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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)
Rationale for reliability incl. deficiencies:
other: guideline study and GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Principles of method if other than guideline:
Lactofen was initially investigated using the Salmonella/microsome plate incorporation test for point mutagenic effects in doses of up to and including 5000 µg per plate on five Salmonella typhimurium L T2 mutants. These comprised the histidine-auxotrophic strains TA 1535, TA 100, TA 1537, TA 98 and TA 102. The independent repeat was performed as preincubation for 20 minutes at 37°C. Other conditions remained unchanged.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
yellow to brown viscous liquid
content: 95.54 %

Method

Target gene:
Salmonella LT2 mutants
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Additional strain / cell type characteristics:
other: Firstly, they are deep rough since certain lipopolysaccharide side chains are missing in the bacterial cell wall. Secondly, their reduced ability to repair damage from UV light allows the phenotypic detection of mutation events
Metabolic activation:
with and without
Metabolic activation system:
S9-mix was made from livers of male Sprague-Dawley rats 5 days after intraperitoneal injection of Aroclor 1254
Test concentrations with justification for top dose:
0, 5000, 1581, 500, 158, 50 µg/plate
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
sodium azide
cumene hydroperoxide
mitomycin C
other: nitrofurantoin, 4-nitro-1,2-phenylene diamine, 2-aminoanthracene

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:
cytotoxicity
Remarks:
Doses up to and including 1581 µg per plate did not cause any bacteriotoxic effects
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Doses up to and including 1581 µg per plate did not cause any bacteriotoxic effects.

Total bacteria counts remained unchanged and no inhibition of growth was observed. At 5000 µg per plate, the substance had only a weak, strain-specific bacteriotoxic effect. Due to the weakness of this effect this dose could nevertheless be used for assessment purposes. Substance precipitation occurred at the dose 5000 µg per plate.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative
Executive summary:

Lactofen was initially investigated using the Salmonella/microsome plate incorporation test for point mutagenic effects in doses of up to and including 5000 µg per plate on five Salmonella typhimurium L T2 mutants. These comprised the histidine-auxotrophic strains TA 1535, TA 100, TA 1537, TA 98 and TA 102. The independent repeat was performed as preincubation for 20 minutes at 37°C. Other conditions remained unchanged.

Doses up to and including 1581 µg per plate did not cause any bacteriotoxic effects. Total bacteria counts remained unchanged and no inhibition of growth was observed. At 5000 µg per plate, the substance had only a weak, strain-specific bacteriotoxic effect. Due to the weakness of this effect this dose could nevertheless be used for assessment purposes. Substance precipitation occurred at the dose 5000 µg per plate.

Evidence of mutagenic activity of Lactofen was not seen. No biologically relevant increase in the mutant count, in comparison with the negative controls, was observed.

The positive controls sodium azide, nitrofurantoin, 4-nitro-1,2-phenylene diamine, mitomycin C, cumene hydroperoxide and 2-aminoanthracene had a marked mutagenic effect, as was seen by a biologically relevant increase in mutant colonies compared

to the corresponding negative controls.

Therefore, Lactofen was negative without and with S9 mix in the plate incorporation as well as in the preincubation modification of the Salmonella/microsome test.