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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

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Toxicological information

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Description of key information

Acute toxicity oral

For acute oral toxicity assessment, the data base compiles 20 studies performed between 1951 and 1999. They used test materials of Synthetic Amorphous Silica produced by different processes including pyrogenic, precipitated, gel and colloidal silica with specific surface area (BET) ranging from 45 to 420 m²/g. 5 of these studies meet the criteria for Klimisch score 1 and 15 studies met the criteria for Klimisch score 2 performed according to OECD guidelines 401, 420 or 423 or similar in either rats or mice. Mortality or significant toxicity were absent in all these studies. LD50 values exceeded the top doses tested.

LD50 values of >2000 mg/kg bw or >5000 mg/kg bw have thereby been established.

 

Acute toxicity inhalation:

For the acute inhalation toxicity assessment of untreated SAS, 6 studies performed between 1972 and 1983 are available and a new one recently conducted in 2019. Different forms of untreated SAS were tested with the specific surface (BET) ranging from 170-420 m2/g. In this long time period of absence of effects only in one study from 1977 one of ten animals died. But this study was unsuitable for the determination of acute inhalation systemic toxicity of inert and non-toxic SAS particles. The majority of the studies were conducted before the release of OECD guideline 403 (1981). Different test set-ups, not comparable, were used, i.e. most studies used the whole-body exposure, while nose-only has now become the preferred route of exposure. The results were recently confirmed by the latest study with a precipitated SAS according to OECD 436 which is the only one achieved a characterized aerosol of 5 mg/L and resulted in a LD50 > 5.01 mg/L air (Vivotecnia, 2019).

All early/former studies have technical deficiencies and do not entirely fulfill the criteria laid down in OECD 403. Due to the limited particle size information and the expected agglomeration of the tested SAS forms after atmosphere generation in the test chamber, the real exposure conditions of the animals in the older tests was not verified. Only one of these studies (Toxicogenics Inc., 1981) fulfills the technical conditions of OECD 403 in a sufficient way to justify a Klimisch rating of 2.

No mortality or significant toxicity was observed in 6 of the 7 studies (only 1 over 10 animal dead in a single study). For all these studies LC50 values are above the maximum achievable concentration or the highest concentration tested. The achievable test concentrations varied over 3 orders of magnitude (>0.139 mg/L and >207 mg/L) and based on the limited data available it is not possible to conclude on any reason for these differences. Maximum concentrations required by guideline were in the past not achievable due to technical limitations and possibly materials properties. However, the recent study (30 years later than the previous one) demonstrated the absence of mortality even under a stable 5 mg/L characterized aerosol, as confirmed by particle size distribution measurements.

  

Acute toxicity dermal:

The assessment of acute dermal toxicity for Set 1 is based on 5 studies performed in 1976 and 2000. Different forms of synthetic amorphous silica with specific surface area (BET) ranging from 115-349 m2/g were used as test materials.

These studies meet the criteria for Klimisch score 2 and were performed according to a protocol comparable to the OECD guideline 402, with certain restrictions. In 4 studies, 4 doses have been tested (2000, 3000, 4000, 5000 mg/kg bw) and the fifth study is a one dose (2000 mg/kg bw) study. Test material was applied once to intact and abraded skin for 24h. LD50 values exceeded the top doses tested. No mortality or significant toxicity were observed in any of the 5 studies.

LD50 values of >2000 mg/kg bodyweight have thereby been established and untreated SAS is therefore considered not toxic by dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline available
Principles of method if other than guideline:
3 dose l., single administration, 7d post obs.
GLP compliance:
no
Specific details on test material used for the study:
Cab-O-Sil (Fluffy)
Species:
rat
Strain:
other: doltzman albino
Sex:
male
Details on test animals or test system and environmental conditions:
117-159 g
food and water ad libitum, but withheld for 3-4 hours prior to dosage
Route of administration:
other: stomach tube
Vehicle:
methylcellulose
Doses:
1.00, 2.15, 3.16 g/kg/bw
No. of animals per sex per dose:
5 (males only)
Control animals:
no
Details on study design:
7 days post observation
Sex:
male
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Mortality:
no mortality
Clinical signs:
no signs
Body weight:
body weight gain within the normal range
Gross pathology:
organs appeared within normal limits
Conclusions:
The acute oral LD50 of Cab-O-Sil (Fluffy) for male albino rats was greater than 3.16 g/kg/bw.
Executive summary:

This badly documented study examined the LD50 of Cab-O-Sil (Fluffy). The substance is not described any further.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 12-26, 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987-02-24
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
fumed silica, M5 - OL, batch no.: 5E05 99A
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
98-116 g at the start of experiment, 6-7 weeks old, 7 days acclimatisation; from: Fredrick Institute, Padappai, India
12h light/dark, 5 animals of same sex per cage, standart pellet feed ad libitum, Aquaguard filtered water ad libitum
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5000 mg/kg/bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
single administration, 14 days of post administration observation
Statistics:
comparison of experimenta with control group using Student's t-test.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortaility
Clinical signs:
no clinical signs observed
Body weight:
on par with controls
Gross pathology:
no test substance related lesions
Conclusions:
The LD50 of Cab-O-Sil fumed silica for wistar rats was considered to be greater than 5,000 mg/kg/bw.
Executive summary:

The experiment examined the oral LD50 of Cab-O-Sil fumed silica (M5).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jan. 14-28, 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
not specified
Specific details on test material used for the study:
experimental fumed silica, batch #SP 12-7033
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
obtained from: Charles River, Margate, Emgland;112-138 g, 4-6 weeks old, housed in groups by sex, 21-24 °C, mean humidity 59%, 12h light/dark; feed: Labsure LAD 1 and water ad libitum, except prior to administration and 4 hours thereafter
Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
25% w/v suspension in corn oil
Details on oral exposure:
adminsitered on two occasions, one hour apart
Doses:
5 g/kg/bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
14-day observation period
macroscopic post mortem on all animals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
pilo-erection in all animals within 5 minutes after dosing and persisting throughout the day of dosing; no other clinical signs
Body weight:
slightly low bw gains for one male and two females in first week and one female in the second week of study
Gross pathology:
autopsy findings were normal
Conclusions:
As no mortality occured, the LD50 of experimental fumed silica was greater than 5 g/kg/bw.
Executive summary:

The acute oral toxicity level of experiment fumed silica (SP 12-7033) was assessed in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Jun. - Sep. 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline available
Principles of method if other than guideline:
1 dose level, single administration in the diet, 14-day observation period
GLP compliance:
not specified
Limit test:
yes
Specific details on test material used for the study:
Aerosil 130, Aerosil 150, Aerosil 200, Aerosil 300, Aerosil 380, Aerosil COK 84, Aerosil MOX 80, Aerosil MOX 170, Aerosil OX 50, Aerosil TT 600, Ultrasil VN 2, Ultrasil VN 3, Kieselsäure FK 160, Kieselsäure FK 300DS, Kieselsäure FK 310, Kieselsäure FK 320, Kieselsäure FK 320 DS, Kieselsäure FK 320 ZF, Kieselsäure FK 383 DS, Kieselsäure FK 700, Mattierungsmittel HK 125, Mattierungsmittel HK 400, Mattierungsmittel TS 100, Sident 3, Sipernat 22, Sipernat 30, Sipernat 42
Species:
rat
Strain:
Wistar
Remarks:
albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
116-328 g (males), 78-160 g (females), 5 per cage, 23 +/- 1 °C, tap water ad libitum
Route of administration:
oral: feed
Vehicle:
other: diet 1:4 (w/w)
Doses:
10 g/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
14-day observation period
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil 130
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil 150
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil 200
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil 300
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil 380
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil COK 84
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil MOX 80
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil MOX 170
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil OX 50
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Aerosil TT 600
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Ultrasil VN 2
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Ultrasil VN 3
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 160
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 300DS
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 310
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 320
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 320 DS
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 320 ZF
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 383 DS
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Kieselsäure FK 700
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Mattierungsmittel HK 125
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Mattierungsmittel HK 400
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Mattierungsmittel TS 100
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Sident 3
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Sipernat 22
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Sipernat 30
Effect level:
> 10 000 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Remarks:
Sipernat 42
Effect level:
> 10 000 mg/kg bw
Mortality:
no mortality with any product
Clinical signs:
None of the tested products induced diarrhoea, changes in condition or behaviour or any other sign of toxicity. Stool changed colour to grey, but showed normal consistency with faecal pellets considerably bigger than normal. 
Gross pathology:
Gross examination did not provide indications of treatment-related changes.
Other findings:
All but 3 animals, fed different products, consumed the supplemented diet quantitatively. 
Conclusions:
It was concluded that the acute oral toxicity of all 27 tested products was greater than 10 g/kg bw, and probably even considerably higher.
Executive summary:

