Silica, amorphous*

Classification/MAK value:
a) colloidal amorphous silica
including pyrogenic and wet
process silica (precipitated
silica, silica gel) and
3
diatomaceous earth (uncalcined) 4 mg/m total dust
evaluation period 8 hours
b) quartz glass, fused silica,
silica fume and calcined
3
diatomaceous earth 0.3 mg/m fine dust
evaluation period 8 hours
Chemical name (CAS): silica
CAS number: 7631-86-9
Molecular formula: SiO2
Synonyms: quartz glass: vitreous silica
silica glass
diatomaceous earth: kieselguhr
fused silica: opal
flint
Characteristics: bluish-white or grey powder
Crystal system: amorphous
Molecular weight: n (60.09)
3
Density: 1.90 to 2.20 g/cm
Refractive index: 1.45
Melting point: 1710 C
Boiling point: 2230 C

* In this report the term "amorphous" is considered to be synonymous with "not crystalline" and
"X-ray amorphous".
158 Silica, amorphous Volume 2

1 Occurrence, Production, Uses and Definitions

Naturally occurring amorphous silicas, synthetic amorphous silicas and amorphous

silicas (silica fume) arising as by-products of industrial processes must be distinguished
with respect to their occurrence, production and uses for purposes of occupational
hygiene. The term "amorphous silica" is used here for the pure forms of SiO2 such as
colloidal silica, precipitated silica, silica gel, pyrogenic silica, silica fume, quartz glass,
fused silica and also the skeletons of Radiolaria and diatoms in the form of diatomaceous
earth. These silica skeletons are comprised of an amorphous opaline substance. It is
currently not clear whether the content of water, which varies from ca. 2 to 20 % w/w,
can invalidate the classification as pure silica. The definition does not include those
amorphous silicas like glass which contain, in addition to SiO2, other partly intentional
constituents such as, e.g., Al2O3, MgO, Na2O. Thus, e.g., window glass, laboratory glass,
fibre glass, rock and slag wools are not to be assessed according to the threshold limit
values given here.**

1.1 Naturally occurring amorphous silicas

Silica occurs naturally in the solid amorphous state as flint, opal or diatomaceous earth.
Some deposits of diatomaceous earth contain considerable quantities of quartz. The
largest deposits are to be found in the USA; others occur in Algeria, Kenya, the USSR,
Mexico, Australia, China and South Korea. Denmark is the most important European
producer of diatomaceous earth (Molererde). In the Federal Republic of Germany there
are economically workable deposits on Luneburg Heath.

1.2 Synthetic amorphous silicas

Synthetic amorphous silicas are produced
as wet process silicas or
as thermal, pyrogenic, airborne fumed silica as well as
as arc furnace silica [2, 3].
Not only the kind of production process but also any subsequent chemical or thermal
treatment (roasting, tempering, calcination) must be considered as an important criterion
in the occupational-medical and toxicological evaluation.

** It seems to be very unlikely that these kinds of glass have fibrogenic effects since such effects
did not come to light in extensive animal experiments and epidemiological studies to clarify the
question of a carcinogenic potential of man-made mineral fibres [1]. The epidemiologists con-
cluded "that there are diffuse pulmonary findings related to exposure which are at the bottom
end of the reaction scale and can only be detected with radiographic methods" and, summariz-
ing, there is still no evidence from long term exposures for clinically relevant disorders of the
respiratory organs. The conclusions from the inhalation studies with rats were also that
exposure to man-made mineral fibres does not cause progressive fibrosis
Volume 2 Silica, amorphous 159

1.2.1 Wet processes

The most important wet process is precipitation. Precipitation from a solution of water-
glass with sulfuric acid yields a highly disperse amorphous silica. About 75 % of
production uses this method. The precipitated silicas are hydrophilic and can be
processed further to make them hydrophobic. Other wet processes are the gel process
and the hydrothermal process.

1.2.2 Pyrogenic processes

In flame hydrolysis, silicon tetrachloride vapour is burned with hydrogen and oxygen
from a burner in a cooled furnace. The exhaust gases leaving the furnace contain all the
silica in the form of an aerosol. Using turbulent flow they are conducted at a defined rate
through a coagulation zone. The silica particles which are formed are tiny and poreless
with a narrow range of diameters (5 to 30 nm, e.g. Aerosil or HDK. The primary
particles form larger, tightly bound tenth micrometer aggregates from which flake-like
tertiary structures (agglomerates) arise on cooling.
Of less importance these days are the arc furnace silicas. These disperse silicas are
produced by reduction of sand to silicon monoxide which is then oxidized to silicon
dioxide.

1.2.3 Quartz glass and fused silica

Quartz glass is a particularly high quality glass which consists almost entirely (> 99.5 %
w/w) of silicon dioxide. Transparent quartz glass is fused from crushed rock crystal in an
acetylene or oxyhydrogen flame. Quartz glass of low purity is produced from sodium
borosilicate glass by extraction and subsequent sintering at 900 C. Optical quartz glass
is obtained by keeping the product free of bubbles, e.g., by fusing it in a vacuum. Fused
silica, on the other hand is a cloudy and translucent quartz glass containing numerous
minute air bubbles. It is produced by fusing pure quartz sand using graphite electrodes.
Mechanical grinding processes during production and processing can release quartz glass
as fine dust.

1.3 Naturally occurring amorphous silicas, diatomaceous earths:

production and processing
Unprocessed (native) diatomaceous earth contains 20 % to 70 % w/w water. Together
with the principle component, the diatoms, it can also contain lesser mineral
constituents, e.g., calcite, clay minerals, mica and quartz. Processing involves drying,
roasting, calcination and activation. Whereas temperatures are far below 600 C during
drying, the calcination and activation temperatures attained range from over 600 C to
1100 C. The process of roasting the earth at high temperature is called calcination.
Additives are used for activation, e.g. sodium chloride is added to remove iron which
then escapes with the fumes as volatile iron chloride. About 59 % of the world's
production of diatomaceous earth is used for filtration aids, about 21 % for fillers, 15 %
for insulating materials. In the Federal Republic of Germany the largest part is also
160 Silica, amorphous Volume 2

probably used for filtration aids and most of that is calcined and activated, only a small
fraction being used as dried diatomaceous earth. This will also be the case for filler and
insulation materials.

1.4 Amorphous silicas as by-products of industrial processes

(silica fume)
Amorphous silicas occur as a by-product of industrial processes in flying ash and filter
dust. When quartz is subjected to high temperatures (1500 C to 2500 C) during
metallurgical or other production processes, grey to bluish fumes are produced.
Chemical analysis reveals that they consist largely of silicon or silicon compounds. X-
ray crystallography sometimes indicates the presence of crystalline SiO2 modifications. It
is not impossible that these fumes may consist of X-ray amorphous silica. Industrial
processes of this kind include particularly electrothermal production of silicon,
ferrosilicon and calcium silicide, also silicon carbide as well as the fusion and blowing
of quartz glass and fused silica. In the electrothermal processes for the production of
silicon and its compounds/alloys, quartz is reduced to silicon with carbon (cokes) in a
resistance oven or arc furnace and converted to alloys or compounds in the presence of
the appropriate additives (iron: ferrosilicon, calcium oxide or carbide: calcium silicide)
or with an excess of carbon (silicon carbide).
Since quartz sand or quartzite are usually the starting materials in these processes, the
suspended dusts in the production areas can contain X-ray crystalline silica as well as the
silicon-containing dust of the end product and the silica fume which was discovered in
this context. Silica fume particles, with geometric diameters between 0.1 and 1 m, are
generally markedly larger than those of pyrogenic silicas (cf. [4]).
Primary particles of pyrogenic silicas with geometric diameters < 30 nm also tend to
change morphologically towards larger particle sizes when subjected to prolonged heat
[5]. It is therefore to be expected that tempered pyrogenic silica will resemble silica
fume in its pathogenic effects.

