Biomedical Engineering Reference
In-Depth Information
furthermore point out a lack of chronic effects data for nanoparticles, with
most studies focusing on acute exposure durations.
Finally, as pointed out by Nowack et al.,
158
most of the tests in laboratory
or simulation studies that have been conducted until now are performed on
pristine nanomaterials and not on materials from the actual releases from
the nanoproducts, which may have different properties due to alterations of
transformations occurring during the nanoproduct life cycle.
Dose-response based on chronic ED50s, NOAEL, and LOAEL:
For a
restricted number of well-studied nanoparticles, chronic test on animals are
increasingly becoming available (Table 11.11).
For these particles, the approach initially proposed by Crettaz et al.
186
for
effect dose of 10% or 50%, its further development by Huijbregts et al.,
187
and
its implementation in USEtox,
8
can be used to determine effect factors as fol-
lows. Dose-response slopes are based on cancer and noncancer ED50 (effect
dose of 50%, which induces a 50% additional risk over background over
human lifetime, in kg/lifetime), applying a linear dose-response and effect
factor of EF = 0.5/ED
50
h,j
.
For carcinogenic and noncarcinogenic effects, the ED
50
h,j
adjusted for
humans (kg/person/lifetime) is derived from the animal TD
50
as follows
8
:
TD
BW LT N
AF AF
50
at j
,,
ED
=
(11.4)
50
hj
,
6
10
a
t
where TD
50
a
,
t
,
j
is the daily dose for animal
a
(e.g., rat) and time duration
t
(e.g., subchronic) per kilogram body weight that causes a disease probabil-
ity of 50% for exposure route
j
(mg/kg/day); TD
50
a
,
t
,
j
is the lowest species-
corrected harmonic mean of tumorigenic dose-rate for 50% of animals in a
chronic, lifetime cancer test; AF
a
is the extrapolation factor for interspecies
differences of 4.1 for rats and 11.3 for mice; AF
t
is the extrapolation factor for
differences in time of exposure, that is, a factor of 2 for subchronic to chronic
exposure and a factor of 5 for subacute to chronic exposure
187
; BW is the aver-
age body weight of humans (70 kg); LT is the average lifetime of humans (70
years); and
N
is the number of days per year (365 days/year).
For chemicals with no evidence of carcinogenicity, the ED
50
can also been
estimated from no observed effect level (NOEL) by a NOEL-to-ED
50
conver-
sion factor of 9. In case only a LOEL is available, a LOEL-to-ED
50
conversion
factor of 2.25 can be applied. New developments for extrapolation of chronic
data from acute data are presented leading to a fixed ratio extrapolation of
ED
50
= LD
50
/26, but with a large additional uncertainty characterized by a
coefficient of variation of a factor of 46.
8
Relating external to internal doses:
Regarding the wide range and size
of different nanoparticles produced, it is unrealistic to think that experi-
mental data will become available for each of them, thus the interest to use