The acute oral toxicities of 27 silicas were examined in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Aug. 16 - Sep. 4, 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Limit test:
yes
Specific details on test material used for the study:
Sident 9
Species:
rat
Strain:
other: WISW (SPFCpb)
Sex:
male/female
Details on test animals or test system and environmental conditions:
from: Winkelmann, Borchen, Germany; males: 9 weeks, 183-191 g; females: 10 weeks, 141-52 g; individually caged; feed: "ssniff R" and tap water ad libitum, except the last 16 hours before treatment; 20.5-22.5°C, 40-70% humidity, 12 h light/dark
Route of administration:
oral: gavage
Vehicle:
other: aqueous suspension stabilizied by 1% carboxymethylcellulose
Doses:
5110 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
14-day pbservation period
gross pathology performed on all animals
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 110 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 5 110 mg/kg bw
Mortality:
no mortality
Clinical signs:
no signs of toxicity were recorded
Body weight:
All animals gained weight.
Gross pathology:
no alterations were detected
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured, the LD50 value for male and female rats was greater than 5110 mg/kg bw.
Executive summary:

The acute oral toxicty of Sident 9 was evaluated in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Nov. 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline available
Principles of method if other than guideline:
single administration, 2 dose levels, 4-week post observation period
GLP compliance:
no
Test type:
standard acute method
Specific details on test material used for the study:
Sipernat 22
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: S. Ivanovas/Kißlegg, Germany
- Age at study initiation: 38 d (male), 42 d (female)
- Weight at study initiation: 100 - 105 g
- Fasting period before study: 15 - 16 h before start of the study
- Housing: single in Macrolon cages
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 +-0.5 °C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:
oral: gavage
Vehicle:
other: water/methyl-hydoxyethyl cellulose 300 P (1%)
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: stabilisation of homogeneous distribution of light insoluble test material in aqueous gel suspension

MAXIMUM DOSE VOLUME APPLIED: yes (higher doses could not be produced)

Doses:
2000 and 5000 mg/kg bw.
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 28 days
- Frequency of observations and weighing: data on days 1, 2, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption mentioned
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
no particular findings
Body weight:
no significant findings
Gross pathology:
no particular findings
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured the LD 50 was greater than 5000 mg/kg bw.
Executive summary:

The acute oral toxicity of Sipernat 22 was assessed in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline available
Principles of method if other than guideline:
5 dose levels, single administration, 14-day post observation
GLP compliance:
no
Specific details on test material used for the study:
Syloid 378
Species:
rat
Strain:
Sprague-Dawley
Remarks:
albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
obtained from: Charles River; males 160-230 g, females 126-180
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Doses:
464, 1000, 2150, 4640, 10000 mg/kg/bw
No. of animals per sex per dose:
5
Details on study design:
14-day observation period
Gross pathology performed on all animals which died or were scarified.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 8 810 mg/kg bw
95% CL:
>= 5 449 - <= 14 224
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 7 376 mg/kg bw
95% CL:
>= 5 210 - <= 10 443
Mortality:
males: 3/5 in highest dose group; no mortality in other groups
females: 4/5 in highest dose group; no mortality in other groups
Clinical signs:
Decreased activity, ptosis, urine strains, involuntary muscle spasm, lacrimation, depression, prostration, irregular respiration, slight cyanosis and high carriage in highest dose groups. Normal appearance in other dose groups.
Gross pathology:
Gross pathology revealed no alterations to organs or tissues.
Conclusions:
The calculated LD50s were 8,810 and 7,376 mg/kg/bw for males and females, respectively.
Executive summary:

The acute oral toxicity level of Syloid 378 was evaluated in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
other: E.U. directive 79/831
Principles of method if other than guideline:
1 dose level, single administration, 14-day post observation
GLP compliance:
yes
Specific details on test material used for the study:
Tixosil 53
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
obtained from: Centre d'élevage d'IFFA CREDO, Saint-Germain sur l'Abresle; males 160-200 g, females 140-180 g, 6-7 weeks old, 5 per cage, feed: UAR AO4 and bottled water ad libitum, except during adminstration and preceeding 16-20 hrs., 22 +/-3 °C, 30 - 70 % humidity, 12 h light/dark
Route of administration:
oral: feed
Vehicle:
other: gum arabic
Doses:
5000 mg/kg/bw
No. of animals per sex per dose:
5
Control animals:
yes
Remarks:
vehicle only
Details on study design:
14-day post observation
necropsy performed on all animals
Preliminary study:
yes, with 1000, 2500 and 5000 mg/kg/bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
no clinical signs
Body weight:
all animals gained body weight (slightly decreased in treated males)
Gross pathology:
no gross pathological changes
Conclusions:
As no mortality occured, the LD50 was greater 5000 mg/kg/bw.
Executive summary:

The acute oral toxicity level of Tixosil 53 was assessed in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single administration, 4 dose levels, 14-day post observation
GLP compliance:
not specified
Specific details on test material used for the study:
Zeo 49
Species:
rat
Strain:
Crj: CD(SD)
Remarks:
SD/N BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
obtained from: Taconia Farm; 100-125 g, 5 per cage, Purina Laboratoty diet and water ad libitum
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
33.3% suspension
Doses:
10,000, 12,600, 15,800, 20,000 mg/kg bw.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
14-day observation period; daily observation for clinical signs and body weight; gross pathology performed
Preliminary study:
yes, with dose levels 1,000 - 20,000 mg/kg bw.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 20 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
Within 8 hours after dosing all animals exhibited white feces. Feces appeared normal by day 1.
Body weight:
All animals gained weight.
Gross pathology:
no abnormalities observed
Conclusions:
As no mortality occured the LD50 was greater than 20,000 mg/kg bw.
Executive summary:

The acute oral toxicity of Zeo 49 was evaluated in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April/May 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single administration, 4 dose levels, 14-day post observation
GLP compliance:
not specified
Specific details on test material used for the study:
Zeofree 153
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
SD/N BR rats weighing 100-125 grams were obtained from Taconic Farms, Inc..
The animals were housed up to five per cage and fed Purina Laboratory diet and water ad libitum.


Route of administration:
oral: gavage
Vehicle:
water
Remarks:
20% suspension
Doses:
Based on the survival pattern in the range finding study, 5 male and 5 female rats were fasted for sixteen hours and gavaged at the following levels: 10,000, 12,600, 15,800, and 20,000 mg/kg of body weight.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed for reactions at 1, 2 and 4 hours after dosing and then daily for 14 days. Body weights were recorded at dosing and at termination. Rats dying or sacrificed were subjected to a gross examination of the viscera.
Preliminary study:
Following a one weeks acclimation to laboratory conditions, a series of range finding studies was conducted at dose levels of: 1000, 2000, 3000, 4000, 5000, 10,000, 20,000 mg/kg of body weight.
The rats were fasted approximately sixteen hours prior to receiving a single gavage of the test material. Dose range animals were observed up to 72 hours after dosing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Mortality:
Only one female of the highest dose group died.
Clinical signs:
Animal #8 on the 20,000 mg/kg dose level exhibited gasping immediately after dosing. On day 3 the animal was found dead.
Animals exhibited white feces diminishing by day 3.
Body weight:
All surviving animals gained weight.
Gross pathology:
No abnormalities were observed in the surviving animals or the dead one.
Interpretation of results:
GHS criteria not met
Conclusions:
As only one out of 10 animals of the highest dose group died, the LD50 was greater than 20,000mg/kg of body weight.
Executive summary:

Zeofree 153 was evaluated for its oral LD50 in the rat.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April/May 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single administration, 4 dose levels, 14-day post observation
GLP compliance:
not specified
Specific details on test material used for the study:
Zeosyl 113
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
SD/N BR rats weighing 100-125 grams were obtained from Taconic Farms, Inc..
The animals were housed up to five per cage and fed Purina Laboratory diet and water ad libitum.