1.5 General Properties

The basic structural unit of both amorphous and crystalline forms of SiO2 is the SiO4
tetrahedron. The corners of the tetrahedra are linked by siloxane bridges ( Si O Si )
so that each oxygen atom is shared by two tetrahedra.
In the crystalline forms the tetrahedra are organized relative to each other in a definite
regular long range order in which both the silicon and the oxygen atoms have defined
positions. This long range order is not present in the amorphous forms where there is
only short range order between neighbours.
The primary particles of the amorphous silicas typically used in industry have
diameters of 530 nm. They can aggregate to flakes which range in size from
microscopic (light microscope) to macroscopically visible. The specific surface area is
still determined by the primary particle [3].
The superficial silanol groups (Si OH) are responsible for the hydrophilic character
of amorphous silica. They are the actual reactive centres on the silica surface, forming
hydrogen bonds with each other and with other substances. In a liquid the silanol groups
Volume 2 Silica, amorphous 161

form hydrogen bonds between neighbouring aggregates which results in a three

dimensional network of primary particles. This restricts the mobility of the molecules of
the liquid so that the viscosity of the system increases (thickening effect). Hydrophobic
products may be synthesized for special applications by reacting the free silanol groups
with dimethyl dichlorosilane [6]. In addition, there are mixed oxides which arise when
silica is subjected to flame hydrolysis together with a second volatile compound (of a
metal).
The thickening ability is a property of amorphous silicas which has important
technical applications. The specific molecular structure of these substances makes them
thixotropic, i.e. they have pseudoplastic and structurally viscous properties.

1.6 Uses
Amorphous silicas are used for a multitude of different purposes [3]. They serve as
reinforcers/fillers in the indiarubber industry and as additives in varnishes, paints and
glues. In addition, amorphous silicas are used in the production of free-flowing powders
for foodstuffs, animal feeds, pharmaceuticals and cosmetics. Adsorbents and insulation
materials are more recent applications. The ability of amorphous silicas to modify flow
properties (thixotropism) is put to use in paint production. Paints should be as easy as
possible to apply, which requires a low viscosity, and once applied should remain on the
painted surface without dripping or forming runs, for which a high viscosity is
necessary.
The properties of amorphous silicas have led to their wide distribution as technical
additives, e.g. in resins. Silicas are added to unsaturated polyester resins (UP resins) and
epoxide resins to adjust their viscosity for industrial applications involving laminar
processes. The rheological properties play a role in mixtures with PVC plastisols for the
production of imitation leather and of underbody protective coatings. Other areas of
application include pharmaceuticals and cosmetics. Amorphous silicas serve to adjust
the viscosity of creams, ointments, suppositories and pastes. Finally they are used in the
production of moulds.
Quartz glass is used mostly in the field of vacuum and irradiation technique to
produce UV lamps, lens and prism systems as well as in high frequency installations for
high voltage insulators. Fused silica finds application particularly in the production of
laboratory glass and chemical apparatus.

2 Analytical Classification of X-ray Amorphous Silicas

with respect to Short Range Crystalline Order
The total absence of crystalline structures is crucial in the toxicological evaluation of
amorphous silicas. The level at which crystalline forms can be detected is, in the first
place, a question of the detection method. X-ray diffractometry is a practicable
procedure with which as little as 0.5 % quartz may be detected in Aerosil. Silica in which
no crystalline structure is revealed with this method may be called X-ray amorphous.
162 Silica, amorphous Volume 2

Table 1. The classification of X-ray amorphous silicas according to [7] and [8]

I: essentially ideally amorphous

synthetic products: precipitated silicas, silica gels, quartz glass manufactured in thin layers at
high temperatures 1750 C (oxyhydrogen blowtorch)

II: weak short range order

synthetic products: various kinds of Aerosil

natural products: biogenic silicas (e.g. rice husk ash, probably also unheated to gently
heated diatomaceous earths, ca. < 700 C)

III: more pronounced short range order

synthetic products: quartz glass from rock crystal just above the melting point (1750 C),
e.g. melted in crucibles.
amorphous quartz made by grinding rock crystal.
amorphous quartz glass as in sections I and II, tempered above
ca. 700 C. On prolonged heating, especially at high temperatures,
SiO2-forms which can be detected by X-ray diffraction are formed.
SiO2 fume, in which short range order cannot be excluded, can arise as
a by-product during electrothermal production of silicon compounds
and alloys from quartz sand (e.g. ferrosilicon and silicon carbide). This
is probably also the case for arc furnace silica.

The examination of luminescence behaviour has been proposed as an analytical

procedure for evaluation of short range crystalline order of even X-ray amorphous silicas
[7, 8]. The method is said to reveal a continuous spectrum of short range order between
X-ray amorphous and X-ray crystalline structures, in which the various levels differ in
their luminescence (Table 1).
The actual structure must depend, on the one hand, on the production process and, on
the other, on the conditions of any subsequent processing of the amorphous silicas. Thus
tempering practically ideally amorphous silicas increases the crystalline order with
increasing temperature and duration until finally they are converted from the X-ray
amorphous state to one in which the crystalline SiO2 modifications are detectable by X-
ray crystallography.
On the other hand, it is possible by intensive milling (vibrating mill) of pure quartz to
achieve an extensive deformation of the crystal lattice or conversion to the amorphous
state so that the quartz can no longer be detected by X-ray crystallography. The
amorphous silica which is produced with this method, however, is not non-luminescent
[7, 8]. Amorphous silicas which are practically non-luminescent include pyrogenic and
wet process silicas as well as thin layers of quartz glass produced at high temperatures
( 1750 C) in an oxyhydrogen blowtorch (Table 1).
More recent studies confirm the luminescence behaviour of heat-treated precipitated
silica and pyrogenic silica [9] but these measurements also indicate that it is essential to
take the increase in the particle size on sintering and the trace element impurities into
account when interpreting the luminescence behaviour as these factors influence the
Volume 2 Silica, amorphous 163

fluorescence spectrum markedly. A connection between the thermo-luminescence values

and structural "short range state of order" has thus not been proved. The thermo-
luminescence method is not suitable for routine characterization of non-crystalline silica.

3 Exposure to Dust
Elevated concentrations of fine synthetic colloidal silica dust can arise during production
and during mixing of silica with other substances. Because of the multitude of different
applications, fine dust containing silica can occur in very many areas of industry.
Especially hydrophobic products have a strong tendency to produce dust. After
integration into the final product, a hazard from SiO2 is no longer likely. Measurements
of total dust concentration during production of Aerosil [4] reveal a decrease from
"up to 100 mg/m3" in 1959 to
"up to 42 mg/m3" between 1974 and 1982.
Measurements carried out in 1984 and 1986 revealed average values of 2.2 mg/m3
and 4.4 mg/m3 total dust. At the same time a total of 27 measurements of fine dust
concentration were obtained using a horizontal elutriator. The results were in the range
0.7 mg/m3 to 1.7 mg/m3 fine dust for 1984 and 1986.
56 measurements of dust levels in works where amorphous silica (quartz glass) was
processed showed fine dust concentrations between 0.04 mg/m3 and 1.9 mg/m3 with an
average of 0.46 mg/m3. The quartz content was between 1 % and 12 % w/w [10]. In the
course of these measurements an attempt was made to estimate the level of amorphous
silica by infrared spectroscopy because no other analytical method was available for this
purpose [11]. However, considerable limitations with respect to the precision of
measurement and to interference had to be taken into account. There are practically no
dust concentrations available for the ferrosilicon industry. For the area of the blast
furnace outlet fine dust concentrations of 2.14 mg/m3 to 19.5 mg/m3 are quoted (n = 5
measurements). The proportion of X-ray crystalline silica ranged from < 1 to 2 % w/w,
of amorphous silica from 30 to 100 % w/w [12].

