FPTI: a general model to predict the toxicity/pathogenicity of mineral fibres - Alessandro F. Gualtieri - EMU school
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FPTI: a general model to predict
the
h toxicity/pathogenicity
/ h off
mineral fibres
Alessandro F. GualtieriWhy a model on the toxicity of mineral fibres?
Ambitious goal of delivering a quantitative classificatory model of
mineral fibres based on the physical/chemical/ crystallographic
parameters that may affect toxicity/pathogenicity.
A basic tool to assess a fibre potential toxicity/pathogenicity (analysis
off the
h nature off the
h fiber)
fib ) from
f the
h perspectivei off the
h iinvader
d
(fibre≡cause), not just the invaded (organism ≡effects)!
FPTI as predictive tool, basis for in vitro and in vivo testing?
To avoid new ex post discoveries like F‐edenite and erionite!
To supply mechanistic evidence for evaluating the carcinogenic
potential of mineral fibres determined using the IARC key
characteristics (KCs) (Smith et al.,
al 2016)
EMU school 2019 – FPTI A.F. GualtieriStructural descriptors of the FPTI model
Parameter Element Major adverse effect Major pathobiological process
Morphometric
length L (1,1) frustrated phagocytosis Inflammation and oxidative stress
diameter D (1,2) frustrated phagocytosis inflammation and oxidative stress
crystal curvature (1,3) reduced surface adhesion of inflammation and oxidative stress?
proteins/cells
crystal habit (1,4) airways deposition depth inflammation and oxidative stress
fiber density (1,5) airways deposition depth inflammation and oxidative stress
hydrophobic character of the surface (1,6) Interaction with biopolymers, inflammation and oxidative stress?
phagocytosis
surface area (1,7) airways deposition depth, frustrated (chronic) inflammation and
phagocytosis oxidative stress
Chemical
Total iron content (1,8) Production of ROS DNA damage and inflammation
f
ferrous iron ( )
(1,9) P d i off ROS
Production DNA damage
d and
d inflammation
i fl i
Surface ferrous iron/iron nuclearity (1,10) Production of ROS DNA damage and inflammation
content of metals other than iron (1,11) Production of ROS DNA damage and inflammation
Biodurability
dissolution rate log(R) (1,12) frustrated phagocytosis … Inflammation …
velocity of iron release (1,13) production of ROS inflammation
velocity of silica dissolution (1,14) production of ROS? oxidative stress and inflammation?
velocity of release of metals (1 15)
(1,15) ROS production DNA damage,
damage inflammation,
inflammation …
Surface activity
ξ potential (1,16) production of ROS and hemolysis Inflammation …
fibers’’ aggregation
fib ti (1,17)
(1 17) frustrated phagocytosis inflammation
Cation exchange in zeolites (1,18) interference with ER cross‐talk? apoptosis, necrosis?
EMU school 2019 – FPTI A.F. GualtieriExperimental procedure to assess the FPTI index
Parameter Element Experimental technique used for its
determination
Morphometric
length L (1,1) SEM/TEM
diameter D (1,2) SEM/TEM
crystal
t l curvature
t (1 3)
(1,3) Diff ti
Diffraction, TEM
crystal habit (1,4) SEM/TEM
fiber density (1,5) diffraction
hydrophobic character of the surface (1,6) electrophoretic mobility
surface area (1,7) BET
Chemical
Total iron content (1,8) EPMA
ferrous iron (1,9) Mössbauer spectroscopy
Surface ferrous iron/iron nuclearity (1,10) XPS, TOF‐SIMS (surface sensitive), FTIR, UV‐Vis
content of metals other than iron (1,11) XRF, ICP‐MS
Biodurability
dissolution rate log(R) (1,12) acellular biodurability
velocity of iron release (1,13) EPMA + acellular biodurability
velocity of silica dissolution (1,14) acellular biodurability
velocity
l i off release
l off metals
l (1 15)
(1,15) XRF ICP‐MS
XRF, ICP MS + acellular
ll l biodurability
bi d bili
Surface activity
ξ potential (1,16) electrophoretic mobility
fibers’ aggregation
fibers (1 17)
(1,17) electrophoretic mobility
Cation exchange in zeolites (1,18) CEC, EPMA ...
