Solvent naphtha (petroleum), heavy aliph.

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1983-01-21 to 1983-06-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restrictions because it was carried out in a method equivalent/similar to OECD TG 476.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

64742-81-0

Cas Number:

64742-81-0

IUPAC Name:

64742-81-0

Constituent 2

Reference substance name:

Hydrodesulfurised kerosine

IUPAC Name:

Hydrodesulfurised kerosine

Test material form:

other: low viscosity liquid hydrocarbon

Details on test material:

Test substance: Hydrodesulfurised kerosine Sample API 81-07, CAS No. 64742-81-0

Method

Species / strain

Species / strain / cell type:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Test concentrations with justification for top dose:

3.91 to 6.25 nl/ml with activation, 6.25 to 37.5 nl/ml without activation.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: none

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

corn oil

Positive controls:

yes

Positive control substance:

triethylenemelamine

Details on test system and experimental conditions:

Mouse lymphoma assay

Results and discussion

Test results

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

The test material induced a good range of toxicities for evaluation (relative growths ranged from 2.8% to 65.3%, -S9, and 6.1 to 107.9% relative growths, +S9)

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: mouse lymphoma L5178Y cells

Any other information on results incl. tables

The test material was immiscible with water and DMSO at 100 µl/ml but was miscible with ethanol at the same concentration. Stocks were prepared by performing serial dilutions in ethanol just prior to each assay. The mutation assays were then initiated by performing final dilutions of the stocks into the assay medium containing the lymphoma cells. The test material appeared soluble in the assay medium up to 125 nl/ml but a white precipitate was noted from 250 to 1000 nl/ml.

Two trials of the assay were initiated.
Trial 1 was performed with and without activation but the non-activation assay was NOT used in the evaluation because of unacceptable suspension growth in the negative controls. The non-activation portion of the assay was therefore repeated in Trial 2.

The report summarized here included the acceptable activation assay from Trial 1 and the acceptable non-activation assay from Trial 2.

The results are summarized below.
 

	Rel	Total	Total	Cloning	Rel	Mutant
	Susp.	mutant	viable	eff.	growth	frequency
	growth	colonies		(%)	10E^-6units
	(% of control)
Non activation assay (Trial 2)
Solvent control (ethanol)
	100	70	392	100	100	17.9
	100	74	287	100	100	25.8
	100	75	367	100	100	20.4
	100	50	324	100	100	15.4
Untreated control
	107.1	82	374	109.2	116.7	21.9
	97.4	70	392	116.5	111.3	17.9
EMS(µl/ml)
0.5	46.7	851	170	49.6	23.2	500.6
0.5	57.3	753	155	45.3	25.9	485.8
API81-07 (nl/ml)
6.25	28.3	83	331	96.6	27.3	25.1
12.5	24.7	61	282	82.3	20.3	21.6
12.5	67.4	89	332	96.9	65.3	26.8
25.0	16.3	87	258	75.3	12.3	33.7
25.0	45.4	61	248	72.4	82.7	24.6
37.5	10.3	105	366	106.8	11	28.7
37.5	6.2	77	143	41.7	2.6	53.8
Activation assay
Solvent control (ethanol)
	100	98	236	100	100	41.5
	100	92	282	100	100	32.6
Untreated control
	128.2	99	226	87.2	111.8	43.8
DMN( µl/ml)
0.3	58.5	151	34	13.1	7.7	444.1
API81-07 (nl/ml)
3.91	100.1	66	194	74.8	74.9	34
7.81	194.1	52	144	55.6	107.9	36.1
15.6	101.7	42	259	99.9	101.6	16.2
31.3	27.3	45	158	61	16.7	28.5
62.5	9	68	175	67.5	6.1	38.9

 
Under non-activation conditions the test material induced a good range of toxicities for evaluation (relative growths ranged from 2.8% to 65.3%).
None of the assays induced a mutant frequency that exceeded the minimum criterion (40.8 x 10-6). The test material was not mutagenic under non-activation conditions.

In the presence of metabolic activation, a wide range of toxicities were induced (6.1 to 107.9% relative growths). The minimum criterion mutant frequency of 69.0 x 10-6 was not exceeded. The test material was therefore considered non mutagenic under activation conditions.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

The test substance does not induce chromosomal aberrations in rat bone marrow cells under the condition of the study. ... (see attached file)

Executive summary:

In a mammalian cell gene mutation assay, mouse lymphoma L5178Y cells, cultured in vitro, were exposed to hydrodesulfurised kerosine at concentrations from 6.25 nL/mL to 37.5 nL/mL without activation and from 3.91 nl/ml to 62.5 nl/ml with S9 metabolic activation. The cells were exposed for four hours both in the presence and absence of the rat liver S9 metabolic activation.

Under non-activation conditions the test material induced a good range of toxicities for evaluation (relative growths ranged from 2.8% to 65.3%). None of the assays induced a mutant frequency that exceeded the minimum criterion (40.8 x 10-6). The test material was not mutagenic under non-activation conditions. In the presence of metabolic activation, a wide range of toxicities were induced (6.1 to 107.9% relative growths). The minimum criterion mutant frequency of 69.0 x 10-6 was not exceeded. The test material was therefore considered non mutagenic under activation conditions.

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was carried out in a method similar/equivalent to OECD TG 471.