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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study has some limitations related to the documentation of the study results (it has been published only as a conference proceeding). However, the methods used have been described in detail in the reports by Glømme (1965) and Glømme (1966-1967). Therefore, the study can be regarded reliable.

Data source

Reference
Reference Type:
other: proceedings
Title:
Tissue reaction to different types of amorphous silica.
Author:
Swensson, Å.
Year:
1967
Bibliographic source:
In: Davies, C.N., ed. Inhaled particles and vapours II. (Proceedings of an International Symposium Organized by the British Occupational Hygiene Society, Cambridge, 28 September - 1 October 1965.) Pergamon Press, Oxford, pp. 95-102.

Materials and methods

Objective of study:
other: lung clearance
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Single intratracheal injections of different forms of silica (silica pume, pyrogenic silica, quartz, quartz-glass and kieselguhr=diatomite) suspended in 1 ml of physiological saline was given to female rats. Animals were killed 1, 2, 4 and 8 months after injection. Silica content of the lungs and lymph nodes were measured.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Fumes, silica
EC Number:
273-761-1
EC Name:
Fumes, silica
Cas Number:
69012-64-2
Molecular formula:
SiO2
IUPAC Name:
Silicon dioxide
Details on test material:
- Amorphous silicon dioxide from the smoke of a ferrosilicon smelting furnace: silica fume with silica content 85%, crystalline components less than 1%, round particles, mean primary particle diameter 0.05 μm
- Crystalline silica: contains 98.3% quartz, angular and irregular particles, particle mean size 1.2 μm
- Pyrogenic silica: produced by combustion of silicon-halogen in an atmosphere of hydrogen gas, no crystalline, spherical particles, mean diameter 0.10 μm
- Quartz-glass: produced by smelting rock crystals, silica content 85%, no crystalline, angular, mean size 0.3 μm
- Kieselguhr: purified from organic matter by treatment with bichromate-sulphuric acid, silica content 81%, no crystalline, ground, most particles <5 μm
- Kieselguhr that has been heated to 800oC for 24 hr: silica content 86%, no crystalline
Radiolabelling:
no

Test animals

Species:
rat
Strain:
not specified
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Weight at study initiation: 200 g

Administration / exposure

Route of administration:
intratracheal
Vehicle:
physiological saline
Details on exposure:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 ml
- concentration (if solution): 40 mg/ml
Duration and frequency of treatment / exposure:
once
Doses / concentrations
Remarks:
Doses / Concentrations:
40 mg of different forms of silica suspended in 1 ml of physiological saline
No. of animals per sex per dose / concentration:
10-20 rats, half of them (5-10) was used for the analysis of silica content
Control animals:
yes, concurrent no treatment
Positive control reference chemical:
yes, quartz
Details on dosing and sampling:
- Tissues and body fluids sampled: lungs andassociated lymph nodes
- Time and frequency of sampling: 1, 2, 4 or 8 months after the instillation
- Silica content was measured by a modified King and Stachey method.
Statistics:
no data

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
More than 50% of the amount of quartz injected was found in the lungs of the animals after observation period of 8 months. In the animals that received pyrogenic silica, quartz-glass and silica fume not more than 20-30% of the amount administered was found. Among these three, the highest percentage (30%) of retention was found in the animals that received silica fume. The transport of silica to, and its retention in, the hilar lymph glands was the highest following the administration of quartz: about 4.5 mg remained in the hilar lymph glands after 8 months. For pyrogenic silica, quartz-glass and silica fume, retention in the lymph glands was between 2.5-3 mg.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: there is similarities in the lung clearance between pyrogenic silica and silica fume
Lung clearance of amorphous silica differs from that of quartz. Lung clearance of silica fume resembles that of pyrogenic silica and quartz-glass.
Executive summary:

Swensson (1967) gavesingle intratracheal injections of 40 mg of different forms of silica suspended in 1 ml of physiological saline in female rats. The particles studied were: amorphous silicon dioxide from the smoke of a ferrosilicon smelting furnace (=silica fume with silica content 85%, crystalline components less than 1%, round particles, mean primary particle diameter 0.05 μm) as well as crystalline silica (contains 98.3% quartz, angular and irregular particles, particle mean size 1.2 μm), pyrogenic silica (produced by combustion of silicon-halogen in an atmosphere of hydrogen gas, no crystalline, spherical particles, mean diameter 0.10 μm), quartz-glass (produced by smelting rock crystals, silica content 85%, no crystalline, angular, mean size 0.3 μm), Kieselguhr (purified from organic matter by treatment with bichromate-sulphuric acid, silica content 81%, no crystalline, ground, most particles <5 μm) and Kieselguhr that has been heated to 800oC for 24 hr (silica content 86%, no crystalline). Animals were killed 1, 2, 4 and 8 months after injection. More than 50% of the amount of quartz injected was found in the lungs of the animals after observation period of 8 months. In the animals that received pyrogenic silica, quartz-glass and silica fume not more than 20-30% of the amount administered was found. Among these three, the highest percentage (30%) of retention was found in the animals that received silica fume. The transport of silica to, and its retention in, the hilar lymph glands was the highest following the administration of quartz: about 4.5 mg remained in the hilar lymph glands after 8 months. For pyrogenic silica, quartz-glass and silica fume, retention in the lymph glands was between 2.5-3 mg. The methods used have been described in detail in the reports by Glømme (1965) and Glømme (1966-1967).