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Genetic toxicity in vitro

Description of key information

In an Ames test with yttrium oxide, europium-doped, the substance is not considered to be mutagenic in the presence and absence of metabolic activation. In addition, in a HPRT study and a chromosome aberration study with substance analogue yttrium oxide no mutagenic effects were observed. This data is read across to yttrium oxide, europium-doped.

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Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 July - 23 July 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
- S. typhimurium: Histidine gene
- E. coli: Tryptophan gene
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
Rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone
Test concentrations with justification for top dose:
Experiment 1
Preliminary test (TA100 and WP2uvrA):
Without and with S9-mix: 3, 10, 33, 100, 333, 1000, 3330 and 5000 µg/plate
Main study (TA1535, TA1537 and TA98):
Without and with S9-mix: 100, 333, 1000, 3330 and 5000 µg/plate
Experiment 2 (all strains):
Without and with S9-mix: 100, 333, 1000, 3330 and 5000 µg/plate
Vehicle / solvent:
- Solvent used: DMSO
- Justification for choice of solvent/vehicle:
A homogeneous suspension could be made in DMSO and DMSO is accepted and approved by authorities and international guidelines.
The stock solution was treated with ultrasonic waves to obtain a homogeneous suspension. Test substance concentrations were used within 2 hours after preparation.
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without S9 Migrated to IUCLID6: 650 µg/plate in DMSO for TA100
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
without S9 Migrated to IUCLID6: 10 µg/plate in DMSO for TA98 and 15 µg/plate for TA1537
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
without S9 Migrated to IUCLID6: 10 µg/plate in DMSO for WP2uvrA
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without S9 Migrated to IUCLID6: 5 µg/plate in saline for TA1535
Positive controls:
yes
Positive control substance:
other: ICR-191 2.5 ug/plate in DMSO for TA1537
Remarks:
without S9
Negative solvent / vehicle controls:
yes
Positive control substance:
other: 2-aminoanthracene in DMSO for all tester strains
Remarks:
with S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hour

NUMBER OF REPLICATIONS:
- Doses of the test substance were tested in triplicate in each strain. Two independent experiments were conducted.

NUMBER OF CELLS EVALUATED: 10E8 per plate

DETERMINATION OF CYTOTOXICITY
- Method: The reduction of the bacterial background lawn, the increase in the size of the microcolonies and the reduction of the revertant colonies.

OTHER EXAMINATIONS:
- The presence of precipitation of the test compound on the plates was determined.
Evaluation criteria:
A test substance is considered negative (not mutagenic) in the test if:
a) The total number of revertants in tester strain TA100 is not greater than two (2) times the concurrent control, and the total number of revertants in tester strains TA1535, TA1537, TA98 or WP2uvrA is not greater than three (3) times the concurrent control.
b) The negative response should be reproducible in at least one independently repeated experiment.

A test substance is considered positive if:
a) A two-fold (TA100) or more or a three-fold (TA1535, TA1537, TA98, WP2uvrA) or more increase above solvent control in the mean number of revertant colonies is observed in the test substance group.
b) In case a repeat experiment is performed when a positive response is observed in one of the tester strains, the positive response should be reproducible in at least one independently repeated experiment.
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: Precipitation of Yttrium Oxide was not observed at the start of the incubation period, however precipitation of Yttrium Oxide was observed on the plates at a concentration of 5000 μg/plate at the end of the incubation period. In addition, in tester strain WP2uvrA also precipitate was observed at 3330 μg/plate (second experiment).

RANGE-FINDING/SCREENING STUDIES:
- No toxicity or mutagenicity was observed up to and including the top dose of 5000 µg/plate

COMPARISON WITH HISTORICAL CONTROL DATA:
- The negative and strain-specific positive control values were within our laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly.

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- No toxicity or mutagenicity was observed up to and including the top dose of 5000 µg/plate
Conclusions:
In an Ames test with Salmonella typhimurium spp. and Escherichia coli performed according to OECD/EC guidelines and GLP principles, the test material was found to be non-mutagenic with or without metabolic activation.
Executive summary:

An Ames test was performed according to current OECD/EC guidelines and GLP principles with Yttrium oxide, europium-doped. All bacterial strains ( TA1535, TA1537, TA98, TA100 and WP2uvrA) showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in two independently repeated experiments with or without metabolic activation. No toxicity was noted but testing was performed up to limit concentrations, precipitation was observed on the plates at a concentration of 5000 μg/plate at the end of the incubation period. In addition in tester strain WP2uvrA also precipitate was observed at 3330 μg/plate (second experiment). The negative and strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly. Based on the results of this study it is concluded that Yttrium Oxide, Europium-Doped is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay with or withouth metabolic activation.

