3.9.2 Exposure Assessment Approaches
The following section is based on human health experiments and observations although some observations may also be relevant for other species.
The respiratory tract acts as a serial filter system and in each of its compartments (nose, larynx, airways, and alveoli) the predominance of characteristic physical mechanisms of particle deposition may change. In addition, these mechanisms significantly change with particle size. Nanoparticles are primarily displaced by Brownian motion and therefore underlie diffusive transport and deposition mechanisms. In practice it means that the smaller the particle the higher is the probability of a particle to reach the epithelium of the lung.
Motor vehicle emissions usually constitute the most significant source of nanoparticles in an urban environment. The relationship to traffic volumes indicates that the accumulation mode particles are associated with emissions from heavy-duty traffic (mainly diesel vehicles) whilst particles in the range 30–60nm show a stronger association with light duty traffic. Both of these size fractions show the anticipated dilution effect with increasing wind speed (Charron and Harrison 2003).
Combustion of fossil fuels, especially in diesel engines, produces waste by-products, including nanoparticles. Today, these combustion waste nanosized particles constitute the most important source of anthropogenic nanoparticles.
Exposure, uptake, distribution and degradation of nanoparticles from the environment have been recently discussed by Oberdörster G et al. (2005). They believe that nanomaterials are likely to enter the environment for several reasons. With nanomaterials now being manufactured in large quantities, it is argued that manufacturing effluent and spillage, use and disposal through landfill, will inevitably result in environmental exposure. Moreover these materials are being used in personal- care products such as cosmetics and sunscreens, which can enter the environment on a continual basis from washing off of consumer products. However, it should be said that currently very little is known about the behaviour of nanoparticles in the environment. One study has shown that iron nanoparticles can travel within ground water over a distance of 20 m and remain reactive for 4-8 weeks (Zhang 2003).
Based on the systematic study by the Institute of Occupational Medicine for the UK Health and Safety Executive it may be assumed that there are a few main industrial activities in which exposure to nanoparticles may occur (HSE 2004):
- Nanotechnology sector, primary research development (universities and other research groups and spin-offs);
- Existing chemical and pharmaceutical companies;
- Powder handling processes including paints, pigments and cement manufacture;
- Other processes where the nanoparticles are by-products.
The potential risks following occupational exposure were also discussed in the same report, summarised in Table 2 (HSE 2004)
Table 2. The potential risks following occupational exposure to nanoparticles
Also in the same report (HSE, 2004) it was estimated that the number of workers in the UK who may be exposed to manufactures nanoparticles in the work environment in the university sector and in emerging nanoparticle companies may be as high as 2,000. Around 100,000 individuals may potentially be exposed to fine powders through various powder handling processes. It is not possible to say what proportion of these may be exposed to nanoparticles. More than 1,000,000 workers in the UK may be exposed to nanoparticles via incidental production in processes such as welding and refining (Aitken et al 2004). In the U.S., an estimated 2 million people work with nanometre-diameter particles on a regular basis in the development, production, and use of nanomaterials or products, this being based on national industry-specific occupational employment estimates by the U.S. Department of Labor’s Bureau of Labor Statistics for the year 2000. If growth in nanotechnology-related industries meets expectations, a similar number of additional workers will be required globally (NIOSH 2005). It should be emphasized that although some industrial processes have involved nanoscale compounds (e.g. carbon black, welding, etc) for decades, occupational exposure data, including size and mass of the particles, is very scarce.
The aim of one major workplace study (BIA 2003) was to gather and catalogue technical measurement information on nanoparticles occurring at different work processes, where those nanoparticles had been released occasionally as by-products of technical processes. Typical examples include welding fumes, metal fumes, soldering fumes, plasma cutting fumes, plasma spraying emissions, polymer fumes, vulcanisation fumes, amorphous silicic acids, powder coating emissions, oil mists, aircraft engine emissions, bakery oven emissions, meat smokery fumes, and particulate diesel motor emissions. The particles were for the most part the products of condensation in thermal and chemical reactions, the primary particles created having a size of only a few nanometres. The most frequently-occurring particle size was between 160 and 300 nm. The total concentration of all particles in the measurement range 14 to 673 nm was between 500,000 and 2,500,000 particles per cm3. A comparison of the occurrence of nanoparticles in different workplace atmospheres is given Table 3 after Möhlmann (2004).
