Cobalt molybdate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

from January 2010 to July 2010

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study was generated according to generally valid and accepted testing guidelines and performed according to GLP. In accordance to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on the read-across substance molybdenum trioxide (CAS 1313-27-5).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

(92/69/EEC)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Molybdenum trioxide

EC Number:

215-204-7

EC Name:

Molybdenum trioxide

Cas Number:

1313-27-5

IUPAC Name:

trioxomolybdenum

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 or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder: Charles River Laboratories, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- 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 (satellite 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 satellite 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

Based on:

test mat.

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 (satellite 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.