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in section 13.
Reason / purpose for cross-reference:
read-across source
Species / strain:
lymphocytes: from healthy donors
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Precipitation of the test item was noted in experiment I and II without and with metabolic activation in all evaluated concentrations.
In both experiments no biologically relevant increase of the aberration rates was noted after treatment with the test item without and with metabolic activation. The aberration rates of all dose groups treated with the test item were within the historical control data of the negative control

Summary: Experiment I and II, without metabolic activation

   Dose Group  Concentration [mM]  Relative mitotic Index [%] Proliferation Index  Mean % Aberrant cells incl. Gaps   Mean % Aberrant cells excl. Gaps   Historical Laboratory Negative Control Range
Experiment I 4h treatment 24h preparation interval  C  0 97 1.22  5.0  3.0  0.0 - 4.0 % aberrant cells 
   S  0 100  1.16  3.0  2.5    0.0 - 4.0 % aberrant cells 
  4 2.5  86  1.16  3.0  2.0    0.0 - 4.0 % aberrant cells 
  5.0  75  1.12  3.0  1.0    0.0 - 4.0 % aberrant cells 
  10.0  66  1.08  1.0  0.5    0.0 - 4.0 % aberrant cells 
  EMS  600 µg/mL  90  9.5 7.0    0.0 - 4.0 % aberrant cells 
Experiment II 4h treatment 24h preparation interval  0  130 1.85  2.5  0.5   0.0 - 4.0 % aberrant cells  
   S  0 100  1.82  2.0  2.0    0.0 - 4.0 % aberrant cells 
   1  0.6  98 1.81  0.5  0.5    0.0 - 4.0 % aberrant cells 
   2  1.2 88  1.72  1.0  0.0    0.0 - 4.0 % aberrant cells 
   3  2.5 83  1.74  1.0  0.5    0.0 - 4.0 % aberrant cells 
   EMS  400 µg/mL 65  11.0  9.5    0.0 - 4.0 % aberrant cells 

The mitotic index was determined in 1000 cells per culture of each test group.

The relative values of the mitotic index are related to the solvent controls.

C: negative control (Culture medium)

S: Solvent control (DMSO)

EMS: Ethylmethanesulfonate

Summary: Experiment I and II, with metabolic activation

   Dose Group  Concentration [mM]  Relative mitotic Index [%] Proliferation Index  Mean % Aberrant cells incl. Gaps   Mean % Aberrant cells excl. Gaps   Historical Laboratory Negative Control Range
Experiment I 4h treatment 24h preparation interval  C  0 113 1.18 4.0   2.0  0.0 - 4.0 % aberrant cells 
   S  0  100 1.09  3.0  1.5    0.0 - 4.0 % aberrant cells 
  4 2.5   95 1.13  1.0  0.5    0.0 - 4.0 % aberrant cells 
  5.0   79 1.22  1.5  0.0    0.0 - 4.0 % aberrant cells 
  10.0   65 1.15  1.0  0.5    0.0 - 4.0 % aberrant cells 
  EMS  5 µg/mL  101  12.5 11.5    0.0 - 4.0 % aberrant cells 
Experiment II 4h treatment 24h preparation interval  0  83 1.53  2.0  0.5   0.0 - 4.0 % aberrant cells  
   S  0  100 1.57  2.0  1.05    0.0 - 4.0 % aberrant cells 
   2  1.0  66 1.59  2.5  0.5    0.0 - 4.0 % aberrant cells 
   3 2.0   66 1.59  0.7  0.0    0.0 - 4.0 % aberrant cells 
   4  4.0  41 1.57  1.5  0.5    0.0 - 4.0 % aberrant cells 
   EMS  5 µg/mL 69  11.0 10.5    0.0 - 4.0 % aberrant cells 

The mitotic index was determined in 1000 cells per culture of each test group.

The relative values of the mitotic index are related to the solvent controls.

C: negative control (Culture medium)

S: Solvent control (DMSO)

EMS: Ethylmethanesulfonate

Conclusions:
In conclusion an in vitro chromosomal aberration test performed according to OECD/EC guidelines and GLP principles, Yttrium Oxide did not induce structural chromosomal aberrations in human lymphocyte cells. Therefore, Yttrium Oxide is considered to be non-clastogenic in this chromosome aberration test. This result is read across to Yttrium oxide, Europium-doped.
Executive summary:

A chromosome aberration assay was carried out in order to investigate a possible potential of Yttrium Oxide for its ability to induce structural chromosome aberrations in Human Lymphocytes.

