Jennings-Gee et al., 2010; Tuomi et al., 2000; Storvik et al., 2011). Currently, there is insufficient research being performed on the levels of zearalenone, known to have oestrogen-like activity in buildings, despite the fact that the fungus Fusarium which produces it is one of the most common mould species in damp buildings (Saremi and Okhovvat, 2006; Jarvis and Miller, 2005; Daisey et al., 2003). The mechanisms of endocrine disruption related to exposure to mould may be seen in the gender differences in the development of asthma caused by moulds (Meyer et al., 2005). On the other hand, moulds are eliminated from the indoor environment using agents that are aromatase inhibitors, which disturb the synthesis of oestrogen in mould cell membranes, thereby halting their growth (Zarn et al., 2003), though the same effect may also be caused in exposed humans.

Ammonia may cause respiratory problems, especially in vulnerable sub-populations such as those suffering from asthma. As a concrete additive in new residential buildings, it was shown that ammonia levels remained high during the entire first year after building was finished (Jarnstrom et al., 2006). The levels of ammonia measured in such buildings (0.11 ppm) are recommended for preliminary remediation actions according to the US Environmental Protection Agency (US EPA, 2003). The possibility of elimination of ammonia levels in indoor air by extra drying of concrete to which urea-based antifreeze substances are added is rarely applied (Bai et al., 2006; Tuomainen et al., 2003).

Flame retardants responsible for saving numerous human lives could be the cause of increased sterility of men and the incidence of testicular cancer in the Western world. Recently, one possible source of reproductive diseases in men is suggested to be the flame retardants tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) (Meeker and Stapleton, 2010).

Data on the interaction of xenobiotics and effects of their mixtures are insufficient, as the basic scientific approach of the twentieth century was reductionism in which the causality between a single agent and disease was investigated. Currently, the approach taken is based on complexity which is possible with the introduction of new software and methods for multi-parametric analysis. The well-known synergism described for smoking, polyvinyl chloride and asbestos (Fucic et al., 1990; National Toxicology Program: Asbestos, Report on Carcinogens, 2005) will soon be incorporated into large systems-biology schemes. Figure 1.1 presents known biological effects and health risks related to indoor environment exposure. The expo-some of indoor air is a complex radiochemical system that soon will be evaluated as a real-time module, thus allowing an estimation of the health risk according to age, gender and metabolic characteristics, with the option of introducing new data.

Exposure of the general population to a low-quality indoor environment in low-income countries is related to increased health risks; however, the sources of indoor air contamination differ from those in developed countries. Application of lead-based paints, asbestos, cooking over an open fire, poor ventilation and insecticides, combined with poor diet and hygiene, can be recognized as contributing to the increased number of respiratory diseases, cancer and inflammations. Heavy air pollution in such countries and the free market in building materials which are prohibited in the Western world will remain an issue in the coming decades, as the world economy unfortunately still exploits these markets as a relevant source of profit.

1.4 Nanoparticles

Due to their size and chemical content, the biological effects of nanoparticles (NP) should be evaluated as both physical and chemical agents. Alongside their complex physicochemical properties the different shape and size of NPs play a significant role in their toxic potency (Borm et al., 2006). The main difference between natural and man-made NPs is in their chemical composition, unique surface chemistry and geometrical forms. Unlike natural NPs, which are mostly crystals or spheroids, artificial NPs may additionally have net and tube forms (Pacheco-Torgal and Jalali, 2011).

The health effects of NPs are more pronounced than fine particles with regard to the equivalent mass concentration. In evaluating the health risks of NPs their aggregation must also be considered as these vary in relation to their physicochemical properties (Soto et al., 2005). Contrary to the controlled transport of metal ions in living organisms, there is no such mechanism for metal oxides NPs and they can enter the cell according to their solubility. Additionally, due to their large surface area, NPs adsorb heavy metals, polyaromatic hydrocarbons, quinolines, etc., and facilitate their incorporation in organisms, which is especially dangerous for the brain as NPs easily cross the blood–brain barrier (Kahru et al., 2008).

There is no specific biomarker for measuring the level of exposure or effect of NPs on living organisms. Due to their dual nature as both physical and chemical agents, investigation of health effects after exposure to NPs is very demanding and requires investigation by multidisciplinary teams. Additionally, as certain NPs are metals which can also act as endocrine disruptors (metal oestrogens, e.g. aluminium) this makes elucidating their interaction with the living organism an even more challenging task.

