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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from January 2010 to July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was generated according to generally valid and accepted testing guidelines and performed according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
(92/69/EEC)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): molybenum trioxide
- Physical state: solid, white powder
- Analytical purity: 99.96 %
- Expiration date of the lot/batch: January 2013
- Stability under test conditions: stable
- Storage condition of test material: at room temperature, in closed container, dry
- Particle size: aerodynamic mass median diameter = 3.1 µm

Test animals

Species:
rat
Strain:
other: Charles-River rat (strain:CD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 49-50 days; females 63-64 days
- Weight at study initiation: males 224-262 g; females 201 - 221 g
- Housing: granulated textured wood cages
- Commercial diet, ssniff® R/M-H V1534 served as food (ssniff Spezialdiäten GmbH, 59494 Soest, Germany
- Water: ad libitum
- Acclimation period: 5 adaption days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature of 20.5°C 0.2°C (main study); 20.8°C 0.2°C (sattelite group)
- humidity (55.7% ± 0.8% (main study) or 52.9% ± 0.5 (satellite group)
- The rooms were lit (150 lux at approx. 1.50 m room height) and darkened for periods of 12 hours each

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: dynamic inhalation apparatus, nose-only exposure chamber
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: animals in pyrex tubes at the edge of the chamber in radial position
- Source and rate of air: compressed air from surrounding atmosphere of laboratory room; inflow = 900 L/h
- At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
- System of generating particulates/aerosols: rotating brush dust generator
- Method of particle size determination: cascade impactor

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric analysis with an air sample filter and pump
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter): 3.085 µm ((main study) or 3.100 µm (satellite animals).
- geometric standard deviation = 2.75 (main study) or 2.78 (satellite animals)

Analytical verification of test atmosphere concentrations:
yes
Remarks:
Dust concentration was measured gravimetrically with an air sample filter and pump controlled by a rotameter. The particle size distribution was analysed using a cascade impactor accoring to May (1975).
Duration of exposure:
4 h
Concentrations:
5.05±0.13 mg MoO3/m³ (main study, 14-day sacrifice) and 5.00±0.13 mg MoO3/m³ (sattelite group, 24-hour sacrifice)
No. of animals per sex per dose:
Three male and three female rats (main study, 14-day sacrifice)
In addition, three male and three female satellite animals for histopathological examination 24 hours post exposure were tested as a sattelite group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
In addition, three male and three female satellite animals for histopathological examination 24 hours post exposure were tested as a sattelite group.
During and following exposure, observations were made and recorded systematically; individual records were maintained for each animal. Careful clinical examinations were made at least twice daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily (in the morning starting on test day 2) to minimize loss of animals to the study, e.g. necropsy or refrigeration of those animals found dead and isolation or sacrifice of weak or moribund animals.
Cageside observations included, but were not limited to: changes in the skin and fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, as well as somatomotor activity and behaviour pattern.
Particular attention was directed to observation of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The animals were also observed for possible indications of respiratory irritation such as dyspnoea, rhinitis etc., as specified in more detail in section 4.7.2 of this report.
Individual weights of animals were determined once during the acclimatisation period, before and after the exposure on test day 1, on test days 3, 8 and 15. Changes in weight were calculated and recorded when survival exceeded one day. At the end of the test, all animals were weighed and sacrificed.
Statistics:
no calculation as no mortality occurred

Results and discussion

Preliminary study:
not applicable
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.05 mg/L air
Exp. duration:
4 h
Mortality:
no deaths
Clinical signs:
other: A 4-hour inhalation exposure to molybdenum trioxide at a concentration of 5.05 mg/L air revealed slight dyspnoea (reduced frequency of respiration with increased volume) on test day 1 immediately after end of exposure until 3 hours post exposure in all 3
Body weight:
all animals gained the expected weight throughout the study period
Gross pathology:
No pathological changes were detected at necropsy.

Other findings:
A 4-hour inhalation exposure to molybdenum trioxide at a concentration of 5.05 mg/L air (main study, 14-day sacrifice) or 5.00 mg/mL air (sattelite group, 24h-sacrifice) did not reveal any test material-related histopathological changes in the nose (5 levels of the nasal turbinates), larynx, trachea and lungs (5 levels).

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Molybdenum trioxide does not require classification either for acute inhalation toxicity or for respiratory irritation.