4 Effects on Man

4.1 Clinical and epidemiological studies of mining and processing

of natural amorphous silica (diatomaceous earth)
There are only a few studies available in the literature on the question of the effects of
amorphous silica on human health. Some of them go back to the thirties. Cases of
pneumoconiosis are reported, especially in connection with mining, production and
processing of diatomaceous earth.
164 Silica, amorphous Volume 2

Of a group of 108 Mexicans who were exposed to amorphous silica during mining of
diatomaceous earth, 66 % had developed pneumoconiosis [13]. Unfortunately, details of
the source of the study collective and of their other occupational exposures, especially to
quartz dust, are not given.
A number of authors report the occurrence of lung X-ray findings specific for
pneumoconiosis induced by diatomaceous earth. In one study, 8 % of those persons for
whom the findings were conspicuous were shown in the occupational anamnesis to have
been exposed as packers of diatomaceous earth [14]. The X-ray findings included the
bilateral linear changes which are typical of diatomaceous earth pneumonconiosis. In
addition, coalescent lesions which might result from pulmonary infections, especially
tuberculosis, were present.
15 severe cases of pneumonconiosis in two factories were reported in workers
producing filter candles from a material containing 80 % diatomaceous earth [15]. The
authors distinguish between mild silicosis, which is observed after exposure to native
diatomaceous earth, and the severe silicosis occurring here which is caused by
diatomaceous earth which has been heated to 1250 C and so contains cristobalite. Since
1931, all cases of silicosis in Sweden have been recorded in a central register [16]. The
register contains a total of 6 cases for which the exposure involved diatomaceous earth.
Here too it is emphasized that calcined diatomaceous earth is particularly dangerous.
The relationship between pneumoconiosis findings in the X-ray examination and
working conditions of the persons examined was studied for a collective exposed to
diatomaceous earth (diatomete workers) [17]. The lung radiographs from 869 employees
from 5 firms (95 % of the total work force) were evaluated. In 78 (9%) of the employees,
doubtful evidence of pneumoconiosis was found. For a second group of 78 persons there
was definite evidence of diatomaceous earth pneumoconiosis. Of these 78 persons, 32
(3.7 %) had confluent disease. The places of work were classified as quarry, mills, office
and administration. In the mills, mild pneumoconiosis was diagnosed in 17 % of
employees with 5 or more years exposure and in 23 % severe pneumoconiosis (confluent
disease). Only 0.4 % of persons employed for shorter periods had mild pneumoconiosis
and none had the severe disease. The situation was similar for persons working in the
quarries. For the X-ray findings in "diatomitis-pneumoconiosis" the authors propose
their own classification system which involves quantification of linear-nodular lesions
into grades LN1 to LN3 with or without additional confluent shadows C1 to C4. They
emphasize, however, the diversity of methods employed in extraction and processing
and the consequent possibilities for modification of simple diatomaceous earths, e.g., the
formation of 40 % to 60 % cristobalite during calcination. Thus it is not unreservedly
possible to conclude from the occurrence of "diatomete-pneumo-coniosis" that it is an
effect of amorphous silica, i.e. of quartz-free, uncalcined diatomaceous earth.
12 patients with silicosis were found among the 106 workers of 6 factories producing
diatomaceous earth in Migaji-Kun, Japan [18]. The silicosis was of grade 3 according to
the rntgenographic classification of Nozaki. The shortest exposure time among the
patients was 3 years. The diatomaceous earth was 86 % SiO2. The dust concentration was
determined with a method which is no longer used. Quartz was not present. No details
were given as to the method used to exclude the presence of quartz.
Volume 2 Silica, amorphous 165

X-ray analyses were carried out on samples of diatomaceous earth from 6 producers
to determine the quartz content of natural uncalcined diatomaceous earth [19]. 1 % to
8 % w/w quartz (low quartz) was found. These authors too conclude that a fibrogenic
effect of diatomaceous earth can be put down to amorphous silica only if the absence of
crystalline silica has been definitively proved.

4.2 Effects of silica fume, flying ash, filter dust and fused silica
Kasuistics are available for a collective of 40 workers from a metallurgical works in the
ferrosilicon industry [20]. The individuals had been employed in the production of
ferrosilicon (silicon metal) for various periods during 11 to 18 years, but never for more
than a total of 2 years at the furnace. In this process, quartz is heated in an arc furnace to
above its melting point to 2350 C. A considerable fraction of the vaporized SiO2 (12 to
14 tons daily) escapes as fumes into the flue or into the air breathed by the workers. X-
ray diffraction analysis revealed the presence of crystalline silica. Lung X-rays showed
changes in 11 of the 40 exposed persons. Unfortunately, no details are given of other
occupational exposures, particularly of exposure to quartz or of other previous
exposures. A Letter to the Editor in response to this publication points out that 6.7 %
w/w crystalline silica was found by means of X-ray diffraction in the dry lung tissue of
dead members of this collective. That is enough to produce nodular fibrosis [21].
Other studies have also produced indications of a weak silicosis-inducing effect of
dusts in ferrosilicon works. Here too, however, the dust situation is such that exposure to
crystalline forms of SiO2, particularly of persons charging the blast furnace, cannot be
ruled out [2224]. Toxicological investigation of the amorphous silica fume on the outlet
side of the furnace revealed a weak fibrogenic effect [25, 26]. The relationship suggested
by the term "ferro alloy workers' disease" between an exposure to high doses of
amorphous silica fume during ferrosilicon production and an initial metal-fume fever, on
the one hand, with a subsequent pneumoconiosis on the other is also not able to exclude
the possibility of an exposure to mixed dusts including crystalline silica [27, 28].
Cases of silicosis are also known from the production of fused silica tubes for blast
furnaces [29]. In this works, amorphous silica imported from America is milled in ball
mills, poured into moulds as a suspension in water and then fired at 1100C. Further
processing is not carried out. In addition, for quality control purposes, continual infrared
spectrophotometric and roentgenographic analyses ensure that crystalline silica and, in
particular, cristobalite are not present in the starting material. There were radiographic
findings indicative of silicosis in 4 of 28 employees of the company (14 %). The period
of exposure to the dusts produced during milling ranged from 2 to 32 years for the 28
employees, on average 8.9 years.
166 Silica, amorphous Volume 2

4.3 Production of synthetic amorphous silica

Until 1957 the workers employed in a firm producing pyrogenic silica (Aerosil) were
subjected twice yearly to an occupational medical examination [30]. In 1960, this data
formed the basis for an evaluation of the industrial medical examinations of 215
workers. Exposure took place during production and packing of synthetic amorphous
silica. Dust concentrations varied depending on the place and nature of the work being
carried out: at times very high concentrations were observed to which the workers were
exposed without protection although dust masks were available. During production the
concentrations were 3 to 7 mg/m3; during packing 2 to 6 mg/m3 were found.
Concentrations between 15 and 100 mg/m3 were measured near the filling jets. These
values are likely to be approximations of total dust levels. The individual workers were
examined up to 12 times during the 12 year industrial medical observation period from
1947 to 1959. In no case were there findings in the respiratory organs which could be
causally related to contact with amorphous silica.
The report includes some casuistics for persons who were exposed for particularly
long periods and at high levels. The only findings mentioned were hairline accentuations
of the interlobular fissures, recognizable in the thorax radiograph as mild interlobular
pleuritis. The report concluded that at total dust concentrations up to about 100 mg/m3 no
unfavourable effects of exposure to colloidal amorphous silica had been found among
215 workers.
More recent studies of the workers exposed to Aerosil in this company cover a further
period of 27 years since 1960 [30]. They are based on the medical examinations carried
out since 1959 at three year intervals according to the "berufsgenossenschaftlichen
Grundsatz G 1.1" (Regulation G 1.1 of the Association of Industrial Injuries Insurance
Institutes). Evidently the X-ray examinations were carried out much more frequently
than that, for 4870 thorax radiographs of about 200 Aerosil-exposed employees are
available from the period 1959 to 1975. The study was restricted to 143 workers who
had been exposed from 1 to 30 years (Table 2). Included in the collective were 8
pensioners who had retired on average 7.6 years previously. In all, symptoms were
recorded for 54 persons (38 %). Most of these were anamnestic complaints such as
coughing, phlegm and respiratory difficulties. Among the total of 68 persons who had
been exposed for more than 15 years, 50 % complained of symptoms. The authors
considered the decisive fact to be that the characteristic X-ray findings, nodular fibrosis
in the form of little round shadows (sizes p, q, r) as are found in quartz dust lung disease,
were not observed among the 143 workers. An increase in interstitial lung markings was
observed in only 18 (in the tabular data 17) workers. For 13 of these 18 it was
established that these changes had already been present when they joined the company
and that they had not worsened in spite of exposure to Aerosil dust, in some cases for
decades. Of the 17 persons described in Table 2 with increased interstitial markings,
previous exposures are recorded for 12. Of these, 9 are from relevant occupations, e.g.,
in mines, foundries or in the abrasive producing industry. 9 of the 17 are smokers.
An estimation of the exposure of these workers is possible from 23 measurements of
total dust carried out in the years 1974 to 1982 with an average level of ca. 20 mg/m3 [4].
In 1984 and 1986 both fine dust (n = 27) and also total dust (1984, n = 26) were
Volume 2 Silica, amorphous 167

