Diiron trioxide

Endpoint summary

Description of key information

Acute toxicity, oral: LD50 > 5000mg/kg bw

Acute toxicity, inhalation: LC50 > 5,05mg/L

Acute toxicity, dermal: Conduct of an acute dermal toxicity study is unjustified as inhalation of the substance is considered as major route of exposure and physicochemical properties and dermal absorption data of the substance do not suggest a significant rate of absorption through the skin (cf. Annex VIII section 8.5 Column 2 of regulation (EC) 1907/2006).

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: short report available

Principles of method if other than guideline:

Single oral application per gavage, post observation time: 14 days, test substance was applied in water

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male

Route of administration:

oral: gavage

Vehicle:

water

Doses:

10000 mg/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Sex:

male

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Clinical signs:

other:

Executive summary:

Single oral application per gavage, post observation time: 14 days, test substance was applicated in water.

Result: no mortality, no signs of toxicity.

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 sufficient documented

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Principles of method if other than guideline:

Five male and 5 female Wistar rats were exposed single to 5 mg/l CERAC-Pigment (average particle size = 35 nm) for 4 hours. The animals were observed for mortality, clinical signs and body weight during a post-observation period of 14 days. A pathological examination was performed on all animals which died during the observation period or were sacrificed at the end of the study period.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

other: snout only exposure

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.05 mg/l

No. of animals per sex per dose:

5 male and 5 female rats

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

discriminating conc.

Effect level:

5.05 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Study Design

The study design comprised 5 male and 5 female animals to determine the tolerability to the maximum aerosol concentration of 5 mg/L. As all animals survived until scheduled termination, no further animal exposures were required and the study was completed.

The following investigations were performed: clinical observations, body weights and necropsy.

Results

Mortality

There were no premature deaths.

Clinical observations

During exposure, from 1h of exposure onwards, all animals had brown staining, recorded as around the head area from 1.5h until the end of exposure. Following exposure on the day, all animals had a rolling gait immediately on completion of exposure, which was no longer evident by 30 min post exposure. All animals were noted to have brown staining following exposure which persisted in all but 2 males until termination on Day 15. Rolling gait was considered to be unremarkable, and brown staining was considered to be test item deposition.

Body weight

A few animals showed a transient and slight body weight reduction post exposure, which is common in inhalation studies and considered to be procedural. All animals had gained body weight by the end of the 14 day post exposure observation period. There was no effect of CERAC-Pigment inhalation on body weight.

Necropsy findings

All findings were considered to be unremarkable. All males had no abnormalities detected, and 3 of 5 females had uterine dilatation with one of these having a scab on the tail. These findings were considered typical for rats of the age and strain used and unrelated to exposure. One female had dark red discolouration of the mandibular lymph node which was considered most likely to be deposition of test item, despite no histopathological evaluation of the tissue.

This finding was considered to be unremarkable in rats exposed to a high concentration of red powder for 4 h. A toxic response to exposure was not established.

Executive summary:

Five male and 5 female Wistar rats were exposed single to 5 mg/l CERAC-Pigment (average particle size = 35 nm) for 4 hours. The animals were observed for mortality, clinical signs and body weight during a post-observation period of 14 days. A pathological examination was performed on all animals which died during the observation period or were sacrificed at the end of the study period.

Following a single snout only inhalation exposures to CERAC-Pigment for four hours at an aerosol concentration of 5 mg/L, all animals tolerated the exposure. The Median Lethal Concentration (MLC) was therefore considered to be in excess of 5 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

5 050 mg/m³ air

Quality of whole database:

GLP guideline study

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

other justification

Justification for data waiving:

other:

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In 2 reliable acute toxicity studies (with nano- and powder material) 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.

In a further study an acute oral toxicity study of Fe2O3-30 (iron oxide nanomaterial) and Fe2O3 powder was conducted following Organization for Economic Cooperation and Development guidelines 420 (OECD, 2001); in brief, the sighting study was conducted with a single female rat with 5, 50, 300, and 2,000 mg/kg doses to understand the dose-toxicity relationship. Because no mortality was observed at any of the above-listed doses by both the compounds tested, a limit test was carried out at the 2,000 mg/kg dose with 5 female rats and observed for 14 days. None of the animals died.

In a GLP guideline study according OECD TG 403 the discriminating dose for acute inhalation toxicity 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

Two valid studies with iron(III)oxide as powder- and nanomaterial are available

Justification for selection of acute toxicity – inhalation endpoint

key study is used

Justification for classification or non-classification

In several acute oral toxicity studies a discriminating dose of 2000 mg/kg bw was determined. The discriminating dose for acute inhalation toxicity was 5050 mg/m³ in a GLP guideline study according OECD TG 403.

In a 2 week inhalation study with Fe2O3 a LD50 > 210 mg/m³ was found (6 h/d, 5 d/wk for 2 weeks. The repeated exposure at this concentration was not associated with any specific clinical signs, changes in body temperature or body weights. Due to the insolubility of Fe2O3 dermal absorption seems not to be a route of an appreciable incorporation of insoluble iron oxides. This fact is supported by the low oral toxicity and no evidence of systemic bioavailability of inhaled particles.

Therefore no classification is required.