Tricarbonyl(methylcyclopentadienyl)manganese

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducte similar to OECD 402 with sufficient information on methodology and results for assessment.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

Only male rats were used. No information on animal husbandry. Also information on temperature and humidity is missing.

GLP compliance:

no

Remarks:

Study conducted prior to GLP guidelines.

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tricarbonyl(methylcyclopentadienyl)manganese

EC Number:

235-166-5

EC Name:

Tricarbonyl(methylcyclopentadienyl)manganese

Cas Number:

12108-13-3

Molecular formula:

C9H7MnO3

IUPAC Name:

tricarbonyl(methyl-η5-cyclopentadienyl)manganese

Details on test material:

- Name of test material (as cited in study report): MMT (methylcyclopentadienyl manganese tricarbonyl)
- Physical state: Liquid
-Density: 1.30 g/ml
- Other: Designated as slightly viscous copper colored liquid.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Breeding Laboratories
- Age at study initiation: No information
- Weight at study initiation: 210-444 g
- Fasting period before study: No
- Housing: Caged in groups of 10
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days


ENVIRONMENTAL CONDITIONS: No information

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Stainless steel exposure chamber
- Exposure chamber volume: 300 liter
- Method of holding animals in test chamber: No information
- Source and rate of air: 200 L/min
- Method of conditioning air:
- System of generating particulates/aerosols: A syringe drive fed the compound, at a known and constant rate, to the 500 ml vaporization flask. Compressed nitrogen was metered at a constant flow rate of 10 L/min past a quartz immersion heating element which raised the temperature, and was then fed to the vaporization flask. The vaporization flask was heated with a heating mantle. Preliminary experiments were conducted in order to define the flask temperature and nitrogen temperature necessary to completely vaporize the experimental compound when added at the highest expected rate.


TEST ATMOSPHERE
- Brief description of analytical method used: Chamber air samples were drawn at a constant flow rate through 20 cmx 2.3 cm diameter fritted tubes packed with 4gr of chromosorb 102. The same sample flow rate was used (0.5 L/min). Duration of the sample was adjusted to collect an amount of sample estimated to be in the middle of the analytical standard curve. Three absorbers were run simultaneouly for each exposure, hexane was used for the elution of mmt, and the volume of hexane recovered was eluted in a volumetric flask. The spectrum of these hexane solution were then recorded from 2000/cm to 1900/cm against a hexane blank utilizing a Perkin-Elmer Model 267 infrared spectrophotometer fitted with matched 0.5 mm cells. The absorption band at 1935/cm was used for analytical purposes. Standards of mmt were prepared in hexane and a series runs performed prior to running chamber samples.
- Samples taken from breathing zone: no

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: No data.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

1 - 4 h

Concentrations:

Animals exposed to mmt vapour for 1 hour
Groups:
I - 0.108 mg/L
II - 0.221 mg/L
III - 0.264 mg/L
IV - 0.309 mg/L

Animals exposed to mmt vapour for 4 hours
Groups:
V - 0.047 mg/L
VI - 0.054 mg/L
VII - 0.070 mg/L
VIII - 0.087 mg/L
IX- 0.100 mg/L

No. of animals per sex per dose:

10 male rats per concentration/time group; 90 total male rats

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: all groups were held for 14-days after exposure for observation of latent effects. Rats were observed dail y for clinical signs. Body weights were recorded prior to exposure and after 7 and 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The 1-hour and 4-hour exposure data were plotted according to Litchfield and Wilcoxon with 95% confidence limit.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LC50

Effect level:

0.247 mg/L air (analytical)

95% CL:

0.229 - 0.271

Exp. duration:

1 h

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

0.076 mg/L air (analytical)

95% CL:

0.067 - 0.087

Exp. duration:

4 h

Mortality:

A dose-response relationship was observed. Mortality in rats exposed for 1 hour, the concentrations applied were higher than for the rats exposed for 4 hours to mmt.
For detailed information please refer to table 1 on the field 'Remarks on results including tables and figures'.

