Tricarbonyl(methylcyclopentadienyl)manganese

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not mentioned

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study performed comparable to OECD 402 with acceptable deviations.

Data source

Reference

Reference Type:

other company data

Title:

Unnamed

Year:

1975

Report date:

1975

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

No information on the sex of the animals or environmental conditions. Only four animals were used, two of which had their skin abraded prior to exposure.

GLP compliance:

no

Remarks:

Test conducted prior to GLP guidelines.

Test type:

standard acute 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: methylcyclopentadienyl manganese tricarbonyl
- Physical state: Dark amber liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: the laboratory stock colony
- Age at study initiation: No data
- Weight at study initiation: 3.323-4.875 Kg
- Fasting period before study: No
- Housing: Individually
- Diet: ad libitum
- Water : ad libitum
- Acclimation period: not relevant, animals bred in the laboratory


ENVIRONMENTAL CONDITIONS
No data

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: upper back area
- % coverage: no data
- Type of wrap if used: impervious band


REMOVAL OF TEST SUBSTANCE
- Washing: no data
- Time after start of exposure: N.A.


TEST MATERIAL
No data.

Duration of exposure:

24 hours.

Doses:

112, 126, 141 and 158 mg/kg

No. of animals per sex per dose:

4 animals per dose, (2 with abraded skin, 2 with intact skin) no information on the sex.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequent observations after dosing and daily for 14 days for illness and mortality. Body weighting were recorded on days 0, 3, 7, 10 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight and skin reactions.

Statistics:

Dermal LD50 calculated according to the methods of Litchfield and Wilcoxon, 1949.

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

140 mg/kg bw

95% CL:

122 - 159

Mortality:

Number of Dead/Dosed per concentration applied:
- 112 mg/kg: 0/4
- 126 mg/kg: 1/4
- 141 mg/kg: 2/4
- 158 mg/kg: 3/4

Clinical signs:

other: General appearance and behaviour of the rabbits were not effected.

Gross pathology:

Gross observations of the viscera reveal congested organs with blood tinged urine at the higher dose levels. Two rabbits with respiratory ailments and one with kidney stones were believed to be non-compound related. A general pattern of red discoloration of the kidneys is present at all dose levels. For detailed information see table 2.

Any other information on results incl. tables

Table 1 - Individual body weights

Rabbit No.	Mg/kg	Day 0	3	7	10	14
216 Abraded	112	4.070	3.987	3.863	3.965	4.002
217 A.		4.412	4.116	4.025	4.102	4.233
212 Intact		4.730	4.503	4.470	4.526	4.670
214 I.		4.875	4.675	4.600	4.675	4.827
204 A.	126	4.525
294 A.		3.345	3.506	3.640	3.407	3.504
228 I.		3.323	3.4199	3.475	3.168	3.273
306 I.		3.660	3.696	3.743	3.969	4.105
218 A.	141	3.595	3.326	3.189	3.195	3.357
219 A.		4.070
220 I.		4.465
231 I.		3.870	3.813	3.765	3.791	3.920
183 A.	158	4.185	4.132	4.006	4.085	4.108
205 A.		3.780
247 I.		4.141	3.646
203 I.		4.085

A - abraded skin

I - intact skin

Table 2 - Clinical signs and gross pathology

Rabbit #	mg/kg	Daily observations	Necropsy
216 Abraded	112	None noted	None noted.
217 A.		None noted	Liver margin swollen
212 Intact		None noted	Kidneys congested.
214 I.		None noted	Kidneys congested.
204 A.	126	Died, Day 2	Lungs discolored. Red tinged urine in bladder. Red tinged kidney – cortex red.
294 A.		None noted	Red tinged kidney – cortex red.
228 I.		None noted	Renal calculi. Red tinged kidney, small with much scar tissue.
306 I.		None noted	Red tinged kidney – spotted red.
218 A.	141	None noted	Kidneys discolored.
219 A.		Died, Day 3	Lungs and liver discolored; small intestine contains yellow fluid.
220 I.		Died, Day 3	Lungs, liver and kidney discolored; small intestine contains yellow fluid.
231 I.		None noted	Respiratory infection
183 A.	158	Died within 24 hours	Lungs dark red, liver spotted red. Spleen discolored red. Kidneys abnormal shape and nodular. Small intestine filled with yellow fluid.
205 A.		None noted	Respiratory disease. Spleen appears swollen; kidneys discolored red.
247 I.		Died, Day 3	Lungs, liver, spleen and kidneys discolored red. Urine red tinged and contains clotted blood. Small intestine filled with yellow fluid.
203 I.		Died, Day 2	Lungs, liver, spleen and kidneys discolored red. Small intestine filled with yellow fluid.

Table 3 - Daily observations of skin

Rabbit No.	Mg/kg	Days
		1	2	3	4	5	6	7	8	9	10	11	12	13	14
216 A. Erythema            Edema	112	1 2	1 1	1 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
217 A. Erythema            Edema		2 2	1 1	1 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
212 I. Erythema            Edema		2 2	1 1	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
214 I. Erythema            Edema		1 1	1 1	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
204 A. Erythema            Edema	126	1 2	1 1
294 A. Erythema            Edema		1 1	1 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
228 I. Erythema            Edema		1 1	1 1	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
306 I. Erythema            Edema		1 2	1 1	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
218 A. Erythema            Edema	141	1 2	1 1	1 0	1 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
219 A. Erythema            Edema		2 1	1 1
220 I. Erythema            Edema		1 1	1 1
231 I. Erythema            Edema		1 2	1 1	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
183 A. Erythema            Edema	158	2 2	1 1	1 0	1 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0	0 0
205 A. Erythema            Edema
247 I. Erythema            Edema		1 1	1 1
203 I. Erythema            Edema		1 0

Evaluation of skin reaction

Erythema and eschar formation:

No erythema 0

Very slight erythema 1

Well-defined erythema 2

Moderate to severe erythema 3

Severe erythema (beet redness to slight

eschar formation (injuries in depth) 4

Edema formation:

No edema 0

Very slight edema 1

Slight edema 2

Moderate edema 3

Severe edema 4

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information H310: Fatal in contact with skin Criteria used for interpretation of results: EU

Conclusions:

Evidence of congestion or possible internal hemorrhage are present in the major organs. Blood tinged urine at the higher dose levels was noted.
Mortality occurred within 24 hours and up to 3 days after application. Dermal reaction were limited to slight to well defined erythema and slight edema persisting to maximum 4 days after application. The dermal LD50 was calculated at 140 mg/kg-bw (95% CL of 122-159 mg/kg-bw).

Executive summary:

In an acute dermal toxicity study, groups of 4 mature healthy New Zealand albino rabbits (2 with abraded skin and 2 with intact skin) were dermally exposed to mmt for 24 hours at doses of 112, 126, 141 or 158 mg/kg bw. Animals were observed for 14 days after dosing. Although the general appearance and behavior of the animals was not altered, dermal reactions like erythema and a slight edema were seen with symptoms subsiding in 1-4 days. A pathological observations indicating evidence of congestion or possible internal hemorrhage were present in the major organs. Blood tinged urine at the higher dose levels was also seen.

 

Dermal LD₅₀= 140 mg/kg bw (95% C.I. 122-159 mg/kg). This LD50 would result in mmt being classified as a Category 2 Acute Dermal Toxicant, H310: Fatal in contact with skin per EC/1272/2008.