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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:
key study
Study period:
30th April 1997 to 19th June 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Compliant reproducibility exceed expectations

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Objective of study:
other: measure biopersistence of the substance to be registered
Test guideline
Qualifier:
according to guideline
Guideline:
other: ECB/TM/26 (rev 7)
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Reference substance name:
amporphous glass fibre formed from the melting and fiberisation of predominately slilcon dioxide, calcium oxide, magnesium oxide
EC Number:
610-130-5
Cas Number:
436083-99-7
Molecular formula:
Amorphous glass consisting of SinO(3n-1)2(n-1) Polymeric anions ionically bonded to Ca2+ and Mg2+ cations or other alkaline earth cations
IUPAC Name:
amporphous glass fibre formed from the melting and fiberisation of predominately slilcon dioxide, calcium oxide, magnesium oxide
Details on test material:
- Name of test material (as cited in study report): Fibre A
- Substance type: calcium, magnesium silicate wool
- Physical state: solid
- Analytical purity: 99.5%
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, FRG
- Age at study initiation: 10 - 11 weeks
- Weight at study initiation: mean, 166.3g
- Housing: Makrolon (polycarbonate) cages type III (37.5 x 21.5 x 20cm), 2 rats/cage
- Individual metabolism cages: no
- Diet (e.g. ad libitum): A commercial chow in pellet form was used, identified as Altromin "1324 N Spec. prepared"
- Water (e.g. ad libitum): ad libitum in cage
- Acclimation period: 1 week before starting tube training


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ±2°C
- Humidity (%): 55% ± 15%
- Photoperiod (hrs dark / hrs light): 12 hour cycle


IN-LIFE DATES: From: June 16, 1997 To: June 19, 1998

Administration / exposure

Route of administration:
inhalation
Vehicle:
unchanged (no vehicle)
Details on exposure:
TYPE OF INHALATION EXPOSURE: nose only

GENERATION OF TEST ATMOSPHERE / CHAMPER DESCRIPTION
- Exposure apparatus: high-pressure pneumatic disperser, flow-past nose/snout only inhalation exposure system
- Method of holding animals in test chamber: Battelle type polycarbonate tubes
- Source and rate of air: 1 l/min
- Method of conditioning air: neutralized by a Ni-63 source
- System of generating particulates/aerosols: high-pressure pneumatic disperser
- Method of particle size determination: SEM analysis of filter samples, aerosol photometer (on-line)
- Treatment of exhaust air: filtered
Duration and frequency of treatment / exposure:
5 days, 6hrs/day
Doses / concentrations
Remarks:
Doses / Concentrations:
Average exposure concentration 104± 13f > 20µm long/ml as recommended in the draft EU guideline
Mean Mass Exposure 44.9mg/m3
No. of animals per sex per dose / concentration:
49
Control animals:
yes, concurrent no treatment
Positive control reference chemical:
not required under EU Protocol
Details on study design:
Sacrifice dates, 1 day, 3 days, 17days, 1 month, 3months, 6 months and 12 months
Details on dosing and sampling:
The aerosol was monitored by an aerosol photometer (online), by determination of numerical concentration of fibres (SEM analysis of filter samples) and by determination of gravimetric concentration.
Statistics:
Differences between groups were considered statistically significant at p <0.05. Data were analysed using analysis variance. If the group means differed significantly by the analysis of variance the means of the treated groups were compared with the means of the control groups based on the Dunnett's test. The kinetic of the elimination of the fibres form the lung was calculated by regression analysis of the logarithm of the number of fibres versus time after end of inhalation. The half time T12 was calculated from the regression coefficient k by: T12 - ln(2)/ k. Additionally the method of nonlinear curve fitting was used as recommended in the protocol.
The kinetic of the elimination of the fibres form the lung was calculated by regression analysis of the logarithm of the number of fibres versus time after end of inhalation. The half time T12 was calculated from the regression coefficient k by: T12 - ln(2)/ k.
Additionally the method of nonlinear curve fitting was used as recommended in the protocol.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
Biopersistence to EU protocol ECB/TM/26 (rev 7). Clearance half-time for fibres more than 20µm long was 7 days.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): other: see conclusion
fibre need not be treated as a carcinogen, fulfils the criteria for exoneration under Note Q of CLP regulations,
Executive summary:

The biopersistence of this fibre is below the limit in Nota Q of CLP regulations. There was no evidence of an adverse effect due to exposure to the test fibre on the parameters measured during the maintenance period (clinical observations and bodyweight) or at necropsy (organ weights). Analysis of the test atmosphere showed that the requirements of the draft protocol were met throughout the study, analysis of retained fibres by electron microscopy provided a robust estimate of biopersistence.