Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
Ames test (OECD 471, BASF SE, 2016): negative
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- and GLP-conformant study
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes (incl. QA statement)
Remarks:
testing lab.
Type of assay:
bacterial reverse mutation assay
Target gene:
histidine operon (S. typhimurium) and tryptophan operon (E. coli)
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:
phenobarbital/b-naphthoflavone-induced rat liver S9 fraction
Test concentrations with justification for top dose:
Experiment 1 (standard plate test): 0, 33, 100, 333, 1000, 2500, 5000 µg/plate
Experiment 2 (standard plate test): 0, 3.3, 10, 33, 100, 333, 1000 µg/plate
Experiment 3 (preincubation test): 0, 1.0, 3.3, 10, 33, 100, 333 (all strains without S9 mix) // 0, 3.3, 10, 33, 100, 333, 1000 µg/plate (TA 1537 with S9) // 0, 10, 33, 100, 333, 1000, 2500 µg/plate (TA 1535, TA 100, TA 98 and E. coli WP2 uvrA with S9 mix)
Experiment 4 (preincubation test): 0, 3.3, 10, 33, 100, 333 and 1000 µg/plate (TA 100 with and without S9 mix)
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Remarks:
sterility controls
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
9-aminoacridine
N-ethyl-N-nitro-N-nitrosoguanidine
other: 4-nitro-o-phenylenediamine (without S9 mix), 2-aminoanthracene (with S9 mix)
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:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
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'.

A bacteriotoxic effect of the test substance was observed in the standard plate test and in the preincubation assay in E. coli from 100 µg/plate onward. Bacteriotoxicity towards S. typhimurium was observed in the standard plate test and the preincubation assay depending on strain and test conditions from 333 µg/plate onward.

Test substance was found to precipitate depending on the test conditions from 1000 µg/plate onward, independent of the presence or absence of S9 mix.

The first standard plate test conducted without S9 mix was repeated with lower concentrations due to bactericidal effects of the test substance at higher doses.

Results from the standard plate test:

 

without metabolic activation

with metabolic activation

Strain

Test group

Dose (µg/plate)

Factor*

Test group

Dose

(µg/plate)

Factor*

TA 1535

Test substance

3.3

0.7

Test substance

33

0.7

10

0.7

100

1.2

33

0.6

333

1.0

100

0.7

1000

1.1

333

0.5

2500P

0.9

1000B

0.2

5000BP

0.4

MNNG

5.0

288.6

2-AA

2.5

17.3

TA 100

Test substance

3.3

1.2

Test substance

33

0.9

10

1.1

100

0.8

33

1.2

333

0.9

100

1.1

1000

0.8

333

1.1

2500BP

0.3

1000B

0.6

5000BP

0.2

MNNG

5.0

47.7

2-AA

2.5

12.0

TA 1537

Test substance

3.3

0.8

Test substance

33

1.1

10

0.9

100

1.0

33

0.7

333

0.5

100

0.9

1000

0.5

333

0.7

2500BP

0.0

1000B

0.2

5000BP

0.0

AAC

100

94.2

2-AA

2.5

14.8

TA 98

Test substance

3.3

0.9

Test substance

33

1.1

10

0.9

100

0.9

33

0.6

333

1.1

100

0.8

1000

0.7

333

0.6

2500BP

0.4

1000B

0.1

5000BP

0.0

NOPD

10

28.6

2-AA

2.5

72.6

E. coli

Test substance

3.3

1.1

Test substance

33

0.9

10

0.9

100

0.7

33

0.8

333

0.9

100

0.5

1000

0.8

333

0.5

2500BP

0.5

1000B

0.1

5000BP

0.0

4-NQO

5.0

55.1

2-AA

60

4.0

Results from the preincubation test:

 

without metabolic activation

with metabolic activation

Strain

Test group

Dose (µg/plate)

Factor*

Test group

Dose

(µg/plate)

Factor*

TA 1535

Test substance

1.0

1.0

Test substance

10

1.1

3.3

0.9

33

0.9

10

0.9

100

1.2

33

0.9

333

1.2

100

1.2

1000P

1.7

333

0.3

2500P

0.5

MNNG

5.0

324.6

2-AA

2.5

23.2

TA 100

Test substance

1.0

1.1

Test substance

10

1.0

3.3

1.1

33

1.0

10

1.1

100

1.0

33

1.3

333

1.1

100

1.1

1000P

1.2

333

0.8

2500P

0.9

MNNG

5.0

35.8

2-AA

2.5

22.3

TA 1537

Test substance

1.0

1.1

Test substance

3.3

0.9

3.3

0.9

10

1.3

10

1.3

33

1.2

33

0.8

100

0.8

100

1.1

333

0.5

333

0.6

1000P

0.4

AAC

100

122.0

2-AA

2.5

12.3

TA 98

Test substance

1.0

1.1

Test substance

10

0.9

3.3

0.8

33

1.1

10

0.8

100

0.8

33

0.7

333

0.8

100

1.1

1000P

0.6

333

0.5

2500P

0.6

NOPD

10

22.5

2-AA

2.5

85.1

E. coli

Test substance

1.0

0.8

Test substance

10

1.3

3.3

0.9

33

1.3

10

0.8

100

1.2

33

1.0

333

1.6

100

0.6

1000P

1.6

333

0.3

2500P

0.4

4-NQO

5.0

32.5

2-AA

60

4.6

 

* Factor, mean revertants per plate (test substance)/mean revertants per plate (control)

BBactericidal effects observed

PPrecipitation observed

MNNG, N-methyl-N’-nitro-N-nitrosoguanidine

AAC, 9-aminocridine

NOPD, 4-nitro-o-phenylenediamine

4-NQO, 4-nitroquinoline-N-oxide

2-AA, 2-aminoanthracene

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

Additional information

Additional information from genetic toxicity in vitro:

Ames test was conducted as standard plate test and preincubation test, testing up to bacteriotoxic concentrations did not lead to increased number of revertant colonies either in the absence or presence of metabolic activation.


Justification for selection of genetic toxicity endpoint
GLP- and guideline-conformant study

Justification for classification or non-classification

Since 1,3,5 -Benzenetricarboxylic acid was not mutagenic in the bacterial reverse mutation test, non-classification is warranted.