Silicon dioxide

Acute Toxicity: inhalation

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

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

Test material

Test material information

1

Reference substance name:

Silicon dioxide

EC Number:

231-545-4

EC Name:

Silicon dioxide

Cas Number:

7631-86-9

Molecular formula:

O2Si

IUPAC Name:

dioxosilane

Test material form:

solid: nanoform, no surface treatment

Details on test material:

not surface-treated SAS, Surface area/BET: 210 m²/g.

Specific details on test material used for the study:

Zeosil Premium 200 MP, precipitated synthetic amorphous silica (SAS)
purity >= 98%

Test animals

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

Administration / 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.

Results and discussion

Preliminary study:

none performed

Effect levels

Effect levels 1

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

Effect levels 2

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.

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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).