1,3,5-Benzenetricarboxylic acid, copper(2+) salt (2:3)

Endpoint summary

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		2500^P	0.9
		1000^B	0.2		5000^BP	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		2500^BP	0.3
		1000^B	0.6		5000^BP	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		2500^BP	0.0
		1000^B	0.2		5000^BP	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		2500^BP	0.4
		1000^B	0.1		5000^BP	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		2500^BP	0.5
		1000^B	0.1		5000^BP	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		1000^P	1.7
		333	0.3		2500^P	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		1000^P	1.2
		333	0.8		2500^P	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		1000^P	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		1000^P	0.6
		333	0.5		2500^P	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		1000^P	1.6
		333	0.3		2500^P	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.