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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:
No data reported
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was carried out according to OECD TG 471.
Justification for type of information:
The standard OECD 471 test is not suitable to test petroleum UVCBs, because it has a tendency to produce false negatives for these substances. Therefore, the petroleum industry has developed a Modified Ames assay, optimized to accurately identify positive results for this endpoint. This deviation from the prescribed testing procedure requires some further explanation which is given in the attached document. The document gives a brief history of the development of the Modified Ames test and outlines Concawe’s proposed work (as part of a wider testing strategy, see Annex 13) to further support the use of this test for PS.

Data source

Reference
Reference Type:
publication
Title:
Estimation of the dermal carcinogenic activity of petroleum fractions using a modified Ames assay
Author:
Blackburn GR, Deitch RA, Schreiner CA, Mehlman MA, and Mackerer CR
Year:
1984
Bibliographic source:
Cell Biol Toxicol, Vol 1(1):67-80

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
not specified
Type of assay:
other: modified bacterial reverse mutation assay (modified Ames test)

Test material

Constituent 1
Reference substance name:
Solvent refined/Hydrotreated heavy naphthenic distillate, (CAS # 64741-96-4/CAS # 64742-52-5)
IUPAC Name:
Solvent refined/Hydrotreated heavy naphthenic distillate, (CAS # 64741-96-4/CAS # 64742-52-5)
Details on test material:
Read Across to Unrefined/Acid Treated Oils

The following substances were tested:

Number 7, Solvent refined/Hydrotreated heavy naphthenic distillate, CAS 64741-96-4/CAS 64742-52-5.
Number 9, 10, and 11, Solvent refined/hydrotreated heavy paraffinic distillate, CAS 64741-88-4/CAS 64742-54-7.
Number 13: Solvent refined/dewaxed heavy paraffinic distillate, CAS 64741-88-4/CAS 64742-65-0.

Method

Target gene:
Not applicable.
Species / strain
Species / strain / cell type:
S. typhimurium TA 98
Details on mammalian cell type (if applicable):
Not applicable.
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with
Metabolic activation system:
Aroclor 1254-induced rat or hamster liver S9
Test concentrations with justification for top dose:
50 uL
Vehicle / solvent:
dimethyl sulphoxide
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: benzo(a)pyrene at 5 μg/plate and 2-aminoanthracene at 2 μg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: not reported
- Exposure duration: not reported
- Expression time (cells in growth medium): not reported
- Selection time (if incubation with a selection agent): not reported
- Fixation time (start of exposure up to fixation or harvest of cells): not reported

NUMBER OF REPLICATIONS: not reported

NUMBER OF CELLS EVALUATED: not reported

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index


Evaluation criteria:
Mutagenicity Index
Statistics:
No data reported.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Additional information on results:
No data reported.
Remarks on result:
other: other: Modified Ames Test using Salmonella typhimurium strain TA 98 and Aroclor 1254-induced hamster liver S-9
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

The modified assay was used to rank the test samples, and a corn oil control, for relative mutagenic activity.  The ranking correlated closely  (r=0.97) with potency ratings from previously determined carcinogenicity bioassays.  Samples subjected to solvent refining were non-carcinogenic.

In the table below, the sample number in the study report along with the study ID and mutagenicity index of each substance is listed.

Sample Number

Sample ID

CAS#

Mutagenicity Index

7

Solvent-Refined/Hydrotreated Heavy Naphthenic Distillate

64741-96-4/

64742-52-5

0

9

Solvent-Refined/Hydrotreated Heavy Paraffinic Distillate

64741-88-4/

64742-54-0

0

10

Solvent-Refined/Hydrotreated Heavy Paraffinic Distillate

64741-88-4/

64742-54-0

0

11

Solvent-Refined/Hydrotreated Heavy Paraffinic Distillate

64741-88-4/

64742-54-0

0

13

Solvent-Refined/Dewaxed Heavy Paraffinic Distillate

64741-88-4/

64742-65-0

0

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

All five solvent refined samples had mutagenicity indices of 0 and are therefore not considered positive in the AMES test for bacterial mutagenicity.
Executive summary:

Read Across Justification

The physical and chemical properties of foots oils are comparable to the other lubricant base oil intermediate streams from which they are derived. Hence their health effects are also similar to those of other lubricant base oils, and the conclusions of the hazard assessment for other lubricant base oils also apply to foots oils.

In an in vitro modified Ames assay, five lubricating base oils were tested using S. typhimurium strain TA98 at concentrations of 50 micrlitres per plate. The solvent-refined samples tested were not mutagenic and had mutagenicity indices of 0. This study received a Klimisch score of 1 and is classified as reliable without restriction because it was carried out according to OECD TG 471.