Route of administration:
oral: gavage
Vehicle:
water
Remarks:
33.3% suspension
Doses:
10,000, 12,600, 15,800, 20,000 mg/kg bw.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed for reactions at 1, 2 and 4 hours after dosing and then daily for 14 days. Body weights were recorded at dosing and at termination. All rats were subjected to a gross examination of the viscera.
Preliminary study:
Following a one weeks acclimation to laboratory conditions, a series of range finding studies was conducted at dose levels of: 1000, 2000, 3000, 4000, 5000, 10,000, 20,000 mg/kg of body weight.
The rats were fasted approximately sixteen hours prior to receiving a single gavage of the test material. Dose range animals were observed up to 72 hours after dosing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 20 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
Animals exhibited white feces beginning day 1, diminishing by day 2.
Body weight:
Animal at all levels gained weight.
Gross pathology:
Upon necropsy, on day 14, no abnormalities were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured , the LD50 was greater than 20,000 mg/kg of body weight.
Executive summary:

Zeosyl 113 was evaluated for its oral LD50 in the rat.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single administration, 4 dose levels, 14-day post observation
GLP compliance:
not specified
Specific details on test material used for the study:
ZEOSYL® 200

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
SD/N BR rats weighing 100-125 grams were obtained from Taconic Farms, Inc..
The animals were housed up to five per cage and fed Purina Laboratory diet and water ad libitum.


Route of administration:
oral: gavage
Vehicle:
water
Remarks:
15% suspension
Doses:
10,000, 12,600, 15,800, 20,000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Animals were observed for reactions at 1, 2 and 4 hours after dosing and then daily for 14 days. Body weights were recorded at dosing and at termination. Rats dying or sacrificed were subjected to a gross examination of the viscera.
Preliminary study:
Following a one week acclimation to laboratory conditions, a series of range finding studies was conducted at dose levels of: 1000, 2000, 3000, 4000, 5000, 10,000, 20,000 mg/kg of body weight.
The rats were fasted approximately sixteen hours prior to receiving a single gavage of the test material. Dose range animals were observed up to 72 hours after dosing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Mortality:
Only one female of the 12,600 mg/kg bw group died.
Clinical signs:
Animal exhibited white feces beginning day 1, diminishing by day 3.
Body weight:
All surviving animals gained weight.
Gross pathology:
Upon gross necropsy, on day 14, no abnormalities were observed in surviving animals. No abnormalities were observed upon necropsy of the dead female of the 12,600 mg/kg bw group.
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortalty occured in the highest dose group, the LD50 was greater than 20,000 mg/kg of body weight.
Executive summary:

Zeosyl 200 was evaluated for its oral LD50 in the rat.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Nov. 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline available
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Specific details on test material used for the study:
Aerosil 200
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: S. Ivanovas/Kißlegg, Germany
- Age at study initiation: 38 d (male), 42 d (female)
- Weight at study initiation: 100 - 105 g
- Fasting period before study: 15 - 16 h before start of the study
- Housing: single in Macrolon cages
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 +-0.5 °C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:
oral: gavage
Vehicle:
other: water/methyl-hydoxyethyl cellulose 300 P (1%)
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: stabilisation of homogeneous distribution of light insoluble test material in aqueous gel suspension


MAXIMUM DOSE VOLUME APPLIED: no data

Doses:
2000 and 3300 mg/kg bw. (higher concentrations could not be produced)
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 28 days
- Frequency of observations and weighing: data on days 1, 2, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, food consumption mentioned
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 300 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 3 300 mg/kg bw
Mortality:
no mortality
Clinical signs:
no particular findings
Body weight:
slight reduction of 4 - 8 %, measured at days 1, 2, and 14
Gross pathology:
no particular findings
Other findings:
- Other observations: feed consumption reduced in the 2000-mg groups (10, 4 and 6 % at day 1, 2, and 14, respectively)
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured the LD 50 was greater than 3300 mg/kg bw.
Executive summary:

The acute oral toxicity of Aerosil 200 was evaluated in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
adm. by stomach tube, 6 dose l., single administration, 14d post obs.
GLP compliance:
no
Specific details on test material used for the study:
F-2 (fine white powder, faintly pungent)
Species:
mouse
Strain:
Swiss
Remarks:
albino
Sex:
male
Details on test animals or test system and environmental conditions:
18-26 grams, not fasted prior to dosing, food and water ad libitum
Route of administration:
other: stomach tube
Vehicle:
corn oil
Doses:
178, 316, 562, 1000, 1780, 3160 mg/kg/bw
No. of animals per sex per dose:
10 (males only)
Control animals:
no
Details on study design:
14 d post observation
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
2 deaths in 1000 mg/kg/bw group, but necropsy findings showed non-treatment-related causes
Clinical signs:
no signs
Body weight:
Overall (natural) weight gain
Gross pathology:
no findings
Conclusions:
The acute oral LD50 of F-2 for male albino Swiss mice was greater than 3160 mg/kg/bw.
Executive summary:

A study with F-2 silica was carried out to determine its acute oral LD50 for mice.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Principles of method if other than guideline:
single dose level, triple administration within 2h , 24h post observation
GLP compliance:
no
Specific details on test material used for the study:
Cab-O-Sil EH-5
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
4 males, 150-250 g, 6-10 weeks old, 12 h light/dark, 65-71 °F, 30-70 % humidity, housed in groups, Agway Prolab rodent feed and tap water ad libitum
Route of administration:
other: intragastric intubation
Vehicle:
water
Details on oral exposure:
3 approximately equal doses separated by 1 h
Doses:
total: 5 g/kg/bw
No. of animals per sex per dose:
4 (males only)
Control animals:
yes
Details on study design:
24 h observation period
Mortality:
no mortality
Clinical signs:
no unusual findings
Body weight:
similar to control group
Other findings:
elevated levels of silica in urine (but might be due to contamination of urine with feces)
Conclusions:
no mortality, no clinical signs, but elevated levels of silica in urine
Executive summary:

The acute oral toxicity potential of Cab-O-Sil EH-5 was evaluated in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
May 14-28, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
2/1987
GLP compliance:
yes (incl. QA statement)
Limit test:
yes
Specific details on test material used for the study:
Cab-O-Sil Fumed Silica M-5
Species:
mouse
Strain:
Swiss
Remarks:
albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
20-24 g, 7 weeks old, 12 h light/dark, housed in groups according to sex, standard pellet feed and Aquaguard filtered water ad libitum
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
destilled
Doses:
5000 mg/kg/bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
14 d post observation period
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
no clinical signs
Body weight:
no significant difference in body weight gain to control
Gross pathology:
no treatment related lesions
Other findings:
no mortality and no clinical signs in control group
Conclusions:
LD50 > 5000 mg/kg/bw
Executive summary:

