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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May-July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline conformant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
Name of test substance: Octadecanoic acid, sulfo-, potassium salt
CAS No.: 67968-63-2
Test substance No.: 14/0449-1
Batch identification: 0012127444
Purity: 51.92% (project No. 14L00285)
Homogeneity: given (visually)
Date of production: 23 Jun 2014
Storage conditions: room temperature

Method

Target gene:
hypoxanthine-guanine phosphoribosyl transferase (HGPRT)
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
rat liver S9 mix induced by phnobarbital i.p. and b-naphthoflavone orally
Test concentrations with justification for top dose:
1st experiment with and without S9 mix: 10.9 (only with S9), 21.9, 43.8, 87.5, 175.0, 350.0, 700.0 (only without S9) ug/mL
2nd experiment with and without S9 mix: 12.5 (only with S9), 25.0, 50.0, 100.0, 200.0, 400.0, 800.0 (only without S9) ug/mL
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ham´s F12
- Justification for choice of solvent/vehicle: Due to the good solubility of the test substance in water, the aqueous culture medium (Ham's
F12) was selected as vehicle, which has been demonstrated to be suitable in the CHO/HPRT assay and for which historical control data are available.
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Remarks:
without metabolic activation: EMS; with metabolic activation: DMBA
Positive control substance:
7,12-dimethylbenzanthracene
ethylmethanesulphonate
Evaluation criteria:
relative and absolute cloning efficiency, mutant frequency

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
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
Untreated negative controls validity:
not applicable
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

1st experiment (without S9 mix):

Test groups (ug/mL)

Mutant frequency (per 106cells)

Uncorrected

Corrected

Vehicle control

2.50

3.16

21.9

n.c.

43.8

0.28

0.30

87.5

5.00

5.66

175.0

1.11

1.33

350.0

1.39

1.82

700.0

n.c.

EMS

85.56

119.59

 

1st experiment (with S9 mix):

Test groups (ug/mL)

Mutant frequency (per 106cells)

Uncorrected

Corrected

Vehicle control

0.28

0.30

10.9

n.c.

21.9

1.11

1.40

43.8

2.50

3.15

87.5

0.28

0.36

175.0

0.00

0.00

350.0

n.c.

DMBA

203.89

334.53

 

2nd experiment (without S9 mix):

Test groups (ug/mL)

Mutant frequency (per 106cells)

Uncorrected

Corrected

Vehicle control

5.28

5.97

25

2.50 2.76

50

3.89

4.75

100

4.72

5.81

200

1.67

2.32

400

nc

nc

EMS

82.22

102.64

 

2nd experiment (with S9 mix):

Test groups (ug/mL)

Mutant frequency (per 106cells)

Uncorrected

Corrected

Vehicle control

3.33

3.49

12.5

n.c.

25

0.28

0.29

50

3.33

4.00

100

2.50

3.04

200

0.56

0.64

DMBA

86.39

107.87

 

n.c. = culture was not continued since a minimum of only four analyzable concentrations is required

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The substance Octadecanoic acid, sulfo-, potassium salt was assessed for its potential to induce gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in Chinese hamster ovary (CHO) cells in vitro. Two independent experiments were carried out, both with and without the addition of liver S9 mix from phenobarbital- and β-naphthoflavone induced rats (exogenous metabolic activation).

Based on the results of the present study, the test substance did not cause any dosedependent increase in the mutant frequencies both without S9 mix and after the addition of a metabolizing system in two experiments performed independently of each other. Thus, under the experimental conditions of this study, the test substance Octadecanoic acid, sulfo-, potassium salt is not mutagenic in the HPRT locus assay under in vitro conditions in CHO cells in the absence and the presence of metabolic activation.