The metaphases were prepared 24 h after start of treatment with the test item. The treatment interval was 4 h with and without metabolic activation (experiment I) and 4 h with and 24 h without metabolic activation (experiment II). Two parallel cultures were set up. Per culture 100 metaphases were scored for structural chromosomal aberrations (for exceptions see Tables).

The following concentrations were evaluated:

Experiment I:

Without and with metabolic activation, 4 h treatment, 24 h preparation interval:

2.5, 5.0, and 10.0 mM

Experiment II:

Without metabolic activation, 24 h treatment, 24 h preparation interval:

0.6, 1.2, and 2.5 mM

With metabolic activation, 4 h treatment, 24 h preparation interval:

1.0, 2.0, and 4.0 mM

Precipitation of the test item was noted in experiment I and II without and with metabolic activation in all evaluated concentrations.

In experiment I and II no biologically relevant decreases of proliferation index were observed.

In experiment I and II with and without metabolic activation, the number of aberrant cells found in the cultures treated with the test item did not show a biologically relevant increase compared to the corresponding negative control. In addition, no dose-response relationship was observed.

In experiment II with metabolic activation only 140 instead of 200 cells could be evaluated due to precipitation at a concentration of 2 mM. However, the assessment of genotoxicity was still possible as at the higher concentration of 4 mM 200 cells could be evaluated.

EMS (400 and 600 µg/mL, respectively) and CPA (5 µg/mL) were used as positive controls and induced distinct and biologically relevant increases in cells with structural chromosomal aberrations, thus proving the ability of the test system to indicate potential clastogenic effects.

No biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item. This result is read across to Yttrium oxide, Europium-doped.

 

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
The rationale to read across the data is attached in Section 13.
Reason / purpose for cross-reference:
read-across source
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Vehicle controls validity:
not applicable
Untreated negative controls validity:
valid
Positive controls validity:
valid

Table 1:Experiment II - Toxicity, without metabolic activation

Dose Group

Concen-tration [mM]

Cell Density [cells/mL]a

Relative Growth [%]a

Number of cells per flask

Cloning Efficiencyb

[%]

I

II

mean

NC1

0

1230000

100

138

115

127

63

NC2

1250000

140

147

144

72

1

0.00316

1320000

106.5

136

145

141

70

2

0.0100

1320000

106.5

113

128

121

60

3

0.0316

1180000

95.2

133

139

136

68

4

0.100

1130000

91.1

111

131

121

61

5

0.316

942000

76.0

114

117

116

58

6

1.0

641000

51.7

126

126

126

63

7

2.5

384000

31.0

116

122

119

60

8

5.0

194000

15.6

112

128

120

60

9

7.5

134000

10.8

108

90

99

50

EMS

300 µg/mL

832000

67.1

96

111

104

52

NC:           negative control / medium control

a:              cell density and relative growth at 1stsubcultivation

b:             mean value of cells per flask/200

EMS:        Ethylmethanesulfonate [300 µg/ml]

 

Table 2: Experiment II – Mutagenicity, without metabolic activation

Dose Group

Concen-tration [mM]

Number of mutant colonies per flaska

Mean

SD

Mutant colonies per 106cellsb

Mutation factor

I

II

III

IV

V

NC1

0

2

3

4

6

11

5.2

3.19

20.55

NC2

7

7

10

10

12

9.2

1.94

32.06

1

0.00316

11

12

15

11

17

13.2

2.40

46.98

1.79

2

0.0100

9

10

10

12

13

10.8

1.47

44.81

1.70

3

0.0316

5

7

8

8

8

7.2

1.17

26.47

1.01

4

0.100

4

7

5

9

12

7.4

2.87

30.58

1.16

5

0.316

2

3

4

5

8

4.4

2.06

19.05

0.72

6

1.0

4

6

9

9

11

7.8

2.48

30.95

1.18

7

2.5

1

5

5

6

7

4.8

2.04

20.17

0.77

8

5.0

0

1

2

4

4

2.2

1.60

9.17

0.35

9

7.5

0

3

5

5

5

3.6

1.96

18.18

0.69

EMS

300 µg/mL

211

191

187

181

186

191.2

10.40

923.67

35.11

NC:           negative control / medium control

a:               number of mutant colonies in flask I to V

b:              mean mutant colonies x 106/ (400000 x Cloning Efficiency/100)

EMS:        Ethylmethanesulfonate [300 µg/ml]

Table 3: Experiment II - Toxicity, with metabolic activation

Dose Group

Concen-tration [mM]