Table 2. Complaints and symptoms (X-ray findings and ventilation disorders) in n = 143
employees at an Aerosil works [30].

Number Exposure time Average age Frequency of increased interstitial

(years) (years) complaints and symptoms markings in radiograph
n % n %
6 < 1 26.5 1 16.0 0 0
23 15 29.3 4 17.4 1 4
23 6 10 37.2 7 30.4 2 9
23 11 15 49.4 8 34.8 4 17
32 16 20 47.7 16 50.0 3 9
24 21 25 47.8 12 50.0 4 17
6 26 30 51.1 3 50.0 1 7
6 > 30 54.8 3 50.0 2 33
143 54 38.0 17 12

measured. Markedly reduced total dust concentrations of 2.2 and 4.4 mg/m3 were found
with fine dust levels of 0.7 and 1.7 mg/m3, respectively. From these data the fine dust
concentration for the period 1974 to 1982 can be estimated as approximately 6 mg/m3. It
is, however, hardly possible to make retrospective estimates of how much higher the
average fine dust levels might have been at earlier times.
The evaluation of medical records for 78 employees exposed to amorphous silica
(HiSil and Silene) has also been reported [31]. The exposures took place between 1941
and 1959. The dust concentrations ranged from 0.1 to 65 mg/m3. No changes were found
on the radiographs. There were no signs of a silicosis nor of any other pulmonary
diseases.
Furthermore, there are reports of an investigation of 165 employees who were
exposed to precipitated amorphous silica (PAS) in two firms [32, 33]. The dust
concentrations, measured using personal samplers, were about 1 mg/m3. It is not clear
whether this was fine dust or total dust. The minimum exposure period was 1 year, the
average 8.6 years. The authors evaluated spirograms, respiratory questionnaires and
radiographs. They found no relationship between the lung function parameters and the
results of the X-ray examinations on the one hand and the intensity and duration of the
PAS exposure on the other. Correlation between a series of symptoms such as cough,
phlegm, respiratory difficulties and wheezing and the PAS exposure was non-existent or,
at best, negative. The respiratory symptoms did, however, correlate with the smoking
habits.

5 Animal Studies on the Toxicity of Amorphous Silica

5.1 Review of the experiments
The first toxicological tests with colloidal silica in the 1930s produced contradictory
results [34, 35]. In the 1950s and 1960s toxicological investigations seeking possible
harmful effects of silica were carried out on a large scale. Much of this was fundamental
168 Silica, amorphous Volume 2

research into the origins of silicosis, for at that time the silica going into solution at the
surface of the quartz was considered to play an essential role in the aetiology of quartz-
induced fibrosis (solubility principle). Other information has been obtained from
occupational hygiene studies which sought primarily to clarify the question of a
fibrogenic effect of amorphous silica.
The available studies include investigations using various kinds of parenteral
application as well as specific toxicological evaluations of the effects of inhalation of
amorphous SiO2 in the rat, rabbit, guinea pig and monkey. Not only has the biological
effectiveness in producing progressive fibrosis been investigated in long term
experiments but also the elimination behaviour of the dusts. Various synthetic amor-
phous silica products derived from the most widely available pyrogenic amorphous
(hydrophilic) silicas have been tested. An important distinguishing characteristic of these
silicas is their specific surface area. Furthermore, some of the products are hydrophobic
because the external reactive groups are occupied. There are also experiments with
quartz glass, with mixed oxides of amorphous silica as well as with the waste products of
the ferrosilicon industry and of quartz glass production.

5.2 Acute toxicity

The toxicological studies of acute parenteral tolerance in the rabbit, guinea pig and rat
reveal high acute toxicity 20 50 mg/kg body weight after intravenous injection [26,
3638]. Applied in smaller individual doses, however, the substances are tolerated in
larger quantities. The marked acute effects are in accordance with the repeatedly
reported severe cell damage silica causes in macrophages and red blood cells in vitro
[3943].
Comparative toxicological studies of various hydrophilic silicas (arc furnace silica,
pyrogenic silica, precipitated silica) reveal that the toxicity after intraperitoneal injection
into rats increases with increasing specific surface area [4446]:
50 m2/g: lethal dose 250 mg (arc furnace silica)
170700 m2/g: lethal dose 50 mg.
Hydrophobic silicas are better tolerated. Therefore it is considered likely that the
toxicity is substantially determined by the more rapid dissolution of water-soluble silica
with larger internal surface area.
Accordingly, 80 % to 90 % of rats were killed directly by intratracheal injections of
doses of 30 mg/kg and 50 mg/kg body weight of amorphous silica condensed during
melting of quartz glass [47]. Similar observations were made when 37.5 mg/rat was
given as three intratracheal injections [48]. The acute histotoxicity was strongly and
positively correlated with the specific surface area of the amorphous silica particles. The
results are, however, also indicative of the importance of the depot effect for long-term
tissue damage [47]. Similar results were obtained after intraperitoneal application [49].
Other studies with intraperitoneal application to the rat, mouse and guinea pig confirm
the relatively high acute tissue damage inflicted by these dusts [48, 50, 51].
Volume 2 Silica, amorphous 169

5.3 Lung clearance of various SiO2 forms

An important aspect in comparative evaluation of various SiO2 dusts is the elimination
behaviour in long term studies. Here the size of the dust particles deposited in the
alveolar region seems to play an important role; the larger the particles in this dust
fraction, the more marked are the histopathogenic properties, but not the cytotoxicity,
and the more marked is the retention in the lung. In comparison with crystalline quartz,
the particularly fine grained pyrogenic silica is rapidly and completely eliminated from
the lung [45, 48, 52, 53]. Elimination of colloidal silica is typically 95 % to 100 %
complete within 5 months. For quartz and corundum ca. 50 % elimination within 8
months is observed. It is supposed that this accounts, at least in part, for the lesser
histopathogenicity of pyrogenic silicas.

5.4 Toxicological studies of amorphous silica, quartz glass

and silica fume in comparison with crystalline SiO2 forms
5.4.1 Intratracheal injection
The studies described below are particularly concerned with the comparison of the tissue
reaction to amorphous and to crystalline forms of SiO2. They sought to make a
contribution to our understanding of the aetiopathogenesis of silicosis for which there
were two opposing theories in the early 1950s: the solubility theory and the crystal
surface area theory.
The effects of quartz, cristobalite, tridymite and fused silica were studied using
intratracheal application to rats [54]. After standardization of the particle sizes of the
substances by sedimentation in water (Atterberg-Schlmmung), the specific surface
areas and the range of particle sizes in the samples tested were very similar. The dusts
were injected intratracheally (50 mg/animal); the observation period lasted up to 450
days. Chemical analysis indicated a high degree of purity of the samples used. X-ray
crystallography revealed the appropriate bands for the tridymite, quartz and cristobalite
samples whereas the fused silica was X-ray amorphous. The experiments permitted a
clear grading of the pathogenic effects: fibrogenicity decreased in the order tridymite,
cristobalite, quartz, fused silica. The quartz, cristobalite and tridymite samples produced
grade V fibrosis according to Belt and King (confluent, hyaline fibrosis) during the last
third of the study. With fused silica the degree of fibrosis did not exceed grade 3
(nodular cellular lesions, closely packed, thick reticulin fibres; marked collagen
formation). Also important: the grade 3 fibrosis was achieved later than in the animals
treated with the various crystalline SiO2 forms, namely after 7 months in comparison to
3, 2 and 1.5 months. With the fused silica further progression of the fibrosis to grades 4
and 5 was not observed. The results indicate that the degree of silicosis produced by the
dusts increases with the degree of crystallinity. The X-ray amorphous fused silica was
distinguished from the crystalline forms, not only by the degree of fibrosis (a) it induced
and the rapidity of its development (b, but also by the fact that the whole process came to
a stop after 7 months (c).
170 Silica, amorphous Volume 2

Experiments have been carried out on the effects of the various forms of silica after
intratracheal injection into animals in the Federal Republic of Germany as well, e.g.,
with silica gel, a pure amorphous hydrated form of silica, with opal, flint and quartz [25,
55]. The solubility of the dusts and their fibroblastic and toxic effects were compared.
Here too it was demonstrated that the toxicity increased and the fibroblastic effects
decreased with increasing solubility of the SiO2 dusts. Thus the silicas could be placed in
order of decreasing toxicity and increasing fibroblastic activity: silica gel, opal, flint,
quartz (see also Section 5.2, Acute toxicity). Opal, with its low degree of crystallinity, is
comparable in its effects with quartz glass: grade II fibrosis according to Belt and King
(cited from [35]).
In another study, groups of 10 to 20 rats were given intratracheal injections of 40 mg
of various forms of silica [56]. The animals were observed for 1, 2, 4 and 8 months. The
lung weights, hydroxyproline levels and silica content were determined. The dusts
studied were
crystalline quartz
colloidal silica without crystalline components detectable by X-ray crystallography
quartz glass without crystalline components
silica fume from a ferrosilicon plant
diatomaceous earth without crystalline components
diatomaceous earth which had been heated to 800 C for 24 hours, also without
crystalline components.
The particle sizes in the various samples were not comparable: the quartz had a mean
diameter of 12 m and the quartz glass of 0.3 m. The author states, however, that the
particle size has no effect on the fibrogenicity. Comparison of the effects revealed that
the crystalline quartz and the quartz glass produced similar initial reactions after 1 and 2
months and that they had a greater effect than the other substances. Later, however, the
progression became slow with quartz glass and markedly less than with quartz. The other
test dusts, apart from the heated but still X-ray amorphous diatomaceous earth, had no
fibrogenic effect. The heated diatomaceous earth produced a much stronger reaction than
the untreated diatomaceous earth. In particular, the collagen production it induced in the
lymph nodes was at least as much as with crystalline quartz.
In yet another comparative study of silicogenesis [57], 12 months after intratracheal
injection of 30 mg X-ray amorphous quartz glass with a mean particle diameter of 0.23
m, fibrotic lesions arose which were described as "very similar" to those observed
under the same experimental conditions with crystalline quartz. The quartz sample was
ground rock crystal with a mean particle diameter of 0.44 m. On the basis of this
experiment quartz glass was said to be just as fibrogenic as quartz. The criticism is
warranted, however, that these observations are not based on accepted toxicological
parameters.

5.4.2 Intraperitoneal injection

In investigations of the lymphatic penetration of various forms of SiO2 (quartz,
tridymite, quartz glass and coesite), the lymph node reaction within a 6 month
observation period after intraperitoneal administration of these dusts (50 mg) to rats
 Volume 2
A B
VI IV
V III-IV
IV III
III II
II I -II
I I
Time
in months 2 4 8 2 4 8 2 4 8 2 4 8 2 4 8 2 4 8 2 4 8 2 4 8 2 4 8 2 4 8 2 4 8
SiO2 Bayer-SiO2 Bayer-SiO2 Aerosil Aerosil quartz fume SiO2 gel pptd SiO2 quartz glass quartz glass quartz diatom-
preparation 8 h 800 C 8 h 800 C (Merck) (Kloster- 48h 1100 C (rock aceous
frau) crystal) earth
calcined
structure amorphous includes amorphous amorphous amorphous amorphous amorphous amorphous crystalline crystalline crystalline
cristobalite cristobalite cristobalite
particle 1020 m 0.052.2 1050 m 0.030.5 40150 m 0.23.0 0.21.2 0.12.0 0.12.0 0.22.0 0.22.5

Silica, amorphous
size
amount 16 g/ml 36 g/ml 58 g/ml 40 g/ml 54 g/ml 100 g/ml 94 g/ml 14 g/ml 4 g/ml 3 g/ml 13 g/ml
dissolved in 6 h
in 24 h

A degree of tissue reaction

B degree of tissue reaction according to KING
Figure 1. Degree of tissue reaction 2, 4 and 8 months after i.p. injection of various forms of SiO2. The shaded section of the columns shows central
collagen hyaline fibrosis which is still cellular at the periphery. The histological changes are subdivided according to Klosterktter into 6 grades of tissue
reaction (left hand scale) and, for comparison, according to King (right hand scale). Details of crystal structure, particle size and rates of dissolution are

171
also given. For Bayer-SiO2 and Aerosil, tempering causes an increase in particle size by at least a factor of 10 [5].
172 Silica, amorphous Volume 2

was studied [58]. Both the various forms of quartz and quartz glass caused similar
weight changes.
In comparative experiments with rats, a total of 11 different silicas were tested by
intraperitoneal injection of 50 mg/animal [5]:
2 commercially available amorphous silicas, (1) precipitated amorphous silica and (2)
amorphous pyrogenic silica (Aerosil)
samples (1) and (2) after tempering for 8 hours at 800 C
silica fume
2 samples of silica gel
quartz glass from ground quartz fibre glass
the same quartz glass tempered for 48 hours at 1100 C
quartz (rock crystal)
calcined diatomaceous earth.
Both the calcined diatomaceous earth and the tempered quartz glass contained
cristobalite. In contrast, the tempered Aerosil remained amorphous according to both X-
ray and electron diffraction. The tempered (precipitated amorphous) silica, on the other
hand, revealed some weak cristobalite lines. Both these samples had been sintered to
hard-baked agglomerates or larger melted particles.
The criterion chosen for evaluation of the dusts was the progression of the induced
fibrosis. The histological changes after 2, 4 and 8 months were scaled into one of 6
grades after staining the tissues with haematoxylin-eosin-azocarmine-aniline blue and
Gomori stain (Figure 1). Progressive fibrosis with the development of cell-free collagen
hyaline nodules was only observed with the crystalline samples of quartz, quartz glass
and diatomaceous earth and with the two silica samples which had been tempered at 800
C. In Figure 1 it may be seen that all these samples produced a grade VI tissue reaction
after 4 and 8 months. A certain amount of fibrosis developed in the other experiments
too. The intensity and persistence increased from the silica gels to the untreated
precipitated and pyrogenic amorphous silicas to the silica fume. The silica fume
occupies a position between the amorphous and the crystalline SiO2 forms. The effect is
initially tempestuous and very violent; later the nodules regress.
The cell damage and increase in connective tissue induced by quartz fibre glass is
unexpectedly slight. Since Strecker obtained completely different results with quartz
glass, results which, in our experience, could be confirmed with scrap glass from
Heraeus, Klosterktter concluded that there must be marked differences between quartz
glass samples [5].

