Dimolybdenum trizinc nonaoxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2019

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 433 draft (Acute Inhalation Toxicity: Fixed Concentration Procedure) (not officially approved)

Version / remarks:

The guideline has been formally now been approved on 28 June 2018.

Deviations:

no

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimolybdenum trizinc nonaoxide

EC Number:

245-322-4

EC Name:

Dimolybdenum trizinc nonaoxide

Cas Number:

22914-58-5

Molecular formula:

Mo2O9Zn3

IUPAC Name:

dimolybdenum trizinc nonaoxide

impurity 1

Reference substance name:

Molybdenum zinc tetraoxide

EC Number:

237-377-8

EC Name:

Molybdenum zinc tetraoxide

Cas Number:

13767-32-3

Molecular formula:

MoO4Zn

IUPAC Name:

molybdenum zinc oxide

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan®:WIST

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS Limited
- Age at study initiation: 69 to 76 days
- Weight at study initiation: 280 to 300 g
- Fasting period before study: No
- Housing: The animals were housed five per cage, unless this number was reduced by mortality or isolation. The cages were made of a polycarbonate body with a stainless steel mesh lid.
- Diet (e.g. ad libitum): Free access to a standard rodent diet. The diet contained no added antibiotic or other chemotherapeutic or prophylatic agent.
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: For at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.7 µm

Geometric standard deviation (GSD):

>= 1.96 - <= 2.09

Remark on MMAD/GSD:

The mean MMAD value were within the ideal range of 1 to 4 microns (2.7 μm), indicating that the generated substance was respirable to the rat.

Details on inhalation exposure:

Exposure system:
The exposure system was composed of a flow-through nose only chamber. This was made from an aluminium alloy construction comprising a base unit, one animal exposure section with 20 exposure ports and a top section. The dimensions of the chamber give an internal volume of ca. 30L. Animals were restrained in a plastic nose-only restraint tube. Aerosol generation was performed by the use of a Wright Dust Feed Mechanism which is designed to produce and maintain test atmospheres containing dust by suspending material scraped from the surface of a compressed powder in a stream of dry air.
Inlet flow: from in-house compressed air system (breathing quality) at 19L/minute.
Extract airflow: Drawn by in-house vacuum system at 20L/minute.
Airflow monitoring: High quality tapered tube flowmeters and in-line flowmeters monitored continuously.

Concentration (aerosol samples collected as follows):
Sample type: Glass microfiber filter, held in an open face filter holder
Sample flow: 2 L/minute
Sample volume: Measured by wet-type gas meter
Sample frequency: Nine samples collected during Group 1 exposure and ten samples collected during Group 2 exposure
Sample location: Animal exposure port
Sample analysis: Gravimetric

Aerosol samples were collected at irregular intervals due to adjustments to operating conditions. A time-weighted average mean aerosol concentration was calculated in order to prevent undue biasing of repeat samples in the overall mean.

Particle size distribution:
Impactor type: Marple 290 Series Personal Cascade Impactor
Configuration: 298
Collection media: Stainless steel substrates and glass microfiber final stage filter
Sample flow: 2L/minute
Sample frequency: Two samples collected during each exposure
Sample location: Animal exposure port
Sample analysis: Gravimetric (MMAD and GSD derived)

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Remarks on duration:

Standard as per OECD guidelines

Concentrations:

Group 1 (target 5 mg/L): Provided a TWA of 4.80 mg/L (SD 0.340).
Group 2 (target 1.0 mg/L): Provided a TWA of 1.06 mg/L (SD 0.0891)

The mean achieved aerosol concentration values were 96% and 106% of target, for groups 1 and 2 respectively.

No. of animals per sex per dose:

5 males per exposure group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Rats were weighed at least once during the week prior to exposure and on Day 1 (prior to exposure) and on Days 2, 4, 8, 15 or at death. Clinical signs were recorded prior to exposure, at hourly intervals during exposure, immediately following exposure and then at 1 hour and 2 hours post-exposure. During the observation period, the animals were observed once in the morning and once toward the end of the experimental day. On the day of study termination there was one observation (morning only).
- Necropsy of survivors performed: yes

Statistics:

Not performed as not a guideline requirement

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LC50

Effect level:

> 1.06 - < 4.8 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

All males exposed to 4.80 mg/L were found dead or euthanized after a single exposure. Two animals exposed to 4.80 mg/L were found dead on Day 2 and two animals exposed to 4.80 mg/L were euthanized on Day 2. The remaining animal exposed to 4.80 mg/L was euthanized on Day 3. No mortality was noted in animals exposed to 1.06 mg/L.

Clinical signs:

other: Following exposure at 4.80 mg/L, all animals were observed with clinical signs, including irregular and/or shallow breathing, wet rales, unsteady gait, closed/partially closed eyes, decreased activity and/or hunched posture. Two animals were found dead at

Body weight:

On the day following exposure at 1.06 mg/L, body weight losses were evident in all animals. Body weight gains were observed from Day 4 or Day 8, which continued to increase for the remainder of the observation period.

Gross pathology:

Decedents in Group 1 (4.8 mg/L)
Lungs and bronchi: Abnormal color (dark) and incomplete deflation was observed in all males exposed to 4.80 mg/L. Pale areas were observed in the two males exposed to 4.80 mg/L found dead on Day 2.
Stomach: Abnormal contents (blue) were noted in the stomach of four males exposed to 4.80 mg/L either found dead or euthanized on Day 2.

Group 2 (1.06 mg/L)
Lungs and bronchi: Pale areas were observed in the majority of animals exposed to 1.06 mg/L.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study, the LC50 (4 hour) of Zinc Molybdate is in excess of 1.06 mg/L (for male rats) but less than 4.80 mg/L where mortality was observed. This test item is Category 4 according to the Globally Harmonized System (GHS; UNITED NATIONS) and the EU CLP Regulation (EC No. 1272/2008, as amended).