Cell Density [cells/mL]a

Relative Growth [%]a

Number of cells per flask

Cloning Efficiencyb

[%]

I

II

mean

NC1

0

865000

100

129

143

136

68

NC2

932000

138

149

144

72

1

0.025

801000

89.1

110

140

125

63

2

0.05

859000

95.6

135

145

140

70

3

0.1

787000

87.6

134

151

143

71

4

0.2

795000

88.5

154

168

161

81

5

0.4

751000

83.6

128

140

134

67

6

0.8

739000

82.2

146

152

149

75

7

1.6

869000

96.7

113

124

119

59

8

3.2

825000

91.8

116

122

119

60

9

6.4

759000

84.5

147

150

149

74

10

10

712000

79.2

145

150

148

74

DMBA

1.0 µg/mL

547000

60.9

126

136

131

66

DMBA

1.5 µg/mL

398000

44.3

104

120

112

56

NC:           negative control / medium control

a:              cell density and relative growth at 1stsubcultivation

b:             mean value of cells per flask/200

DMBA:    7,12-Dimethylbenz(a)anthracene

 

Table 4: Experiment II – Mutagenicity, with metabolic activation

Dose Group

Concen-tration [mM]

Number of mutant colonies per flaska

Mean

SD

Mutant colonies per 106cellsb

Mutation factor

I

II

III

IV

V

NC1

0

3

3

5

7

9

5.4

2.33

19.85

NC2

6

7

8

8

13

8.4

2.42

29.27

1

0.025

0

1

3

5

5

2.8

2.04

11.20

0.46

2

0.05

3

6

8

8

13

7.6

3.26

27.14

1.11

3

0.1

1

3

3

7

9

4.6

2.94

16.14

0.66

4

0.2

3

5

6

9

10

6.6

2.58

20.50

0.83

5

0.4

0

1

1

2

3

1.4

1.02

5.22

0.21

6

0.8

1

1

3

5

4

2.8

1.60

9.40

0.38

7

1.6

0

1

2

3

4

2.0

1.41

8.44

0.34

8

3.2

0

2

7

10

12

6.2

4.58

26.05

1.06

9

6.4

4

7

8

9

10

7.6

2.06

25.59

1.04

10

10

2

5

7

7

7

5.6

1.96

18.98

0.77

DMBA

1.0 µg/mL

78

91

94

75

106

88.8

11.27

338.93

13.80

DMBA

1.5 µg/mL

108

137

121

121

104

118.2

11.62

527.68

21.48

NC:           negative control / medium control

a:               number of mutant colonies in flask I to V

b:                mean mutant colonies x 106/ (400000 x Cloning Efficiency/100)

DMBA:    7,12-Dimethylbenz(a)anthracene

Conclusions:
Based on an in vitro cell gene mutagenicity test performed according to OECD guideline and GLP principles, Yttrium Oxide was found to be non-mutagenic in the HPRT locus using V79 cells of the chinese hamster. This result is read across to Yttrium oxide, Europium-doped.

Executive summary:

The test item Yttrium Oxide was assessed for its potential to induce gene mutations at the HPRT locus using V79 cells of the Chinese hamster. The main experiments were carried out without and with metabolic activation.

In experiment I: (with and without metabolic activation) 10 mM was selected as the highest concentrations.

In experiment II : 7.5 mM (without metabolic activation) and 10 mM (with metabolic activation) were selected as the highest concentrations.

Most of the experiments were performed as 4h short-time exposure only experiment II was performed as 20 h long time exposure assay (without metabolic activation).

Precipitation: Precipitation of the test item was noted in the whole experiment I at concentrations of 1.0 mM and higher and in experiment II at concentrations of 1.0 mM and higher (without metabolic activation) and at concentrations of 0.8 mM and higher (with metabolic activation).

Toxicity (Experiment II results presented in Table 1 and 3): A biologically relevant growth inhibition (reduction of relative growth below 70%) was observed after the treatment with the test item in experiment I and II without metabolic activation. In experiment I without metabolic activation the relative growth was 41.6% for the highest concentration (10 mM) evaluated. The highest biologically relevant concentration evaluated wit hmetabolic activation was 10 mM with a relative growth of 90.0%. In experiment IIwithoutmetabolic activation the relative growth was 10.8% for the highest concentration (7.5 mM) evaluated. The highest concentration evaluatedwithmetabolic activation was 10 mM with a relative growth of 79.2%.