The acute oral LD50 of Cab-O-Sil (fumed silica) M-5 was examined in mice.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
1 dose level, single administration, 14 d post observation
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Cab-O-Sil (fumed silica) M-5
Species:
rat
Strain:
Sprague-Dawley
Remarks:
albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
individually caged, feed: Purina Certified Rodent Chow 5002, filtered tap water ad libitum, 12 h light/dark, 68-73 °F, 50-78 % humidity
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionized
Details on oral exposure:
dose administered in 2 portions approximately 4 h apart
Doses:
5 g/kg/bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
14-day post observation period
Mortality:
no mortality
Clinical signs:
One female exhibited gasping from 0 to 3 hours after administration of the first dose. One male exhibited moist rales on days 4 and 5.
No other clinical signs were observed.
Body weight:
All animals gained weight during the study.
Gross pathology:
no abnormalities observed
Conclusions:
virtually no clinical signs (no secure relationship to test article in two mild cases), no abnormalities upon necropsy
Executive summary:

An acute oral toxicity study with Cab-O-Sil M-5 was conducted in rats. No dose descriptor effect levels were evaluated.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline available
Principles of method if other than guideline:
adm. by stomach tube, 6 dose l., single administration, 14d post obs.
GLP compliance:
no
Specific details on test material used for the study:
M-5 (fine white powder with no discernible odor)
Species:
mouse
Strain:
Swiss
Remarks:
albino
Sex:
male
Details on test animals or test system and environmental conditions:
18-26 grams, not fasted prior to dosing, food and water ad libitum
Route of administration:
other: stomach tube
Vehicle:
corn oil
Doses:
178, 316, 562, 1000, 1780, 3160 mg/kg/bw
No. of animals per sex per dose:
10 (males only)
Control animals:
no
Details on study design:
14 days post observation
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 3 160 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
One death in 1000 mg/kg/bw group, but necropsy findings showed non-treatment-related effects.
Clinical signs:
no signs
Body weight:
overall (natural) weight gain
Gross pathology:
no findings
Conclusions:
The acute oral LD50 of M-5 for male albino Swiss mice was greater than 3160 mg/kg/bw.
Executive summary:

A study with M-5 silica was carried out to determine its acute oral LD50 for mice.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Principles of method if other than guideline:
n.a. (3 dose l., single administration, 4wk post obs.)
GLP compliance:
no
Specific details on test material used for the study:
TS 100 (also named: TK 100)
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
100 - 105g, 38 days-old males, 42 days-old females
Route of administration:
oral: gavage
Vehicle:
other: methyl hydroxyethylcellulose
Doses:
3180, 4000, 5040 ml/kg/bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
post observation: 4 weeks; but LD50 determined after 24h and 7d
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 040 mL/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
no mortality
Clinical signs:
no indications of intolerance
Body weight:
slight drcrease in feed intak and body weight development, non-dose-depending
Gross pathology:
no specific findings
Conclusions:
LD50 > 5040 mg/kg/bw (after 24h and 7d)
Executive summary:

The experiment investigated into the LD50 of TS 100 (also called TK 100 in the study) in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
7 dose levels, single administration, 14-day post observation
GLP compliance:
not specified
Specific details on test material used for the study:
Ludox WP (colloidal silica)
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male
Route of administration:
other: intragastric intubation
Vehicle:
water
Doses:
670, 2250, 3400, 5000, 7500, 11000, 17000 mg/kg/bw
No. of animals per sex per dose:
not specified
Control animals:
not specified
Details on study design:
sacrifice after 14-day post observation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 17 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
no mortality
Clinical signs:
none
Conclusions:
The Approximate Lethal Dose (ALD) of Ludox WP was greater than 17,000 mg/kg/bw.
Executive summary:

Ludox WP was administered by intragastric intubation to male rats. Only the summary page of this study was provided.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
July 1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline available
Principles of method if other than guideline:
1 dose level, single administration, 14-day post observation
GLP compliance:
no
Specific details on test material used for the study:
Syloid 244
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Route of administration:
oral: gavage
Vehicle:
water
Doses:
5620 mg/kg (max. attainable dose)
No. of animals per sex per dose:
30 (males only)
Control animals:
no
Sex:
male
Dose descriptor:
LD0
Effect level:
> 5 620 mg/kg bw
Clinical signs:
no symptoms of toxicity
whitish faeces

No clinical symptoms; the stools were white coloured
(reversible after 2 days).
    -----------------

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 after a 24-hour and 14-day observation period was greater 5.62 g/kg/bw.
Executive summary:

The acute oral toxicity level of Syloid 244 was evaluated in rats.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Principles of method if other than guideline:
Guidelines of the department of Transportation
1 dose level, 48-hour post observation
GLP compliance:
not specified
Specific details on test material used for the study:
Syloid 244
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Doses:
31,600 mg/kg/bw
No. of animals per sex per dose:
10 animals in total
Details on study design:
48-hour post observation period
Preliminary study:
2 rats each with 2,510, 3,980, 10,000 mg/kg/bw. No mortality occured.
Dose descriptor:
LD50
Effect level:
> 31 600 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Dose descriptor:
LD0
Effect level:
>= 31 600 mg/kg bw
Mortality:
no mortality
Clinical signs:
Animals were normal in appearance and behaviour.
Gross pathology:
Macroscopic changes were not observed in the viscera.
Conclusions:
As no mortality occured, the LD50 was greater 31,600 mg/kg/bw.
Executive summary:

The acute oral toxicity of Syloid 244 was assessed in rats. This study is only badly documented since one page, presumably containing the study's method, is missing.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 21 - Oct. 4, 2019; experimental phase: May 21 - Jun. 5, 2019
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
First study of its kind reporting a characterized respirable aerosol of 5 mg/L for untreated SAS.
Qualifier:
according to guideline
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Version / remarks:
9/2009
Deviations:
yes
Remarks:
MMAD slightly below recommended size; second GSD measurement above recommended value. None of the deviations was considered to have impact on the quality / integrity of the results or the study.
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Specific details on test material used for the study:
Zeosil Premium 200 MP, precipitated synthetic amorphous silica (SAS)
purity >= 98%
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
obtained from: Envigo RMS Spain S.L., 08182 - Sant Feliú de Codines, Barcelona – Spain; 8 - 12 weeks old, 3 per cage, 12 h light / dark, 19.3 -23.9 °C, 30-66% humidity, food (Global diet 2914C) and tap water ad libitum except during exposure
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
0.975 µm
Geometric standard deviation (GSD):
ca. 1.42 - ca. 4
Remark on MMAD/GSD:
As the particle size was smaller than acceptance range, the aerosol could be considered as fully respirable.
The second Geometrical Standard deviation (GSD) measurement was 4.00 (first one: 1.42), slightly above criteria recommended by the OECD guideline Nº 436 (i.e. 1.5 - 3). Since the Mean Mass Median Aerodynamic Diameter (MMAD) was smaller than criterion for that measurement and a total of 90.91 % of the particles were ≤ 4 μm, the aerosol could be considered fully respirable.
Details on inhalation exposure:
A dust aerosol was generated from the sieved test item using a Dust Generator SAG 410.
Inhalation exposure was performed using a flow-past, nose-only exposure system. The animals were confined separately in restraint tubes which were positioned radially around the exposure chamber. The exposure system ensured a uniform distribution and provided a constant flow of test material to each exposure tube. The mean flow of air at each tube was approximately 0.844 L/min, which was sufficient to minimize re-breathing of the test aerosol as it is more than twice the respiratory minute volume of rats. Exposure chambers type EC-FPC-232 (anodised aluminium, volume inside compartment: approximately 3 L), equipped with glass exposure tubes were used. The rats were individually exposed in glass tubes matching their size. Before treatment start, the homogeneity for the different levels of the exposure chamber was confirmed. The temperature and relative humidity of the test atmosphere in the exposure chamber were maintained as required by experimental conditions. Air flow was monitored regularly.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
5.01 mg/L
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
14-day observation period
Statistics:
No statistical analysis was required.
Preliminary study:
none performed
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.01 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 5.01 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
no mortality
Clinical signs:
other: Piloerection and wet fur were observed post-exposure in most animals. Piloerection lasted up to day 3 for animals ID1 (male) and ID6 (female). These signs are commonly associated to nose-only exposure studies and commonly observed in vehicle aerosols and/
Body weight:
A decrease in mean body weight was observed between study day 1 (exposure) and study day 2. This decrease is normally observed in nose-only exposure inhalation studies due to the stress caused by the restraining and the fasting conditions during the exposure period. In general, from study day 2 to the end of
the observation period (day 15), body weight increased gradually in all animals.
Gross pathology:
No relevant macroscopic findings were observed in any of the animals.

