2-ethylhexanoic acid, molybdenum salt

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-08-22 to 1990-09-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study similar or equivalent to guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 12 May 1981

Deviations:

yes

Remarks:

minor temperature deviation (1°C for the holding area and 3-4°C for chamber air temperature); nominal concentration and 95 per cent confidence level is missing.

GLP compliance:

yes

Remarks:

The study report states that the study was conducted in compliance with Good Laboratory Practice Standards, e.g. by the United Kingdom Compliance Programme, Department of Health & Social Security 1986 and subsequent revision, Department of Health, 1989.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

molybdenum sulfide (MoS2), roasted

IUPAC Name:

molybdenum sulfide (MoS2), roasted

Constituent 2

Reference substance name:

86089-09-0

Cas Number:

86089-09-0

IUPAC Name:

86089-09-0

Constituent 3

Reference substance name:

Molybdenum sulfide (MoS2), roasted

EC Number:

289-178-0

EC Name:

Molybdenum sulfide (MoS2), roasted

IUPAC Name:

289-178-0

Details on test material:

- Name of test material (as cited in study report): Technical molybdenum oxide
- EC Name: molybdenum sulfide (MoS2), roasted
- Synonyms: roasted molybdenite concentrate
- Physical state: greyish granular powder
- Composition of test material, percentage of components: MoO3 content = 90%
- Stability under test conditions: Under test conditions the test substance was stable
- Storage condition of test material: stored in the dark at room temperature and in the original container.

No further significant information on test material was stated.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: about 6 weeks (males) and 8 weeks (females) old
- Weight at study initiation: ca. 200g on the day of exposure
- Housing: The rats were housed 5 of like sex to a cage. The cages were made of polypropylene (size 38 cm X 56 cm X 18 cm height) and had detachable wire mesh tops and floors. The cages were suspended on a movable rack.
- Diet: free access to a measured excess amount of food (Labsure LAD 1)
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: at least 5 days before the day of exposure



ENVIRONMENTAL CONDITIONS
- Temperature: within the limits of 18°C to 24 °C
- Humidity: withing the range of 35 % to 65%

No further significant information on test animals were stated.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

other: clean air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
System of generating particulates/aerosols: A wright dust generator was used to produce a test atmosphere containing the dust of Technical molybdenum oxide. The generator 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.

- Exposure apparatus: Whole-body exposure chambers of square section made of perspex, internal volume approximately 120 l. For exposure the rats were held in cages of stainless steel mesh partitioned to provide 10 individual animal compartments. A supply of clean dried compressed air was connected to the dust generator and the supply pressure was adjusted to give a flow rate of 25 litres per minute measured at the generator outlet nozzle.

The control group was treated similarly but received clean air only for 4 hours. The control rats were returned to the holding room at the end of the exposure procedure.

- Method of particle size determination: Two air samples were taken using a Marple Model 296 cascade impactor. The contents of the stages were weighed to determine the particle size distribution in the atmosphere. The air sample was taken at flow rate of 2.0 litres per minute and the cut-points for the stages of the Marple impactor at this flow rate were 0.52, 0.93, 1.55, 3.5 6.0 and 9.8 µm aerodynamic diameter.

- Temperature, humidity: The air temperature in the exposure chamber was measured with a mercury-in-glass thermometer. The chamber mean air temperatures and the standard deviations (SD) of the means were: Group 1 (Control) 27°C (SD = 1.2); Group 2 (Test) 28 °C (SD = 0.8). The small difference in air temperature between the control and test groups was considered not to have influenced the results of the study. The concentration of water vapour in the chamber air was monitored using an Analytical Development Co. Ltd., water vapour analyser, model 225. The relative humidity was calculated from the recorded data for the water vapour content and temperature of the chamber air. The mean relative humidity of the chamber air and the standard deviation (SD) of the mean during the exposure was: Group 1 (Control) 48 % RH (SD = 6.9); group 2 (test) 48 % (RH SD = 6.0).

TEST ATMOSPHERE
Five air samples were taken from the chamber during the exposure.
Each air sample was withdrawn through a glass fibre filter (Whatman GF/A) held in an open face filter holder, at a rate of 4 litres/minute. The volume of the air sample was measured with a wet-type gas meter. The filters were weighed to determine the concentration of test substance in the chamber air.
TEST ATMOSPHERE
- Particle size distribution: On average , 36 % of the dust collected was 3.5µm or less in aerodynamic diameter
- MMAD/ GSD: 4.2 µm (GSD = 2.19)

No further significant information was stated.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see "details on inhalation exposure" above

Duration of exposure:

4 h

Concentrations:

The mean actual concentration of Technical molybdenum oxide was 3.92 mg/l. The variation in concentration (range of values x 100/mean) was 40% and within acceptable limits. The concentration of 3.92 mg/L was the highest that was practically achievable as a stable test atmosphere.

No. of animals per sex per dose:

Control group: 5 males/5 females
Test group: 5 males / 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed continuously for signs of reaction to the test substance during exposure and at least twice daily throughout the observation period. All rats were weighed daily from the day of delivery to the Huntingdon Research Centre until the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: The amount of food and water consumed by cage of rats was measured daily from the day following arrival. The daily mean intakes of food and water for each rat were calculated from the recorded data.
At the end of the 14-day observation period, the rats were anaesthetised by intraperitoneal injection of pentobarbitone sodium and killed by exsanguination.
The rats were subjected to a detailed macroscopic examination. The lungs were removed, dissected clear of surrounding tissues and weighed in order to calculate the lung weight to bodyweight ratio.
The lungs were infused with, and preserved in buffered 10 % formalin together with samples of the liver and kidneys.
The fixed lungs were embedded in paraffin wax and processed routinely. Four-micron sections were prepared, stained with haematoxylin and eosin and examined under the licht microscope.
The liver and kidneys were preserved.

Statistics:

not required

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3.92 mg/L air

Exp. duration:

4 h

Mortality:

There were no deaths during the study.

Clinical signs:

other: During exposure: Partial closing of the eyes was the only sign seen in rats exposed to technical molybdenum oxide. This sign was considered to be consistent with a non-specific response to exposure to a high concentration of dust. During the observation p

Body weight:

Small losses in bodyweight or a reduced rate of bodyweight gain were observed in a proportion of rats exposed to technical molybdenum oxide for up to 3 days following exposure. Subsequently the rate of weight gain for the exposed and control rats was similar.

Gross pathology:

Macroscopic pathology:
There were no macroscopic abnormalities in the rats exposed to technical molybdenum oxide and no abnormailties in the control rats.
Microscopic pathology:
No changes considered to be of toxicological significance were observed in the lungs sections examined.

Other findings:

The lung weight to bodyweight ratio was considered to be within normal limits for all rats.

Food consumption:
Food consumption was reduced for 2-3 days following exposure to technical molybdenum oxide. Subsequently, food consumption for exposed rats was similar to that for the control rats.

Water consumption:
Water consumption was slightly increased for a few days following exposure to technical molybdenum oxide.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU