2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)

Genetic toxicity: in vitro

Administrative data

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:

2005

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is not performed according to the current genetic toxicity guidelines, but seems similar to it. In addition, GLP requirements are not met and some information is lacking. Despite these shortcomings, the study reveals usefull data considering in vitro genetic toxicity.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)

EC Number:

230-743-8

EC Name:

2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl bis(2-ethylhexanoate)

Cas Number:

7299-99-2

Molecular formula:

C37H68O8

IUPAC Name:

3-[(2-ethylhexanoyl)oxy]-2,2-bis({[(2-ethylhexanoyl)oxy]methyl})propyl 2-ethylhexanoate

Constituent 2

Reference substance name:

2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl-bis(2-ethylhexanoate)

IUPAC Name:

2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]propane-1,3-diyl-bis(2-ethylhexanoate)

Details on test material:

- Name of test material (as cited in study report): Pentaerythritol tetraiso-octylate (English name: Hexanoic acid,2-ethyl-,2,2-bis[[(2-ethyl-1-oxohexyl)oxy]methyl]-1,3-propanediyl ester)
- Substance type: clear, colorless liquid
- Physical state: liquid
- Analytical purity: 98.4%
- Purity test date: not mentioned
- Lot/batch No.: not mentioned
- Expiration date of the lot/batch: not mentioned
- Storage condition of test material: room temperature, sealed container, avoiding light

Method

Target gene:

Histidine gene in S. TyphimuriumTryptophan gene in E. Coli

Species / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain 2

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

rat S9

Test concentrations with justification for top dose:

Dose-range finding: 0, 8.19, 20.5, 51.2, 128, 320, 800, 2000 µg/plate.Main test: 0, 78.1, 156, 313, 625, 1250, 2500 µg/plate.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: acetone- Justification for choice of solvent/vehicle: insoluble in water

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

Migrated to IUCLID6: AF-2, sodium azide, 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)DURATION- Preincubation period: 20 min- Exposure duration: 48 hours

Evaluation criteria:

The results were determined to be positive if the revertant colony count increased to a level that was 2 times or more the count in the solvent control, and if this increase showed either dose-dependence or reproducibility.

Statistics:

No testing using statistical methods was performed.

Results and discussion

Test results

Test results 1

Species / strain:

E. coli WP2 uvr A

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

Test results 2

Species / strain:

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

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:

TEST-SPECIFIC CONFOUNDING FACTORS- Precipitation:Dose range: During test substance treatment, an oil-drop precipitate was observed on the plates with a dose of 2000 μg/plate or more for both treatment methods (±S9). After the completion of pre-incubation, the oil-drop precipitate had disappeared from the plates with a dose of 2000 μg/plate or more without S9 treatment (−S9 mix). During measurement of the colony count, an oil-drop and oil-film precipitate was observed on the plates with a dose of 2000 μg/plate or more for both treatment methods.Main study:During test substance treatment, an oil-drop precipitate was observed on the plates with a dose of 1250 μg/plate or more for both treatment methods (±S9). After the completion of pre-incubation, the oil-drop precipitate had disappeared from the plates with a dose of 1250 μg/plate or more without S9 treatment (−S9 mix). During measurement of the colony count, an oil-drop and oil-film precipitate was observed on the plates with a dose of 1250 μg/plate or more for both treatment methods.RANGE-FINDING/SCREENING STUDIES:Dose range:The revertant colony count during pentaerythritol tetraiso-octylate treatment showed no clear tendency to increase at any of the doses for any of the study strains, excluding TA1535 (−S9 mix). Bacterial contamination was observed in some of the plates for TA1535 (−S9 mix), so no measurements were made of the colony count. No growth inhibition effects were observed in any of the treatment groups of the study strains. Main study:In two independent experiments, in the case of the test substance treatment group, no clear trend for an increase in the revertant colony count was observed in any of the strains either with or without metabolic activation. No growth inhibition effects was observed in relation to any of the study strains in any of the treatment groups.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):negativeThe gene reverse mutation test was performed using Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA. No clear increase in the revertant colony count was observed in comparison to the negative control in the pentaerythritol tetraiso-octylate treatment groups, either with or without metabolic activation. Based on the described results, pentaerythritol tetraiso-octylate was not considered to express reverse mutagenicity under the present study conditions.