Biomedical Engineering Reference
In-Depth Information
11.3.3.3 Human Health Dose-Response and Effect Factor
Dose metrics:
In the absence of specific epidemiological data and with a
restricted number of experimental data on the impact of nanoparticle on
higher organisms, compared with the large range of different nanoparticles
produced, major uncertainties remain regarding their impact on human
health.
133
The very same aspects that make these materials so interesting for
a vast range of technological applications renders their impact on human
health difficult to predict: they may have entirely different behavior com-
pared with the bulk materials they are made from. Oberdörster et al.
134
demonstrated how TiO
2
, nontoxic in its bulk form, shows toxic effects as
a nanoparticle. Choi and Hu
135
studied Ag nanoparticles of different sizes
and found that those with diameters <5 nm were more toxic to bacteria not
only compared with bulk size Ag but also larger nanoparticular Ag. They
also attributed the toxic effects to the generation of reactive oxygen species
in cells. Physico-chemical parameters such as size and surface area may be
important modifiers of uptake mechanisms, dose, and toxicity (e.g., Wahreit
et al.
80
and Roser et al.
136
).
Traditionally, risk and LCA assessments evaluate dose-response relations
on the basis of mass concentration or dose, and assess risks by comparing
exposure levels to these mass-based doses.
137
Because of the unique prop-
erties of some nanometer-scale particles, using mass as the sole basis for
determining toxicity has previously resulted in erroneous findings, includ-
ing equivocal results of toxicological studies on similar materials in different
test systems.
138 -140
Many of the existing indicators and data are therefore not
applicable or representative for their toxicological behavior. Nano-specific
metrics such as surface area or particle sizes and number need to be tested
and eventually included in dose-response models that currently only
account for mass-based exposure.
Types of endpoints:
On a cellular level, nanoparticles may (i) penetrate
cell membranes
141,142
; (ii) penetrate further into mitochondrion and nucleus,
potentially inducing toxic effects including DNA damage, oxidative stress,
and inflammation on tissue-scale level
143 -147
; (iii) cause oxidative damage to
cells via promotion of oxyradicals
148
; and (iv) alter the expression of cancer
genes
149
and genes involved in cell signaling.
150
Mobility of nanoparticles was
observed within higher organisms showing that after inhalation they might
be transported via the bloodstream from the lung into other organs such as
the heart, brain, or liver where a fraction might be found months after expo-
sure has stopped.
107,141,151,152
Toxic effects such as pulmonary fibrosis and lung
tumor formation were observed in rats.
153
A major issue with many current toxicity studies is the uncertainty about
realistic environmental concentrations of nanoparticles. Handy et al.
154
argue that the concentrations applied in the majority of toxicity studies
is of unknown environmental relevance. In line with Luoma,
155
the Royal
Commission on Environmental Pollution
156
and the European Commission
157
