silica dust, crystalline, in the form of quartz or cristobalite - IARC ...

IARC MONOGRAPHS – 100C
4.2 Mechanisms of carcinogenicity
It is generally accepted that alveolar
macrophages and neutrophils play a central role
in diseases associated with exposure to crystalline
silica (Hamilton et al., 2008). An inflammationbased
mechanism as described in IARC (1997) is
a likely mechanism responsible for the induction
of lung cancer associated with exposure to crystalline
silica, although reactive oxygen species
can be directly generated by crystalline silica
polymorphs themselves, and can be taken up by
epithelial cells. For this reason, a direct effect on
lung epithelial cells cannot be excluded (Schins,
2002; Fubini & Hubbard, 2003; Knaapen et al.
2004).
4.2.1 Physicochemical features of
crystalline silica dusts associated with
carcinogenicity
The major forms or polymorphs of crystalline
silica are the natural minerals quartz,
tridymite, cristobalite, coesite, stishovite, and the
artifical silica-based zeolites (porosils) (Fenoglio
et al., 2000a). Humans have been exposed only
to quartz, tridymite, cristobalite, the other forms
being very rare. Several amorphous forms of silica
exist, some of which were classified in Group 3
(not classifiable as to their carcinogenicity) in the
previous IARC Monograph (IARC, 1997). Also, it
has been shown that this cytotoxicity is lowered
with lowering hydrophilicity (Fubini et al., 1999),
which depends upon the circumstances under
which the surface was created. For example,
silica in fly ashes or volcanic dusts is generated
at high temperatures, and is mostly hydrophobic.
The classification in Group 1 (carcinogenic to
humans) of some silica polymorphs in the previous
IARC Monograph (IARC, 1997) was preceded by
a preamble indicating that crystalline silica did
not show the same carcinogenic potency in all
circumstances. Physicochemical features – polymorph
characteristics, associated contaminants
– may account for the differences found in
humans and in experimental studies. Several
studies on a large variety of silica samples, aiming
to clarify the so-called “variability of quartz
hazard” have indicated features and contaminants
that modulate the biological responses to
silica as well as several surface characteristics
that contribute to the carcinogenicity of a crystalline
silica particle (Donaldson & Borm, 1998;
Fubini, 1998a; Elias et al., 2000; Donaldson et al.,
2001). The larger potency of freshly ground dusts
(e.g. as in sandblasting) has been confirmed in
several studies; Vallyathan et al., 1995), as immediately
after cleavage, a large number of surfaceactive
radicals are formed that rapidly decay
(Damm & Peukert, 2009). The association with
clay or other aluminium-containing compounds
inhibits most adverse effects (Duffin et al., 2001;
Schins et al., 2002a), iron in traces may enhance
the effects but an iron coverage inhibits cytotoxicity
and cell transformation (Fubini et al.,
2001). One study on a large variety of commercial
quartz dusts has shown a spectrum of variability
in oxidative stress and inflammogenicity
in vitro and in vivo, which exceeds the differences
previously found among different polymorphs
(Bruch et al., 2004; Cakmak et al., 2004; Fubini
et al., 2004; Seiler et al., 2004). Subtle differences
in the level of contaminants appear to determine
such variability. New studies in vitro and in vivo
on synthesized nanoparticles of quartz (Warheit
et al., 2007) indicate a variability of effects also at
the nanoscale. These new data clearly show that
more or less pathogenic materials are comprised
under the term “crystalline silica dusts.” However,
most studies, so far, have failed to identify strict
criteria to distinguish between potentially more
or less hazardous forms of crystalline silica.
The pathogenic potential of quartz seems
to be related to its surface properties, and the
surface properties may vary depending on the
origin of the quartz. The large variability in
silica hazard even within quartz particles of
the same polymorph may originate from the
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