Triiron tetraoxide

Endpoint summary

Description of key information

Two reliable studies for oral toxicity were evaluated. In an acute inhalation toxicity study rats were exposed to a concentration of 640mg/m³ (maximum attainable concentration) Fe3O4 nanoparticles. None of the animals died. In an additional acute inhalation toxicity study with Fe2O3 as a surrogate for the iron oxide group the discriminating dose was 5050 mg/m³.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Full report available; non GLP study

Principles of method if other than guideline:

Single oral application per gavage. Observation period: 14 days. The test substance was applied in water/chremophor

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

other: water + Cremophor

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Clinical signs:

other:

A single dose of 5000 mg/kg bw was tolerated by all male and female animals without any reaction

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

Executive summary:

Rats were dosed with 5000 mg/kg bw of test substance. Neither symptoms nor mortality were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

scientifically acceptable and well documented

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: scientifically acceptable and well documented

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

In this study, the toxicity responses of rat following a continuous 4 h inhalation exposure of only the head and nose to iron oxide nanoparticles (Fe3O4 NPs, size = 15–20 nm) was investigated. The rats for the investigation were exposed to a concentration of 640mg/m³ (maximum attainable concentration) Fe3O4NPs.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

640 mg/m³ (maximum attainable concentration)

No. of animals per sex per dose:

18 male and 18 female animals/dose

Control animals:

yes

Sex:

male/female

Dose descriptor:

discriminating conc.

Effect level:

> 640 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 640 mg/m³ = maximum attainable concentration

The results showed a significant decrease in the cell viability, with the increase in the levels of lactate dehydrogenase, total protein, and alkaline phosphatase in the BALF. Total leukocyte count and the percentage of neutrophils in BALF increased within 24 h of postexposure. Immediately following acute exposure, rats showed increased inflammation with significantly higher levels of lavage and blood proinflammatory cytokines and were consistent throughout the observation period. Fe3O4 NPs exposure markedly increased malondialdehyde concentration, while intracellular reduced glutathione and antioxidant enzyme activities were significantly decreased in lung tissue within 24-h postexposure period. On histological observation, the lung showed an early activation of pulmonary clearance and a size-dependant biphasic nature of the Fe3O4NPs in causing the structural alteration.Collectively, the data illustrate that Fe3O4NPs inhalation exposure may induce cytotoxicity via oxidative stress and lead to biphasic inflammatory responses inWistar rat.

Executive summary:

In this study, the toxicity responses of rat following a continuous 4 h inhalation exposure of only the head and nose to iron oxide nanoparticles (Fe3O4 NPs, size = 15–20 nm) was investigated. The rats for the investigation were exposed to a concentration of 640mg/m³ (maximum attainable concentration) Fe3O4NPs.

The results showed a significant decrease in the cell viability, with the increase in the levels of lactate dehydrogenase, total protein, and alkaline phosphatase in the BALF. Total leukocyte count and the percentage of neutrophils in BALF increased within 24 h of postexposure. Immediately following acute exposure, rats showed increased inflammation with significantly higher levels of lavage and blood proinflammatory cytokines and were consistent throughout the observation period. Fe3O4 NPs exposure markedly increased malondialdehyde concentration, while intracellular reduced glutathione and antioxidant enzyme activities were significantly decreased in lung tissue within 24-h postexposure period. On histological observation, the lung showed an early activation of pulmonary clearance and a size-dependant biphasic nature of the Fe3O4NPs in causing the structural alteration.Collectively, the data illustrate that Fe3O4NPs inhalation exposure may induce cytotoxicity via oxidative stress and lead to biphasic inflammatory responses inWistar rat.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating conc.

Value:

640 mg/m³ air

Quality of whole database:

scientifically acceptable and well documented

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In 2 reliable acute toxicity studies rats received per gavage doses of 10000 or 5000 mg/kg bw of the test substance. Neither symptoms nor mortality were observed. Therefore the LD50 is > 5000 mg/kg bw. Rats exposed to 640 mg/m³ (maximum attainable concentration) revealed not death. In an additional acute inhalation toxicity study with Fe2O3 as a surrogate for the iron oxide group the discriminating dose was 5050 mg/m³. No study for acute dermal toxicity is available. Due to its structure and physico-chemical properties (insoluble in water and organic solvents) no systemic bioavailability is expected.

Justification for selection of acute toxicity – oral endpoint

key study used

Justification for selection of acute toxicity – inhalation endpoint

key study used

Justification for classification or non-classification

In 2 reliable acute toxicity studies rats received per gavage doses of 10000 or 5000 mg/kg bw of the test substance. Neither symptoms nor mortality were observed. Therefore the LD50 is > 5000 mg/kg bw. Rats exposed to 640 mg/m³ (maximum attainable concentration) revealed no death. In an additional acute inhalation toxicity study with Fe2O3 as a surrogate for the iron oxide group the discriminating dose was 5050 mg/m³.

Due to the insolubility of Fe3O4 dermal absorption seems not to be a route of an appreciable incorporation of insoluble iron oxides. This fact is supported by the low oral and inhalation toxicity.

No classification is required.