Table 3. Comparison of nanoparticles in workplace air
With respect to carbon nanotubes, Maynard et al (2004) carried out a laboratory based study, then complemented by a field study, in which airborne and dermal exposure to single-walled carbon nanotube material (SWCNT) was measured in 4 sampling sites where workers handled unrefined material. Estimates of nanotube concentrations ranged from 0.7 to 53 µg.m-3. Filter samples indicated that many of the particles may have been compact, rather than having an open, low density structure more generally associated with unprocessed SWCNT. Glove deposits were estimated at between 0.2 and 6 mg per hand.
Exposure to carbon black has been a major concern for decades. Furnace black account for 98% of the worldwide production and has an average aggregate diameter of 80-500 nm and an average primary particle diameter of 17-70 nm. (IARC 1996). The exposure to carbon black dust has been measured in two phases of a large multi-national study (Gardiner et al 1996). The highest mean exposure was experienced by the warehouse packers and they are also most likely to exceed the OES 3.5 mg.m-3 The range of means for 14 job titles varied from 0.3 to 10.4 mg.m-3. In another study, exposure to inhalable dust in carbon black manufacturing industry was measured during three sampling periods (from 1987 to 1995) in several European countries. Prior to the exposure measurements, all workers were categorized into 14 job titles, which were amalgamated into eight job categories. Average inhalable dust exposure (directly calculated using the exposure data, dropped from 1.3 mg.m-3 in Phase I (1987-89) to 0.8 mg.m-3 in Phase II (1991-1992) and 0.7 mg.m-3 in Phase III, 1994-95, (van Tongeren et al 2000).
There is very little data in the literature on potential exposure through the skin, even though nanomaterials have been used in cosmetics and pharmaceuticals for many years. Currently, most of the dermal exposure concerns skin preparations that use nanoparticles. A recent review of dermal exposure issues concluded that there was no evidence to indicate specific health problems are currently arising form dermal penetration of nanoparticles (HSE 2004).
In theory, harmful effects arising from skin exposure may either occur locally within the skin or alternatively the substance may be absorbed through the skin and disseminate via the bloodstream, possibly causing systemic effects, although there is no evidence of this as yet. Most studies concerning penetration of nanoparticles into the skin have focused on whether or not drugs penetrate through the skin using different formulations containing chemicals and/or particulate material as a vehicle. The main types of particulate materials commonly used are liposomes, poorly soluble solid materials such as TiO2, ZnO2 and polymer particulates and submicron emulsion particles such as solid lipid nanoparticles.
There is only limited data on the fate of nanoparticles of titanium dioxide when used in sunscreens and other products on the skin and it appears unlikely that this does not penetrate beyond the dermis. The investigations of Schulz et al. using optical and electron microscopy proved that neither surfacecharacteristics, particle size nor shape of the micronised pigments result in any dermal absorption of this substance. Micronised titanium dioxide is solely deposited on the outermost surface of the stratum corneum and has not been detected by light and electron microscopy in deeper stratum corneum layers, the human epidermis and dermis (Schulz et al 2002).
It was already recognized in 1926 (by Kumagai cited by Salata 2004) that particles could translocate from the lumen of the intestinal tract via aggregations of intestinal lymphatic tissue (Peyer’s patches), containing M cells. It is now known that uptake of inert particles can occur not only through immune cells present in Peyers’ patches but also through enterocytes, and to lesser extent across para-cellular pathways (Aprahamian et al 1987). However, once again data in the literature on potential exposure through the GI tract are very scarce.
Szenkuti (1997) observed that cationic nanometre-sized latex particles became entrapped in the negatively charged mucus, whereas repulsive carboxylated fluorescent latex nanoparticles were able to diffuse across this layer. The smaller the particle diameter the faster they could permeate the mucus to reach the colonic enterocytes; 14 nm diameter permeated within 2 min, 415 nm particles took 30 min, while 1000 nm particles were unable to cross this barrier.
After oral gavage for several days, a sparse accumulation of charged latex particulates in the lamina propria was found compared to uncharged latex nanoparticles in the same size range (Jani et al 1989). The same authors (Jani at el 1990) investigated the body distribution after translocation of polystyrene particles ranging from 50 nm to 3000 nm. Rats were fed by gavage daily for 10 days at a dose of 1,25 mg.kg-1. It was found that as much as 34% and 26% of the 50 nm and 100 nm particles were absorbed, respectively. Those larger than 300 nm were absent from the blood. No particles were detected in heart or lung tissue.