Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
The registration substance was not mutagenic in a guideline conform Salmonella typhimurium reverse mutation assay (Ames test) using five tester strains with and without metabolic activation (S9-mix from induced rat liver). Likewise, the submission substance was also not mutagenic in a guideline compliant mammalian cell gene (HPRT) mutation assay in V79 Chinese hamster cells and did not induce chromosome aberrations or clastogenic effects in a guideline conform cytogenetic study in V79 cells in vitro with and without metabolic activation.
Link to relevant study records
Reference
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:
2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study acoording to GLP
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium, other: TA 97a
Species / strain / cell type:
S. typhimurium TA 98
Species / strain / cell type:
S. typhimurium TA 100
Species / strain / cell type:
S. typhimurium TA 102
Species / strain / cell type:
S. typhimurium TA 1535
Metabolic activation:
with and without
Metabolic activation system:
post-mitochondrial (S9) fraction of induced rat liver
Test concentrations with justification for top dose:
TA 97a: 0.0016 - 0.16 mg/plate (-S9), 0.016 - 1.6 mg/plate (+S9)
TA 98: 0.05 - 5 mg/plaze (+/-S9)
TA 100: 0.016 - 1.6 mg/palte (+/-S9)
TA 102: 0.05 - 5 mg/plate (+/-S9)
TA 1535: 0.016 - 1.6 mg/plate (+/-S9)
Vehicle / solvent:
Bidistilled water
Untreated negative controls:
yes
Remarks:
aqua bidest
Negative solvent / vehicle controls:
no
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
cumene hydroperoxide
other: 4-nitro-o-phenylenediamine, nitrofurantoine, 2-aminoanthracene, danthron, ICR 191
Details on test system and experimental conditions:
NUMBER OF REPLICATIONS: 3

Evaluation criteria:
Induction rate of mean values from revertant colonies of test item and revertant colonies of corresponding control
Species / strain:
S. typhimurium, other: TA 97a
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Untreated negative controls validity:
valid
Positive controls validity:
valid
Conclusions:
Hostapon TPHC is not point mutagenic in the Ames test
Executive summary:

The point mutagenic effects of sodium methyl oleyl taurate were investigated in the reverse bacterial mutation assay (Ames tets) according to OECD TG 471 in two independent studies following the principles of GLP. Test systems used were Salmonella typhimurium strains TA97a, TA98, TA100, TA102 and TA1535 with and without the metabolic activation system S9 from induced rat liver. Positive and negative controls had been included. Duration of each study was 48 hours. The test item was dissolved in bidestilled water and applied once at concentrations between 0.0016 mg/plate up to 5.0 mg/plate (depending on cytotoxicity). Under the conditions of this test, no increase in revertant colonies in any of the tester strains were obderved. Based hereupon, it is concluded that the test item is not mutagenic in this bacterial test system.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

The registration substance was tested for potential point mutation in a guideline conform bacterial reverse mutation assay (Ames test) according to OECD TG 471 with and without metabolic activation. Independent experiments using several test concentrations up to the limit dose of 5000µg/platedid not cause gene mutations by base pair changes or frameshifts in the genome of any of the tester strains used. Therefore, the submission substance is considered to be non-mutagenic in this bacterial reverse mutation assay. This study was selected as key study.

The registration substance was tested for potential gene mutation in a guideline conform mammalian cell gene mutation assay (HPRT locus) according to OECD TG 476 in V79cells of the Chinese hamster. Using independent experiments, no biologically relevant increase of mutants was found after treatment with the test item, neither with nor without metabolic activation. No dose-response relationship was observed. Therefore, the submission substance is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese hamster. This study was selected as key study.

The submission substance was tested for the potentialto induce structural chromosome aberrations in an guideline conform in vitro cytogenetic assay in Chinese hamster V79 cells according to OECD TG 473. Two independent experiments with and without metabolic activation were carried out using test item concentrations up to the limit of 5000µg/mL. The aberration rates of all dose groups treated with the test item were within the historical control data of the negative controls. No biologically relevant increase of the aberration rates and no biologically relevant increase in the frequencies of polyploid cells were noted after treatment with the test item as compared to the controls. Distinct and biologically relevant increases in cells with structural chromosomal aberrations were induced by the positive controls and confirmed the sensiticvity of the test system.. The test item did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line and is thus considered to be non-clastogenic in this test. This study was selected as key study.

In conclusion, the submission substance is found to be not mutagenic in the bacterial reverse mutation assay, the mammalian (HPRT) mutation test in V79 cells and in the in vitro chromosome aberration test in V 79 cells.


Justification for selection of genetic toxicity endpoint
There are several key studies covering bacterial point mutation testing, testing for gen mutations in mammalian cells as well as chromosome mutations in mammalian cell systems. All studies are guideline conform tests according to GLP with a Klimisch rating of 1.

Justification for classification or non-classification

Based on the available data from three independent mutagenicity assays, a respective mutagenic potential of the test item can most probably be excluded. Thus, the registration substance does not have to be classified for mutagenicity in accordance with the criteria laid down in the EU Dangerous Substances Directive (67/548/EEC) as well as in the EU Classification, Labellling and Packaging Regulation (1272/2008/EC).