Pentaerythritol, ethoxylated, esters with acrylic acid

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:

November 2006-February 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to OECD guideline No. 471 and under GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Pentaerythritol, ethoxylated, esters with acrylic acid

EC Number:

500-111-9

EC Name:

Pentaerythritol, ethoxylated, esters with acrylic acid

Cas Number:

51728-26-8

Molecular formula:

(C2 H4 O)n (C2 H4 O)n (C2 H4 O)n (C2 H4 O)n C17 H20 O8

IUPAC Name:

Pentaerythritol, ethoxylated, esters with acrylic acid (> 1 < 8.5 mol EO)

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): C-SAT 060061
- Substance type: UVCB
- Physical state: almost colourless liquid
- Analytical purity: 100% active ingredient
- Lot/batch No.: S763030113
- Expiration date of the lot/batch: April 30, 2007
- Storage condition of test material: in the refrigerator, protected from light
- Stability under test conditions: DMSO solution considered to be stable for one week under storage conditions

Method

Target gene:

histidine gene in Salmonella typhimurium

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9 mix

Test concentrations with justification for top dose:

In the first experiment (toxicity testing): 3, 10, 33, 100, 333 , 1000, 2500 and 5000 µg/plate.
In the second experiment :33, 100, 333 , 1000, 2500 and 5000 µg/plate.

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: sodium azide for TA 1535 and TA 100; 4-nitro-o-phenylene-diamine for TA 1537 and TA 98, methyl methane sulfonate for TA 102: 2-aminoanthracene for all strains in the presence of metabolic activation.

Details on test system and experimental conditions:

Two independent experiments were performed both with and without liver microsomal activation. The first experiment was conducted to evaluate the toxicity of the test substance in all strains with 8 concentrations ranging from 3 to 5000 µg/plate, using the plate incorporation test. The second experiment was conducted using a pre-incubation assay with 6 concentrations ranging from 33 to 5000 µg/plate.

Concentrations of the test chemical which are overtly toxic are easily visualized as showing no bacterial growth on the plate (i.e. absence of background lawn). Lower levels of toxicity may be seen as a thin or sparse bacterial lawn, a reduction in the number of revertants, or the appearance of microcolonies (overgrown background lawn). Positive and negative controls were run concurrently with the test chemical, and appropriate responses for these controls are prerequesites for evaluating the response of the bacteria to the test chemical.

Evaluation criteria:

The Salmonella typhimurium reverse mutation assay is considered acceptable if it meets the following criteria:
- regular background growth in the negative and solvent control
- the spontaneous reversion rates in the negative and solvent control are in the range of the historical control data of the laboratory
- the positive control substances should producer a significant increase in mutant colony frequencies

Statistics:

According to OECD guideline No. 471, a statistical analyis of the data is not mandatory.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Additional information on results:

A reduced background growth was observed from 2500 to 5000 µg/plate with and without metabolic activation in the first experiment and with metabolic activation in the second experiment. No toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation.

No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with the test substance at any concentration level, neither in the presence nor absence of metabolic activation. There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally accepted border of biological relevance.

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

It can be stated that under the experimental conditions reported, the test substance did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used. Therefore, the test substance is considered to be non-mutagenic in the Salmonella typhimuirum reverse mutation assay.

Executive summary:

The study was performed to investigate the potential of the test substance to induce gen mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment II) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102. The assays were performed both with and without liver microsomal activation.

The test substance was tested at the following concentrations:

Experiment I: 3, 10, 33, 100, 333, 1000, 2500 and 5000 µ/gplate

Experiment II: 33, 100, 333, 100, 2500 and 5000 µg/plate

Reduced background growth was observed from 2500 to 5000 µ/gplate with and without metabolic activation in experiment I and with metabolic activation in experiment II. No toxic effects, evident as a reduction in the number of revertants, occurred in the test groups with and without metabolic activation.

No substantial increase in revertant colony numbers of any of the tester strains was observed following treatment with the test substances at any dose level, neither in the presence nor absence of metabolic activation (S9 mix). There was also no tendency og higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological significance.

Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.