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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No mutagenic activity was detected in bacteria with BVE.

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with minor restrictions (no data about historical negative control [but number of revertants within literature range])
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Remarks:
(BASF AG, Department of Toxicology)
Type of assay:
bacterial reverse mutation assay
Target gene:
His- and Trp-
Species / strain / cell type:
bacteria, other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2uvrA
Metabolic activation:
with and without
Metabolic activation system:
S9-mix; S9-fraction from Aroclor 1254-induced (i.p. 500 mg/kg bw 5 days prior to sacrifice) male Sprague-Dawley rat liver
Test concentrations with justification for top dose:
0; 20; 100; 500; 2500 and 5000 µg/plate in 1) the standard plate test and 2) in the preincubation assay
Vehicle / solvent:
DMSO
Negative solvent / vehicle controls:
yes
Remarks:
plus sterility control
Positive controls:
yes
Positive control substance:
other: With S9: 2.5 µg/plate 2-aminoanthracene (all tester strains of S.typhimurium) and 60 µg/plate of this substance for E. coli. Without metabolic activation (MA) see remarks
Remarks:
Without MA: 5 µg/plate N-methyl-N'-nitro-N-nitrosoguanidine in TA 100 and TA 1535; 10 µg/plate 4-nitro-o-phenylendiamine in TA 98; 100 µg/plate 9-aminoacridine in TA 1537; 10 µg/plate N-ethyl-N'-nitro-N-nitrosoguanidin in E. coli WP2uvrA
Details on test system and experimental conditions:
Standard plate test (1st experiment) and preincubation assay (2nd experiment) with and without metabolic activation (MA), triplicate plates.
Evaluation criteria:
(i) doubling of the spontaneous mutation rate, (ii) dose-response relationship, (iii) reproducibility of results
Statistics:
means +- standard deviation of 3 test plates per dose or per control
Species / strain:
bacteria, other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2uvrA
Metabolic activation:
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:
bacteria, other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2uvrA
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(at >= 2500 µg/plate; details in remarks on results)
Vehicle controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Only in strains tested with MA in the preincubation assay cytotoxic effects were detected, however, authors tested up to the limit dose recommended in OECD TG471 (5 mg/plate).

Ames test with BVE
Standard plate test

Dose level in µg/plate

TA1535

TA100

TA1537

TA98

E. coli WP2uvrA

-

Without metabolic activation

Vehicle control

19+-1

126+-11

9+-2

33+-6

33+-4

20

21+-6

121+-14

9+-2

36+-3

33+-4

100

20+-4

128+-9

8+-5

32+-3

25+-4

500

13+-2

115+-10

7+-1

31+-7

26+-4

2500

15+-2

105+-8

4+-1

33+-4

29+-4

5000

19+-6

100+-10

4+-2

32+-4

33+-4

Positive control

760+-106

1252+-141

715+-22

958+-27

651+-46

-

With metabolic activation

Vehicle control

19+-2

136+-21

11+-3

40+-4

43+-4

20

17+-2

112+-17

11+-2

34+-5

38+-3

100

16+-3

105+-7

11+-1

48+-2

35+-2

500

19+-1

102+-11

10+-3

44+-3

32+-7

2500

11+-3

96+-3

5+-1

46+-5

23+-6

5000

5+-2

83+-6

4+-3

25+-5

13+-2

Positive control

114+-11

905+-77

114+-6

1182+-76

206+-13

Mean revertants +- standard deviation of 3 plates

Ames test with BVE
Preincubation assay

Dose level in µg/plate

TA1535

TA100

TA1537

TA98

E. coli WP2uvrA

-

Without metabolic activation

Vehicle control

19+-2

106+-8

9+-2

26+-3

42+-10

20

18+-2

117+-6

8+-2

26+-6

42+-8

100

18+-2

104+-9

12+-4

22+-1

41+-10

500

16+-1

97+-9

9+-2

24+-4

34+-7

2500

15+-1

83+-8

11+-4

25+-3

37+-10

5000

15+-3

87+-12

10+-2

26+-4

41+-5

Positive control

1296+-74

943+-33

746+-71

1305+-30

825+-50

-

With metabolic activation

Vehicle control

19+-1

108+-12

10+-2

32+-3

33+-4

20

19+-1

118+-4

8+-4

28+-3

27+-5

100

17+-5

104+-7

9+-4

25+-3

28+-6

500

14+-2

110+-3

5+-3

21+-3

26+-7

2500

10+-1

102+-18

6+-1T

25+-5

25+-4T

5000

7+-2

86+-2T

6+-0T

22+-3T

23+-3T

Positive control

129+-6

1360+-62

124+-3

1002+-9

177+-5

Mean revertants +- standard deviation of 3 plates

T: reduced background lawn

 

 

Conclusions:
Interpretation of results (migrated information):
negative

BVE gave negative results in the standard plate test and the preincubation assay according to OECD Guideline 471 in S. typhimurium TA1535, TA100, TA1537, TA98 and E. coli WP2uvrA both in the absence and in the presence of a metabolic activation system at concentrations up to 5000 µg/plate.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Key Ames Test (Butylvinylether)

BVE gave negative results in the standard plate test and the preincubation assay according to OECD Guideline 471 in S. typhimurium TA1535, TA100, TA1537, TA98 and E. coli WP2uvrA both in the absence and in the presence of a metabolic activation system at concentrations up to 5000 µg/plate (BASF 1998).

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available study is considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered not to be classified under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation No 605/2014.

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