Samarium (III) oxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-05-02 to 2012-05-11

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guidance study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesamt für Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Kaiser-Friedrich-Straße 7, 55116 Mainz

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Samarium (III) oxide

EC Number:

235-043-6

EC Name:

Samarium (III) oxide

Cas Number:

12060-58-1

Molecular formula:

O3Sm2

IUPAC Name:

disamarium(3+) trioxidandiide

Constituent 2

Reference substance name:

not stated

IUPAC Name:

not stated

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): Samarium oxide
- Molecular formula (if other than submission substance): Sm2O3
- Molecular weight (if other than submission substance): not stated
- Analytical purity: > 99,9%
- Lot/batch No.: 228672
- Expiration date of the lot/batch: March 2015
- Stability under test conditions: not stated
- Storage condition of test material: The test item was stored in a closed vessel dry at room temperature: (20 +- 5°C).

Method

Target gene:

his operone

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 97a, TA 98, TA 100, TA 102, TA 1535

Metabolic activation:

with and without

Metabolic activation system:

Liver S-9 Fraction of Aroclor 1254-induced male Sprague-Dawley rats. Batch No: 2861 Trinova Biochem. Gießen.

Test concentrations with justification for top dose:

TA 97a, TA 98, TA 100, TA 102 and TA 1535 (first experiment):
Four plates with and four plates without S9 mix were used per strain and dose.
without and with activation: 0, 51, 157, 498, 1497 and 5007 µg/plate;
Plate incorporation method.

TA 97a, TA 98, TA 100, TA 102 and TA 1535 (second experiment):
317, 626, 1255, 2508 and 5011 µg/plate
Pre-incubation method.

Vehicle / solvent:

water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

benzo(a)pyrene

other: 4-Nitro-1,2-phenylene diamine and 2-Amino-anthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION:
- Plate incorporation method (first experiment)
- preincubation (second experiment)


DURATION
- Preincubation period: 20 min.
- Temperature: 37°C
- Exposure duration: 2 days

NUMBER OF REPLICATIONS: 4

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

The colonies were counted visually, the numbers were recorded. A spreadsheet software (Microsoft Excel (R)) was used to calculate mean values and standard deviations of each treatment, solvent control and positive control. The increase factor f(I) of revertant induction (mean revertants divided by mean spontaneous revertants) were also calculated.
A test item is considered to have mutagenic potential, if a significant, reproducible increase of revertant colonies per plate (increase factor >=2) in at least one strain can be observed. A concentration-related increase over the range tested can also be taken as a sign of mutagenic activity.

Results and discussion

Test results

Species / strain:

other: TA 97a, TA 98, TA 100, TA 102, TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

First Experiment:

The mean revertant values of the four replicates are presented in the following table. Concentrations of the test item are stated as nominal concentrations, as suspensions had to be tested due to the poor solubility of the test item. As no complete dissolution was possible, undissolved particles were visible on the plates.

Strain		TA97a		TA98		TA100		TA102		TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
H2O	Mean	108	116	15	16	87	89	140	146	13	15
	sd	13.1	5.1	3.9	1.4	10.2	3.6	7.9	7.7	1.5	2.6
DMSO	Mean	104	108	12	17	88	91	150	149	15	17
	sd	6.5	13.1	1.7	1.2	6.8	11.4	14.7	10.2	1.7	1.0
Positive Controls	Mean	531	583	245	217	516	559	582	632	212	202
	sd	74	88	15	15	38	28	25	39	21	21
	f(I)	5.11	5.40	20.42	12.76	5.93	6.14	3.88	4.24	16.31	11.88
5007 µg/pl.	Mean	113	118	17	15	79	77	152	144	15	15
	sd	6	4	2	1	6	10	6	9	4	1
	f(I)	1.05	1.02	1.13	0.94	0.91	0.87	1.09	0.99	1.15	1.00
1497 µg/pl.	Mean	117	119	16	15	84	93	145	142	17	15
	sd	3	5	2	1	11	13	10	9	4	2
	f(I)	1.08	1.03	1.07	0.94	0.97	1.04	1.04	0.97	1.31	1.00
498 µg/pl.	Mean	120	121	16	16	77	96	148	137	16	16
	sd	2	2	2	1	8	9	5	6	3	2
	f(I)	1.11	1.04	1.07	1.00	0.89	1.08	1.06	0.94	1.23	1.07
157 µg/pl.	Mean	114	116	16	15	76	93	129	147	15	14
	sd	3	4	2	2	22	16	10	13	4	1
	f(I)	1.06	1.00	1.07	0.94	0.87	1.04	0.92	1.01	1.15	0.93
51 µg/pl.	Mean	120	113	15	16	82	84	144	133	14	14
	sd	3	5	4	1	5	6	8	12	3	1
	f(I)	1.11	0.97	1.00	1.00	0.94	0.94	1.03	0.91	1.08	0.93

Second Experiment:

The mean revertant values of the four replicates are presented in the following table. Concentrations of the test item are stated as nominal concentrations, as suspensions had to be tested due to the poor solubility of the test item. As no complete dissolution was possible, undissolved particles were visible on the plates.

Strain		TA97a		TA98		TA100		TA102		TA1535
Induction		-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
H2O	Mean	116	106	21	20	66	83	135	137	14	14
	sd	15.9	7.5	2.5	2.3	4.3	12.0	18.3	18.2	1.3	3.0
DMSO	Mean	112	109	15	18	70	84	138	146	14	13
	sd	3.0	6.7	2.6	2.9	9.7	5.7	9.2	4.5	2.2	3.4
Positive Controls	Mean	449	301	885	824	683	617	593	692	343	232
	sd	75	38	47	53	82	98	36	67	80	8
	f(I)	4.01	2.76	59.00	45.78	10.35	7.35	4.30	4.74	24.50	17.85
5011 µg/pl.	Mean	101	103	16	17	114	102	138	134	15	16
	sd	7	7	2	4	6	7	3	15	2	2
	f(I)	0.87	0.97	0.76	0.85	1.73	1.23	1.02	0.98	1.07	1.14
2508 µg/pl.	Mean	102	101	15	19	92	100	132	141	15	16
	sd	5	12	2	2	19	4	5	2	1	3
	f(I)	0.88	0.95	0.71	0.95	1.39	1.20	0.98	1.03	1.07	1.14
1255 µg/pl.	Mean	112	96	13	18	85	100	151	146	14	14
	sd	8	4	3	2	10	7	7	9	1	3
	f(I)	0.97	0.91	0.62	0.90	1.29	1.20	1.12	1.07	1.00	1.00
626 µg/pl.	Mean	93	98	15	14	87	96	151	129	16	14
	sd	3	6	1	2	6	8	8	4	2	3
	f(I)	0.80	0.92	0.71	0.70	1.32	1.16	1.12	0.94	1.14	1.00
317 µg/pl.	Mean	97	93	15	14	84	105	136	145	16	14
	sd	4	3	2	3	11	9	6	10	2	1
	f(I)	0.84	0.88	0.71	0.70	1.27	1.27	1.01	1.06	1.14	1.00

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metaboic activation

Executive summary:

The test item didn't show mutagenic effects in both experiments. The number of revertant colonies was not increased in comparison with the spontaneous revertants (solvent only). Cytotoxicity of the test item was not detected. The background lawn was visible and the number of revertants was not significantly decreased.

As no complete dissolution was possible, undissolved particles were visible on the plates.

Therefore it can be stated, that under the test conditions, the test item Samarium oxide is not mutagenic in the Bacterial Reverse Mutation Test using Salmonella typhimurium, strains TA 97a, TA 98, TA 100, TA 102 and TA 1535.