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Toxicological information

Genetic toxicity: in vitro

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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
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
- Name of test material: 4-Methylpyridine

Method

Target gene:
TA 1535 - contains a histidine missense mutation but is also deficient in a DNA repair system (uvr B) and has a defective lipopolysaccharide coat on the cell wall. It is reverted by many agents causing base-pair substitutions, but is not sensitive to frameshift mutagens.

TA 1537 - bears a histidine frameshift mutation. Like TA 1535, it is defective in a DNA repair system and lipopolysaccharide coat. It is sensitive to agents causing frameshift mutations involving insertion or deletion of a single base-pair.

TA 1538 - contains another histidine frameshift mutation. Again it has a defective DNA repair system and lipopolysaccharide coat. It is reverted by agents causing deletion of two adjacent base-pairs (double frameshift mutations).

TA 100 - is the same as TA 1535 but contains a resistance transfer factor conferring ampicillin resistance and increasing sen~itivity to some mutagens (plasmid pKM 101). In addition to base-pair substitutions, it is also able to detect certain frameshift mutagens.

TA 98 - is TA 1538 with the addition of the pKM 101 plasmid. It is reverted by a variety of mutagens, but not by simple alkylating agents causing base-pair substitutions.
Species / strain
Species / strain / cell type:
S. typhimurium, other: TA 98, TA 1538, TA 100, TA 1535 and TA 1537
Metabolic activation:
with and without
Metabolic activation system:
Rat S9 activated microsomal fraction
Test concentrations with justification for top dose:
50 to 5000 ug per plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: distilled water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
benzo(a)pyrene
other: 2-Aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: twice in triplicate

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth
Evaluation criteria:
Number of revertant colonies

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA 98, TA 1538, TA 100, TA 1535 and TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

It was concluded that the test item was devoid of mutagenic activity under the conditions of the test.