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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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-standard animal species; non-GLP
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Long-term clearance of inhaled magnetite and polystyrene latex from the lung: a comparison
Author:
Schlesinger RB, Halpern M, Lippman M
Year:
1981
Bibliographic source:
Health Physics 42, 68-73

Materials and methods

Objective of study:
toxicokinetics
Principles of method if other than guideline:
Commercial magnetite of an MMAD of ~3 µm was selected. Measurement indicated an MMAD of 3.4 µm. The purity was 98%. The material was neutron-activated to produce an activity of 125 µCi/g of 59Fe Number of animals: 4 Duration of Exposure: 4 h
Concentration: 30- 85- 151- 161 mg/m³ corresponding to lung burdens of 21- 64- 75- 110 mg Clearance
was measured radiometrically 1-2-4-7 days after exposure, then weekly for 12 weeks and bimonthly until ~210 days post
exposure. Activity at 24 h post dose was set as 100% (= no clearance from the alveoli)
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: magnetite (purity 98%)
Radiolabelling:
yes

Test animals

Species:
other: donkey
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Vehicle:
not specified
Duration and frequency of treatment / exposure:
4 hour(s)
Doses / concentrations
Remarks:
Doses / Concentrations:
Males: 30, 85, 151, 161 mg/m³ Females: 30, 85, 151, 161 mg/m³
No. of animals per sex per dose:
Males: 2 Females: 2
Control animals:
no

Results and discussion

Preliminary studies:
no data

Toxicokinetic / pharmacokinetic studies

Details on absorption:
no data
Details on distribution in tissues:
no data
Details on excretion:
see toxicokinetik parameters
Toxicokinetic parametersopen allclose all
Toxicokinetic parameters:
half-life 2nd: 42 - 173 days
Toxicokinetic parameters:
half-life 1st: 15 - 22 days

Metabolite characterisation studies

Metabolites identified:
no
Details on metabolites:
inert particles - no metabolites identified (not examined)

Any other information on results incl. tables

Magnetite showed a two-phase lung clearance with halflives of about 3 weeks in the first phase and several months in the second phase

Applicant's summary and conclusion

Executive summary:

Commercial magnetite of an MMAD of ~3 µm was selected . Measurement indicated an MMAD of 3.4 µm.

The purity was 98%. The material was neutron-activated to produce an activity of 125 µCi/g of 59Fe Number

of animals: 4 Duration of Exposure: 4 h Concentration: 30- 85- 151- 161 mg/m³ corresponding to lung burdens

of 21- 64- 75- 110 mg Clearance was measured radiometrically 1-2-4-7 days after exposure, then weekly for

exposure. Activity at 24 h post dose was set as 100% (= no clearance from the alveoli)

As a result Magnetite showed a two-phase lung clearance with halflives of about 3 weeks in the  first phase and several months in the second phase