Nanoparticles can be inhaled or ingested, while some cross the skin and placenta (Wu et al., 2009, Vega-Villa et al., 2008). When inhaled they can enter the systemic circulation via the lungs and also enter the brain (Oberdörster et al., 2004; Elder et al., 2006; Rückerl et al., 2007; Ferin et al., 1992; Nemmar et al., 2001). However, it is unknown how and by which dynamic NPs are eliminated from the body and whether there are age and gender differences in this process. The difference in the bioaccumulation of NPs in children can vary, as small children breathe more air than adults per body mass, and their lungs are still developing. Nanoparticles translocate to different organs after intake, though the time of translocation between organs is still not known (El-Ansary and Al-Daihan, 2009). However, the ability of NPs to enter different organs from the gastrointestinal tract has already been applied in pharmaceutical practice (El-Ansary and Al-Daihan, 2009; Balbus et al., 2007). Different and conflicting results in the investigation of the distribution of NPs in mammals can be explained by the different experimental models applied, exposure measurements and types of NPs that can significantly change the biological response (Brown et al., 2002; Mills et al., 2006; Nemmar et al., 2001). The ability of NPs to adsorb proteins, which will be used in new generations of drugs, shows that NPs may disturb signalling via receptors. This is of special concern if they are present during prenatal and postnatal development.

Pulmonary diseases related to inhaled nanoparticles seem to include reactive oxygen species (ROS) via the Fenton/Haber-Weiss reaction, deviations in mitochondrial function, inflammation and activation of cell death receptor pathways (Coultas and Strasser, 2000). The iron ion seems to play a critical role in these mechanisms. Genome damage caused by ROS produced by NPs is similar to that described for some chemicals and radiation.

Especially disturbing is the fact that NPs are transplacental agents (Oberdörster et al., 2004; Hagens et al., 2007), which may disturb brain development in the foetus (Takahashi et al., 2010) by altering blood–brain integrity (Lockman et al., 2004).

The most frequently applied NPs in building technology are TiO₂, Al₂O₃, Fe₂O₃ and SiO₂ (Pacheco-Torgal and Jalali, 2011). However, many new types of NPs are introduced each year following the needs of advanced technologies in building construction and aimed especially towards a better standard of living for occupants (Granqvist et al., 2007).

Although silicosis (Thomas and Kelley, 2010) is a well-known disease related to exposure to silica fibres, the health risks related to silica NPs are unknown. Recent results show that long nanotubes have the same inflammatory effect as asbestos (Donaldson et al., 2010). Similar in structure, nanocrystalline silica (SiO₂) has a more detrimental effect on the lungs than amorphous silica (Soto et al., 2005). Available experimental studies show that silica NPs have specific routes of bioaccumulation. It has been shown that they may even cause production of ROS in the brain at very low levels, changes in proinflammatory gene activity, genome damage and immunologic disturbances (Choi et al., 2010; Grassian et al., 2007; Gong et al., 2010). Silica NPs in sizes from 20 nm to 80 nm, which are used as cement additives, cause cytotoxicity and oxidative stress in hepatic cells (Ye et al., 2010). It is also interesting to note that NPs used in cancer radiotherapy enhance the effects of ionizing radiation (Berbeco et al., 2010; Hamoudehm et al., 2008). Experiments show that silica-based NPs increase production of ROS when they enter the brain, causing inflammation at very low concentrations (Choi et al., 2010).

Titanium dioxide is frequently used in the production of paints, paper, and plastics, welding rod-coating material and cosmetics, as it was thought to have low toxicity (Hext et al., 2005). Recent studies on rat lungs demonstrated that exposure to TiO₂ can produce differential pulmonary effects, based upon their composition and crystal structure (Warheit et al., 2007). Due to the formation of ROS and inflammation, TiO₂ may cause genome damage and gene function disturbances. As a transplacental agent in animal models it causes genome damage in the foetus of exposed dams (Dunford et al., 1997; Trouiller et al., 2009; Halappanavar et al., 2011). The significance of animal models in investigating the transdermal effect of TiO₂ is shown in a study in which TiO₂ did not penetrate through isolated porcine skin, but after 60 days of exposure through the skin of the ear in animals TiO₂ NPs were detected in the liver and brain. The most significant pathological changes were observed in skin and liver (Wu et al., 2009). It has also been shown that the pulmonary toxicity of TiO₂ depends additionally on the changes of pH in the exposed tissues. Disturbances of pH differ and are related to a combination of TiO₂ particle size and concentration, and thus pH varies in range from 3.7 to 5.3 for NP sizes of 3–20 nm and at concentrations from 0.1 to 10 mg/mL (Li et al., 2007).

