AVITERA ROSE SE

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test substance in bacterial reverse mutation assay is considered as non-mutagenic.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental Starting Date 17 March 2021 Experimental Completion Date 26 April 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted on July 21st, 1997 and corrected June 26th, 2020

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

Identification: FAT 40879/B TE
Appearance: Dark red powder
Batch Number: BOP 05-20 (MC- 0065114700/800 1:1)
Degree of Purity (% (w/w)): 80.5 % all colored organic constituents; main constituent 66:9 %
Manufacture Date: June 26, 2020
Expiry Date: September 08, 2025
Storage Conditions: Freezer (-15 to -20 °C)

Target gene:

Histidine

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

Uninduced hamster liver S9

Test concentrations with justification for top dose:

In the pre-experiment, the concentration range of the test item was 0.002 - 5.0 mg/plate based on the solubility and precipitation test.
In tester strains, TA 98 and TA 100 tested at 5.0 mg/plate (T8) concentration, no reduction in colony count but moderate inhibition of back ground lawn was observed both in the absence (-S9) and in presence (+S9) of metabolic activation

Vehicle / solvent:

Distilled Water

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

Without metabolic activation: TA 1535, TA 100

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 4-Nitro-o-phenylenediamine

Remarks:

Without metabolic activation: TA 1537, TA 98

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Remarks:

Without metabolic activation: TA 102

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Remarks:

With metabolic activation: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on test system and experimental conditions:

TA 1535, TA 1537, TA 98, TA 100 and TA 102
Plate incorporation and pre-incubation method

Evaluation criteria:

A test item is considered as a mutagen, if a biologically relevant increase in the number of revertants exceeding the threshold of twice (strains TA 98, TA 100 and TA 102) or thrice (strains TA 1535 and TA 1537) the colony count of the corresponding control is observed

Species / strain:

S. typhimurium, other: 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 nor precipitates, but tested up to recommended limit concentrations

Remarks:

5 mg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: All strains were used

Study Plan Amendment No. 1: Dose Selection for Main Study.

Conclusions:

FAT 40879/B did not induce gene mutations by base pair changes and frame shifts in the genome of the strains used and considered non-mutagenic.

Executive summary:

A GLP-compliant study according to OECD guideline 471 was performed to evaluate the potential of FAT 40879/B TE to induce gene muta­tions in comparison to negative control according to the plate incorporation method (Trial I) and the pre-incubation method (Trial II) using the Salmonella typhimurium strains TA 1537, TA 1535, TA 98, TA 100 and TA 102.The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the negative, vehicle and positive controls was tested in triplicate. Based on the solubility and precipitation test results eight different concentrations viz. 0.002, 0.005, 0.016, 0.050, 0.158, 0.501, 1.582 and 5.0 mg/plate were selected for pre-experiment. Based on the pre-experiment results, the test item was tested with the following concentrations: 0.050, 0.158, 0.501, 1.582 and 5.0 mg/plate for main study, both in the presence of metabolic activation (+S9) and in the absence of metabolic activation (-S9).No substantial increase in revertant colony numbers in any of the tester strains were observed following treatment with FAT 40879/B at any dose level in both the trials, neither in the presence nor in the absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance. The spontaneous reversion rates in the negative and positive controls are within the range of in-house historical data. The positive controls used for various strains showed a distinct increase in induced revertant colonies in both the methods i.e. Plate incorporation method and Pre-incubation method. In conclusion, FAT 40879/B did not induce gene mutations by base pair changes and frame shifts in the genome of the strains used and considered non-mutagenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A GLP-compliant study according to OECD guideline 471 was performed to evaluate the potential of FAT 40879/B to induce gene muta­tions in comparison to negative control according to the plate incorporation method (Trial I) and the pre-incubation method (Trial II) using the Salmonella typhimurium strains TA 1537, TA 1535, TA 98, TA 100 and TA 102. The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the negative, vehicle and positive controls was tested in triplicate. Based on the solubility and precipitation test results eight different concentrations viz. 0.002, 0.005, 0.016, 0.050, 0.158, 0.501, 1.582 and 5.0 mg/plate were selected for pre-experiment. Based on the pre-experiment results, the test item was tested with the following concentrations: 0.050, 0.158, 0.501, 1.582 and 5.0 mg/plate for main study, both in the presence of metabolic activation (+S9) and in the absence of metabolic activation (-S9). No substantial increase in revertant colony numbers in any of the tester strains were observed following treatment with FAT 40879/B at any dose level in both the trials, neither in the presence nor in the absence of metabolic activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance. The spontaneous reversion rates in the negative and positive controls are within the range of in-house historical data. The positive controls used for various strains showed a distinct increase in induced revertant colonies in both the methods i.e. Plate incorporation method and Pre-incubation method. In conclusion, FAT 40879/B did not induce gene mutations by base pair changes and frame shifts in the genome of the strains used and considered non-mutagenic.

Justification for classification or non-classification

Based on the findings from Ames assay, the test substance does not considered to be classified according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.