Dodecene

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1983-01-27 to 1983-02-07

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable with restrictions because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the study appears to be in general accordance with OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

While the study report does not provide a specific statement regarding whether this study was conducted according to GLP or equivalent, the study appears to be in general accordance with OECD guidelines.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Alkenes, C10/C11/C12/C13

IUPAC Name:

Alkenes, C10/C11/C12/C13

Details on test material:

This substance is very similar with regard to health endpoints to the substance being registered.

- Name of test material (as cited in study report): Olefin 103 PQ/II
- Substance type: Alkenes C10/C11/C12/C13
- Physical state: Yellow liquid

Method

Target gene:

Not specified

Species / strain

Species / strain 1

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not specified

Species / strain 3

Species / strain / cell type:

Saccharomyces cerevisiae

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Test concentrations with justification for top dose:

31.25, 62.5, 125, 250, 500, I000, 2000 or 4000 ug/plate for Ames assay; 0.01, 0.1., 0.5, 1.0 or 2.0 mg/mL for Saccharomyces cerevisiae gene conversion assay

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: Ethanol/Tween 80
- Justification for choice of solvent/vehicle: Not provided

Details on test system and experimental conditions:

METHOD OF APPLICATION: In agar (plate incorporation)


DURATION
- Exposure duration: 48-72 hours; 3 days for Saccharomyces cerevisiae

Evaluation criteria:

Number of revertant colonies were counted in the Ames assay; number of prototrophic colonies were counted in the Saccharomyces cerevisiae gene conversion assay

Statistics:

Statistical methods, if employed, are not reported in the study

Results and discussion

Test results

Test results 1

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:

not examined

Positive controls validity:

valid

Test results 2

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:

not examined

Positive controls validity:

valid

Test results 3

Species / strain:

Saccharomyces cerevisiae

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The cell survival in yeast was decreased in relation to dose in the absence of S9. Cell survival was relatively unaffected in the presence of S9.

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Olefin 103 PQ/11 did not cause an increase in the reverse mutation rates in bacteria or in the mutation gene conversion rates in yeast in the presence or absence of metabolic activation. The cell survival in yeast was decreased in relation to dose in the absence of S9. Cell survival was relatively unaffected in the presence of S9.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Olefin 103 PQ/11 did not cause an increase in the reverse mutation rates in bacteria or in the mutation gene conversion rates in yeast in the presence or absence of metabolic activation.

Executive summary:

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps for single carbon number isomerised olefin substances using multiple carbon number isomerised olefin substance analogues. Studies indicate that changing the carbon number, the location of the double bond, or adding branching does not measurably alter the effects on mammalian health endpoints. There is a consistent toxicity potency pattern for isomerised olefins with a range of carbon numbers and they are considered to have minimal acute toxicity potential. Genotoxicity studies indicate that these materials are not mutagenic. No adverse systemic toxicity was observed in a 90-day repeated oral dose study in which rats were exposed to alkenes, C20-24. The toxicological profile of multiple carbon number isomerised olefins alkenes described above indicates a low hazard potential for human health. Since multiple carbon number isomerised olefins, alkenes is comprised of a mixture of single carbon number isomerised olefins, no significant toxicological differences are expected between the two categories of substance and read across between these two categories can be justified.

In a mutagenicity test procedure, three separate assays were used to determine the mutagenic potential of Olefin 103 PQ/11. Following an initial preliminary toxicity test, the main mutagenicity test was conducted in Salmonella typhimurium strains, TA1537, TA1535, TA100 and TA98 and Escherichia coli WP2 uvrA, both in the presence and absence of rat liver fraction S9, at 31.25, 62.5, 125, 250, 500, I000, 2000 or 4000 µg per plate. The cultures were incubated at 37°C for 48-72 hours before the revertant colonies were counted.

 

The test material was also tested in Saccharomyces cerevisiae. Liquid suspension cultures of log-phase cells of Saccharomyces cerevisiae JDI were dosed with of 0.01, 0.1., 0.5, 1.0 or 2.0 mg/mL, both in the presence and in the absence of rat liver S9 fraction. After 18 hours incubation at 30°C in the absence of S9 fraction, or 2hours at 37°C followed by 16 hours at 30°C in the presence of S9 fraction, the cultures were seeded onto the appropriate culture media for the selection of prototrophic colonies. After 3 days incubation at 30°C, the numbers of prototrophic colonies were counted.

 

Olefin 103 PQ/11 did not cause an increase in the reverse mutation rates in bacteria or in the mutation gene conversion rates in yeast in the presence or absence of metabolic activation. The cell survival in yeast was decreased in relation to dose in the absence of S9. Cell survival was relatively unaffected in the presence of S9. Positive controls indicated that the test systems were working appropriately. 

 

This study received a Klimisch score of 2 and is classified as “reliable with restrictions” because while there is no statement regarding whether this study was conducted according to GLP or equivalent, the study appears to be in general accordance with OECD guidelines.

 

This study will influence the DNEL(s).