2-Naphthalenecarboxylic acid, 6-[[[4-[(1-oxo-2-propen-1-yl)oxy]butoxy]carbonyl]oxy]-

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The analogue substance is mutagenic in the Ames test.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study, available as unpublished report, Test itm purity less than 80%., fully adequate for assessment.

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

, only one positive control used to test efficacy of the S9-mix.

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Deviations:

yes

Remarks:

, only one positive control used to test efficacy of the S9-mix.

GLP compliance:

yes (incl. QA statement)

Remarks:

Experimental Toxicology and Ecology, BASF Aktiengesellschaft, 67056 Ludwigshafen/Rhein, Germany

Type of assay:

bacterial reverse mutation assay

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:

Male S.D. rats liver S9, induced by Aroclor 1254

Test concentrations with justification for top dose:

- 1st experiment: 0, 20, 100, 500, 2500 and 5000 µg/plate
- 2nd experiment (TA 1535): 0, 4, 20, 100, 500, and 1000 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Due to the Iimited solubility of the test substance in water, DMSO was selected as the vehicle, which had been demonstrated to be suitable in bacterial reverse mutation tests and for which historical control data are available.

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

2.5 µg/plate, dissolved in DMSO (60 µg/plate for Escherichia coli WP2 uvrA)

Positive control substance:

other: 2-aminoanthracene (2-AA)

Remarks:

With metabolic activation for all strains

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

5 µg/plate, dissolved inDMSO

Positive control substance:

other: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)

Remarks:

Without metabolic activation for strains TA 1535 and TA 100

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

10 µg/plate, dissolved in DMSO

Positive control substance:

other: 4-nitro-o-phenylendiamine (NOPD)

Remarks:

Without metabolic activation for strain TA 98

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

100 µg/plate, dissolved in DMSO

Positive control substance:

9-aminoacridine

Remarks:

Without metabolic activation for strain TA 1537

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Remarks:

5 µg/plate, dissolved in DMSO

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

Without metabolic activation for strain E. coli WP2 uvrA

Details on test system and experimental conditions:

EXPERIMENT 1 (TA 1535, TA 100, TA 1537, TA 98, E. coli WP2 uvrA) and 2 (TA 1535)
- METHOD OF APPLICATION: in agar (plate incorporation)
- DURATION: Exposure duration: 48 -72 h
- NUMBER OF REPLICATIONS: 3 test plates per dose or per control
- DETERMINATION OF CYTOTOXICITY: reduced his- or trp- background growth, decrease in the number of revertants, reduction in the titer

Evaluation criteria:

The test chemical is considered positive in this assay if the following criteria are met:
- A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one tester strain either without S-9 mix or after adding a metabolizing system.
A test substance is generally considered nonmutagenic in this test if:
- The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in two experiments carried out independently of each other.

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

from about 20 µg/plate (factor 1.9 - 2.3) onward with an increase in the number of his+ revertants by a factor of 72.1 at 5000 µg/plate.

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

positive

Remarks:

Slight increase in the number of revertant colonies from about 100 - 500 µg (factor 1.5 - 4.5) onward with a maximum response at 2500 µg/plate (factor 8.8).

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

bacteria, other: S. typhimurium TA 1537, TA 98; E. coli WP2 uvra

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TOXICITY:
- A bacterio-toxic effect (reduced his- or trp- background growth, decrease in the number of revertants, reduction in the titer) was observed depending on the strain and test conditions from about 2500 µg/plate onward.

SOLUBILITY
- No test substance precipitation was found

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
positive with metabolic activation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vitro:

The analogue was tested with a crude sample obtained during production and showed a clear dose-dependent increase in the number of revertants in a number of strains. In theory it is possible that this was caused by the major side product. However, there is a mechanistic alert for DNA binding reactivity for the main component.