Poly[oxy(methyl-1,2-ethanediyl)], α-hydro-ω-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), 2-propenoate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From June 07, 2016 to June 17, 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Propylidynetrimethanol, propoxylated

EC Number:

500-041-9

EC Name:

Propylidynetrimethanol, propoxylated

Cas Number:

25723-16-4

Molecular formula:

C9 H20 O4

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol

Constituent 2

Reference substance name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), mono-2-propenoate

Cas Number:

1378240-17-5

Molecular formula:

(C3H6O)n(C3H6O)n(C3H6O)nC9H16O4

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), mono-2-propenoate

Constituent 3

Reference substance name:

Poly[oxy(methyl-1,2-ethanediyl)], α-hydro-ω-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), di-2-propenoate

Cas Number:

104956-81-2

Molecular formula:

(C3H6O)n(C3H6O)n(C3H6O)nC12H18O5

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], α-hydro-ω-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), di-2-propenoate

Constituent 4

Reference substance name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), mono[3-[(1-oxo-2-propen-1-yl)oxy]propanoate] mono-2-propenoate

Cas Number:

1378240-19-7

Molecular formula:

(C3H6O)n(C3H6O)n(C3H6O)nC12H18O5 + C3H4O2

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), mono[3-[(1-oxo-2-propen-1-yl)oxy]propanoate] mono-2-propenoate

Constituent 5

Reference substance name:

Propylidynetrimethanol, propoxylated, esters with acrylic acid

EC Number:

500-123-4

EC Name:

Propylidynetrimethanol, propoxylated, esters with acrylic acid

Cas Number:

53879-54-2

Molecular formula:

(C3H6O)n(C3H6O)n(C3H6O)nC15H20O6

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], .alpha.-hydro-.omega.-[(1-oxo-2-propenyl)oxy]-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol

Constituent 6

Reference substance name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), mono[3-[(1-oxo-2-propen-1-yl)oxy]propanoate] di-2-propenoate

Cas Number:

1378240-20-0

Molecular formula:

(C3H6O)n(C3H6O)n(C3H6O)nC15H20O6 + C3H4O2

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol (3:1), mono[3-[(1-oxo-2-propen-1-yl)oxy]propanoate] di-2-propenoate

Constituent 7

Reference substance name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol, ester ether with 3-hydroxypropanoic acid (6:2:1), [3-[(1-oxo-2-propen-1-yl)oxy]propanoate] tri-2-propenoate

Cas Number:

1378240-22-2

Molecular formula:

(C3H6O)n(C3H6O)n(C3H6O)nC12H18O5 + (C3H6O)n(C3H6O)n(C3H6O)nC15H20O6

IUPAC Name:

Poly[oxy(methyl-1,2-ethanediyl)], a-hydro-w-hydroxy-, ether with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol, ester ether with 3-hydroxypropanoic acid (6:2:1), [3-[(1-oxo-2-propen-1-yl)oxy]propanoate] tri-2-propenoate

Constituent 8

Reference substance name:

Michaël adduct of propoxylated trimethylolpropane monoacrylate (TMP(PO)MA) with propoxylated trimethylolpropane triacrylate (TMP(PO)TA) and propoxylated trimethylolpropane monoacrylate (TMP(PO)MA)

Molecular formula:

Not available (UVCB substance)

IUPAC Name:

Michaël adduct of propoxylated trimethylolpropane monoacrylate (TMP(PO)MA) with propoxylated trimethylolpropane triacrylate (TMP(PO)TA) and propoxylated trimethylolpropane monoacrylate (TMP(PO)MA)

Constituent 9

Reference substance name:

Sum of other constituents

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Sum of other constituents

Test material form:

liquid

Specific details on test material used for the study:

Batch no.: JBIJ0009V
Purity: 100% (UVCB)
Appearance: yellowish liquid

Method

Target gene:

histidine

Species / strain

Species / strain / cell type:

other: S. Typhimurium TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Metabolic activation system:

S9-mix (rat liver S9-mix induced by Aroclor 1254)

Test concentrations with justification for top dose:

Based on a pre-test, the following nominal concentrations were prepared for experiments 1a and 1b: 5000 μg/plate, 1500 μg/plate, 500 μg/plate, Based on a pre-test, the following nominal concentrations were prepared for experiments 1a and 1b: 5000, 1500, 500, 150 and 50 μg/plate.
The following nominal concentrations were prepared for experiment 2: 5000, 2500, 1250, 625, 313, 156 and 78 μg/plate.

