Lactofen

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

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

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

Test material information

Constituent 1

Reference substance name:

(2-ethoxy-1-methyl-2-oxoethyl)-5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate

EC Number:

616-466-9

Cas Number:

77501-63-4

Molecular formula:

C19H15ClF3NO7

IUPAC Name:

(2-ethoxy-1-methyl-2-oxoethyl)-5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoate

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

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.