Tricarbonyl(methylcyclopentadienyl)manganese

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented publication. No guideline available for this type of study nor is this route considered for classification purposes.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1982

Materials and methods

Test guideline

Qualifier:

no guideline available

GLP compliance:

no

Remarks:

Study conducted prior to GLP guidelines

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: methylcyclopentadienyl manganese tricarbonyl

Test animals

Species:

other: mouse and rat

Strain:

other: BALB/c mice and CD/CR rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: bred in the lab facilities (mice); Charles River Laboratories (rats)
- Age at study initiation: 8 to 12 weeks old (mice); 3 to 6 months old (rats)
- Weight at study initiation: 20 to 25g (mice); 250 to 300 g (rats)
- Fasting period before study: no
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

corn oil

Details on exposure:

mmt was dissolved in corn oil and administered by ip injection to rats at 5 mg/kg and mice at 120 mg/kg.

Doses:

see details on exposure

No. of animals per sex per dose:

8 to 10 mice and 4 to 6 rats.

Control animals:

yes

Details on study design:

Immediately after each treatment, half of the treated animals and half of the controls were placed within their cages for 6 days, inside a 450-liter plastic chamber which was continuously being ventilated with 80% O2 at an average flow rate of 15 liters/min. The temperate within the chamber remained at 24 to 25 ° C with a relative humidity of 55 to 65%. Oxygen concentrations within the chamber was periodically monitored with an oxygen meter and stayed within ± 3% of the desired concentration. Control animals were kept in room air. After 6 days, the animals were removed from the O2 and kept in room air. Animals were killed for histologic examination and for measurement of lung hydroxyproline levels 3 weeks after administration of the pneumotoxic agent.

Statistics:

Data were calculated as mean ± SE, and comparisons between groups were made with Student's t test. A p value of 0.05 or less was considered to be significant. Where appropriate, one-way analysis of variance was performed on data followed by comparisons of the means by the honestly significant difference procedure, values were considered significant at 5% level.

Results and discussion

Mortality:

-

Clinical signs:

-

Body weight:

-

Gross pathology:

Exposure of Controls to 80% 02

The exposure to 80% O2 alone produced a statistically significant increase (13% increase in total lung hydroxyproline over controls in mice) once in more than 20 different experiments. No effect of 80% O2 alone was found in rats.

Mice or rats exposed to O2 for 6 days, followed by a 2- week recovery period, did not show any significant histopathologic changes in the lungs..

Methylcyclopentadienyl manganese tricarbonyl (mmt) exposure

Three weeks after mmt treatment alone , total lung hydroxyproline was only slightly increased as compared to controls; the difference was statistically not significant.

However, in mice treated with mmt and exposed to 80% 02, a significant increase in the hydroxyproline content was found (Fig. 1A). Histopathological examination showed interstitial thickening characterized by mild hypercellularity and fibrosis, localized primarily around terminal bronchioles and alveolar ducts. It was determined that combined treatment of mmt and O2 produced collagen accumulation and interstitial fibrosis by biochemical and histopathologic criteria. A significant increase in total lung hydroxyproline was found biochemically (fig. 1A).

In rats, oxygen exposure failed to further increase lung collagen, contrary to what had been found in mice. On histopathologic examination, lungs of rats exposed to both mmt and 80% O2 were indistinguishable from those animals treated with mmt alone.

Other findings:

-

Applicant's summary and conclusion

Conclusions:

In the present study, more than 80% of the treated animals survived the 3 weeks post-exposure. In mice, the development of fibrosis was significantly enhanced if animals treated with mmt were exposed to 80% O2 immediately following the acute lung injury. Mice treated with mmt alone did not produce a significant increase in hydroxyproline, however when preceded by exposure to 80% oxygen, the hydroxyproline content increased significantly in the lung. In rats, mmt alone caused an increase in hydroxyproline content, and in contrast with the mice, the oxygen post-exposure did not produce any changes of hydroxyproline levels in the rat lung.