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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro DNA damage and/or repair study
Remarks:
Type of genotoxicity: DNA damage and/or repair
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1987-07-29 to 1988-04-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restrictions because it closely followed OECD Guideline 479 and appears to be GLP compliant

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 479 (Genetic Toxicology: In Vitro Sister Chromatid Exchange Assay in Mammalian Cells)
GLP compliance:
yes
Remarks:
Study report states that the study was conducted in compliance with GLP regulations
Type of assay:
sister chromatid exchange assay in mammalian cells

Test material

Constituent 1
Reference substance name:
64742-80-9
Cas Number:
64742-80-9
IUPAC Name:
64742-80-9
Constituent 2
Reference substance name:
Hydrodesulfurised middle distillate
IUPAC Name:
Hydrodesulfurised middle distillate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): API 81-10
Details of test material from report: API (1986a). Four Week Subchronic Inhalation Toxicity Study in rats. Testing laboratory: International Research and Development Corporation, Mattawan, Michigan. Report no.: 418-027. Owner company: American Petroleum Institute. Study number: 33-32724. Report date: 1986-08-28.
- Substance type: Hydrodesulfurized Middle Distillate
- Physical state: Clear liquid
- CAS number: 64742-80-9
- Gravity API degrees: 34.9
- Sulfur wt %:0.28
- Nitrogen ppm: 97
- Flash Point °F: 160
- Boiling range (ASTM D-86) 10-95%: 421-637 °F
- Initial Boiling Point 342 °F
- End Boiling Point 651 °F
- Composition % by MS:
olefins 0
aromatics 30.9
paraffins 48.9
naphthenes 20.2

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Test concentrations with justification for top dose:
0.008, 0.016, 0.03 and 0.06 µl/ml
Vehicle / solvent:
acetone

Results and discussion

Test resultsopen allclose all
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
statistically significant increase in the frequency of SCEs was observed at the lowest two doses
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not examined
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
without
Genotoxicity:
negative
Remarks:
no statistically significant increase in the frequency of SCEs was observed
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
not examined
Untreated negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
ambiguous with metabolic activation
negative without metabolic activation

The study authors concluded that Hydrodesulfurised middle distillate did not induce an increase in sister chromatid exchange (SCE) in CHO cells in the absence of S-9 activation. In the presence of S-9, since there was statistically significant increase in the frequency of SCEs at the lower doses, Hydrodesulfurised middle distillate was concluded to be equivocal in the SCE assay.
Executive summary:

Justification for Read Across

Compositional and physico-chemical data show that Straight-Run Gas Oils are very similar to Other Gas Oils. It is considered appropriate, therefore, to read across from the Other Gas Oil data to SRGOs.

In a sister chromatid exchange (SCE) assay, Chinese hamster ovary (CHO) cells were initially tested with Hydrodesulfurised middle distillate in acetone at doses ranging from 1.0 to 0.0001 µl/ml in a preliminary toxicity test to determine the dose range to be used for the main SCE assay. Following the results from this preliminary test, Hydrodesulfurised middle distillate dose levels of 0.008, 0.016, 0.03 and 0.06 µl/ml in the absence of S-9 and dose levels of 0.13, 0.25, 0.5, and 1µl/ml in presence of S-9 activation were selected for the SCE assay. A harvest time of 27 hours after study initiation was selected to ensure that enough analysable second division metaphase cells can be collected at the high dose. In addition to treated cells, a solvent control group and positive controls consisting of trimethylenemelamine (TEM) for inactive studies (no S-9) and cyclophosphamide (CP) for active studies (with S-9) were also used to test the efficacy of the SCE assay.

Hydrodesulfurised middle distillate did not induce an increase in SCEs in the CHO cells in the absence of S-9 activation. In contrast, in cells treated with the test material in the presence of S-9 activation, there was a statistically significant increase in the frequency of SCEs at two consecutive low dose levels compared to the solvent control. However, an inverse dose-response trend was observed with no significance at the highest two doses tested. The positive control CP induced SCEs as expected. Based on these results, the study authors concluded that Hydrodesulfurised middle distillate did not induce an increase in SCEs in CHO cells in the absence of S-9. However, due to a statistically significant increase in SCE frequency at two consecutive low dose levels, the study authors concluded that Hydrodesulfurised middle distillate was equivocal for induction of SCEs in the CHO cells in the presence of S-9.

This study received a Klimisch rating of "reliable without restriction" because it closely followed OECD Guideline 479 and appears to be GLP compliant.