(RS)-3-Allyl-2-methyl-4-oxocyclopent-2- enyl (1R,3R)-2,2-dimethyl-3-(2-methyl prop-1-enyl)-cyclopropanecarboxylate (mixture of 2 isomers 1R trans: 1R/S only 1:3) (Esbiothrin)

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

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

Reference

Name:

Unnamed

Test material form:

liquid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Purity : 96.7 %

Method

Target gene:

histidine

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S9 mix: 5% and 10% v/v consisted of an S9 fraction fraction (Aroclor 1254 induced rat liver homogenate)

Test concentrations with justification for top dose:

The test concentration was selected based on the solubility and precipitation tests. Cytotoxicity to the tester strain was tested at 0.019, 0.039, 0.078, 0.156, 0.312, 0.625, 1.25, 2.5, 5.0 mg test item/plate. Cytotoxicitywas observed at 5.0 mg/plate in the presence of metabolic activation. Hence, 5.0 mg was selected as the highest concentration to be tested in the mutagenicity study.

Trial I: dose levels of 0.156, 0.312, 0.625, 1.25, 2.5 and 5.0 mg/plate with and without S9 mix.
Trial II: dose levels of 2.0, 0.8, 0.32, 0.0512 mg/plate with and without S9 mix.

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

Statistics:

Simple linear regression analysis was performed to all strains to assess the dose dependent nature of any increase in revertant colonies.

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: all tester strains

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

at 5.0 mg/plate with metabolic activation

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

The analysis of the results of Trial I and II did not reveal any statistically significant increase in the number of revertant colonies both in the presence and in the absence of metabolic activation.
The linear regression analysis did not reveal any significant increase in the number of revertant colonies in both the trial.

Applicant's summary and conclusion

Conclusions:

It is concluded that d-trans Allethrin 75/25, up to 5.0 mg/plate, both in the absence and in presence of metabolic activation, is non mutagenic to all the five Salmonella thyphi. tester strain, TA 1537, TA1535, TA98, TA100 and TA102 when tested under the specified conditions.