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Administrative data

Endpoint:
acute 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: GLP guideline study
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
As demonstrated in the category approach justification, in regard to structure, physicochemical properties, environmental fate characteristics, ecotoxicity and toxicity, the grouping of Fe2O3 (diiron trioxide), Fe3O4 (triiron tetraoxide), FeOOH (iron hydroxide oxide), (Fe,Mn)2O3 (iron manganese trioxide), (Fe,Mn)3O4 (manganese ferrite), and ZnFe2O4 (zinc ferrite) in the "Iron Oxides Category" is justified (for further details see Category justification document).

ZnFe2O4 is considered as a mixture of zinc oxide and iron oxide.

An acute toxicity study of Fe2O3 by inhalation administration in rats was conducted according to OECD TG 403 (Morgan A, 2015). In this study five male and 5 female Wistar rats were exposed to 5.05 mg/L Fe2O3 (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 at the end of the study period. Following a single snout only inhalation exposures to Fe2O3 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.

Rats exposed for 3 hours to ZnO particles at concentrations ranging from 25 to 50 mg/m³ demonstrated transient pulmonary inflammatory responses which were evident after 24 and 72 hours but returned to control levels by 1 week post-exposure (for further details see Category Justification document).

These study results indicate a LC 50 for insoluble ZnFe2O4 assumed to be above the general dust threshold value of 10 mg/m³.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report date:
2015

Materials and methods

Test guideline
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

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
Test material form:
solid: nanoform
Details on test material:
Test item: CERAC-Pigment
CAS-No.: 1309-37-1
EC-No.: 215-168-2
Chemical Name: Diiron trioxide
Physical description: Red powder
Purity 100%
gamma-form
Storage conditions: Ambient (<30ºC), dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

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

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
discriminating conc.
Effect level:
5.05 mg/L air
Based on:
test mat.
Exp. duration:
4 h

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.