Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Modified version of a standard Ames test, good experimental detail, suitable for assessment

Data source

Reference
Reference Type:
publication
Title:
Evaluation of the Genetic Toxicity of Middle Distillate Fuels
Author:
R.H. McKee, M.A. Amoruso, J.J. Freeman and R.T. Przygoda
Year:
1994
Bibliographic source:
Environmental and Molecular Mutagenesis 23:234-238 (1994)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
[1] extraction step designed to concentrate possible mutagenic aromatic compounds. [2] use of S-9 at 8x recommended concentration. [3] Use of only 1 strain Salmonella Typhimurium (TA 98) most sensitive to complex mixture of PAHs
Principles of method if other than guideline:
Method of Blackburn: Ames test modified to optimise detection of mutagenic PAHs in petroleum-based oils (see derivation of standard Ames test)
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent

Method

Target gene:
Not applicable
Species / strain
Species / strain / cell type:
other: Salmonella Typhimurium TA 98
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with
Metabolic activation system:
Aroclor-induced hamster S9 used at 8x standard Ames test concentration, with pre-incubation
Test concentrations with justification for top dose:
DMSO extracts: 5, 10, 15, 20, 30, 40, 50, 60 (represents extractable material from approx. 0.8-9.6 mg of the test substance)
Cyclohexane extracts: 1, 5, 10, 25, 50 uL/plate (represents extractable material from approx. 0.16-8 mg of the test substance)
Vehicle / solvent:
Extraction solvent: DMSO and cyclohexane
Controls
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene

Results and discussion

Test results
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with
Genotoxicity:
ambiguous
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Observations:
DMSO extract: tested at 5-60 ul/plate, toxic at 50 and 60
ul/plate. Revertant count doubled (2.2x) at 60 ul/plate
compared with solvent control, but no clear dose-response
relationship. Mutagenic index calculated as 1.3
revertants/ul. Result concluded equivocal.
Remarks on result:
other: strain/cell type: bacteria
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
ambiguous with metabolic activation

It is expected based on the results of the analogus substance Renewable Diesel has weak genotoxic potential in vitro, which is likely to be attributable to the content of aromatics, particularly polycyclic aromatic hydrocarbons (PAHs).