Reaction mass of Silicic acid, calcium salt and Silicic acid, magnesium salt

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The secondary literature is a compilation of four bioassay studies implemented to compare pulmonary responses in rats after short-term inhalation exposure to various silica dust.

Data source

Reference

Reference Type:

publication

Title:

Differential pulmonary responses in rats inhaling crystalline, colloidal or amorphous silica dusts

Author:

Warheit DB, McHugh TA, Hartsky MA

Year:

1995

Bibliographic source:

Scand J Work Environ Health

Materials and methods

Principles of method if other than guideline:

The compiled bioassays were designed to evaluate pulmonary responses in rats after short-term inhalation exposure
to two forms of crystalline silica, one form of amorphous silica and one form of colloidal silica particles.
Rats were exposed for 3 days at aerosol concentrations of either 10 or 100 mg/m3 precipitated amorphous silica. Cells and fluids from sham- and silica-exposed rats were recovered by bronchoalveolar lavage (BAL). Lactate
dehydrogenase (LDH), protein, and N-acetyl glucosaminidase (NAG) were repeatedly measured in BAL fluids postexposure.

GLP compliance:

not specified

Test material

Test material information

Constituent 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:

Silicon dioxide

Test material form:

solid

Specific details on test material used for the study:

Synthetic amorphous silicon dioxide, precipitated. CAS no.: 112926-00-8, Zeofree 80, 2.4-3.4 µm.

Test animals

Species:

rat

Strain:

other:

Remarks:

CD rats

Sex:

not specified

Details on test animals or test system and environmental conditions:

24 CD rats were exposed for 3 days at 10 mg/m3 or 100 mg/m3 amorphous silica.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

not specified

Vehicle:

not specified

Mass median aerodynamic diameter (MMAD):

>= 2.4 - <= 3.4 µm

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6 h a day for 3 days.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

10 mg/m³ air

Doses / concentrations 2

Dose / conc.:

100 mg/m³ air

No. of animals per sex per dose:

Not specified

Control animals:

yes

yes, sham-exposed

Examinations

Observations and examinations performed and frequency:

Cells and fluids from sham- and silica-exposed rats were recovered by bronchoalveolar lavage (BAL). Lactate
dehydrogenase (LDH), protein, and N-acetyl glucosaminidase (NAG) were repeatedly measured in BAL fluids postexposure.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Following exposure to amorphous silicon dioxide, a transient inflammatory response was observed, characterized by the presence of granulocytes
(primarily neutrophils) in BAL fluids. The response was abrogated within 8 days post-exposure. Exposure to amorphous silica also resulted in pulmonary toxicity characterized as extracellular LDH in the BAL fluids. The BAL fluid LDH values increased within 24 h following exposure, however, returned to control values within 8 days post-exposure. NAG values in rats exposed to amorphous silica were not significantly different to controls following 8 days postexposure.

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Key result

Dose descriptor:

other: See "Remarks"

Remarks:

Exposure to synthetic amorphous silicon dioxide (10 and 100 mg/m3) gave rise to a transient inflammatory response which was present 24 h post-exposure. Within 8 days post-exposure, this effect was abrogated.

Based on:

not specified

Sex:

not specified

Basis for effect level:

clinical biochemistry

Remarks on result:

other: See "Remarks"

Remarks:

Exposure to synthetic amorphous silicon dioxide (10 and 100 mg/m3) gave rise to a transient inflammatory response which was present 24 h post-exposure. Within 8 days post-exposure, this effect was abrogated. No effect level was specified.

Target system / organ toxicity

Key result

Critical effects observed:

not specified

Lowest effective dose / conc.:

10 mg/m³ air

System:

other: Inflammatory response in lungs of rats characterized by the presence of granulocytes (primarily neutrophils) in BAL fluids.

Organ:

lungs

Any other information on results incl. tables

A pulmonary inflammatory response was seen in lungs of rats following exposure to amorphous silicon dioxide. Within 8 days post-exposure, this effect was abrogated. Exposure to amorphous silica also resulted in pulmonary toxicity characterized as extracellular LDH in the BAL fluids. The BAL fluid LDH values increased within 24 h following exposure, however, returned to control values within 8 days post-exposure. NAG values of rats exposed to amorphous silica were not significantly different from control animals following 8 days postexposure.

Applicant's summary and conclusion

Conclusions:

A pulmonary inflammatory response was seen in lungs of rats following exposure to amorphous silicon dioxide via inhalation (10 and 100 mg/m3). Within 8 days post-exposure, this effect was abrogated. Exposure to amorphous silica also resulted in pulmonary toxicity characterized as extracellular LDH in the BAL fluids. The BAL fluid LDH values increased within 24 h following exposure, however, returned to control values within 8 days post-exposure. NAG values of rats exposed to amorphous silica were not significantly different from control animals following 8 days postexposure. Taken together, exposure to amorphous silica particles via inhalation gave rise to a transient pulmonary inflammatory response in rats.

Executive summary:

The study was designed to investigate pulmonary responses in rats following short-term inhalation exposure to different silicas including amorphous silica. A pulmonary inflammatory response was seen in lungs of rats following exposure to amorphous silicon dioxide for 6 h a day for 3 days (10 and 100 mg/m3). Within 8 days post-exposure, this effect was abrogated. Exposure to amorphous silica also resulted in pulmonary toxicity characterized as extracellular LDH in the BAL fluids. The BAL fluid LDH values increased within 24 h following exposure, but returned to control values within 8 days post-exposure. NAG values of rats exposed to amorphous silica were not significantly different from control animals following 8 days postexposure. It was concluded that the crystalline forms of silica dust were much more potent in terms of producing pulmonary toxicity compared to amorphous or colloidal forms of silica.