The ranges of aerosol concentration, temperature, relative humidity and air flow rate were considered satisfactory for a study of this type. In addition, the test item was considered to be respirable to rats.

Piloerection and wet fur were observed post-exposure in most animals. Piloerection lasted up to day 3 for animals ID1 (male) and ID6 (female). These signs are commonly associated to nose-only exposure studies and may not be correlated to test item. Additionally, loud breathing, loss of stability in females and respiratory crackles in males were observed punctually after exposure. All the signs disappeared after day 2 of the study. These signs are not uncommon in inhalation studies involving very high level of exposure to particles (limit concentration) and as such are not considered as signs of an intrinsic property of the test substance.

From study day 4 until the end of the 14 day-observation period, no clinical signs were observed in any of the animals and all of them exhibited a normal behavior.

A decrease in mean body weight was observed between study day 1 (exposure) and study day 2. This decrease is normally observed in nose-only exposure inhalation studies due to the stress caused by the restraining and the fasting conditions during the exposure period. In general, from study day 2 to the end of the observation period (day 15), body weight increased gradually in all animals.

No necropsy macroscopical findings were observed in animals of any of the sexes exposed to test item.

Interpretation of results:
GHS criteria not met
Conclusions:
The LC50 of the test item was greater than 5.01 mg/L air (gravimetric aerosol concentration). Based on the GHS classification criteria, the test item can be considered as “unclassified”.
Executive summary:

The present study has been designed to evaluate the acute inhalation toxicity of the test item ZEOSIL PREMIUM 200 MP in male and female Sprague Dawley rats by the acute toxic class (ATC) method (OECD test guideline Nº 436).

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
18 April - 02 May 1983
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The used method is unsuitable test system and the study was disregarded due to major methodological deficiencies
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
1981-05-12
Deviations:
yes
Remarks:
The highest attainable exposure concentration was not applied due to technical limitations. Air exchange of the inhalation chamber was lower than recommended 0.8/h instead of 10 - 15/h.
GLP compliance:
yes
Limit test:
yes
Specific details on test material used for the study:
Aerosil 200
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Central Institute for Breeding of Laboratory Animals TNO, Zeist/NL
- Age at study initiation:
- Weight at study initiation: 191 - 199 g: av. 194 g (male); 144 - 149 g: av. 147 g (female)
- Fasting period before study: no
- Housing: single during exposure
- Diet: institute's stock diet ad libitum until start
- Water: tap water ad libitum until start
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +-1
- Humidity (%): 50 - 60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
- Animals per cage: 5


Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel exposure chamber provided with glass windows
- Exposure chamber volume: 1.5 m3
- Method of holding animals in test chamber: single
- Source and rate of air: entrance near the pyramidal top; 1.2 m3/h ==> exchange rate = 0.8/hour
- Method of conditioning air: no data
- System of generating particulates/aerosols: Dispersing the powder continuously by means of a "Buerstendosierer" Typ III/A
- Method of particle size determination: cascade impactor
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data


TEST ATMOSPHERE
- Brief description of analytical method used:
gravimetrically - amount of dust on glass fiber filter divided by the amount of air applied (at 4 time point during exposure)
Nominal concentration calculated from the the total quantity of test material devided by the amount of air applied
- Samples taken from breathing zone: no data


TEST ATMOSPHERE
- Particle size distribution: approx. 47 - 50 mass% =< 6 µm

from Report Tab. 1:
distribution aerodynamic
in % of total weight diameter (µm)
----------------------------------------
4.7 0.47
6.0 0.7
7.2 1.1
6.6 1.7
2.2 2.5
4.2 3.4
6.4 4.3
9.9 5.7
52.7 >=7.7
_________________________________________

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD = ~3.2 µm / GSD: no data
Note: calculated from the VMD (Volume Mean Diameter) of 63.0 µm multiplied with the density of abouit 0.05 g/cm3.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: maximum attainable concentration
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
maximum technically attainable analytical concentration: av. 139 mg/m3 (range 110 - 190 mg/m3)
Nominal concentration: 16.7 g/m3
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight on days 0, 2, 4, 7, and 14
- Necropsy of survivors performed: yes, on all
- Other examinations performed: clinical signs, body weight
Statistics:
not relevant
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 139 mg/m³ air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 139 mg/m³ air (analytical)
Exp. duration:
4 h
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
no mortality
Clinical signs:
other: Restlessness and half-closed eyes during exposure.
Body weight:
Both males and females showed growth retardation on the second day of the observation period.
However, by mistake the animals were deprived of drinking water during a period of 16 hours succeeding the termination of the exposure. Consequently food intake will have been very small during this period resulting in growth retardation. It is therefore impossible to indicate whether the growth retardation observed was an effect of the Aerosil 200 exposure or an effect of the water depriviation.
Gross pathology:
no abnormalities found
Other findings:
none
Interpretation of results:
study cannot be used for classification
Conclusions:
From the results of the present acute inhalation study, it was concluded that an exposure of rats during 4 hours to the maximum attainable concentration of Aerosil 200 in the atmosphere (i.c. 139 mg/m3 air) failed to induce mortality.
Executive summary:

The acute inhalative toxicity of Aerosil 200 could not be evaluated in rats maximum attainable concentration of Aerosil 200 in the atmosphere (i.c. 139 mg/m3 air) failed to induce mortality.

Whole body is not state of the art. Nowadays nose-only studies are applied for particle inhalation assessment. Unsuitable for the determination of acute inhalative systemic toxicity of inert /non-toxic SAS particles.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The used method is unsuitable test system and the study was disregarded due to major methodological deficiencies
Qualifier:
according to guideline
Guideline:
other: Acute Inhalation Exposure in Rats: Federal Hazardous Substances Labeling Act
Principles of method if other than guideline:
single dose level, 1h administration, 14 d post observation
GLP compliance:
not specified
Specific details on test material used for the study:
Cab-O-Sil EH-5
Species:
rat
Strain:
not specified
Remarks:
albino
Sex:
male
Details on test animals or test system and environmental conditions:
initially weighing between 200-300 grams
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The test material was generated by means of a pulse-puff aerosol (powder) generator. A steady airstream maintained at 5 l/min carried the powder aerosol into the chamber.
Duration of exposure:
1 h
Concentrations:
207 mg/l
No. of animals per sex per dose:
10 (males only)
Control animals:
no
Details on study design:
14-day post observation period
Sex:
male
Dose descriptor:
LC50
Effect level:
> 207 mg/L air (nominal)
Exp. duration:
1 h
Mortality:
no mortality
Clinical signs:
other: hypoactivity, increased respiratory rate, gasping, abdominal respiration, and exudates from the eyes, nose and mouth.
Gross pathology:
no necropsies performed
Other findings:
During the first two days of the postexposure period, all rats had dried brown material around the nose and mouth. The fur appeared chalky to the touch. However, these conditions subsequently disappeared and all rats appeared normal throughout the remainder of the 14-day postexposure observation period.
Interpretation of results:
study cannot be used for classification
Conclusions:
Based on exposure some particle related clinical findings were observed but disappeared completely during recovery. No mortality was observed.
Executive summary:

The objective of this study was to determine the inhalation toxicity in rats resulting from a one-hour, dynamic exposure to a predetermined concentration of a Cab-O-Sil EH-5.

No guideline followed. Only 1 hour exposure, only nominal concentrations reported, no exposure concentrations were determined.

