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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: 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

Constituent 1
Chemical structure
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 parametersopen allclose all
Toxicokinetic parameters:
half-life 1st: 24 hours
Toxicokinetic parameters:
half-life 2nd: 33d
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)

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