Tricarbonyl(methylcyclopentadienyl)manganese

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study, similar to OECD 401 with sufficient information on methodology and result for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1980

Report date:

1980

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Remarks:

Information on body weight and complete description of necropsy results is missing.

GLP compliance:

not specified

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): methylcyclopentadienyl manganese tricarbonyl
- Physical state: Orange liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 180-230 g
- Fasting period before study: No data
- Housing: No data
- Diet : ad libitum
- Water : ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 hrs / 12 hrs

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

mmt was given in corn oil (3 ml/kg)

Doses:

30, 47.4, 75 and 118 mg/kg.

No. of animals per sex per dose:

5 male rats per dose.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations for mortality performed daily
- Necropsy of survivors performed: no data

Statistics:

Student's t test was used for determination of statistical significance. The moving average interpolation method of Thompson and Weil (1952) was used to estimate the LD50.

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

51.8 mg/kg bw

Remarks on result:

other: ± 10.9 (SD)

Mortality:

Yes, detailed information on table 1.

Clinical signs:

other: Not recorded.

Gross pathology:

Necroscopy of animals that died within 24 hrs after mmt dosing, showed grossly distended lungs with a blood-containing fluid.

Other findings:

- Potential target organs: lungs

Any other information on results incl. tables

Table 1 - Mortality in rats following administration of mmt

Dose^a (mg/kg)	Mortality^b/Dosed	Length of survival Of animals dying
30	0/5
47.4	2/5	2 – 3 days
75	5/5	2 – 3 days
118	4/5	<48 hr

^ammt doses given in corn oil (3 ml/kg) to rats weighting 190-210 g.

^bCummulative mortality during 14 after dosing.

Table 2 - Effects of MMT on liver and lung

Treatment Group^a	N	Body wt (g)	Lung wt x 10³/ Body wt	GPT (units/ml)	G-6-Pase (mg Pi/g Liver/20 min	Hepatic Triglyceride (mg/g liver)
A. Control	7	198 ± 4	5.58 ± 0.21	34 ± 2	7.47 ± 0.70	5.29 ± 0.27
mmt^b	6	218 ± 12	11.95 ± 1.18^c	29 ± 1	8.96 ± 0.53	5.42 ± 0.98
mmt+PB	7	210 ± 12	5.78 ± 0.30^d	133 ± 34^d	5.68 ± 0.52^d	5.94 ± 1.33
B. Control	5	196 ± 3	6.52 ± 0.15	32 ± 2	14.32 ± 0.32	nd
mmt	5	189 ± 2	16.09 ± 3.52^c	36 ± 4	13.29 ± 0.94	nd

^ammt was administered po at a dose of 125 mg/kg in corn oil (3 ml/kg). Part A reports results (mean ± SE) obtained 24 h and part B 12 h after dosing with mmt. Rats were given Phenobarbital (60 mg/kg, ip) for 3 days.

^bThese data are from 6 survivors of 14 treated animals.

^cSignificantly different from control, p<0.05

^dSignificantly different from mmt alone, p<0.05

^eNot determined

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Acute oral toxicant category 3: H300 "Toxic if swallowed"..

Conclusions:

The oral LD50 for mmt in male rats was determined to be 51.8 mg/kg day.

Executive summary:

In an acute oral toxicity study, groups of 5 male Sprague-Dawley rats were given a single oral dose of mmt in corn oil (3ml/kg) at doses of 30, 47.4, 75 and 118 mg/kg, and observed for 14 days. In a concurrent study, 125 mg/kg of mmt in corn oil (3 ml/kg) was administrated orally to rats with or without pre-treatment with phenobarbital (PB) to assess effects on body and lung weight, GPT, G-6-Pase and hepatic triglyceride. Effects were measured at 12 and 24 hours after treatment.

 

Necropsy of examination of animals which died within 24 hours after mmt showed lungs grossly distended with a blood-containing fluid.

For the study of the effect of mmt on liver and lung, the following were observed:

- Rats without PB pre-treatment exhibited a significant increase of lung weight (the weight doubled in relation to the control);

-  Rats pretreated with PB had lung weights comparable to the control;

- The concentration of GPT increased greatly in rats pretreated with PB in relation to both control and mmt-treated rats.

- No significant elevation in GPT in mmt rats without PB pretreatment.

As elevated concentrations of GPT is a potential indicator of liver damage, the results indicate that that Phenobarbital pre-treatment may shift the toxicity of mmt from the lungs to the liver.

The male rat oral LD50 was determined to be 51.8 ± 10.9 mg/kg