Methyl undec-10-enoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Read-across from a Klimisch-1-rated study on mammalian cell gene mutation performed with undecylenic acid. Justification for read-across : This study performed with undecylenic acid is used for read-across to evaluate methyl 10 -undecenoate. This read-across is based on the following justification. Referring to ECHA's "Guidance on information requirements and chemical safety assessment - Chapter R.6: QSARs and grouping of chemicals", endpoint information is read-across from a structural analogue. A structural analogue is a source chemical whose physico-chemical and toxicological properties are likely to be similar to the target chemical as a result of structural similarity. The similarity may be based on a common precursor and/or breakdown product, that results via physical or biological processes (metabolic pathway similarity). This is used to examine related chemicals, such as acid/ester/salt. Since the target chemical methyl-10-undecenoate is the methyl ester of the source chemical undecylenic acid, read-across between the two substances based on structural analogy therefore technically is possible. The scientific justification for the read-across of the study on oral repeat dose toxicity from undecylenic acid to methyl-10 –undecenoate is based on the similiar behaviour of the two substances observed during the six in-vivo studies on acute effects.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.17 (Mutagenicity - In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Undecylenic acid

IUPAC Name:

Undecylenic acid

Constituent 2

Reference substance name:

Undec-10-enoic acid

EC Number:

203-965-8

EC Name:

Undec-10-enoic acid

Cas Number:

112-38-9

IUPAC Name:

undec-10-enoic acid

Details on test material:

no data

Method

Target gene:

hypoxanthine-phosphoribosyl-transferase (HPRT)

Species / strain

Species / strain / cell type:

Chinese hamster lung fibroblasts (V79)

Details on mammalian cell type (if applicable):

- Type and identity of media: DMEM 10% FCS, Pen/Strep/fungizone
- Properly maintained: yes
-obtained as cryopreserved stock from Institute de Recherches Scientifiques sur le Cancer, Villejuif, France

Metabolic activation:

with and without

Metabolic activation system:

S 9 (from the liver of Arochlor-induced rats)

Test concentrations with justification for top dose:

10, 30, 100, 300, 500, 600 µg/ml

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

Migrated to IUCLID6: and Dimethylnitrosamin with S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk


DURATION
- Preincubation period:
- Exposure duration: 3 h
- Expression time (cells in growth medium): 6 days
- Selection time (if incubation with a selection agent): 10 days on 6-thioguanine

STAIN (for cytogenetic assays): Giemsa


NUMBER OF REPLICATIONS: 2 studies (6 and 10 replicates/condition, respectively)



DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency;

Evaluation criteria:

mutagic if: 3 times mutation frquency of untreated cells + dose-dependent, statistically significant increase in mutation frequency + reproducible in repeat-experiment

Statistics:

no data

Results and discussion

Test results

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

up to limit of solubility

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

>= 500 μg/ml in the presenc of S9

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Water solubility: <= 500 μg/ml

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

According to CLP criteria, no classification of undecylenic acid is required. Therefore it is proposed also not to classify the methyl-10-undeceonate.

Executive summary:

The in vitro mutagenic activity of the test substance undecylenic acid was investigated in the chinese hamster V79/HPRT-test. The test substance was applied to cell cutures at concentrations of 30 -500 µg/ml in the presence or absence of metabolic activation system (S9 -mix). The mutation frequency of treated cell cultures was equal to that of untreated controls, while cell cultures treated with positive controls presented higher mutation frequencies.

Under the described experimental conditions, the test substance undecylenic acid is not mutagenic in the chinese hamster V79/HPRT gene mutation assay.

Justification for read-across:

This robust study summary is a read-across, based on a Klimisch-1-rated mammalian cell gene mutation study on the structural analogue undecylenic acid. For this read-across the following justification is given.

Referring to ECHA's "Guidance on information requirements and chemical safety assessment - Chapter R.6: QSARs and grouping of chemicals", endpoint information is read-across from a structural analogue. A structural analogue is a source chemical whose physico-chemical and toxicological properties are likely to be similar to the target chemical as a result of structural similarity. The similarity may be based on a common precursor and/or breakdown product that results via physical or biological processes (metabolic pathway similarity). This is used to examine related chemicals, such as acid/ester/salt.

Since the target chemical methyl-10-undecenoate is the methyl ester of the source chemical undecylenic acid, read-across between the two substances based on structural analogy therefore technically is possible. The scientific justification for the read-across of the in-vitro cell gene mutation study from undecylenic acid to methyl-10-undecenoate is based on the same behaviour of the two substances observed during other genotoxicity in-vitro studies, which lead for both chemicals to the result “no classification” (see following table). Since furthermore the physical-chemical properties of source and target substance mostly are similar as well, to accepting the above suggested read-across is being proposed.

 

	Methyl-10-undecenoate  (methyl ester of undecylenic acid)	Undecylenic acid
Genetic toxicity in vitro: Ames test	No classification	No classification
Genetic tox. in vitro: chromosome aberration	No classification	No classification
Genetic tox. in vitro: mammalian cell gene mutation test	No classification proposed Read across from undecylenic acid	No classification