EMU school 2019 – FPTI A.F. GualtieriCross correlations: hierarchy and weighing scheme
EMU school 2019 – FPTI A.F. GualtieriCross correlations: hierarchy and weighing scheme
The FPTIi of each fiber is calculated according to the
following equation:
n
FPTIi = ∑ w1 × w2 × Ti
i=1
with:
• Ti= class value of the parameter i of the model;
• w1=1/H weight of the parameter according to its
hierarchy H;
• w2=1/U weight of the parameter according to the
uncertainty U of its determination.
EMU school 2019 – FPTI A.F. GualtieriCross correlations: hierarchy and weighing schemes
parameters matrix element element correlation hierarchy H uncertainty U
w'=1/H w''=1/U
Morphometric
mean length (1,1) 1 1
mean diameter (1,2) 1 1
crystal curvature (1,3) 1 2
crystal habit (1,4) 1 1
fiber density (1,5) 2 1
hydrophobic character of the (1,6) (1,17) 2 1
surface
surface area (1 7)
(1,7) (1 1) (1 2) (1 4)
(1,1),(1,2),(1,4) 2 1
Chemical
Total iron content (1,8) 1 2
ferrous iron (1,9) (1,9) 2 1
S f
Surface F ’’ / nuclearity
Fe’’ l it (1 10)
(1,10) (1 9) (1 10)
(1,9),(1,10) 3 2
content of toxic elements (1,11) 1 1
Biodurability
fiber dissolution rate (1,12) (1,4) 2* 1
mean velocity
l i off iiron release
l ( 3)
(1,13) ( )( )(
(1,4),(1,9),(1,13)
) 3 1
velocity of amorphous silica (1,14) (1,4),(1,13) 3 2
production with dissolution
velocity release of toxic (1,15) (1,4),(1,12),(1,13) 3 1
elements
Surface activity
Zeta potential (1,16) (1,8) 1 2
Zeta potential induced fiber (1,17) (1,7),(1,8),(1,17) 3 1
aggregation
Zeolite related
Cation exchange capacity (1,18) 1 3
EMU school 2019 – FPTI A.F. GualtieriWeb‐FPTI
j
Django P th
Python
MVC
(Model View Controller)
http://fibers‐fpti.unimore.it
p // p
EMU school 2019 – FPTI A.F. GualtieriWeb‐FPTI – Parameters EMU school 2019 – FPTI A.F. Gualtieri
Web‐FPTI ‐ Materials EMU school 2019 – FPTI A.F. Gualtieri
Web‐FPTI ‐ charts
To be improved…
EMU school 2019 – FPTI A.F. GualtieriWeb‐FPTI – login page and Insert New Material
EMU school 2019 – FPTI A.F. GualtieriApplication of the FPTI model EMU school 2019 – FPTI A.F. Gualtieri
Application of the FPTI model
fibrous glaucophane from Marin County CA, USA
EMU school 2019 – FPTI A.F. GualtieriWork in progress
• Optimise
O i i theh software
f ((errors)) and
d “B
“Beta tests”;
”
• Increase the statistics of the analysed fibres
• National network for the determination of FPTI?
• Revision and validation in collaboration with competent
authorities/agencies;
th iti / i
• Application
pp to synthetic
y fibres ((MMMF,, CNTs …)?
)
EMU school 2019 – FPTI A.F. GualtieriPlease try yourself as “Beta
Beta tester
tester”
of the code!
http://fibers‐fpti.unimore.it
EMU school 2019 – FPTI A.F. GualtieriYou can also read