Aluminium is a widely used toxic agent with several major pathways of carcinogenesis which likely include an impact on oestrogen receptors in the body. For Al₂O₃ NPs it has been shown that in addition to producing ROS they also disturb cell division and have a specific impact on genes involved in carcinogenesis (Dey et al., 2008).

There is no evidence to date as to how the ageing process of buildings influences the emission of NPs into the air. The European Construction Industry Federation performed an evaluation of safety issues concerning the use of NPs in construction. The conclusion of this evaluation was that (a) the marketing and application of NPs will grow; (b) information on NP composition is generally lacking; and (c) as health risks for workers involved in building and for consumers are unknown, a precautionary approach is suggested (van Broekhuizen and van Broekhuizen, 2009).

Silica NPs and carbon nanotubes have been introduced in the production of cement mortars and NPs (Jo et al., 2007; Nazari et al., 2010; Morsy and Aglan, 2007), in particular because they increase their quality when a higher percentage of fly ash is used (which also contains NPs) (Gilmour et al., 2004; Chaipanich et al., 2010). Application of NPs in concrete production clearly shows the need for precautionary measures, as they allow for more extensive use of fly ash which in turn increases the radioactivity of concrete. Consequently, a redefinition of building waste disposal is needed, as such building materials demand special handling similar to that required for asbestos or lead.

1.5 Conclusion and future trends

The development of building technologies is closely connected with the energy-saving demands of a growing population, significant waste issues and an economy that is attempting to be self-sustainble in balancing profit, social trends such as fashion, the need for a higher standard of living, and raising awareness of the irreversible destruction of nature. In such a social and economic environment, the construction sector is incorporating new technologies and materials which have brought a significant improvement in meeting all these demands but while also producing a new complex indoor radiochemical environment.

Living organisms have their own robustness of systems and pathways (repair, signalling adaptation, etc.) developed during evolution, which buffer the effects of variations in environmental conditions. By producing artificial microclimates in buildings which have practically no communication or exchange with the atmosphere (in the Western world very often exclusively via ventilation) the limits of achieving living homeostasis are exceeded. The health risks of indoor air cannot be analysed if isolated from other factors such as smoking habits, application of biocides, cleaning agents, air fresheners, candles, scented sticks (Singer et al., 2006), occupational exposure of occupants, and the quality of the diet.

A decrease of environmental exposure to known carcinogens such as lead or asbestos in developing countries did not slow the increase in cancer incidence in adults and children. This can be attributed to the constant introduction of new xenobiotics. However, due to the long latency period for the development of some cancer types, such as mesothelioma caused by asbestos, elimination of agents from the living environment will show a reduction of cancer incidence only in the coming decades (Marinaccio et al., 2012).

Studies evaluating the use of fly ash in the production of concrete and light concrete agree that such technology is favourable for both economic and environmental reasons. However, these technologies should be accompanied by adequate radiation protection measurements, such as regular radioactivity measurements of fly ash for each new delivery from thermal plants, as radioactivity varies among coal sources (Nisnevich et al., 2008; Kovler, 2009; Cevik et al., 2007; Turhan et al., 2011). Leaching of metals from concrete with a high percentage of fly ash is a matter for future research.

VOC levels could be controlled by issuing building use permits only after their levels due to the evaporation and ventilation processes in finished buildings drop to below those associated with health risks. However, data on the levels of VOCs in children and evaluations of their susceptibility are anecdotal and should be done in future (Adgate et al., 2004; Delfino et al., 2003). Tight-fitting windows decrease air exchange rates and lower the dilution of indoor air mass with ambient air, thus additionally increasing VOC levels. This phenomenon makes homes more isolated from the natural environment than ever before in human history. In the near future temperature, humidity, ion composition and the smell of indoor air may become a custom-made product, delivered to consumers via ventilation systems.

Nanoparticle measurement standardization must also be defined in the future, as this will enable the introduction of dose–response curves and possible threshold values for exposures related to health risks. As TiO₂ NPs are shown to increase accumulation of cadmium and other pollutants (Sun et al., 2007; Zhang et al., 2007) in the body, it is of great significance that the biological microenvironments in which NPs change their charge and other physicochemical properties be explored (Navarro et al., 2008). It could be suggested that biomonitoring of the population exposed to NPs should follow the knowledge and experience of the pharmaceutical industry, as the potency of NPs is recognized in drug production.

Human society is not able to follow large amounts of scientific data and options aimed at improving living environments. This is why strong efforts should be made towards ensuring the interdisciplinarity, education of policymakers and more dynamic incorporation of available knowledge into the legislation.

1.6 References