Clinical signs:

other: A decrease in general activity, labored respiration (Dyspnea) and slight incidence of tissue inflamation around the eyes (conjunctivitis) were the clinical toxicity signs were observed. For the 1-hour exposures, dyspnea and a decrease in activity persis

Body weight:

On average, rats exposed to mmt vapours for 1-hour to concentrations between 0.108 and 0.264 mg/l, lost weight or did not gain body weight during the seven days post-exposure. By 14-days of post-exposure, these same rats regained and increased their body weight .

Rats exposed to mmt vapour for 4-hours at a concentration of 0.047 mg/L, showed some weight gain during the first seven days of the post-exposure period, and normal weight gain by 14-days post-exposure. Rats exposed to mmt vapours for 4-hours surviving concentrations between 0.054 and 0.087 mg/L, exhibited weight loss during the first 7 days, but resumed normal weight gain by 14-days post-exposure.

Gross pathology:

Rats surviving 1-hour exposures to mmt vapours and sacrificed 14 days post-exposure exhibited a moderate incidence of focal areas of hemorrhage in the lungs while animals exposed for 4-hours showed only a slight incidence of these hemorrhagic foci. These were the only gross abnormalities observed.

Other findings:

- Potential target organs: Lungs

Any other information on results incl. tables

Table 1 - Mortality of the rats exposed to mmt

Group No.	Exposure Conc. Mg/L	Duration of exposure (Hours)	Number dead Days post-exposure					CUMM. Mortality %
			1	2	3	4	5
I	0.108	1.0	0	0	0	0	0	0
II	0.221	1.0	0	1	0	0	0	10
III	0.264	1.0	2	3	1	2	0	80
IV	0.309	1.0	5	2	3			100
V	0.047	4.0	0	0	0	0	0	0
VI	0.054	4.0	0	1	0	0	0	10
VII	0.070	4.0	0	0	3	0	0	30
VIII	0.087	4.0	1	5	1	0	0	70
IX	0.100	4.0	7	3				100

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category I

Remarks:

Migrated information Category 1 Acute inhalation toxicant: H330: ‘Fatal if inhaled’, per EC/1272/2008.

Conclusions:

Based on the results, the male rat LC50 based on a 1-hour exosure to mmt vapour was 0.247 mg/L (CL= 0.229 - 0.271 mg/L). the male rat LC50 based on a 4-hour mmt vapour exposire was determined to be 0.076 mg/L (Cl = 0.067 to 0.087 mg/L). For classification purposes, using the four hour exposure values, mmt would be classified as a Category 1 Acute inhalation toxicant: H330: ‘Fatal if inhaled’, per EC/1272/2008.

Executive summary:

An acute inhalation toxicity study was performed in nine groups of ten male Sprague-Dawley rats. The rats were exposed via a whole body inhalation to mmt vapours. The groups consisted of 1-hour exposures to concentrations of 0.108, 0.221, 0.264 or 0.309 mg/L or 4-hour exposures to concentrations of 0.047, 0.054, 0.070, 0.087 or 0.100 mg/L. Animals were observed for 14-days post-exposure. Decreased activity and dyspnea persisted for a maximum of 4 days post-exposure in the 1-hour exposure for 1-hour, and for two days in the 4-hour exposure groups. Animals surviving 1-hour exposures to concentrations between 0.108 and 0.264 mg/L did not gain body weight during the first 7 days post-exposure, but resumed weight gain by 14 days post-exposure. Body weights were depressed in animals exposed for 4-hours to concentrations between 0.054 and 0.087 mg/L for the first seven days only. The only gross abnormality observed at necropsy in animals surviving the full 14 days was a moderate incidence of focal haemorrhagic areas in the lungs of rat exposed for 1-hour exposures and slight incidence in rats exposed 4-hours.

Based on the results, the 1-hour male rat LC50 for mmt vapours was determined to be 0.247 mg/L (Cl 0.229 - 0.271 mg/L), and the 4-hour male rat LC50 for mmt vapours was determined to be 0.076 mg/L (Cl = 0.067 to 0.087 mg/L).