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Genetic toxicity: in vitro

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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:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not specified
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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 / strainopen allclose all
Species / strain / cell type:
E. coli WP2 uvr A
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 resultsopen allclose all
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
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.