Feldspar minerals, magnetite and quartz, calcination products of copper mining residues.

Basic toxicokinetics

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 for cross-reference:

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

Test material information

Constituent 1

Reference substance name:

Triiron tetraoxide

EC Number:

215-277-5

EC Name:

Triiron tetraoxide

Cas Number:

1317-61-9

Molecular formula:

Fe3O4

IUPAC Name:

Triiron tetraoxide

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 / concentration:

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 parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

half-life 2nd: 42 - 173 days

Toxicokinetic parameters 2

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