Synthetic amorphous magnesium silicate, with molar ratio (SiO2:MgO) range of 1.4-4

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

Justification for read-across is warranted given the similarities in toxicity profile and physico-chemical properties for silicon dioxide and magnesium silicate.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Objective of study:

other: deposition and clearance

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 413

Deviations:

yes

Remarks:

Special modifications as compared with standard study:  Focus upon lung, respiratory  tract, and regional lymph nodes. Post-exposure recovery period up to one year.

Principles of method if other than guideline:

Measurements of Si in lung and lymph nodes within repeated-dose toxicity study: Analytical method for silica determination (Report, part 1, p. 25):
Lung and lymph node tissue were ashed according to the temperature program up to 650 °C in a platinum crucible. Following this, the ash was dissolved in 10 % hydrogen fluoride for 30 min. at 50 °C, and a saturated boric acid solution (silicon standard solution, 1 mg/ml) was added. The Si content of the solution was determined using a Varian ASS flame atomic absorption spectrometer.

GLP compliance:

yes

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:

dioxosilane

Details on test material:

- Test material: SIPERNAT 22S
CAS-Name: Silica, precipitated, crystalline-free;
CAS-No.: 112926-00-8

Surface area (Ströhlein): 160 - 195 m2/g
Primary particle size: see Test Condition
- Substance type: inorganic
- Physical state: solid
- Surface area (BET): 192 m2/g (Report p. 64 Specification Certificate)
- Analytical purity: >98 % (SiO2)
- Impurities: 0.8 % Na2O, 0.2 Al2O3
- Particle size: The range of the geometric agglomerate/aggregate size distribution was 1  to about 120 µm for the amorphous silicas 
with a maxima at approx. 10 µm and 100 µm (Report 1987, p. 13)    
- Stability under test conditions: stable
- Storage condition of test material: room temperature

Specific details on test material used for the study:

- Test material: SIPERNAT 22S
CAS-Name: Silica, precipitated, crystalline-free;
CAS-No.: 112926-00-8

Surface area (Ströhlein): 160 - 195 m2/g
Primary particle size: see Test Condition
- Substance type: inorganic
- Physical state: solid
- Surface area (BET): 192 m2/g (Report p. 64 Specification Certificate)
- Analytical purity: >98 % (SiO2)
- Impurities: 0.8 % Na2O, 0.2 Al2O3
- Particle size: The range of the geometric agglomerate/aggregate size distribution was 1  to about 120 µm for the amorphous silicas 
with a maxima at approx. 10 µm and 100 µm (Report 1987, p. 13)    
- Stability under test conditions: stable
- Storage condition of test material: room temperature

Radiolabelling:

no

Test animals

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: 4 weeks
- Weight at study initiation: 50 - 70 g
- Fasting period before study: no
- Housing: single during exposure
- Diet: no access during exposure
- Water: no access during exposure
- Acclimation period: 10 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +-2
- Humidity (%): 50 - 70
- Air changes (per hr): 12x/h
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

inhalation

Details on exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: stainless steel exposure chamber, multitiered (manufactered by Hazelton)
- Exposure chamber volume: 2.3 m3
- Method of holding animals in test chamber: single
- Exposure type: whole body
- Source and rate of air: Aerosol entrance at top of the chamber
- Method of conditioning air: no data
- System of generating particulates/aerosols: Institute´s dust generator with compressed air operating atomizer
- Temperature, humidity, pressure in air chamber: av. 21 - 23 °C, minimum 19.1, max. 25.4 °C /
65 - 75 % rel. humidity, during extreme weather occasionally up to 95.5 % or down to 48 %.
- Air flow rate: approx. 40 m3/h
- Air change rate: 40 / 2.3 = ~17/h
- Method of particle size determination: due to electrostatic charge of the particles not measured:
technical failure of the 10-stage Mercer cascade impactor and the QCM cascade (Report p. 16)
- Treatment of exhaust air: filtered before release


TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrically - Air samples are drawn through glass fiber filters (Sartorius)
and weighed (3 - 4 time per day)
- Samples taken from breathing zone: no data

Duration and frequency of treatment / exposure:

90 day(s)

Doses / concentrations

Remarks:

Doses / Concentrations:
35 mg/m3 (mean analytical values)

No. of animals per sex per dose / concentration:

10 each after exposure (13 weeks) and recovery period (1, 13, 29, 39, and 52 wks):
i.e. 50 m / 50 f animals per group were kept for a recovery period of at most 52 wks 

Control animals:

yes, concurrent no treatment

Positive control reference chemical:

no, but comparative study also including quartz

Details on study design:

- Dose selection rationale: see 7.5.3

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion) of SiO2
- Tissues and body fluids sampled: lung and mediastinal lymph nodes
- Time and frequency of sampling: 1, 13, 29, 39, and 52 weeks post exposure, 10 animals each

Statistics:

The statistical assessment of the findings for the different parameters considered was based on analysis of variance (ANOVA) and Dunnett´s test

Results and discussion

Preliminary studies:

No data

Toxicokinetic / pharmacokinetic studies

Details on absorption:

See overall remarks

Details on distribution in tissues:

See overall remarks

Details on excretion:

See overall remarks

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: ca. 7 wks (males) (from lung)

Toxicokinetic parameters 2

Test no.:

#2

Toxicokinetic parameters:

half-life 2nd: <7 wks (females) (from lung)

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

Absolute silicon content in lung and mediastinal lymph nodes 1, 13, 29, 39, and 52 weeks post exposure

[Sipernat 22S, 35 mg/m³ (mean analytical value), 13 weeks] [Report, Tab. 59 + 61]

	Lung [mg]		Lymph nodes [mg]
	Male #1	Female #2	Male	Female
Sipernat 22S
Day 98	0.510 ±0.024 ^+) (n=10)^++)	0.347 ±0.017 (n=10)	0.037 ±0.007 (n=3)	0.034 ±0.002 (n=5)
Day 188	0.127 ±0.011  (n=10)	0.114 ±0.006 (n=7)	0.030 ±0.000 (n=2)	0.050 ±0.004 (n=4)
Day 297	0.049 ±0.004   (n=10)	0.083 (n=1)	0.027 ±0.003 (n=4)	0.030 (n=1)
Day 370	No Si detected	No Si detected	0.030 ±0.000 (n=2)	No Si detected
Day 462	No Si detected	No Si detected	0.030 (n=1)	No Si detected
C ontrol [untreated]
Day 188	0.032 (n=1)	No Si detected	0.030 (n=1)	No Si detected

⁺⁾ ±SEM (Standard Error of the Mean)

^{++) n represents the number of animals with Si found,}

^{the total number of animals measured was always 10 per group.}

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results