Registration Dossier

Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Objective of study:
distribution
Principles of method if other than guideline:
Distribution/clearance of MWCNT, using Cobalt determination as marker of exposure.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
inhalation: dust
Vehicle:
unchanged (no vehicle)
Duration and frequency of treatment / exposure:
1 x 6hrs with a maximum recovery period of 3 months
Doses / concentrations
Remarks:
Doses / Concentrations:
target concentrations: 0, 10, 250 mg/m³
No. of animals per sex per dose:
40
Control animals:
yes, sham-exposed

Results and discussion

Main ADME resultsopen allclose all
Type:
other: translocation
Results:
Increased cobalt (as marker of exposure) was found only at the portal of entry (Iung). Thus, extrapulmonary translocation of Co causally linked to the exposure of test substance was not apparent at any exposure concentration and time point.
Type:
other: translocation
Results:
The time-related clearance over a 3 months post-exposure period was 96% (10 mg/m³) and 43% (250 mg/m³). From that it is deduced that the biopersistence is higher at high concentration (overload-like conditions).

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:
R

Applicant's summary and conclusion

Executive summary:

Rats (40 males/dose group) were exposed to 11 or 241 mg MWCNT/m³ of respirable, solid aerosol for 6-hours on a single day which was followed by a maximum postexposure period of 3 months. Cobalt (as marker of exposure) was determined in lungs, lung-associated Iymph nodes (LALN), brain, kidneys, testes, and liver.

A concentration-dependent increase of cobalt occurred in the lung. The determinations in the remaining tuissues (brain, liver, kidneys testes) were unobtrusive. Thus, due to the lack of any significant concentrations of cobalt in extrapulmonary organs it can be concluded that the test substance meeting the form described in section 4.5 of the IUCLID dossier - or granular break-down products thereof - are not translocated to or distributed within the systemic circulation. The time-related clearance over a postexposure period of 3 months was 96% and 43% at the intermediate and high exposure level, respectively. From that it is deduced that at non-overloading, more realistic exposure levels the biopersistence of the test substance (assuming that Co is not leached from the tubular structure) in pulmonary tissue is lower than anticipated (alveolar clearance half-time at non-overloading conditions approximately 60 days).