5.5 Inhalation toxicology of amorphous silica

5.5.1 Experiments with rats, guinea pigs and rabbits
In studies of inhalation toxicology in the rat, guinea pig and rabbit, concentrations of 50
mg/m3 to 150 mg/m3 of various synthetic amorphous silicas induced signs of
desquamative pulmonary catarrh [48]. Marked multiplication of macrophages was very
evident. The granulomas were highly cellular but even after lengthy exposure periods
(several months) contained, at most, reticular fibres. Emphysema-like modifications of
Volume 2 Silica, amorphous 173

the lung parenchyma were sometimes observed in the rats. All these changes, including
the pulmonary distension, were reversible after termination of the exposure. In the
experiments with pyrogenic amorphous silicas, genuine fibroblastic lung reactions were
never observed [47, 48, 50]. In toxicological studies of hydrophobic colloidal silica,
inhalation of high concentrations (100 mg/m3) for several months also led to
desquamative catarrh and macrophage granulomas with slight reticulin fibre formation.
These changes too regressed completely in the postinhalative phase of the experiment. In
contrast to these findings, one of the colloidal silicas tested, produced by the arc furnace
method, was clearly shown to induce silicosis; this product never became commercially
available [59].
Quartz glass (X-ray amorphous, "VP 203-006") was compared with quartz in an
inhalation study with rats to investigate the effect of increased pressure [60]. The dust
concentrations tested were 10 mg/m3 and exposures lasted for a total of 84 days. Organ
weights and qualitative histologically detectable lesions in the lungs and mediastinal
lymph nodes were evaluated. In addition, the fine tissue changes were analysed
histomorphometrically. Nodular lung lesions with connective tissue formation were
established for both kinds of SiO2: about twice as many for quartz as for quartz glass. A
similar difference was seen in the lymph node weights. Histologically the lymph nodes
from the quartz glass animals contained more hyaline collagen fibres (some actually
organized in concentric layers) than did the lymph nodes from the quartz series.
More recent unpublished studies tested the effects of colloidal amorphous silicas in
an inhalation test in the rat [53]. An untreated pyrogenic silica (Aerosil 200) at
concentrations of 1, 6 and 30 mg/m3 total dust, a surface-modified pyrogenic silica
(Aerosil R 974) and a precipitated silica, both at concentrations of 30 mg/m3, were
tested. The effects were compared with those of inhalation of 60 mg/m3 quartz. Exposure
was for 13 weeks, 5 days per week and 6 hours per day. In the subsequent 52 week
observation period
mortality
respiration rate
weight of body, lung and thymus
blood and urine status
lung levels of collagen and SiO2
pathological modification of the respiratory tract
were investigated. The effects observed included:
increased respiration rate
slower body weight gain
markedly increased lung weight
increased leukocyte count
increased collagen level
granulomatous changes
focal interstitial fibrosis
necrosis and slight atrophy of the nasal mucous membrane.
In general the findings were most pronounced with untreated pyrogenic silica and
least with precipitated silica. The precipitated silica, however, was retained in the lung
and lymph nodes to a far greater extent than the treated and untreated pyrogenic silica.
174 Silica, amorphous Volume 2

After as little as three months exposure to 6 mg/m3 total dust, "focal interstitial
fibrosis" was seen in some animals. This effect too was most pronounced with untreated
pyrogenic silica (Aerosil 200) and least with silica gel. It is not possible to assess the
significance of this effect unambiguously because it was completely reversible. The
authors' interpretation, that there is a threshold concentration for adverse effects below 1
mg/m3 total dust (Aerosil 200), can only apply to the reversible increases in lung weight,
collagen level and alveolar cell number found after inhalation of 1 mg/m3 untreated
pyrogenic silica. Furthermore, in all groups at the end of the exposure, focal necroses
and slight atrophy of the olfactory epithelium of the nose were observed; at later times
these changes were not registered.

5.5.2 Comparison of the effects of silica gel, pyrogenic silica

and precipitated silica in an inhalation experiment with monkeys

Effects of chronic inhalation of various synthetic amorphous silicas were studied in three
different species [61]. Three kinds of amorphous silica, silica gel, pyrogenic silica
(fumed silica) and precipitated silica were used. Electron microscopic particle size
analysis showed the geometric mean diameters of the aggregates to be 0.27 m, 0.38 m
and 0.17 m. The experimental animals were rats, guinea pigs and monkeys.
Concentrations of 15 mg/m3 were used for a maximum period of 12 to 18 calender
months. Exposures were carried out daily for 5 to 6 hours on 5 days of the week. As well
as histopathological tests, lung function, respiratory mechanics (compliance, forced
expiratory volume), diffusing capacity, single breath nitrogen washout and the closing
volume. The rats were examined after 3, 6 and 12 months, the guinea pigs after 12
months exposure. The monkeys were examined after 13 months exposure to pyrogenic
silica and silica gel and after 18 months exposure to precipitated silica. The
histopathological findings were most pronounced in the monkeys. Independent of the
kind of silica administered, aggregations of mononuclear cells were apparent in the
lungs. With increasing severity of these initial changes, the substances could be placed in
order of increasing harmfulness: silica gel, pyrogenic silica and precipitated silica.
Reticulin fibres were present to a similar extent in the cell aggregates in all treated
groups. In contrast, collagen was only observed in the monkeys exposed to pyrogenic
silica. 5 % to 50 % of the cell aggregates contained collagen fibres in 6 of 9 monkeys
exposed to pyrogenic silica. In 3 monkeys, no collagen or practically none was found in
the lesions. Lung function tests (compliance, resistance) were carried out for all exposed
monkeys a total of 5 times during the experiment but were only evaluated at the end of
the study because of differences in the weight of the animals. Multivariate analysis
revealed differences in the respiratory mechanics only of those animals exposed to
pyrogenic silica and silica gel. For pyrogenic silica, the differences were also statistically
significant when the lung function parameters were analysed singly (univariate analysis).
Univariate analysis for silica gel revealed no significant differences except in two cases
where they were in the opposite direction to that expected and so were classified as the
result of random statistical error.
This inhalation study provides another indication that one of the kinds of silica
administered (pyrogenic silica) has weak nodular fibrotic effects. The macrophage
Volume 2 Silica, amorphous 175

granulomas should not be included in any quantitative grading of the effects, as

recommended by the authors, because the experimental conditions used do not allow any
conclusions as to reversibility. There are also no meaningful data as to the amounts of
silica retained, which might have produced evidence for differences in retention times
after exposure-free intervals. The lung function tests as carried out here are not
influenced by the presence of macrophage granulomas. More serious developments,
however, and specifically collagen production do seem to be reflected in the pathological
lung function test result. In the opinion of the authors, conclusions as to a clinical
significance for man cannot be deduced from the results of the lung function tests
because there is at present no scientific basis for the extrapolation of the results of lung
function tests from monkeys to man.

6 Manifesto (MAK value, classification)

6.1 Differentiation between the various forms of silica
A comparison of the pathogenic effects of the various crystalline and amorphous silicas
for toxicological and occupational medical purposes must take into account, above all,
the silicosis induced. Therefore the evaluation of the silicosis induced by the various
dusts must be based on the pathogenic event which is most significant in silicosis,
namely fibrosis. Increase in lung weight and acute cell damage cannot be taken as an
indication of the silicosis-inducing effect of a dust. The progression of the fibrosis during
long-term testing plays a particularly important role. This is the basis for the conclusions
that follow.

6.2 Crystalline silica

Quartz and also the crystalline forms of silica, cristobalite and tridymite, are unam-
biguously capable of inducing silicosis [5, 54]. Therefore the unambiguously crystalline
modifications of SiO2 should continue to have their own threshold limit value which is
the same as the value for quartz. It is important to note that, in particular, cristobalite and
tridymite can be formed from amorphous forms by heating for long enough at high
enough temperatures.

