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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
Sunflower oil, ester with sorbitol
EC Number:
306-248-9
EC Name:
Sunflower oil, ester with sorbitol
Cas Number:
96690-53-8
IUPAC Name:
Sunflower oil, ester with sorbitol
Test material form:
liquid
Details on test material:
Batch Number: P08/002
Expiry Date: 2010-03-01
Stability of Polyethyleneglycol: stable for hours

Method

Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
Phenobarbital/ß-Naphtholflavone induced rat liver S9
Test concentrations with justification for top dose:
In preliminary cytoxicity test, no significant cytotoxicity was found. Therefore the main studies (Exp I and Exp II) were performed up to the dose of 5000 µg/plate.
Vehicle / solvent:
DMSO was used
Controls
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
other: see the additional information

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535
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
Key result
Species / strain:
S. typhimurium TA 1537
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
Key result
Species / strain:
S. typhimurium TA 98
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
Key result
Species / strain:
S. typhimurium 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
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

Table: Summary of Results_Experiment I

 

Metabolic

Activation

Test

Group

Dose Level

(µg/plate)

Revertant Colony Counts (Mean ±SD)

 

 

 

 

TA 1535

TA 1537

TA 98

TA 100

WP2 uvrA

 

Without metabolic

Activation

DMSO

 

22 ± 2B M

14 ± 2

27 ± 4

114 ± 15

45 ± 6

Untreated

 

23 ± 5B M

10 ± 3

36 ± 3

115 ± 13

47 ± 1

Hostacerin SFO

3µg

24 ± 1B M S

14 ± 5

32 ± 9

114 ± 14

44 ± 5

10µg

21 ± 4B M

11 ± 2

31 ± 3

112 ± 7

47 ± 9

33µg

20 ± 4B M

12 ± 4

34 ± 6

112 ± 7

43 ± 7

100µg

20 ± 5B M

8 ± 2

33 ± 7

113 ± 7

45 ± 7

333µg

22 ± 4B M

11 ± 2

35 ± 7

110 ± 8

41 ± 4

1000µg

18 ± 3P B M

9 ± 2P

32 ± 3P

108 ± 7P

38 ± 3P

2500µg

17 ± 5P B M

11 ± 3P

30 ± 0P

109 ± 10P

50 ± 2P

5000µg

14 ± 2P B M

12 ± 3P

25 ± 1P M

113 ± 7P

38 ± 6P M

NaN3

10 µg

3126 ± 67

 

 

2708 ± 167

 

4-NOPD

10 µg

 

 

516 ± 22

 

 

4-NOPD

50 µg

 

99 ± 6

 

 

 

MMS

3.0 µg

 

 

 

 

917 ± 65

 

With metabolic activation

DMSO

 

26 ± 3B M

25 ± 5

47 ± 3

104 ± 7

66 ± 12

Untreated

 

28 ± 3B M

27 ± 1

43 ± 4

118 ± 10

50 ± 9

Hostacerin SFO

3µg

23 ± 4B M

21 ± 4

44 ± 7

111 ± 5

61 ± 10

10µg

23 ± 4B M

26 ± 1

41 ± 6

114 ± 4

61 ± 8

33µg

24 ± 3B M

22 ± 5

41 ± 4

110 ± 5

60 ± 5

100µg

21 ± 3B M

19 ± 2

46 ± 5

110 ± 15

50 ± 14

333µg

23 ± 4B M

20 ± 0

44 ± 1

112 ± 4

53 ± 2

1000µg

17 ± 1P B M

21 ± 8P

45 ± 6P

99 ± 1P

52 ± 4P

2500µg

19 ± 1P B M

21 ± 7P

43 ± 13P

101 ± 1P

56 ± 2P

5000µg

19 ± 3P B M

18 ± 3P

30 ± 4P M

94 ± 5P M

45 ± 1P M

2-AA

2.5 µg

224 ± 14

150 ± 14

1633 ± 69

1096 ± 96

 

2-AA

10.0 µg

 

 

 

 

359 ± 15

NaN3: sodium azide

2-AA: 2-aminoanthracene

4-NOPD: 4-nitro-o-phenylene-diamine

MMS: methyl methane sulfonate

P: Precipitate

MB: Manual count

B: Extensive bacterial growth

Table: Summary of Results_Experiment II

 

Metabolic

Activation

Test

Group

Dose Level

(µg/plate)

Revertant Colony Counts (Mean ±SD)

 

 

 

 

TA 1535

TA 1537

TA 98

TA 100

WP2 uvrA

 

Without metabolic

Activation

DMSO

 

39 ± 2

13 ± 4

28 ± 6

130 ± 15

47 ± 16

Untreated

 

39 ± 1

20 ± 2

25 ± 2

153 ± 12

47 ± 4

Hostacerin SFO

33µg

38 ± 5

10 ± 1

29 ± 8

123 ± 10

48 ± 4

100µg

32 ± 2

12 ± 1

24 ± 4

122 ± 14

48 ± 9

333µg

38 ± 2

11 ± 3

26 ± 8

129 ± 10

56 ± 5

1000µg

31 ± 4P

12 ± 6P

23 ± 1P

108 ± 10P R

52 ± 6P

2500µg

25 ± 7P

7 ± 1P R

25 ± 7P

91 ± 14P R

43 ± 3P

5000µg

15 ± 2M R P

7 ± 2P M R

7 ± 1P M R

76 ± 6P M R

31 ± 7P M R

NaN3

10 µg

2642 ± 177

 

 

2794 ± 49

 

4-NOPD

10 µg

 

 

615 ± 42

 

 

4-NOPD

50 µg

 

140 ± 6

 

 

 

MMS

3.0 µg

 

 

 

 

355 ± 143

 

With metabolic activation

DMSO

 

33 ± 6

18 ± 6

43 ± 5

134 ± 15

56 ± 8

Untreated

 

33 ± 7

20 ± 5

43 ± 8

157 ± 10

47 ± 9

Hostacerin SFO

33µg

35 ± 11

17 ± 4

40 ± 8

139 ± 15

59 ± 5

100µg

34 ± 11

18 ± 9

44 ± 8

136 ± 3

62 ± 6

333µg

30 ± 7

20 ± 8

40 ± 8

133 ± 10

51 ± 10

1000µg

35 ± 1P

18 ± 4P

43 ± 8P

130 ± 21P

64 ± 6P

2500µg

20 ± 4P R

11 ± 2P M R

38 ± 8P

95 ± 2P R

48 ± 6P M

5000µg

19 ± 3P M R

5 ± 3P M R

14 ± 3P M R

40 ± 2P M R

40 ± 8P M R

2-AA

2.5 µg

276 ± 8

209 ± 5

1872 ± 143

2337 ± 376

 

2-AA

10.0 µg

 

 

 

 

243 ± 1

NaN3: sodium azide

2-AA: 2-aminoanthracene

4-NOPD: 4-nitro-o-phenylene-diamine

MMS: methyl methane sulfonate

P: Precipitate

R: Reduced background count

MB: Manual count

Applicant's summary and conclusion

Conclusions:
The genotoxicity of the registration substance was investigated in bacterial reverse muation test (Ames test) according to the Guideline OECD 471. No mutagenicity was found.
Executive summary:

The genotoxicity of the registration substance was investigated in bacterial reverse muation test (Ames test) according to the Guideline OECD 471. using TA 1535, TA 1537, TA 98, TA 100 and WP2 uvrA as test systems. At concentrations 1000 µg/plate and above precipitation occured. Up to the highest concentration of 5000 µg/plate no cytoxicity and no mutagenicity was found.