Whole body is not state of the art. Nowadays nose-only studies are applied for particle inhalation assessment.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
Sep. 14-28, 1981
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Principles of method if other than guideline:
1 dose level, 4h administration, 14d post observation
GLP compliance:
no
Specific details on test material used for the study:
Cab-O-Sil fumed silica M-5
Species:
rat
Strain:
Sprague-Dawley
Remarks:
albino
Sex:
male/female
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
air
Mass median aerodynamic diameter (MMAD):
0.76 µm
Geometric standard deviation (GSD):
3.11
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.08 mg/l
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
14 d post obervation period
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.08 mg/L air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 2.08 mg/L air (analytical)
Exp. duration:
4 h
Mortality:
no mortality
Clinical signs:
other: nasal discharge, crusty eyes, alopecia, crusty nose
Body weight:
animals exhibited body weight gains
Gross pathology:
no gross lesions, discoloration of the lung was observed in one test animal
Other findings:
no mortality, no clinical signs, normal body weight gain and normal pathological appearance in control group
Conclusions:
LC50 > 2.08 mg/l (no mortality with 2.08 mg/l)
Executive summary:

The acute inhalation toxicity of Cab-O-Sil (fumed silica) M-5 was evaluated in rats.

Whole body is not state of the art. Nowadays nose-only studies are apllied for particle inhalation assessment.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The used method is unsuitable test system and the study was disregarded due to major methodological deficiencies.
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substances Labeling Act
Principles of method if other than guideline:
single dose level, 1h administration, 14 d post observation
GLP compliance:
not specified
Specific details on test material used for the study:
Cab-O-Sil M-5
Species:
rat
Strain:
not specified
Remarks:
albino
Sex:
male
Details on test animals or test system and environmental conditions:
200-300 g
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
The test material was generated by means of a pulse-puff aerosol (powder) generator. A steady airstream maintained at 5 l/min carried the powder aerosol into the chamber.
Duration of exposure:
1 h
Concentrations:
191.3 mg/l
No. of animals per sex per dose:
10 (males only)
Control animals:
no
Details on study design:
14-day post observation period
Sex:
male
Dose descriptor:
LC50
Effect level:
> 191.3 mg/L air (nominal)
Exp. duration:
1 h
Mortality:
no mortality
Clinical signs:
other: hypoactivity, gasping, abdominal respiration, nasal exudation
Gross pathology:
no necropsies performed
Other findings:
During the first two days of the postexposure period, all rats had dried brown material around the nose and mouth. The fur appeared chalky to the touch. However, these conditions subsequently disappeared and all rats appeared normal throughout the remainder of the 14-day postexposure observation period.
Interpretation of results:
study cannot be used for classification
Conclusions:
Based on exposure some particle related clinical findings were observed but disappeared completely during recovery. No mortality was observed.
Executive summary:

The objective of this study was to determine the inhalation toxicity in rats resulting from a one-hour, dynamic exposure to a predetermined concentration of a Cab-O-Sil M-5.

No common guideline followed. Only 1 hour exposure, only nominal concentrations reported, no exposure concentrations were determined. Whole body is not state of the art. Nowadays nose-only studies are applied for particle inhalation assessment.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
02 Feb. - 16 Feb. 1983
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The used method is unsuitable test system and the study was disregarded due to major methodological deficiencies
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
The highest attainable exposure concentration was not applied due to technical limitations. Air exchange of the inhalation chamber was lower than recommended 0.8/h instead of 10 - 15/h.
GLP compliance:
yes
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Central Institute for Breeding of Laboratory Animals TNO, Zeist/NL
- Age at study initiation:
- Weight at study initiation: 168 - 179 g: av. 174 g (male); 142 - 146 g: av. 144 g (female)
- Fasting period before study: no
- Housing: single during exposure
- Diet: ad libitum until start
- Water: ad libitum until start
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +-1
- Humidity (%): 50 - 60
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel exposure chamber provided with glass windows
- Exposure chamber volume: 1.5 m3
- Method of holding animals in test chamber: single
- Source and rate of air: entrance near the pyramidal top; 1.2 m3/hour ==> 0.8/h
- Method of conditioning air: no data
- System of generating particulates/aerosols: Dispersing the powder continuously by means of a "Buerstendosierer" Typ III/A
- Method of particle size determination: cascade impactor
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: no data


TEST ATMOSPHERE
- Brief description of analytical method used:
gravimetrically - amount of dust on glass fiber filter divided by the amount of air applied (at 4 time point during exposure)
Nominal concentration calculated from the the total quantity of test material devided by the amount of air applied
- Samples taken from breathing zone: no data


TEST ATMOSPHERE
- Particle size distribution: approx. 65 mass% =< 6 µm (note: 45 mass% with <5 µm are stated on p.6 of the report. This is not in agreement with the profile given in Table 1., see below.)

from Report Tab. 1:
distribution aerodynamic
in % of total weight diameter (µm)
----------------------------------------
1.8 0.47
2.8 0.7
4.3 1.1
5.0 1.7
8.1 2.5
9.4 3.4
14.3 4.3
19.2 5.7
35.1 >=7.7
_________________________________________

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD = ~0.6 µm / GSD: no data
Note: calculated from the VMD (Volume Mean Diameter) of 11.5 µm multiplied with the density of abouit 0.05 g/cm3.



CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: maximum attainable concentration
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
maximum attainable concentration: 691 mg/m3 (range: 650 - 725 mg/m3)
Nominal concentration: 36.7 g/m3
No. of animals per sex per dose:
5
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight on days 0, 2, 4, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not relevant
Sex:
male/female
Dose descriptor:
LC0
Effect level:
>= 691 mg/m³ air (analytical)
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 691 mg/m³ air (analytical)
Exp. duration:
4 h
Mortality:
no mortality
Clinical signs:
other: Restlessness, half-closed eyes
Body weight:
males: normal; females: some delay until day 2, then normal
Gross pathology:
no particular findings
Other findings:
none

No clinical symptoms except some restlessness and eye closing. Body weight gain was not affected in males, but females hardly gained weight during two days after exposure, however, subsequently, showed normal development. 

No findings at autopsy after 14 d post-treatment. 
   

Interpretation of results:
other: non-toxic
Conclusions:
Exposure of rats for 4 hours to the maximum attainable concentration of Sipernat 22 S in the atmosphere (c. 691 mg/m³ air) did not result in any adverse effects: LC50 > 691 mg/m³
Executive summary:

The acute inhalative toxicity of Sipernat 22 S could not be assessed in rats as the maximum attainable aerosol concentration in the chamber could not be reached. Unsuitable for the determination of acute inhalative systemic toxicity of inert /non-toxic SAS particles.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The used method is unsuitable test system and the study was disregarded due to major methodological deficiencies
Qualifier:
no guideline followed
Principles of method if other than guideline:
1 dose level, 1-hour administration, 14-day post observation
GLP compliance:
no
Specific details on test material used for the study:
synthetic amorphous silicon dioxide Syloid 244
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
obtained from: Charles River Breeding Laboratories, caged together, Purina cubed diet and tap water ad libitum
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Duration of exposure:
1 h
Concentrations:
2 mg/l
No. of animals per sex per dose:
10 (males only)
Details on study design:
14-day observation period
Sex:
male
Dose descriptor:
LC50
Effect level:
> 2 mg/L air (nominal)
Exp. duration:
1 h
Mortality:
1/10 (animal died 2 hours post exposure)
Clinical signs:
other: During exposure signs of irritation and dyspnea were apparent in most animals.
Body weight:
normal body weight gain
Gross pathology:
slight to moderate incidences of pulmonary abnormalities when observed at necropsy at 14 days post esposure
Interpretation of results:
study cannot be used for classification
Conclusions:
As only 1 out of 10 animals died, the acute LC50 was greater than 2 mg/l.
Executive summary:

The acute inhalative toxicities of 24 compounds were assessed in rats. One of them was synthetic amorphous silica Syloid 244 which is documented here.

