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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 based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1194-12 to 1995-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because the study closely followed OECD 471 guidelines and was GLP compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
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): Alkane-5
- Substance type: Alkane 5
- Physical state: Clear colourless liquid

Method

Target gene:
Base-pair substitution in genetic material or frame shift mutation from histidine dependent to independent forms
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S-9 from livers of male Sprague-Dawley rats
Test concentrations with justification for top dose:
0, 15, 50, 150, 500, 1500, 5000 ug/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ethanol (test material was suspended in an approximate half-log suspension of in pluronic in ethanol)
- Justification for choice of solvent/vehicle: Not provided
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)


DURATION
- Preincubation period: Not provided
- Exposure duration: 48 hours
- Expression time (cells in growth medium):



NUMBER OF REPLICATIONS: Three


NUMBER OF CELLS EVALUATED: Not reported





Evaluation criteria:
There has to be a significant increase in mutation rate (of at least twice the spontaneous reversion rate) in one or more strains of bacteria in the presence and/or absence of the S9 microsomal enzymes at sub-toxic dose levels. For the results to be negative, the number of induced revertants compared to spontaneous revertants should be less than twofold at each dose level tested.
Statistics:
Data were statistically analysed using UKEMS (5) and the Dunnetts method of linear regression was used to evaluate the results.

Results and discussion

Test resultsopen allclose all
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:
valid
Positive controls validity:
valid
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:
valid
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES: Alkane-5 was non-toxic in the strains of bacteria used (TA 100 and E. coli WP2uvrA)


Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

There were no significant increases of revertant colonies for any bacterial strain at any dose level, ±S9. Positive, vehicle, and solvent controls responded appropriately. Alkane 5 was considered non-mutagenic under the conditions of this test.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Alkane 5 was considered non-mutagenic under the conditions of this test.
Executive summary:

Justification for Read Across

Several criteria justify the use of the read across approach to fill data gaps for the poly alpha olefin 1-dodecene polymer with 1-decene hydrogenated (CAS number 151006-60-9) using alkane 5 (1-decene 1-dodecene homoploymer) as an analog. Both of these compounds are poly alpha olefins, i.e., highly branched isoparaffinic chemicals produced by oligomerization of 1-octene, 1-decene, and/or 1-dodecene. They have similarities in chemical structure and physiochemical properties. The literature also indicates that alkanes with 30 or more carbon atoms are unlikely absorbed when administered orally. In turn, studies indicate that they have similar health effect endpoints. Both of these poly alpha olefins have low order acute toxicity and repeated dose toxicity. Additionally gene mutations assays in bacterial cells, as well as in vitro chromosomal aberrations in mammalian cells assays demonstrate no evidence of genotoxicity regardless of metabolic activation. In vivo chromosomal aberrations assays in rats and mice also show no mutagenic potential regardless of metabolic activation. There do not appear to be any toxicological differences between 1-dodecene polymer with 1-decene hydrogenated and alkane 5. Therefore, read across between 1-dodecene polymer with 1-decene hydrogenated and alkane 5 can be justified.

In a mammalian microsome reverse mutation assay, TA 1537, 1535, 100 and 98 and E-Coli WP2uvrA were treated with various concentrations of Alkane-5 using an agar plate and incubated for 48 hours. In addition to the test chemical, a vehicle and negative control and a positive control were also assessed. Treated plates were evaluated using evaluation criteria described previously in sections above.

 

No significant increase of revertant colonies for any bacterial strain was reported at any of the treated doses, both in the presence and absence of S9. Positive, vehicle, and negative controls responded appropriately. Based on these study results, Alkane-5 is considered to be non-mutagenic.

 

This study received a Klimisch score of 1 and is classified as “reliable without restrictions” because the study closely followed OECD 471 guidelines and was GLP compliant.

 

This study will influence the DNEL(s)