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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation of amorphous and crystalline silica.
Author:
Johnston, C. J., K. E. Driscoll, et al.
Year:
2000
Bibliographic source:
Toxicol Sci.56(2): 405-13.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
In a subchronic inhalation study, rats were exposed 6h/d, 5 d/wk to 50 mg SiO2/m3 of hydrophilic pyrogenic silica (Aerosil® 200, MMAD 0.81 µm) or cristobalite (MMAD 1.3 μm) 3 mg/m3 for up to 13 weeks. The lung burden was measured after 6.5 and 13 weeks of exposure and after 3 and 8 months of recovery.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- tradename of pyrogenic silica: Aerosil® 200 (hydrophilic)
- Mass Median Aerodynamic Diameter (MMAD): 0.81 µm for pyrogenic silica and 1.3 µm for cristobalite
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
Male Fisher rats weighting 200-250 g in the time of study initiation were kept in whole body chambers in compartmental 300 l horizontal laminar flow.

Administration / exposure

Route of administration:
inhalation: dust
Vehicle:
unchanged (no vehicle)
Details on exposure:
TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Aerosols were generated by a screw-feed mechanism in combination with a venturi -type dust feeder
Duration and frequency of treatment / exposure:
6 hours/day, 5 days/week, up to 13 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
50 mg/m3 (pyrogenic silica) or 3 mg/m3 (cristobalite)
No. of animals per sex per dose:
4 rats/group
Control animals:
yes, concurrent no treatment
Positive control:
cristobalite
Details on dosing and sampling:
After 6.5 or 13 weeks of exposure or after 3 and 8 months recovery period rats were killed by pentobarbital followed by exsanguination of abdominal aorta and lung burdens of silica were analysed using emission spectroscopy at a wavelength of 251.612.
Statistics:
no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
Lung burden after 6.5 and 13 weeks exposure was 759 and 883 μg SiO2/lung for amorphous silica, respectively, and 336 and 819 μg SiO2/lung for crystalline silica. Lung burden of amorphous silica reduced rapidly after the exposure: three months after exposure, the lung burden was 165 μg SiO2/lung (81% reduction) and after 8 months it had decreased further to 93 μg SiO2/lung, which represents a 90% reduction. The burden of crystalline silica remained relatively unchanged post exposure being 658 and 743 μg SiO2/lung after 12 and 32 weeks, respectively. The authors explained the rapid clearance of amorphous silica by its better solubility. Silica levels of control rats varied between 28-59 μg SiO2/lung.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: no significant lung accumulation
Amorphous silica caused a steep increase in silica levels during the first 6.5 weeks, but after this time point the increment was significantly lower suggesting that the equilibrium between retention and elimination was reached. When compared to crystalline silica the clearance rate of amorphous silica was relatively rapid.
Executive summary:

In a subchronic inhalation study of Johnston et al. (2000), rats were exposed 6h/d, 5 d/wk to 50 mg SiO2/m3of hydrophilic pyrogenic silica (Aerosil® 200, MMAD 0.81 µm) or cristobalite (MMAD 1.3 μm) 3 mg/m3 for up to 13 weeks. The lung burden was measured after 6.5 and 13 weeks of exposure and after 3 and 8 months of recovery. Lung burden after 6.5 and 13 weeks exposure was 759 and 883 μg SiO2/lung for amorphous silica, respectively, and 336 and 819 μg SiO2/lung for crystalline silica. The lower increasement between 6.5 and 13 weeks of exposure suggests a phase in which retention and elimination are in equilibrium. Lung burden of amorphous silica reduced rapidly after the exposure: three months after exposure, the lung burden was 165 μg SiO2/lung (81% reduction) and after 8 months it had decreased further to 93 μg SiO2/lung, which represents a 90% reduction. The burden of crystalline silica burden remained relatively unchanged post exposure being 658 and 743 μg SiO2/lung after 12 and 32 weeks, respectively. The authors explained the rapid clearance of amorphous silica by its better solubility