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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Negative in the complete in vitro testing battery according to OECD 471, 473 and 476 (read-across: 2,4,7,9-Tetramethyl-5-decyne-4,7-diol)

Link to relevant study records

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Endpoint:
in vitro gene mutation study in bacteria
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: the substances start with an acetylene group as core structure; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl); the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) is further functionalised with ethylene oxide and has an ethoxylation degree of 1.3; the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) has an ethoxylation degree of 3.8
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Therefore, read-across from the existing toxicity, ecotoxicity, environmental fate and physicochemical studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S-9 mix
Test concentrations with justification for top dose:
0, 10, 50, 100, 500, 1000, and 5000 ug/plate
Vehicle / solvent:
DMSO
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Migrated to IUCLID6: Sodium azide, 2-Nitrofluorene, 2-Anthramine
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: Salmonella typhimurium strains TA1535, TA1537, TA98, TA100, and E-coli strain WP2(uvrA).
Conclusions:
Interpretation of results: negative
Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: the substances start with an acetylene group as core structure; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl); the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) is further functionalised with ethylene oxide and has an ethoxylation degree of 1.3; the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) has an ethoxylation degree of 3.8
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Therefore, read-across from the existing toxicity, ecotoxicity, environmental fate and physicochemical studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Test concentrations with justification for top dose:
19.5, 39.1, 78.1-78.3, 156.3, 312.5, 1250, and 3500 ug/ml
Vehicle / solvent:
DMSO
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 312.5
Untreated negative controls validity:
valid
True negative controls validity:
not examined
Positive controls validity:
valid
Conclusions:
Interpretation of results: negative

Endpoint:
in vitro gene mutation study in mammalian cells
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar toxicological properties because
- they are manufactured from similar precursors under similar conditions
- they share structural similarities with common functional groups: the substances start with an acetylene group as core structure; geminal hydroxyl groups on the alpha carbon atoms; distal to the geminal hydroxyl groups is an isobutyl group (methyl isopropyl); the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) is further functionalised with ethylene oxide and has an ethoxylation degree of 1.3; the source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (3.8) has an ethoxylation degree of 3.8
- they have similar physicochemical properties and thus, show a similar toxicokinetic behaviour
- they are expected to undergo similar metabolism: oxidation of the terminal methyl groups to result in alcohol, aldehyde and finally the corresponding acid

Therefore, read-across from the existing toxicity, ecotoxicity, environmental fate and physicochemical studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across: supporting information
Type of assay:
mammalian cell gene mutation assay
Species / strain / cell type:
mouse lymphoma L5178Y cells
Details on mammalian cell type (if applicable):
- Type and identity of media:
- Periodically "cleansed" against high spontaneous background: yes
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
8.83 to 2260 µg/ml
Vehicle / solvent:
DMSO
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
Migrated to IUCLID6: ethylmethanesulphonate in in the absence of of metabolic activation; cyclophosphamide in the presence of metabolic activation
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Two independent experiments wre performed. In Experiment 1, L5178Y TK +/- 3.7.2c mouse lymphoma cells (heterozyous at the thymidine kinase locus) were treated with the test material at up to eight dose levels, in duplicate, together with vehicle (solvent) and positive controls using 4 -hour exposure groups both in the asence and presence of metabolic activation (2% S9). In experiment 2, the cells were treated with the test material at up to eight dose levels using a 4 -hour exposure group in the absence of metabolic activation.
The dose range of test material was selected following the results of a preliminary toxicity test and for the first experiment was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 280 µg/ml in the presence of metabolic activation. For the second experiment the dose range was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 210 µg/ml in the presence of metabolic activation.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results: negative non-mutagenic

The test material was considered to be non-mutagenic to L5178Y cells under the conditions of the test.

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

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Experimental data on genotoxicity of 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3) are not available. However, a complete in vitro testing battery (bacterial reverse mutation assay, gene mutation study in mammalian cells, chromosome aberration test) was conducted with the structurally related source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol. Since 2,4,7,9-Tetramethyl-5-decyne-4,7-diol is a major component of the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3), the results obtained with the source substance are applicable also to the target substance. A justification for read-across is attached to iuclid section 13.

 

Bacterial reverse mutation test

The source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol was not mutagenic in a plate incorporation procedure with S. typhimurium strains TA1535, TA1537, TA98, and TA100 and E. coli strain WP2 (uvrA) over a dose range of 10 to 5000 µg/plate in both the presence and absence of an Aroclor 1254-induced rat-liver metabolic activation system. The initial experiment used 5 percent (v/v) metabolic activation and the repeat experiment used 10 percent (v/v) metabolic activation. The 5000 ug/plate dose formulation appeared to be immiscible in the tubes and on the plates. Precipitate was also observed in the tubes and on the plates at a dose level of 5000 ug. However, after the 48-hour incubation period the precipitate was no longer seen on the plates. Cytotoxicity, indicated by thinning of the background bacterial lawn and the formation of pinpoint nonrevertant colonies, was observed for all strains generally at dose levels of 1000 and 5000 µg/plate. No 2,4,7,9-tetramethyl-5-decyne-4,7-diol treatments of the test strains resulted in an increase in revertant numbers that was considered indicative of any mutagenic activity. 