No guideline followed. Only 1 hour exposure, only nominal concentrations reported, no exposure concentrations were determined. Unsuitable for the determination of acute inhalative systemic toxicity of inert /non-toxic SAS particles.


Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
12.03.2020 - 06.07.2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
A comprehensive method to test the bioactivity of respirable synthetic amorphous silica (SAS) in vitro is the alveolar macrophage assay, as offered by the IBE R&D gGmbH. Based on longstanding experience with primary alveolar macrophages (AMs) the assay circumvents the use of animals as it is carried out with cultured NR8383 macrophages (a cell line derived from rat lung). The relevance of the assay relies on the fact that lung alveolar macrophages are the first line of defense against inhaled (nano)materials, which they ingest and transport to the mucociliary escalator, to eventually clear the lung from inhaled foreign material. If the population of AMs is harmed, the lung epithelium will react with signs of inflammation. The predictivity of the alveolar macrophage assay for inflammatory effects of particles has best been demonstrated by Martin Wiemann and his group in a paper published in 2016 (J. Nanobiotechnology 14:16). In that paper the assay was compared to 19 inhalation studies (carried out by BASF under GLP conditions) and it was shown that the classification criteria matched what was found by BASF pathologists, as the assay was able to distinguish between active and passive (nano)materials. Up to now no other assay has been validated against a similarly high number of inhalation studies carried out with exactly the same (nano)materials. Due to these features the assay has been used in several national (NanoGEM, NanoGRAVUR, InnoMat.Life) and EU projects (NanoToxClass, Refine) and meanwhile is mentioned in many papers. Importantly, the assay has been suggested as a tool for grouping nanomaterials in a tiered approach as suggested by Wohlleben and the NanoGRAVUR consortium (2019). More specifically, and with respect to SAS analysis, the assay was successfully used to analyze the bioactivity of 14 different SAS including colloidal, fumed, precipitated, and gel qualities.
Qualifier:
no guideline required
GLP compliance:
no
Test type:
other: in vitro assay with alveolar macrophages
Specific details on test material used for the study:
untreated SAS:
AEROSIL® 50
CAB-O-SIL® (E)L-90
CAB-O-SIL® S17D
DAVISIL® XWP1500A
LUDOX® SM
LUDOX® TM-50
SIPERNAT® 350
SYLOID® AL-1FP

silanized SAS:
AEROSIL® R 504
AEROSIL® R 711
AEROSIL® R 816
CAB-O-SIL® TGC413TRD
CAB-O-SIL® TS610
CAB-O-SIL® TS720
HDK® H15
HDK® H2000
SIPERNAT® D 17
Species:
other: rat alveolar macrophage cell line NR8383
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
in vitro cell culture model
Route of administration:
other: in vitro cell culture model
Type of inhalation exposure:
other: in vitro cell culture model with alveolar macrophages
Vehicle:
other: cell culture medium
Concentrations:
11.25-90 μg/mL
Details on study design:
A dose range of 11.25-90 μg/mL was administered to NR8383 alveolar macrophages in cell culture dishes without further addition of protein and the release of lactate dehydrogenase (LDH), glucuronidase (GLU), and tumor necrosis factor α (TNF) was measured after 16 h. Hydrogen peroxide (H2O2) production was assessed after 90 min.
Conclusions:
Synthetic amorphous silica (SAS) build up a large class of industrial nanomaterials (NM). Based on their different production processes, precipitated, fumed, gel and colloidal SAS can be distinguished. Previous tests carried out with all four classes of SAS provided by Evonik Resource Efficiency GmbH have demonstrated for most materials a highly similar biological activity (e.g. cytotoxicity or inflammatory potential) on NR8383 alveolar macrophages under serum free-conditions (Wiemann et al 2019). On the other hand, phosphonate coating of a colloidal SAS has been shown to mitigate its bioactivity, both in vitro and in vivo. In this study we tested untreated as well as surface-treated SAS which are mostly relevant for industrial applications.
Five untreated and nine surface treated SAS were tested. While untreated and one surface-treated SAS were dispersed as published before using an ultrasonic dispersion energy of 270 J/mL, strongly hydrophobic surface treated SAS were dispersed according to the NanoGenoTox protocol which requires pre-wetting of the SAS powder with ethanol, followed by an extensive ultrasonic dispersion in H2O in the presence of low serum albumin concentration (0.05% w/v). Further dispersion in cell culture medium had minor effects on agglomeration. A dose range of 11.25-90 μg/mL was administered to NR8383 alveolar macrophages without further addition of protein and the release of lactate dehydrogenase (LDH), glucuronidase (GLU), and tumor necrosis factor α (TNF) was measured after 16 h. Hydrogen peroxide (H2O2) production was assessed after 90 min.
The overall pattern of the in vitro response to untreated SAS was dose-dependent and highly similar to those of the previous study: According to the releases of LDH, GLU cytotoxicity was noted (in decreasing order) for CAB-O-SIL® S17D, CAB-O-SIL® (E)L-90, AEROSIL® 50, LUDOX® TM-50, LUDOX® SM, and AEROSIL® R816. TNF was induced by all untreated SAS. However, CAB-O-SIL® S17D was the only SAS which induce a significant induction of H2O2 release and, like LUDOX® SM and LUDOX® TM-50, evoked a comparatively high TNF response.
In contrast, all these responses were missing for the surface-treated SAS (CAB-O-SIL® TGC413TRD, CAB-O-SIL® TS601, CAB-O-SIL® TS, HDK® H15, HDK® H2000, AEROSIL® R504, AEROSIL® R711, and SIPERNAT® D17) except for the highest concentration of AEROSIL® R504. This striking difference in cytotoxicity between untreated and surface-treated SAS remained when untreated SAS were also dispersed according to the NanoGenoTox protocol, as tested in a pilot experiment.
Overall the study confirms the previously demonstrated high biological activity of untreated SAS under protein free conditions. Importantly, it suggests that the various surface coatings leading to high hydrophobicity abrogate the cytotoxic and pro-inflammatory effect of SAS in vitro under serum-free conditions.
Executive summary:

Overall the study confirms the previously demonstrated high biological activity of untreated SAS under protein free conditions. Importantly, it suggests that the various surface coatings leading to high hydrophobicity abrogate the cytotoxic and pro-inflammatory effect of SAS in vitro under serum-free conditions.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
according to guideline
Guideline:
other: Guidelines of the Department of Transportation
Principles of method if other than guideline:
single dose level, 24h administration, 48h post observation
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Syloid 244
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals or test system and environmental conditions:
obtained from: Skippack Breeding Farm; app. 3 kg, individually caged, feed: Purina rabbit chow
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
Application to the intact (5 rabbits) and abraded skin (5 rabbits) for 24 h
Duration of exposure:
24 h
Doses:
2 g/kg bw
No. of animals per sex per dose:
10 in total
Control animals:
no
Details on study design:
Duration of observation period following administration: 48h
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Sex:
not specified
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
No changes in skin condition were nited in any animal during the test period.

