Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

From the in-vitro results ECB (1997) and OECD (2002) dossiers also indicate that Alkylate 215 did not exhibit mutagenic activity in the Ames bacterial assay and that Alkylate 215 and Alkylate 225 were negative in the CHO/HGPRT mammalian cell forward gene mutation assay.

From the in-vivo results it may be questioned whether there was a proof of distribution to the bone marrow because no bone marrow clastogenicity or myelotoxicity was evidenced. However:

- This question was not raised in ECB (1997) and OECD (2002) dossiers, necessarily implying that systemic exposure has been considered adequate incl. by European safety assessors;

- The administered dose-levels were extremely high and largely above regulatory requirements.

- Significant systemic distribution is evidenced for LAB and BAB based on all available data (see toxicokinetic discussion: Serfass, 2011).

- The very high lipophilicity (log Kow) and relatively small size of the substance makes it very likely to partition to lipid-rich compartments such as the bone marrow.

Therefore, overall, the negative results are considered to be reliable and to exclude mutagenicity to somatic cells.


Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995-2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: We do not have the full study but only a robust study summary given in OECD SIDS "C10-16 Alkyl derivatives"
Qualifier:
no guideline available
Principles of method if other than guideline:
Adetailed description of the method is not included in the study report. According to that report the method is based on Ames et al. 1975.
The tested specie is rat (Sprague-Dawley) and the route is oral (gavage)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
no data
Test concentrations with justification for top dose:
up to 3.0 mg/plate
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:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: other:
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

The test gave negative results with and without activation
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: We do not have the full report but only the EU/RAR on Benzene C10-13 alkyl derivatives
Principles of method if other than guideline:
A detailed description of the method is not included in the report. Acording to that report the method is based on Ames et al.1975
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 hepatic fraction
Test concentrations with justification for top dose:
1st test : 0,100,1000,4000,8000 and 10000 micro g/plate (EEC B14, ref 34)
2nd test : 0.3,12,60,300,1000,3000 micro g/plate
Vehicle / solvent:
DMSO
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:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.
Conclusions:
The results of both tests were negative
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: We do not have the complete test report but only an extract given in the OECD SIDS report : Benzene C10-16 alkyl derivatives
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Principles of method if other than guideline:
Method EPA/TSCA bone marrow chromosome abberation
GLP compliance:
yes
Type of assay:
chromosome aberration assay
Species:
rat
Strain:
Sprague-Dawley
Sex:
not specified
Route of administration:
oral: gavage
Vehicle:
no data
Details on exposure:
no data
Positive control(s):
no data
Details of tissue and slide preparation:
no data
Sex:
not specified
Genotoxicity:
negative
Toxicity:
yes
Remarks:
lowest producing toxicity : 127000 mg/kg
Additional information on results:
Effect on Mitotic index or P/N Ratio : no effect
Conclusions:
Interpretation of results (migrated information): negative
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: We do not have the full study report but only an extract given in EU RAR : Benzene C10-13 alkyl derivatives
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
not specified
GLP compliance:
not specified
Type of assay:
chromosome aberration assay
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
no data
Route of administration:
oral: gavage
Vehicle:
undiluted or in corn oil
Details on exposure:
one exposure
Duration of treatment / exposure:
no data
Remarks:
Doses / Concentrations:

Basis:
no data
No. of animals per sex per dose:
18-24
Control animals:
yes
Details of tissue and slide preparation:
no data
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
not specified
Negative controls validity:
not specified
Positive controls validity:
not specified
Additional information on results:
No statiscally significant increases in chromosal aberration ot gaps were observed in the treated groups at any of the sampling times.
Both mean chrosome numbers and mean mitotic indices were similar in test and vehicle control groups
Conclusions:
Interpretation of results (migrated information): negative
Executive summary:

Substance was given via gavage undiluted or dissolved in corn oil. The solutions were given once to three groups of 18 -24 male and

female rats at dosages of 1200, 4000 and 12 700 mg:kg bw.

A significant mean body weight loss was found in the groups treated with the highest dose. No statistically significant increases in

chromosome aberration or gaps were observed in the treated groups at any of the sampling times.

Both mean chromosome numbers and mean mitotic indices were similar in test and vehicle control groups.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Justification for classification or non-classification

Based on data assessed by OECD and EU, LAB do not induce gene mutations in bacteria and mammalian cells in vitro, and do not induce chromosome aberrations in rodent bone marrow. Adequate exposure of the bone marrow can be inferred although not demonstrated s.s. Therefore, mutagenicity to somatic cells is excluded. 

Based on this result and the existence of a hemato-testicular barrier, it seems reasonable to consider that the substance is also non mutagenic to germ cells.

However, all data and conclusions apply to BAB and in no case to any impurity which would not belong to this class. Concerning this, it is noteworthy that CLP note P (with a benzene cut-off of 0.1% for classification as a mutagen) does not apply because the substance is not obtained from complex oils, but by reaction of benzene with propylene oligomers.