C14-16 (even numbered) and C16 (branched) saturated and unsaturated aliphatic hydrocarbons

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:

1995-09-22 to 1995-10-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restriction because it was conducted in accordance with OECD 471 guideline for reversion assays and was GLP compliant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

The identity, strength, purity, and stability of the test chemical were not provided in the study report.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

C14-16 (even numbered) and C16 (branched) saturated and unsaturated aliphatic hydrocarbons

EC Number:

700-762-0

Molecular formula:

All molecules present in the mixture have the general molecular formula CnH2n for olefins or CnH2n+2 for the paraffin’s with n being an even number

IUPAC Name:

C14-16 (even numbered) and C16 (branched) saturated and unsaturated aliphatic hydrocarbons

Test material form:

liquid: viscous

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

S-9

Test concentrations with justification for top dose:

50, 158, 500, 1580, and 5000 micrograms per plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: None provided

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Remarks:

2-nitrofluorene was also used as a positive control

Details on test system and experimental conditions:

METHOD OF APPLICATION: In agar (plate incorporation)


DURATION
- Preincubation period: None
- Exposure duration: 2 days


NUMBER OF REPLICATIONS: Three


DETERMINATION OF CYTOTOXICITY
- Method: other: background lawn

Evaluation criteria:

Not reported.

Statistics:

None reported.

Results and discussion

Test results

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:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: An appropriate preliminary toxicity assay was performed to select an adequate dose range for testing in the mutagenicity assay.

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

Based on these results, the study authors concluded that SHOP internal olefins C134 was not cytogenic to the four Salmonella typhimurium strains treated with concentrations up to 5000 µg/plate either in the presence or absence of S9.

Executive summary:

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps for Category C substances using Category D substance analogues. Category C is comprised of isomerised olefins.  Category D is comprised of isomerised olefins with a range of carbon numbers. Studies indicate that changing the carbon number or the location of the double bond, or adding branching does not measurably alter the mammalian health endpoints. There appears to be no critical difference across Category D isomerised olefins with a range of carbon numbers with regard to health endpoints. Toxicity concerns are low for acute exposure to Category D substances. Genotoxicity studies indicate that these materials are not mutagenic. There was no adverse systemic toxicity observed in a 90-day repeated oral dose study, in which rats were exposed to C20-24 branched and linear alkenes. As a result, all of the above tested mammalian toxicity endpoints indicate a low hazard potential for human health. There do not appear to be any toxicological differences between Category D isomerised olefins with a range of carbon numbers and Category C is comprised of isomerised olefins.  Therefore, read across between these two categories can be justified.

In a reverse gene mutation assay in bacteria, four strains of Salmonella typhimurium (TA 98, 100, 1535, and 1537) were exposed to SHOP internal olefins C134 dissolved in ethanol at concentrations of 50, 158, 500, 1580, and 5000 µg/plate in the presence and absence of mammalian S-9 metabolic activation using a plate incorporation assay and incubated for 2 days. An appropriate preliminary toxicity assay was performed to select an adequate dose range for testing in the mutagenicity assay. The test conditions appear to comply with OECD 471 guideline requirements. Positive and negative controls indicated that the test system was working appropriately. None of the test chemical treated bacterial strains showed increases in reversions. Based on these results, the study authors concluded that SHOP internal olefins C134 was not cytogenic to the four Salmonella typhimurium strains treated with concentrations up to 5000 µg/plate either in the presence or absence of S9. 

This study received a Klimisch score of 1 and is classified as reliable without restrictions because it was conducted in accordance with OECD 471 guideline for reversion assays and was GLP compliant. This study will influence the DNEL.