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

benzo(a)pyrene

other: 2-Amino-anthracene, 4-nitro-1,2-phenylene diamine,

Details on test system and experimental conditions:

Mutagenicity test:
Top agar was prepared for the Salmonella strains by mixing 100 mL agar (0.6% agar, 0.5% NaCl) with 10 mL of a 0.5 mM histidine-biotin solution. The following ingredients were added (in order) to x mL of molten top agar at 45°C:
- 0.1 mL of an overnight nutrient broth culture of the bacterial tester strain
- 0.1 mL test compound solution
- 0.5 mL S-9 Mix (if repuired) or buffer
After mixing, the liquid was poured into a petridish with minimal agar (1.2% agar, Vogel-Bonner E medium with 2% glucose). After incubation for 48 to 72 hours at 37°C in the dark, colonies (his+ revertants) were counted.

Rationale for test conditions:

Toxicity experiments and dose range finding

Evaluation criteria:

Number of his+ revertants

Statistics:

The number of colonies per plate with each strain as well as mean values of 3 plates, corrected to the next whole number

Results and discussion

Test results

Key result

Species / strain:

other: Salmonella typhimurium strains TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

cfr "Any other information on results incl. tables"

Remarks on result:

other: not mutagenic

Any other information on results incl. tables

Experiment 1a:

The test substance (dissolved in DMSO) was tested up to concentrations of 5000 μg/plate in the absence and presence of S9-mix (0.74 % final concentration in the treatment) in the strains TA97a, TA100, TA102 and TA1535 using the plate incorporation method. The test substance showed no precipitates on the plates at any of the concentrations. The bacterial background lawn was not reduced at any of the concentrations and no relevant decrease in the number of revertants was observed in all bacteria strains. The test substance showed no signs of toxicity towards the bacteria strains in both the absence and presence of metabolic activation. The results of this experiment showed that none of the tested concentrations caused a significant increase in the number of revertants in all tested strains, in the presence and the absence of metabolic activation.

Experiment 1b:

The test substance (dissolved in DMSO) was tested up to concentrations of 5000 μg/plate in the absence and presence of S9-mix (0.74 % final concentration in the treatment) in the strain TA98 using the plate incorporation method. The bacteria strain TA98 was tested separately from the other strains, because of a pipetting error in the experiment 1a. The test substance showed no precipitates on the plates at any of the concentrations. The bacterial background lawn was not reduced at any of the concentrations and no relevant decrease in the number of revertants was observed in all bacteria strains. The test substance showed no signs of toxicity towards the bacteria strains in both the absence and presence of metabolic activation.

The results of this experiment showed again that none of the tested concentrations caused a significant increase in the number of revertants in the bacteria strain, in the presence and absence of metabolic activation.

Experiment 2:

On the base of the experiment 1a, the test substance was tested up to concentrations of 5000 μg/plate in the absence and presence of S9-mix (0.74% final concentration in the treatment) in all bacteria strain using the pre-incubation method. The test substance showed no precipitates on the plates at any of the concentrations. The bacterial background lawn was not reduced at any of the concentrations and no relevant decrease in the number of revertants was observed in all bacteria strains. The test substance showed no signs of toxicity towards the bacteria strains in both the absence and presence of metabolic activation. The results of this experiments showed that the test substance caused no increase in the number of revertants in all bacteria strains compared to the solvent control, in both the absence and presence of metabolic activation. The test substance did not induce a dose-related increase in the number of revertants colonies in all strains, in the presence and absence of metabolic activation.

Based on the results of this study it was concluded that the test substance was not mutagenic in the Salmonella typhimurium strains TA97a, TA98, TA100, TA102 and TA1535 in the absence and presence of metabolic activation under the experimental conditions in this study.

Applicant's summary and conclusion

Conclusions:

Under the study conditions, the test substance was not mutagenic in a bacterial reverse mutation test with and without metabolic activation.

Executive summary:

A study was conducted to determine the mutagenic potential of the test substance according to OECD Guideline 471 and EU Method B13/14 (bacterial reverse mutation assay), in compliance with GLP. Five Salmonella typhimurium strains (i.e. TA 97a, TA 98, TA 100, TA 102, TA 1535) were exposed to the test substance for 48 to 72 h, at concentrations of 50 to 5000 µg/plate (with 3 plates per condition). At the end of the incubation period, the number of His+ revertants was counted. The test substance did not cause a significant increase in the number of revertant colonies with any of the tester strains, either in the absence or presence of metabolic activation. Positive and negative (vehicle) controls gave expected results; the experiment was therefore considered valid. Under the study conditions, the test substance was not mutagenic in a bacterial reverse mutation study with and without metabolic activation (Andres, 2016).