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Toxicological information

Repeated dose toxicity: inhalation

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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

Constituent 1
Chemical structure
Reference substance name:
Trimanganese tetraoxide
EC Number:
215-266-5
EC Name:
Trimanganese tetraoxide
Cas Number:
1317-35-7
Molecular formula:
Mn3O4
IUPAC Name:
dimanganese(3+) manganese(2+) tetraoxidandiide
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 / concentrationsopen allclose all
Dose / conc.:
0.042 other: mg / Mn3O4/m³ nominal
Dose / conc.:
0.42 other: mg / Mn3O4/m³ nominal
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.

Applicant's summary and conclusion