Nanotechnology White Paper - US Environmental Protection Agency

56 EPA Nanotechnology White Paper
example, 1 nm particles are preferentially deposited in the nasopharyngeal region while 5nm
particles are deposited throughout the lung and 20 nm particles are preferentially deposited in the
distal lung within the alveolar gas exchange region (Oberdörster et al., 2005a). Host
susceptibility factors such as pre-existing lung disease significantly affect the amount and
location of particles deposited within the lung. For example, individuals with chronic obstructive
pulmonary disease have 4-fold higher levels of particles deposited in their upper bronchioles
when compared to health individuals exposed to the same concentration of particles (U.S. EPA,
2004). Also, pulmonary deposited ultrafine particles can evade the normal pulmonary clearance
mechanisms and translocate by a variety of pathways to distal organs (Oberdörster et al. 2004a,
2005a; Kreyling et al., 2002; Renwick et al., 2001). Additional studies that provide information
on the deposition and fate of inhaled nanomaterials include studies in animals (Takenaka et al.,
2001; Oberdörster et al., 2002) and studies in humans (Brown et al., 2002; Chalupa et al., 2004).
The deposition and fate of the class of nanomaterials called dendrimers have been
examined to some degree due to their potential drug delivery applications (Malik et al 2000;
Nigavekar et al., 2004.). Both studies demonstrated the critical role which surface charge and
chemistry play in regulating the deposition and clearance of dendrimers in rodents.
A significant amount of intradermally injected nanoscale quantum dots were found to
disperse into the surrounding viable subcutis and to draining lymph nodes via subcutaneous
lymphatics (Roberts, D.W. et al., 2005). Other studies (Tinkle et al., 2003) have shown
enhanced penetration of submicron fluorospheres into the stratum corneum of human skin
following dermal application and mechanical stimulation. Drug delivery studies using model
wax nanoparticles have provided evidence that nanoparticle surface charge alters blood-brain
barrier integrity and permeability (Lockman et al., 2004). It has recently been reported that
quantum dots with different physicochemical properties (size, shapes, coatings) penetrated the
stratum corneum and localized within the epidermal and dermal layers of intact porcine skin
within a maximum 24 hours of exposure (Ryman-Rasmussen et al., 2006). A recent review
noted that quantum dots cannot be considered a uniform group of substances, and that size,
charge, concentration, coating, and oxidative, photolytic, and mechanical stability are
determining factors in quantum dot toxicity as well as their absorption, distribution, metabolism
and excretion (Hardman, 2006). Toxicological studies have demonstrated the direct cellular
uptake of multi-walled carbon nanotubes by human epidermal keratinocytes (Monteiro-Riviere et
al., 2005).
Very little is known regarding the deposition and fate of other types or classes of
intentionally produced nanomaterials following inhalation, ingestion, or dermal exposures.
Knowledge of tissue and cell specific deposition, fate and persistence of engineered or
manufactured nanomaterials, as well as factors such as host susceptibility and nanoparticle
physicochemical properties regulating their deposition and fate, is needed to determine exposuredose-response
relationships associated with various routes of exposures. Information on the fate
of nanomaterials is needed to assess their persistence in biological systems, a property that
regulates accumulation of these particles to levels that may produce adverse health effects
following long-term exposures to low concentrations of these particles.