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Toxicological information

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:
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

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.