No erythema or edema occured. The skin irritation according to the Draize Scoring System was 0.0. (cf. attachement below)

Interpretation of results:
GHS criteria not met
Conclusions:
As there was no mortality, the LD50 in the rabbit was greater 2 g/kg/bw. Also no skin irritation appered, the score (Draize) was 0.0.
Executive summary:

The acute dermal toxicity if Syloid 244 was assessed in rabbits. Also its skin irritation potential was evaluated.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single application for 24 hours, on intact and abraded skin, 4 dose levels, 14-day post observation period
GLP compliance:
not specified
Specific details on test material used for the study:
Zeo 49
Species:
rabbit
Strain:
New Zealand White
Remarks:
albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
Mature healthy New Zealand White albino rabbits were selected from the stock colony. Animals were individually housed in stainless steel suspended cages with Purina Rabbit Chow and water ad libitum.
Type of coverage:
occlusive
Vehicle:
water
Remarks:
distilled
Details on dermal exposure:
Rabbits were clipped free of hair over the dorsal area. A single dermal application was employed and test sites were occluded with an impervious bandage for 24 hours.
Duration of exposure:
24 h
Doses:
2000, 3000, 4000, 5000 mg/kg bw
No. of animals per sex per dose:
4 in total per dose: 2 with abraded and 2 with inract skin
Control animals:
no
Details on study design:
Animals were observed for reactions at 4 hours after dosing, and then daily for 14 days. Body weights were recorded at dosing and at termination. Rabbits sacrificed were subjected to a gross examination of the viscera.
Preliminary study:
Four rabbits were clipped free of hair over the dorsal area. A single dermal application at the following levels was employed: 2000, 3000, 4000, and 5000 mg/kg of body weight.
Test sites were occluded with an impervious bandage. After 24 hours, the bandages were removed. The animals were observed for signs of illness or death for up to four days.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
not specified
Dose descriptor:
LD0
Effect level:
>= 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
Dermal reactions were limited to slight erythema on day 1 in one rabbit with abraded skin treated with 3000 mg/kg bw. The other 15 animals showed no reactions. There was no dose-dependent relationship.
Body weight:
All rabbits at all dose levels gained weight.
Gross pathology:
Upon necropsy, at day 14, no gross pathology was noted in the viscera.
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured, the LD50 of Zeo 49 was greater than 5000 mg/kg bw.
Executive summary:

Zeo 49 was evaluated for its dermal LD50 in the rabbit. Single applications were made to the intact and abraded skin.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single application for 24 hours, on intact and abraded skin, 4 dose levels, 14-day post observation period
GLP compliance:
not specified
Specific details on test material used for the study:
Zeofree 153
Species:
rabbit
Strain:
New Zealand White
Remarks:
albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
Mature healthy New Zealand White albino rabbits were selected from the stock colony. Animals were individually housed in stainless steel suspended cages with Purina Rabbit Chow and water ad libitum.
Type of coverage:
occlusive
Vehicle:
water
Remarks:
destilled
Details on dermal exposure:
Rabbits were clipped free of hair over the dorsal area. A single dermal application was employed and test sites were occluded with an impervious bandage for 24 hours.
Duration of exposure:
24 hours
Doses:
2000, 3000, 4000, 5000 mg/kg bw
No. of animals per sex per dose:
4 in total per dose: 2 with abraded and 2 with inract skin
Control animals:
no
Details on study design:
Animals were observed for reactions at 4 hours after dosing, and then daily for 14 days. Body weights were recorded at dosing and at termination. Rabbits sacrificed were subjected to a gross examination of the viscera.
Preliminary study:
Four rabbits were clipped free of hair over the dorsal area. A single dermal application at the following levels was employed: 2000, 3000, 4000, and 5000 mg/kg of body weight.
Test sites were occluded with an impervious bandage. After 24 hours, the bandages were removed. The animals were observed for signs of illness or death for up to four days.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
not specified
Dose descriptor:
LD0
Effect level:
>= 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
Dermal reactions were limited to slight erythema and edema. Dermal reactions diminished by day 5 after application. They showed no dose-dependent relationship and their duration was in general not longer on abraded skin than on intact one.
Body weight:
All rabbits at all dose levels gained weight.
Gross pathology:
Upon necropsy, at day 14 no gross pathology was noted in the viscera.
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured, the dermal LD50 was greater than 5000 mg/kg of body weight.
Executive summary:

Zeofree 153 was evaluated for its dermal LD50 in the rabbit. Single applications were made to the intact and abraded skin.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single application for 24 hours, on intact and abraded skin, 4 dose levels, 14-day post observation period
GLP compliance:
not specified
Specific details on test material used for the study:
Zeosyl 113
Species:
rabbit
Strain:
New Zealand White
Remarks:
albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
Mature healthy New Zealand White albino rabbits were selected from the stock colony. Animals were individually housed in stainless steel suspended cages with Purina Rabbit Chow and water ad libitum.
Type of coverage:
occlusive
Vehicle:
water
Remarks:
distilled
Details on dermal exposure:
Rabbits were clipped free of hair over the dorsal area. A single dermal application was employed and test sites were occluded with an impervious bandage for 24 hours.
Duration of exposure:
24 hours
Doses:
2000, 3000, 4000, 5000 mg/kg bw
No. of animals per sex per dose:
4 in total per dose: 2 with abraded and 2 with inract skin
Control animals:
no
Details on study design:
Animals were observed for reactions at 4 hours after dosing, and then daily for 14 days. Body weights were recorded at dosing and at termination. Rabbits sacrificed were subjected to a gross examination of the viscera.
Preliminary study:
Four rabbits were clipped free of hair over the dorsal area. A single dermal application at the following levels was employed: 2000, 3000, 4000, and 5000 mg/kg of body weight.
Test sites were occluded with an impervious bandage. After 24 hours, the bandages were removed. The animals were observed for signs of illness or death for up to four days.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
not specified
Dose descriptor:
LD0
Effect level:
>= 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
Dermal reactions were limited to slight erythema, which diminished by day 4 after application. Reactions showed no dose-dependent relationship and dimished only slightly later on abraded skin, than they did on intact one.
Body weight:
All rabbits at all dose levels gained weight.
Gross pathology:
Upon necropsy, at day 14 no gross pathology was noted in the viscera.
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured the dermal LD50 was greater than 5000 mg/kg of body weight.
Executive summary:

Zeosyl 113 was evaluated for its dermal LD50 in the rabbit. Single applications were made to the intact and abraded skin.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
single application for 24 hours, on intact and abraded skin, 4 dose levels, 14-day post observation period
GLP compliance:
not specified
Specific details on test material used for the study:
Zeosyl 200
Species:
rabbit
Strain:
New Zealand White
Remarks:
albino
Sex:
not specified
Details on test animals or test system and environmental conditions:
Mature healthy New Zealand White albino rabbits were selected from the stock colony. Animals were individually housed in stainless steel suspended cages with Purina Rabbit Chow and water ad libitum.
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
Rabbits were clipped free of hair over the dorsal area. A single dermal application was employed and test sites were occluded with an impervious bandage for 24 hours.
Duration of exposure:
24 hours
Doses:
2000, 3000, 4000, 5000 mg/kg bw
No. of animals per sex per dose:
4 in total per dose: 2 with abraded and 2 with inract skin
Control animals:
no
Details on study design:
Animals were observed for reactions at 4 hours after dosing, and then daily for 14 days. Body weights were recorded at dosing and at termination. Rabbits sacrificed were subjected to a gross examination of the viscera.
Preliminary study:
Four rabbits were clipped free of hair over the dorsal area. A single dermal application at the following levels was employed: 2000, 3000, 4000, and 5000 mg/kg of body weight.
Test sites were occluded with an impervious bandage. After 24 hours, the bandages were removed. The animals were observed for signs of illness or death for up to four days.
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Remarks on result:
not determinable due to absence of adverse toxic effects
Sex:
not specified
Dose descriptor:
LD0
Effect level:
>= 5 000 mg/kg bw
Mortality:
no mortality
Clinical signs:
With 5,000 mg/kg bw, dermal reactions were limited to slight erythema, which diminished after day 2 or 4 after application on intact or abraded skin, repectively. With lesser doses, those were dimished by day 2 after application (on intact and abraded skin).
Body weight:
All rabbits at all dose levels gained weight.
Gross pathology:
Upon necropsy, at day 14, no gross pathology was noted in the viscera.
Interpretation of results:
GHS criteria not met
Conclusions:
As no mortality occured the dermal LD50 was greater than 5000 mg/kg of body weight.
Executive summary:

Zeosyl 200 was evaluated for its dermal LD50 in the rabbit. Single applications were made to the intact and abraded skin.

Additional information

Justification for classification or non-classification

Synthetic amorphous silicas did not induce toxicity or lethality by any route of exposure.

According to Annex I of the Regulation (EC) 1272/2008 and GHS (Globally Harmonized Classification System), the test substance requires no classification and has no mandatory label requirement.