Feldspar minerals, hematite 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: well documented and scientifically acceptable

Data source

Reference

Reference Type:

publication

Title:

Deposition and elimination of iron oxide aerosol from the lung of rats: comparison with ICRP predictions for man

Author:

Hewitt PJ

Year:

1974

Bibliographic source:

Proc Int Congr Int Radiat Prot Assoc 2, 1249-1254.

Materials and methods

Objective of study:

toxicokinetics

Principles of method if other than guideline:

rats have been exposed to iron oxide aerosol (MAD 0.3 µm) at iron concnetrations up to 700 mg/m³ for continuos periods up to 235 min, and for immediate periods of 30 min over a 10 day period. Rats were killed one day post each exposure and also at several predetermined periods up to 100 d post exposure in oder to follow the elimination of deposited iron from the lung. The total lung being removed and iron was determined by instrumental neutron activation analysis

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Diiron trioxide

EC Number:

215-168-2

EC Name:

Diiron trioxide

Cas Number:

1309-37-1

Molecular formula:

Fe2O3

IUPAC Name:

Diiron trioxide

Details on test material:

TS-Freetext:
iron oxide;
particle size: 0.3µm
no further data

Radiolabelling:

no

Test animals

Species:

rat

Strain:

not specified

Sex:

male

Administration / exposure

Route of administration:

inhalation

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

up to 235 min

Doses / concentrations

Remarks:

Doses / Concentrations:
males: 143 to 664 mg Fe/m3 as aerosol

No. of animals per sex per dose / concentration:

no data

Control animals:

yes

Results and discussion

Toxicokinetic / pharmacokinetic studies

Toxicokinetic parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

half-life 1st: 24 hours

Toxicokinetic parameters 2

Toxicokinetic parameters:

half-life 2nd: 33d

Toxicokinetic parameters 3

Toxicokinetic parameters:

half-life 3rd:

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

the slower clearance represents that fraction of the initial pulmonary 
deposited iron oxide translocated to the gastro-intestinal tract. Blood, 
liver and kidney samples were removed from pairs of rats one day post 
exposure and all samples were analyzed for iron. The contribution of 
inhaled iron oxide to the blood and to organs other than lung tested 
proved to be insignificant. It is concluded that iron oxide behaves as 
an 'insoluble' material efficiently eliminated from the gasto-intestinal 
tract in the faces.

Applicant's summary and conclusion

Executive summary:

rats have been exposed to iron oxide aerosol (MAD 0.3 µm) at iron concentrations up to 700 mg/m³ for continuos periods up to 235 min, and for immediate periods of 30 min over a 10 day period. Rats were killed one day post each exposure and also at several predetermined periods up to 100 d post exposure in oder to follow the elimination of deposited iron from the lung. The total lung being removed and iron was determined by instrumental neutron activation analysis. The elimination of deposited iron from the rat lung can be described by a 2 component exponential expression. Phase I (T1/2 = 24 h) and phase II clearance (T1/2 = 33 d)