Poly(oxy-1,2-ethanediyl), alpha-[2-[bis(2-aminoethyl)methylammonion)ethyl]-, omega-hydroxy, N,N'-di-Limnanthes alba seed oil acyl derivatives, methyl sulfates (salts)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance was negative in the Ames test (bacterial reverse mutation assay) employing Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA102, both in the presence and absence of a metabolic activation system (rat liver S9).

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 November 2001 - 24 December 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

21 July 1997

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Batch number: CW-4896
Storage conditions: at room temperature
Purity: 85.9% actives
Expiry: 2 years from receipt

Species / strain / cell type:

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

Additional strain / cell type characteristics:

other: rfa mutation; uvrB mutation, inclusion of plasmid pKM 101 has been added to strains TA98, TA100 and TA102; pAQ1 tetracycline resistant plasmidic factor has been added to the TA102 strain.

Metabolic activation:

with and without

Metabolic activation system:

Rat liver post-mitochondrial (S9) fraction from rats induced with Aroclor 1254.

Test concentrations with justification for top dose:

Preliminary test: the substance was poorly soluble and toxic at the highest dose employed (5000 µg/plate). The doses chosen for the main test were based on level of precipitation and toxicity.
Main test: 156.25, 312.5, 625, 1250 and 2500µg/plate for all tester strains, with and without S9.
Main test 2: 78.125, 156.25, 312.5, 625 and 1250 µg/platefor all tester strains, with and without S9.

Vehicle / solvent:

Dimethyl sulphoxide (DMSO).

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

mitomycin C

other: 2-Anthramine

Rationale for test conditions:

As per guideline.

Evaluation criteria:

A reproducible 2-fold increase in the number of revertants compared with controls, in any strain at any dose level and/or evidence of dose-response relationship was considered as positive result. Reference to historical data, or other considerations of biological relevance may also be taken into account in the evaluation of the data obtained.

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Moderate to marked cytotoxicity was observed at concentration of 1250µg/plate and above in the absence of S9 and at 2500 µg/plate in the presence of S9.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Moderate to marked cytotoxicity was observed at concentration of 1250µg/plate and above in the absence of S9 and at 2500 µg/plate in the presence of S9.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Moderate to marked cytotoxicity was observed at concentration of 1250µg/plate and above in the absence of S9 and at 2500 µg/plate in the presence of S9.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Moderate to marked cytotoxicity was observed at concentration of 1250µg/plate and above in the absence of S9 and at 2500 µg/plate in the presence of S9.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Moderate to marked cytotoxicity was observed at concentration of 1250µg/plate and above in the absence of S9 and at 2500 µg/plate in the presence of S9.

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

In the TA 1537 strain, some two-fold increases in the number of revertants were noted. However, since these increases were very slight (up to 2.6-fold the vehicle control value) and in the absence of a dose-response relationship, they were considered as artefactual by the study facilitators and attributed to the low number of revertants in the vehicle control and therefore considered as not relevant.

Conclusions:

The substance did not induce any mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA102.

Executive summary:

In the in vitro genotoxicity study (Ames test) the substance was tested for mutagenicity in Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and TA 102. Concentrations of up to 5000 μg/plate were tested in the preliminary study. The substance was poorly soluble and toxic at the highest dose employed (5000 µg/plate). The doses chosen for the main test were based on level of precipitation and toxicity. In the main test the doses employed were 156.25, 312.5, 625, 1250 and 2500µg/plate for all tester strains, with and without S9. In the second main test the concentration employed were 78.125, 156.25, 312.5, 625 and 1250 µg/platefor all tester strains, with and without S9. No evidence of mutagenic activity was seen at any concentration of the substance in either test. Moderate to marked cytotoxicity was observed at concentration of 1250µg/plate and above in the absence of S9 and at 2500 µg/plate in the presence of S9. It was concluded that the substance showed no evidence of mutagenic activity in this bacterial system under the test conditions employed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the findings of a reliable reverse bacterial mutagenicity study conducted on the substance, classification of the substance is not justified.