Feldspar minerals, hematite and quartz, calcination products of copper mining residues

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study - very well documented, study was performed with Fe3O4 as a representative for the iron oxide group - see Category approach for Fe2O3, Fe3O4, FeOOH, (Fe,Mn)2O3, (Fe,Mn)3O4, ZnFe2O4

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)

GLP compliance:

yes

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

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: MMAD was 1.3 µm, GDS ~2

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

6 hours/day 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
4.7, 16.6, 52.1 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

20

Control animals:

yes

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Remarks:

Toxicity

Effect level:

4.7 mg/m³ air

Based on:

test mat. (dissolved fraction)

Sex:

male/female

Basis for effect level:

other: See remarks

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Rats exposed subchronically to three different concentrations of Fe3O4 revealed findings clearly consistent with and typical for a poorly  soluble particle. Congruent with previous studies addressing the  retention kinetics of inhaled Fe3O4 particles, neither analytical nor  toxicological evidence existed that free, biosoluble iron was liberated  from the inhaled dust to any appreciable extend. Also in this study no  evidence of extrapulmonary toxicity existed. With regard to indices  considered to be adverse, viz. increased counts of cells and especially  PMNs in BAL, elevated LDH as marker of cytotoxicity, and ß-NAG as marker of increased lysosomal activities 4.7 mg/m³ constitute an exposure level  without evidence of adversity. These findings match those observed by  histopathology.

Applicant's summary and conclusion

Executive summary:

Rats exposed subchronically to three different concentrations of Fe3O4 revealed findings clearly consistent with and typical for a poorly soluble particle. The retention kinetics of inhaled Fe3O4 particles revealed neither analytical nor toxicological evidence that free, biosoluble iron was liberated from the inhaled dust to any appreciable extend. Also in this study no evidence of extrapulmonary toxicity existed. The results of this study support the view, that the NOAEL of Fe3O4 is 4.7 mg/m³.