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Description of key information

In an oral acute toxicity study 10 animals were treated with 10000 mg/kg bw manganese ferrite black spinel. During an observation  time of 14 days none of the animals showed signs of toxicity or died. In an 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.

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
Principles of method if other than guideline:
Single oral application per gavage, observation time 14 days
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:
not specified
Sex:
male
Dose descriptor:
discriminating dose
Effect level:
> 10 000 mg/kg bw

no mortality, no symptoms

Executive summary:

Single oral application per gavage, observation time 14 days

Result: no symptoms, no mortality

Discriminating dose > 10000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
10 000 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:
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).
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.

There are no animal studies available concerning acute or chronic inhalation of Mn2O3. For other manganese oxides in the literature acute toxicity data from intratracheal studies are published. According to these studies MnO (particle size not specified) has a lethal dose of > 50 mg/kg, MnO2 (particle size not specified) has a lethal dose of 50 mg/kg, and for Mn3O4 (particle size not specified) the lowest published lethal dose is 375 mg/kg. All studies were conducted with rats. The observed toxic effects affected mainly the respiratory system and were emphysema and edema.
1. HYPOTHESIS FOR THE CATEGORY APPROACH (ENDPOINT LEVEL)
[Describe why the read-across can be performed]

2. CATEGORY APPROACH JUSTIFICATION (ENDPOINT LEVEL
[Summarise here based on available experimental data how these results verify that the read-across is justified]
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
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

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a reliable acute toxicity studies rats received per gavage doses of 10000 mg/kg bw of manganese ferrite black spinel. Neither symptoms nor mortality were observed. Therefore the discriminating dose is > 10000 mg/kg bw.

In an 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 (for further details see Category justification document).

Justification for selection of acute toxicity – oral endpoint

Key study is used

Justification for selection of acute toxicity – inhalation endpoint

key study is used

Justification for classification or non-classification

In a reliable acute toxicity studies rats received per gavage doses of 10000 mg/kg bw of manganese ferrite black spinel. Neither symptoms nor mortality were observed. Therefore the discriminating dose is > 10000 mg/kg bw.

In an 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.

A classification is not required.