6.3 The MAK value for quartz glass, fused silica, silica fume
and calcined diatomaceous earth
In animals, quartz glass generally induces silicosis which varies in severity from a mere
suggestion to moderate disease. In most of the studies examined here which specifically
compare the effects of quartz, quartz glass or amorphous silica, it was observed that
quartz glass is not as effective in inducing silicosis as quartz or other crystalline forms of
silica. Thus during toxicological comparison with crystalline SiO2 modifications, quartz
glass induced fibrosis which attained grade 3 less rapidly and did not progress further to
176 Silica, amorphous Volume 2

grade 4 [54]. Similar effects were reflected in the degree of tissue reaction according to
King after intraperitoneal injection of various untreated amorphous and crystalline forms
of SiO2 and of ground quartz fibre glass (Figure 1) [5]. After 2, 4 and 8 months in this
experiment, heated pyrogenic silicas had marked effects which were comparable with
the fibrogenic effect of quartz, although some of the substances still appeared to be
amorphous. Other observations indicate moderate histotoxicity after longer exposures to
X-ray amorphous silica fume and quartz glass if organ weights and collagen content are
also taken into consideration [56]. Marked collagen formation in the lymph nodes is also
conspicuous after exposure to calcined diatomaceous earth [56].
Only one study reported equal effects of quartz and X-ray amorphous quartz glass,
i.e. fused ground rock crystal. In this case, however, unlike in the studies discussed
above, a truly differentiated evaluation on the basis of accepted toxicological parameters
was not undertaken [57].
Diatomaceous earth, silica fume, quartz glass and secondarily tempered silicas cannot
be specifically identified as such. An analytical differentiation of silica fume and quartz
glass from colloidal silica can only be carried out on the basis of the appearance of
luminescence and the very much larger particle size of the dusts. These methods are not
suitable for routine analysis of the air inhaled at work. The effect of quartz glass and
tempered silica is in general less than that of quartz, particularly in the long term.
It is therefore justifiable to establish a specific MAK value for those amorphous
silicas which, in spite of being X-ray amorphous, because of the conditions under which
they originate must be considered to possess short range crystalline order and a different
range of particle sizes from the highly disperse colloidal silicas. They include quartz
glass, fused silica, silica fume and possibly also secondarily tempered silicas such as
calcined diatomaceous earth. Sufficient experience of adverse effects on man of quartz
glass, fused silica, silica fume and tempered amorphous silicas is not available.
On the other hand, there are few clear casuistics of silicosis which is unambiguously
a result of exposure to quartz glass or fused silica [29]. Animal studies provide evidence
for a fibrogenic effect which is in general weaker than that of the X-ray crystalline forms
[5, 54]. In some experiments, however, they come close to the effects of quartz (see
Figure 1). An adequate quantitative estimation of the difference in these effects from the
available animal studies is therefore not possible. The MAK value for quartz glass, fused
silica, silica fume and calcined diatomaceous earth is therefore set at 0.3 mg/m3 fine dust
with an evaluation time of 8 hours.

6.4 The MAK value for colloidal synthetic amorphous silica

and uncalcined diatomaceous earth
The primary particles of colloidal amorphous silicas including pyrogenic silica and wet
process silica are very fine and their particle size range classifies them exclusively as
fine dust. In the air at work, aggregation gives rise to particles of diameter up to 100 m.
Measurements carried out in 1984 and 1986 revealed 2.2 mg/m3 and 4.4 mg/ m3 total
dust. At the same time 0.7 mg/m3 and 1.7 mg/m3 fine dust was found by means of the
horizontal elutriator [4].
Volume 2 Silica, amorphous 177

All the available epidemiological and animal data are based on total dust
concentrations. Some of the injurious effects were found in the upper respiratory tract
[53]. Therefore, deviating from the recommendations for fumes, only a MAK value for
total dust can be established for colloidal synthetic amorphous silicas.
Adverse effects of these dusts have not yet been observed in man [30]. In acute
toxicity studies in animals, colloidal amorphous silicas are very toxic after intraperi-
toneal or intratracheal administration [26, 3638]. There are differences between the
various kinds of amorphous silica depending on the size of the primary particle, i.e. the
specific surface area and the rate of solution: higher solution rates increase the toxicity
[4446]. This is sufficient reason to set the evaluation period at 8 hours. This is not the
case for the chronic tissue damage. As a rule, after inhalation of these silicas there are
signs of desquamative catarrh, i.e. an increase in intra-alveolar cells (mostly alveolar
macrophages). Stable emphysematous or fibrotic lesions do not usually occur. In an
inhalation study in monkeys with pyrogenic silica (15 mg/m3, 15 months), collagen
fibres were also observed in the cellular granulomas in some animals. Some lung
function parameters also differed from the control values. The significance of these
findings for man is still unclear. With the other kinds of silica tested in this study, silica
gel and precipitated silica, no adverse effects were observed.
More recent studies of pyrogenic silicas, both untreated and after secondary chemical
treatment, and of precipitated silica were carried out by means of inhalation experiments
with rats. 1, 6 and 30 mg/m3 total dust were studied for Aerosil 200 and 30 mg/m3 total
dust for surface modified pyrogenic silica (Aerosil R 974) and precipitated silica.
Untreated pyrogenic silica produced effects at a concentration as low as 6 mg/m3 total
dust [53]. "Focal interstitial fibrosis" was seen in some animals after 3 months exposure.
This effect was most pronounced with pyrogenic silica (Aerosil 200) and weakest for
precipitated silica (Sipernat 22S). It is not possible to make a clear assessment of its
significance because it regressed completely. Further studies are therefore urgently
necessary. The authors' interpretation, that there exists a concentration threshold for
adverse effects below 1 mg/m3 Aerosil 200 total dust can only apply to statistically non-
significant changes which, in the opinion of the authors, are anyway reversible. The
toxicological significance of these effects also requires further experimental study.
On the basis of these inhalation studies the MAK value for
colloidal amorphous silica
including pyrogenic silica and
wet process silica (precipitated silica and silica gel)
as well as
diatomaceous earth (uncalcined)
is set at 4 mg/m3 total dust with an evaluation period of 8 hours.
It is emphasized that, in comparison with the general threshold limit value for dust,
this value is not just numerically less by a factor of 1.5. The evaluation time is 8 hours
rather than one year and the value applies for total dust and not for fine dust.
178 Silica, amorphous Volume 2