 

 Mutagenicity (Experiment II results presented in Table 2 and 4): In experiment I without metabolic activation most mutant values of the negative controls andtest item concentrations found were within the historical control data of the lanoratory test facility (about 1-39 mutants per 106cells). No dose-response relationship could be observed. The mutation frequencies found in the groups treated with the test item did not show a biologically relevant increase as compared to the negative controls. The highest mutation rate (compared to the negative control values) of 1.58 was found at a concentration of 5.0 mM with a relative growth of 60.7%.With metabolic activation all mutant values of the negative controls, andtest item concentrations found were within the historical control data of the laboratory test facility (about 2-39 mutants per 106cells). No dose-response relationship could be observed. The mutation frequencies found in the groups treated with the test item did not show a biologically relevant increase as compared to the negativecontrols.The highest mutation rate (compared to the negative control values) of 1.12 was found at a concentration of 0.100 mM with a relative growth of 96.7%.

In experiment II without metabolic activation most mutant values of the negative controls andtest item concentrations found were within the historical control data of the laboratory test facility (about 1-39 mutants per 106cells). No dose-response relationship could be observed. The mutation frequencies found in the groups treated with the test item did not show a biologically relevant increase as compared to the negative controls. The highest mutation rate (compared to the negative control values) of 1.79 was found at a concentration of 0.00316 mM with a relative growth of 106.5%.

In experiment II with metabolic activationall mutant values of the negative controls and test item concentrations found were within the historical control data of the laboratory test facility (about 2-39 mutants per 106cells). No dose-response relationship could be observed. The mutation frequencies found in the groups treated with the test item did not show a biologically relevant increase as compared to the negativecontrols.The highest mutation rate (compared to the negative control values) of 1.11 was found at a concentration of 0.05 mM with a relative growth of 95.6%.

This result is read across to Yttrium oxide, Europium-doped.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An Ames test was performed according to current OECD/EC guidelines and GLP principles with Yttrium oxide, europium-doped. All bacterial strains (TA1535, TA1537, TA98, TA100 and WP2uvrA) showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in two independently repeated experiments with or without metabolic activation. No toxicity was noted but testing was performed up to limit concentrations, precipitation was observed on the plates at a concentration of 5000 μg/plate at the end of the incubation period. In addition in tester strain WP2uvrA also precipitate was observed at 3330 μg/plate (second experiment). The negative and strain-specific positive control values were within the laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly. Based on the results of this study it is concluded that Yttrium Oxide, Europium-Doped is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay with or without metabolic activation.

No further studies with yttrium oxide, europium doped are available. However, studies with yttrium oxide are present. The justification for this analogue approach is described in a report (see section 13 of IUCLID).

Substance analogue yttrium oxide was tested for its potential to induce gene mutations at the HPRT locus using V79 cells of the Chinese hamster. The main experiments were carried out without and with metabolic activation. In experiment I, 10 mM (with and without metabolic activation) was selected as the highest concentration, while in experiment II, 7.5 mM (without metabolic activation) and 10 mM (with metabolic activation) were selected as the highest concentrations. Most of the experiments were performed as 4h short-time exposure only experiment II was performed as 20 h long time exposure assay (without metabolic activation). Precipitation was observed in both experiments. In addition, toxicity was observed. The mutation frequencies found in the groups treated with the test substance did not show a biologically relevant increase with and without metabolic activation as compared to the negative controls. Therefore, the substance is considered to be non-mutagenic in this study.

Furthermore, a chromosome aberration assay was carried out in order to investigate a possible potential of yttrium oxide for its ability to induce structural chromosome aberrations in human lymphocytes. The metaphases were prepared 24 h after start of treatment with the test item. The treatment interval was 4 h with and without metabolic activation (experiment I) and 4 h with and 24 h without metabolic activation (experiment II). Two parallel cultures were set up. Per culture 100 metaphases were scored for structural chromosomal aberrations. Precipitation of the test item was noted in experiment I and II without and with metabolic activation in all evaluated concentrations. In experiment I and II no biologically relevant decreases of proliferation index were observed. In experiment I and II with and without metabolic activation, the number of aberrant cells found in the cultures treated with the test item did not show a biologically relevant increase compared to the corresponding negative control. In addition, no dose-response relationship was observed.

Based on the positive and negative controls, it was concluded that the test system functioned properly. No biologically relevant increase in the frequencies of polyploid cells was found after treatment with the test item.

Taken all data together, it was concluded that there is sufficient data to fill this endpoint and that there are no indications that yttrium oxide, europium-doped has genotoxic properties.

 

Justification for classification or non-classification

Based on the available information, yttrium oxide, europium doped is not classified for mutagenicity according to CLP Regulation (EC) No. 1272/2008 including its amendments.