 

Chromosome aberration test

The source substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol was negative for chromosomal aberrations at concentrations of 19.5, 78.3, 312.5, 1250, and 3500 µg/ml in the presence or absence of metabolic activation (MA). A high dose of 3500 ug/ul was used based on the limit of solubility of the test article in dimethylsulfoxide (DMSO). Cells were exposed to the test article in the absence of MA for 3 and 21 hr and in the presence of MA for 3 hr. At 21 hr after exposure initiation, cells were harvested and evaluated. All of the cultures from the top two dose levels exhibited a significant decrease in confluency (0 to 25 percent) and therefore were not harvested. For cultures exposed to the test article for 3 hr in the presence or absence of MA, no significant reduction in mitotic index was observed at dose levels of 312.5 µg/ml and below. Cultures exposed for 21 hr to the test article at 312.5 µg/ml showed a significant reduction in mitotic index. Based on the cytotoxicity results, the initial chromosome aberration study was performed by exposing CHO cells for 3 hr to 2,4,7,9-tetramethyl-5-decyne-4,7-diol at concentrations of 19.5, 39.1, 78.1, 156.3, and 312.5 µg/ml in both the absence and presence of MA. At 21 hr after initiation of exposure, cells were harvested and evaluated. Cytotoxicity was evident in cultures exposed to 312.5 µg/ml under both MA conditions, so the cells were not harvested for evaluation. In cultures at the three dose levels scored in both MA conditions (39.1, 78.1, and 156.3 µg/ml), there was no statistically significant increase in the number of cells with structural aberrations and the mitotic index was comparable to that for the control. No increases in polyploidy were observed in the presence or absence of MA. The dose levels for the replicate experiment were based on the results of the cytotoxicity experiment (-MA) and the initial experiment (+MA) which indicated cytotoxicity and a significant reduction in confluency at the 312.5 µg/ml dose level. The replicate experiment was performed by exposing CHO cells for 21 hr to the test article at concentrations of 9.8, 19.5, 39.1, 78.1, and 156.3 µg/ml in the absence of MA and for 3 hr at concentrations of 19.5, 39.1, 78.1, and 156.3 µg/ml in the presence of MA. At 21 hr after initiation of exposure, cells were harvested and evaluated. At the three dose levels scored in both MA conditions (39.1, 78.1, and 156.3 µg/ml), there was no statistically significant increase in the number of cells with structural aberrations and the mitotic index was comparable to that for the control. No increases in polyploidy were observed in the presence or absence of metabolic activation. 

 

Gene mutation study in mammalian cells

The study was conducted according to a method that was designed to assess the potential mutagenicity of the test material 2,4,7,9-Tetramethyl-5-decyne-4,7-diol on the thymidine kinase, TK +/-, locus of the L5178Y mouse lymphoma cell line. The method used meets the requirements of the OECD (476) and the Method B17 of Commission Regulation (EC) No. 440/2008 of 30 May 2008.

Two independent experiments were performed. In Experiment 1, L5178Y TK +/- 3.7.2c mouse lymphoma cells (heterozygous at the thymidine kinase locus) were treated with the test material at up to eight dose levels, in duplicate, together with vehicle (solvent) and positive controls using 4 -hour exposure groups both in the absence and presence of metabolic activation (2% S9). In experiment 2, the cells were treated with the test material at up to eight dose levels using a 4 -hour exposure group in the absence of metabolic activation.

The dose range of test material was selected following the results of a preliminary toxicity test and for the first experiment was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 280 µg/ml in the presence of metabolic activation. For the second experiment the dose range was 4.38 to 140 µg/ml in the absence of metabolic activation, and 17.5 to 210 µg/ml in the presence of metabolic activation.

Results:

The maximum dose level used in the mutagenicity test was limited by test material-induced toxicity. Precipitate of the test material was not observed at any of the dose levels in the mutagenicity test. The vehicle (solvent) controls had acceptable mutant frequency values that were within the normal range for the L5178Y cell line at the TK +/- locus. The positive control materials induced marked increases in the mutant frequency indicating the satisfactory performance of the test and of the activity of the metabolising system.

The test material did not induce any toxicologically significant dose-related increases in the mutant frequency at any dose level, either with or without metabolic activation, in either the first or the second experiment.

The test material was considered to be non-mutagenic to L5178Y cells under the conditions of the test.

 

There are no data gaps for the endpoint genetic toxicity. Based on structural similarity, this outcome is also applied to the target substance 2,4,7,9-Tetramethyl-5-decyne-4,7-diol, ethoxylated (1.3), which is also considered to be not mutagenic nor clastogenic.

Justification for classification or non-classification

According to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) Part 3 Chapter 3.5 this substance is not causing concern to be mutgenetic/genetic toxic.