Trimanganese tetraoxide

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to high standard, however, typical parameters were not reported; no clinical observations, no blood biochemistry

Data source

Reference

Reference Type:

publication

Title:

Influence of particle solubility on the delivery of inhaled manganese to the rat brain: manganese sulfate and manganese tetroxide pharmokinetics following repeated (14-day) exposure

Author:

Dorman DC, Struve Mf, James RA, Marshall MW, Parkinson CU and Wong BA

Year:

2001

Bibliographic source:

Toxicology and Applied Pharmacology 170, 79-87

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimanganese tetraoxide

EC Number:

215-266-5

EC Name:

Trimanganese tetraoxide

Cas Number:

1317-35-7

Molecular formula:

Mn3O4

IUPAC Name:

trimanganese tetraoxide

Test material form:

solid: particulate/powder

Details on test material:

- Name of test material (as cited in study report): Manganese (II, III) tetraoxide
- Physical state: solid, crystalline powder
- Composition of test material, percentage of components: 72% Mn

Test animals

Species:

rat

Strain:

other: Crl:CD (SD)BR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Inc
- Age at study initiation: 8 weeks
- Housing: Rats were individually housed in suspended stainless steel cages with an automatic watering system.
- Diet (e.g. ad libitum): NIH-07 rodent chow available ad libitum except during exposure periods
- Water (e.g. ad libitum): Reverse osmosis purified water was available ad libitum
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5 - 21.5 °C
- Humidity (%): 40-50%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: aerosol

Remarks on MMAD:

MMAD / GSD: 1.5 - 2 µm with a geometric standard deviation <2

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:1-m3 chamber
- System of generating particulates/aerosols: Atmospheres were generated as dry powder using a Wright Dust Feeder with a delivery pressure of 25 psi.
- Temperature, humidity, pressure in air chamber: measured every 30 mins, temperature maintained at 22.2°C. Relative humidity was maintained at 30-70% with a target of 50%.
- Air flow rate: 200-250 L/min
- Air change rate: 12-15 /hour

TEST ATMOSPHERE
- Brief description of analytical method used: Optical particle sensor
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.042 other: mg / Mn3O4/m³ nominal

Doses / concentrations 2

Dose / conc.:

0.42 other: mg / Mn3O4/m³ nominal

Doses / concentrations 3

Dose / conc.:

4.2 other: mg / Mn3O4/m³ nominal

No. of animals per sex per dose:

12 males per dose

Control animals:

yes

Results and discussion

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Tissue manganese concentrations: Increased lung Mn concentrations were observed following exposure to ≥0.3mg Mn/m³. Increased olfactory bulb concentrations were observed following exposure to 3 mg Mn/m³. Increased femur and bile concentrations were observed following exposure to 3 mg Mn/m³.