Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
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".