1H-Indole-6-carboxylic acid, 1-(2-chloroacetyl)-2,3-dihydro-3-(methoxyphenylmethylene)-2-oxo-, methyl ester, (3E)-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 August - 1 December 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 471) and in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

PD 283 XX

IUPAC Name:

PD 283 XX

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report): PD 283 XX
- Physical state: yellow solid substance
- Analytical purity: 99.1 %
- Purity test date: 24 august 2011 (date of release)
- Purity to be retested: february 2014
- Lot/batch No.: 0002
- Storage condition of test material: Room temperature in the dark (ambient humidity)

Method

Target gene:

TA 1537 hisC3076 rfa uvrB - Frameshift
TA 98 hisD3052 rfa uvrB pKM101 Frameshift
TA 100 hisG46 rfa uvrB pKM101 Base substitution
TA 1535 hisG46 rfa uvrB - Base substitution
TA 102 hisG428 rfa + pKM101, pAQ1 Base substitution

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

10, 30, 100, 300, 600 µg/plate of test substance

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-acetylaminofluorene

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

other: 2-aminofluorene

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate test and the preincubation method were used

DURATION
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 3 per concentration

Evaluation criteria:

The assessment and interpretation of the results follows the OECD Guideline No. 471, i. e. a concentration-dependent increase in the number of revertants of at least one tester strain over the vehicle control value and/or outside the historical control range is indicative of genotoxic activity.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no 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'.

Any other information on results incl. tables

SOLUBILITY AND CYTOTOXICITY

PD 283 XX precipitated at concentrations higher than or equal to 300 μg/plate using the plate

test and preincubation method with S9 mix. Precipitation was observed starting at 30 μg/plate

using the preincubation method in absence of S9 mix and at 10 μg/plate in a repeat

experiment using the strain TA 1537 in absence of S9 mix. No bacteriotoxicity was observed

up to the highest concentration of 600 μg/plate.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with and without metabolic activation

PD 283 XX caused neither base-pair substitutions nor frameshift mutations in different
S. typhimurium strains in the absence and presence of metabolic activation system when
tested up to insoluble concentrations. Based on these results it was concluded, that
PD 283 XX is "Ames negative".