potassium ferrite

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Report date:

2005

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

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

Constituent 2

Reference substance name:

Iron(III)oxide

IUPAC Name:

Iron(III)oxide

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Remarks on MMAD:

MMAD / GSD: MMAD = 1.3 - 1.5 µm; GSD = 1.9 - 2.2

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

6 hours/day, 5 days/week

No. of animals per sex per dose:

48

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEC

Remarks on result:

not determinable

Remarks:

no NOAEC identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

In summary, histopathological evaluation of rat lungs exposed to iron oxides revealed findings consistent with a 'poorly suluble particle' effect after the 2 -week exposure period, including the 3 -month postexposure period. Conclusive evidence of bioavailable iron or iron particles that were translocated to extrapulmonary organs was not observed.

Applicant's summary and conclusion

Executive summary:

In a subacute inhalation toxicity study Fe3O4, FeOOH and Fe2O3 particles were administered to Wistar rats (48 male per group) by means of the dynamic directed-flow nose-only technique, with exposure at mean actual concentrations of 0, 185.2, 195.7 and 210.2 mg/m3 air for 6 hours per day, 5 days/week for a total of 2 weeks. As a positive control for lung damage DQ12 was used, administered at 200.4 mg/m3. During the course of a 3-month postexposure period subgroups of rats were sacrified and examined on days 15, 29, 59 and 107. The MMAD of the particles was 1.3 -1.5 µm with a GSD of 1.9 -2.2. The exposure was not associated with any specific clinical signs and consistent changes in body weights. No NOAEC was defined. Iron oxides related findings could not be detected in the extrapulmonary organs (kidneys, testes, liver) both at the end of exposure and after 2 weeks of

recovery. Solubilized Fe was detected within/around the alveolar macrophages, but not in the interstitium and hepatic tissue.

Histopathological evaluations of the lungs demonstrated an effect-pattern consistent with that of poorly soluble particles.

This subacute inhalation toxicity study in the Wistar rats is acceptable and satisfies the guidelines requirement for a subacute inhalation study OECD 412 in rodents.