Tricarbonyl(methylcyclopentadienyl)manganese

Repeated dose toxicity: dermal

Administrative data

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

Not mentioned

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Dermal study investigating the effects of mmt in a gasoline carrier with insufficient study documentation for assessment.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

grey literature

Title:

Unnamed

Year:

1972

Report date:

1972

Materials and methods

Test guideline

Qualifier:

no guideline followed

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 (as cited in study report): Methylcyclopentadienyl Manganese Tricarbonyl in gasoline
- Physical state: Liquid
- Analytical purity: 98.05%

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Type of coverage:

not specified

Vehicle:

other: Gasoline

Details on exposure:

The test material was administrated to the animals in either leaded or non-leaded gasoline
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg was applied on the skin of rabbits and rats

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 weeks for rabbits and 22 weeks for rats.

Frequency of treatment:

Single daily administration, 5 days per week.

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 0.4, 2.4 and 16.0 g/L
Basis:
no data

No. of animals per sex per dose:

No data

Control animals:

no

Details on study design:

None.

Positive control:

No.

Examinations

Observations and examinations performed and frequency:

The animals were observed for signs of illness, skin injury and body weight.

Sacrifice and pathology:

No.

Other examinations:

None.

Statistics:

No.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Dermal irritation:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Details on results:

RABBITS
Body weight loss and severe local injury at the site of application of the gasoline (leaded and non-leaded) were found. The mortality and local effectsshad no relationship with the concentration of mmt or to the presence of tetraethyl lead in the gasoline.

RATS
Mild skin injury and no signs of ilness. All animals increase their body weight.

Effect levels

Dose descriptor:

NOEL

Effect level:

16 other: g/l

Based on:

not specified

Sex:

male/female

Basis for effect level:

other: Body weight

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Table 1 - The average week bw of male rabbits dermally exposed to leaded and non-leaded gasoline containing MMT

Average bw (kg)  on the  specified week	Conc. MMT (g/l)
	Leaded gasoline				Non-leaded gasoline
	0	0.4	2.4	16.0	0	0.4	2.4	16.0
-1	3.98	4.21	3.96	3.94	4.14	3.86	4.21	3.94
S	4.06	4.41	4.04	4.00	4.27	3.96	4.20	4.00
1	3.86	4.22	3.92	3.91	4.13	3.85	4.16	3.91
2	3.71*	3.91	3.70	3.63	3.92	3.66	3.89*	3.63*
3	3.43	3.67	3.55	3.58	3.74	3.68*	3.80*	3.58
4	3.37	3.46	3.67	3.49	3.51*	3.62	3.60	3.49
5	3.33	3.64*	3.59	3.44	3.64	3.53*	3.51	3.44
6	3.32	3.61	3.65	3.46	3.56	3.57	3.58	3.46
7	3.30	3.51	3.70	3.36	3.46	3.52	3.49	3.36
8	3.29	3.51	3.62	3.36	3.38	3.32	3.32	3.36
9	3.23	3.48	3.54	3.39	3.22*	3.56*	3.35	3.39
10	3.24*	3.49	3.40	3.26	3.56	3.53	3.29	3.26
11	3.29	3.46	3.63	3.35	3.61	3.47	3.32	3.35*
12	3.28	3.44	3.60	3.41	3.53	3.37	3.30	3.41
13	3.26	3.66	3.65	3.42	3.42	3.31	3.26	3.42

Table 2 - The average week bw of female rats dermally exposed to leaded and non-leaded gasoline containing MMT

Average bw (kg)  on the  specified week	Conc. MMT (g/l)
	Leaded gasoline				Non-leaded gasoline
	0	0.4	2.4	16.0	0	0.4	2.4	16.0
Start	116	116	119	121	115	112	118	118
1	131	128	133	124	129	126	120	127
2	160	150	155	162	161	161	155	159
3	166	166	168	170	170	172	172	171
4	178	177	179	192	179	188	184	187
5	194	190	189	206	195	204	198	199
6	200	198	194	211	201	208	204	204
7	206	210	214	223	214	219	217	219
8	215	213	207	228	218	221	218	218
9	224	223	221	236	226	237	230	232
10	225	229	221	242	228	237	230	229
11	235	236	228	246	234	243	240	238
12	240	242	232	251	243	248	241	241
13	241	244	236	256	241	250	244	243
14	250	250	241	262	245	256	251	245
15	248	257	246	266	252	262	257	252
16	249	262	241	264	251	261	259	250
17	256	264	246	269	254	267	261	254
18	260	270	251	274	259	269	263	254
19	263	275	249	276	261	273	262	259
20
21	266	276	253	283	267	273	273	263
22	271	280	257	283	270	281	275	266
23	270	281	259	284	275	285	274	269
24	277	283	263	292	276	291	282	269
25	276	288	268	293	280	293	282	270

Table 3 - The average week bw of male rats dermally exposed to leaded and non-leaded gasoline containing MMT

Average bw (kg)  on the  specified week	Conc. MMT (g/l)
	Leaded gasoline				Non-leaded gasoline
	0	0.4	2.4	16.0	0	0.4	2.4	16.0
Start	146	136	149	149	144	136	149	144
1	167	156	171	174	167	154	145	161
2	226	213	206	233	192	212	210	211
3	252	232	243	254	232	234	251	235
4	286	264	274	293	273	268	284	275
5	313	292	305	322	307	289	303	305
6	321	301	313	335	319	300	317	314
7	352	318	336	350	340	315	336	323
8	357	336	358	362	350	330	349	345
9	380	249	369	376	365	346	367	366
10	392	365	380	393	382	363	380	387
11	404	373	396	403	396	379	387	397
12	414	385	409	410	405	382	392	408
13	423	396	416	415	412	394	400	406
14	431	412	429	429	423	407	415	430
15	440	420	439	440	436	414	422	449
16	453	424	441	443	439	423	423	453
17	465	432	457	451	444	426	438	463
18	468	437	467	453	447	437	446	470
19	478	457	472	470	461	446	459	484
20
21	487	469	482	486	469	457	465	494
22	495	477	492	496	478	463	475	401
23	507	476	494	495	483	470	481	511
24	507	491	505	504	487	474	487	523
25	524	500	517	519	499	484	494	530

Applicant's summary and conclusion

Conclusions:

Based on the findings, mmt in leaded and non-leaded gasoline did not produced toxic effects in female and male rats or male rabbits in concentrations up to 16 g/l, with a NOAEC being set for 16.0g/l.

Executive summary:

In a  repeat-dose dermal toxicity study performed in the University of Cincinnati, mmt in leaded and non-leaded gasoline was applied to male rabbits and mal and female rats for 5 days per week for 14 weeks (rabbits) and 22 weeks (rats).

The rabbits showed loss in body weight and severe local injury at the site of application of the test material, however these effects were also seen in the controls implying that the findings were related to the gasoline itself rather than mmt. The rats showed mild skin injury and no signs of illness. No mortality was observed and all female and male rats increased their body weight. Based on the findings the NOAEL was derived to be 16.0 g/l for both rabbit and rat.