1-Dodecene, polymer with 1-decene and 1-octene, hydrogenated

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:

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

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Alkane 5

IUPAC Name:

Alkane 5

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 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:

valid

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:

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)