7 References
1. World Health Organization: Report of a WHO/IARC meeting, 2022 April 1982, Euro-Re-
ports and Studies 81, European regional office, Copenhagen, DK, 1982
2. Ullmanns Encyklopdie der technischen Chemie, 4th ed., Vol. 21, p 472, Verlag Chemie, D-
6940 Weinheim, 1982
3. Degussa AG: ,,Pulverfrmige amorphe synthetische Kieselsureprodukte; Herstellung und
Charakterisierung", in: Degussa AG (Ed.): Schriftenreihe Pigmente, Vol. 32, 1977
4. Ferch, H.: Arbeitsmed. Sozialmed. Prventivmed. 22(1), 6 (1987)
5. Klosterktter, W.: in Jtten, K. W., W. Klosterktter (Eds.): Die Staublungenerkrankungen,
Vol. 3, p 326, Verlag Steinkopff, D-6100 Darmstadt, 1957
6. Brnner, H., D. Schutte: Chem. Z. chem. App. 89, 437 (1965)
7. Boden, G.: Sprechsaal 116(5), 430 (1983)
8. Boden, G.: Sprechsaal 117(5), 467 (1984)
9. Flrke, O. W., M. Schmcker: Untersuchungen an nichtkristallinen technischen Kieselsuren
unter besonderer Bercksichtigung des thermischen Transformationsverhaltens, Report from
the Institut fr Mineralogie, Ruhr-Universitt D-4630 Bochum; in cooperation with W.
Kriegeis und A. Scharmann, I. Physkalisches Institut, Justus-Liebig-Universitt D-3208
Gieen; Bochum, 31.7.1988
10. Rhl, R.: Unpublished communication presented at an information day at BG Keramik, D-
5205 St. Augustin, 6.7.1987
11. Heidermanns, G.: Unpublished communication presented at an information day at BG
Keramik, D-5205 St. Augustin, 6.7.1987
12. Prochazka, R.: Staub-Reinhalt. Luft 31(9), 361 (1971)
13. Legge, R. T., E. Rosencrantz: Amer. J. publ. Hlth 22, 1055, (1932)
14. Caldwell, D. M.: Amer. Rev. Tuberc. 77, 644 (1958)
15. Vigliani, E. C., G. Mottura: Brit. J. industr. Med. 5, 148 (1948)
16. Beskow, R.: Scand. J. resp. Dis. 59, 216 (1978)
17. Oechsli, W. R., G. Jacobson, A. E. Brodeur: Amer. J. Roentgenol. 85(2), 263 (1961)
18. Ebina, T., Y. Takase, Y. Inasawa: Sci. Rep. Res. Inst. Tohoku Univ., Ser. C 4, 65 (1952)
19. Bell, Z. G., D. D. Dunnom, H. Lott: Amer. industr. Hyg. Ass. J. 39(5), 418 (1978)
20. Vitums, V., M. Edwards, N. Niles, J. Borman, R. Lowry: Arch. environm. Hlth 32, 62 (1977)
21. Gross, P.: Arch. environm. Hlth 33, 100 (1978)
22. Pancheri, G.: Rass. Med. industr. 17, 1 (1948)
23. Jung, H., W. Dress: Bergakademie Freiberg 3, 157 (1960)
24. Bruce, T.: J. industr. Hyg. 19, 155 (1937)
25. Klosterktter, W.: in Jtten, K. W., K. Klosterktter (Eds.): Die Staublungenerkrankungen,
Vol. 2, p 73, Verlag Steinkopff, D-6100 Darmstadt, 1954
26. Swensson, A., J. Glomme, G. Bloom: Arch. industr. Hlth 14, 482 (1956)
27. Bowie, D. S. J.: Cent. Afr. J. Med. 24(5), 81 (1978)
28. Robalo-Cordeiro, A. J. A., M. F. Baganha, R. Azevedo-Bernada, A. C. P. Leite, O. R. G.
Almeida, U. F. Bairos, E. Casper, M. F. Garao, M. A. M. Lima, M. A. S. Rosa, A. F. Tega, J.
M. P. Bastos: in Beck, E. G., J. Bignon (Eds.): In vitro effects of mineral dusts, p 489, Springer
Verlag, New York, USA, 1985
29. Mohrmann, W., J. Kann: Paper read at the 25th Annual Meeting of the Deutschen Gesellschaft
fr Arbeitsmedizin in D-4600 Dortmund, p 587, Gentner Verlag, D-7000 Stuttgart, 1985
30. Ferch, H., H. Gerofke, H. Itzel, H. Klebe: Arbeitsmed. Sozialmed. Prventivmed. 22(2), 33
(1987)
31. Plunkett, E. R., B. J. de Witt: Arch. environm. Hlth 5, 469 (1962)
32. Wilson, R. K., P. M. Stevens, H. B. Lovejoy, Z. G. Bell, R. C. Richie: J. occup. Med. 21, 399
(1979)
33. Wilson, R. K., P. M. Stevens, H. B. Lovejoy, Z. G. Bell, R. C. Richie: Amer. Soc. Test. Mat.
Spec. techn. Publ. 732, 185 (1981)
34. Koppenhfer, G. F.: Virchows Arch. path. Anat. 297, 18a (1936)
35. Giese, W.: Klin. Wschr. 19(23), 558 (1940)
Volume 2 Silica, amorphous 179

36. Gye, W. E., W. J. Purdy: Brit. J. exp. Path. 3, 75 (1922)

37. Gye, W. E., W. J. Purdy: Brit. J. exp. Path. 3, 86 (1922)
38. Gye, W. E., W. J. Purdy: Brit. J. exp. Path. 5, 238 (1924)
39. Arayani, C., D. E. Gardner, J. L. Huisingh: in Proceedings of the Symposium of health effects
of synthetic silica particulates, p 48, Marbella, Spain, 37 Nov. 1979
40. Davies, R.: in Proceedings of the Symposium of health effects of synthetic silica particulates, p
67, Marbella, Spain, 37 Nov. 1979
41. Bye, E., R. Davies, B. Gylseth, D. M. Griffiths, C. B. Moncriess: Brit. J. industr. Med. 41, 228
(1984)
42. Harley, J. D., J. Margolis: Nature (Lond.) 189, 1010 (1961)
43. Stalder, K.: Beitr. Silikose-Forsch. 22(5), 239 (1970)
44. Klosterktter, W.: Arch. Hyg. (Berl.) 152, 7 (1968)
45. Klosterktter, W.: Arch. Hyg. (Berl.) 149(7/8), 577 (1965)
46. Klosterktter, W.: Arch. Hyg. (Berl.) 150, 542 (1966)
47. Schlipkter, H., J. Rothes, A. Defeche: Z. Hyg. Infekt.-Kr. 143, 533 (1957)
48. Schepers, G. W. H.: Arch. industr. Hlth 16, 125 (1957)
49. Lundgren, K. D., A. Swensson: Acta med. scand. 165, 85 (1953)
50. Glmme, J., A. Swensson: in Jtten, K. W., W. Klosterktter (Eds.): Die
Staublungenerkrankungen, Vol. 3, p 231, Verlag Steinkopff, D-6100 Darmstadt, 1958
51. Rttner, J. R., W. Willy, A. Baumann: Schweiz. Z. allg. Path. 17(3), 352 (1954)
52. Klosterktter, W., G. Bnemann: in Davies, C. N. (Ed.): Inhaled Particles and Vapours, Vol.
1, p 327, Pergamon Press, Oxford, England, 1961
53. Reuzel, P., R. Woutersen, J. Bruntjes: Civo institutes tno, Report No. V 86.347/240718, p 13,
commissioned by Degussa AG, Frankfurt, Zeist, NL, 1987
54. King, E. J., G. P. Mohanty, C. V. Harrison, G. Nagelschmidt: Brit. J. industr. Med. 10, 9
(1953)
55. Klosterktter, W., K. W. Jtten: Arch. Hyg. (Berl.) 137(8), 626 (1953)
56. Swensson, A.: in Davies, C. N. (Ed.): Inhaled Particles and Vapours, Vol. 2, p 95, Pergamon
Press, Oxford, England, 1965
57. Brieger, H., P. Gross: Arch. environm. Hlth 14, 299 (1967)
58. Strecker, F. J.: in Jtten, K. W., K. Klosterktter (Eds.): Die Staublungenerkrankungen, Vol. 3,
p 220, Verlag Steinkopff, D-6100 Darmstadt, 1958
59. Jtten, K. W., K. Klosterktter: Arch. Hyg. (Berl.) 136(1), 1 (1952)
60. Hilscher, W., K. Bieniek, K. Wierschem, R. Grover: in Tiefbau-Berufsgenossenschaft (Ed.):
Die sichere Anwendung der Spritzbetonbauweise unter Druckluft, p 67; Order No. 793.1, D-
8000 Mnchen, 1986
61. Groth, D. H., W. J. Moorman, D. W. Lynch, L. E. Stettler, W. D. Wagner, R. W. Hornung: in
Proceedings of the Symposium of health effects of synthetic silica particulates, p 118,
Marbella, Spain, 37 Nov. 1979

completed 10.4.1989