Hydrocarbons, C9-16, hydrotreated, dearomatized

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian cell study: DNA damage and/or repair

Remarks:

Type of genotoxicity: DNA damage and/or repair

Type of information:

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

Adequacy of study:

key study

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 479 with modifications.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 479

Deviations:

yes

Remarks:

Test was conducted in vivo and not in vitro as recommended by the guideline

GLP compliance:

yes

Type of assay:

sister chromatid exchange 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:

- Name of test material: Hydrodesulfurised kerosine, sample API 81-07, CAS No. 64742-81-0
- Substance type: complex combination of hydrocarbons produced by the distillation of crude oil
- Carbon Number Range: C9 through C16
- Physical state: clear liquid
- Analytical purity: not applicable, complex hydrocarbon mixture
- Composition of test material: 47% paraffins, 1% olefins, 35% naphthenes and 18% aromatics
- Storage: room temperature, protected from light
- Gravity, API: 41.9
- Sulfur, Wt %: 0.07
- Flash, ° F: 140
- Distillation, °F (ASTM D-86): 392-506 (10-95%)
Initial BP, °F: 362
Final BP, °F: 535

Test animals

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Weight at study initiation: Toxicity Study: Male 21-28 grams. Female 12-22 grams. SCE Assay: Male 22-31 grams. Female 18-23 grams.
- Assigned to test groups randomly: No.
- Housing: Plastic autoclavable cages with wire lids. Hardwood chips for bedding.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Quarantined for 10-14 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23-26 degrees Celsius
- Humidity (%): relative
- Photoperiod (hrs dark / hrs light): 12/ 12

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: corn oil.

Duration of treatment / exposure:

The animals were exposed for 20-22 hours

Frequency of treatment:

The animals were administered a single dose.

Doses / concentrations

Remarks:

Doses / Concentrations:
400, 2000 & 4000 mg/kg
Basis:
no data

No. of animals per sex per dose:

SCE Assay: five males and five females.

Positive control(s):

cyclophosphamide
- Preparation: dissolved in distilled water at concentration 1 mg/ml
- Route of administration: was administered intraperitoneally

API-81-15
Preparation: Dissolved in corn oil at concentration 400 mg/ml

Examinations

Tissues and cell types examined:

Sister Chromatid Exchanges per individual animals

Details of tissue and slide preparation:

Cells were collected by centrifugation, resuspended to opalescene in fresh fixative.
Two to four drops of fixed cells were dropped onto a wet slide and air dried. Slides were stained by Hoechst 33258-black light-Giemsa technique. Two to five slides were prepared from each animal.

Metaphase cells were examined under oil immersion without prior knowledge of treatment groups.

Evaluation criteria:

The number of SCEs per total second-division metaphase cells scored were recorded for each group, along with the range of SCEs/metaphase for animals within groups.

Statistics:

Kruskall Wallis test was used. Mann Whitney Test was used if required.
Test article is considered to induce a positive response if a dose-related increased in SCEs/metaphase is observed relative to the vehicle control (p< or = 0.05 Mann Whitney)

Results and discussion

Test results

Test results 1

Sex:

male

Genotoxicity:

positive

Toxicity:

yes

Remarks:

ration and on the following day. In the high dose and the mid-dose males there was a slight weight loss.

Test results 2

Sex:

female

Genotoxicity:

negative

Toxicity:

yes

Remarks:

. In the high dose females there was a slight weight loss.

Any other information on results incl. tables

The high dose male mice were lethargic shortly after dose administration and on the following day. In the high dose males and females and the mid-dose males there was a slight weight loss. Body weights were measured between the time of the pre-treatment and when the animals were treated with colchicine on the following day.
The body weight changes are shown below:

Treatment	Sex	% change (+ or -)
Corn oil		24 hr
10 ml/kg	M	0
	F	- 2.9
API 81-07	M	- 1.4
400 mg/kg	F	- 0.5
2000 mg/kg	M	- 3.5
	F	- 1.9
4000 mg/kg	M	- 4.3
	F	- 4.7
API81-15	M	0
4000 mg/kg	F	+ 3.8
Cyclophosphamide
10 mg/kg	M	+ 2.6
	F	- 3.8

The SCEs were counted in 50 second-division metaphase cells and these data are summarized in the following table.

Treatment	Sex	Range of mean SCEs/cell for Individual Animals	Average SCEs/cell per mouse (a)
Corn oil	M	4.68 - 5.84	5.44±0.47 (5.64)
	F	5.28 - 7.36	6.25±0.86 (6.06)
API81-07
400 mg/kg	M	6.76 - 10.46	8.26±1.51 (5.64)**
	F	6.98 - 8.26	7.56±0.52 (7.56)
2000 mg/kg	M	5.68 - 7.58	6.74±0.87 (6.86)**
	F	6.8 - 9.84	8.26±1.22 (8.54)
4000 mg/kg	M	5.72 - 7.66	6.86±0.75 (7.06)*
	F	6.56 - 12.3	9.20±2.49 (9.88)
API81-15
4000 mg/kg	M	6.68 - 9.28	7.94±0.93 (7.94)**
	F	7.28 - 8.54	7.86±0.58 (7.56)*
Cyclophosphamide
10 mg/kg	M	36.6 - 44.18	40.3±3.53 (38.5)**
	F	18.34 - 31.64	25.5±5.44 (25.06)**
(a) Mean ± standard deviation (Median SCEs/cell)
*P < 0.05
** P < 0.01 (Mann Whitney test)

It was concluded that the negative and positive controls fulfilled the requirements and that API 81-07 was positive in male mice.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): positive positive in male mice, negative in female mice
No statistically significant effect was observed in the female mice, whereas the female mice responded positively to administration of both cyclophosphamide (10 mg/kg) and a carcinogenic heavy fuel oil (4000 mg/kg) which were used as positive control.
Under the conditions described in this report, the test article hydrodesulfurised kerosine does induce a significant increase in bone marrow SCEs in male B6C3F1 mice. However, the doses of the test article were rather high (400, 2000 and 4000 mg/kg) and the males in the highest dose groups showed signs of toxicity (lethargy and weight loss) on the day of the administration of the kerosine and the day after (when they were sacrificed).

Executive summary:

In a mammalian cell SCE assay, four hours after agar-coated BrdUrd pellet implantation, the mice were given hydrodesulfurised kerosine as a single i.p. dose of either 400, 2000 or 4000 mg/kg in corn oil at a dose volume of 10 mL/kg (doses based a range finding study). A solvent control group was given corn oil at a dose of 10 mL/kg. Two positive control groups were used. One received cyclophosphamide i.p. at a dose of 10 mL/kg and the other received API 81-15 (a carcinogenic heavy fuel oil component) at a dose level of 4 g/kg, also at an injection rate of 10 mL/kg.

 

Positive control group API 81 -15 induced a significant increase in SCEs/cell/mouse relative to the vehicle control, as did the cyclophophamide. The results of the assay indicate that under the conditions described in this report, the test article, hydrodesulfurised kerosine, does induce a significant increase in bone marrow SCEs in male B6C3F1 mice, but not in female mice. The female mice responded positively to administration of both cyclophosphamide (10 mg/kg) and a carcinogenic heavy fuel oil (4000 mg/kg). The doses of the test article were rather high (400, 2000 and 4000 mg/kg) and the males in the highest dose groups showed signs of toxicity (lethargy and weight loss) on the day of the administration of the kerosine and the day after (when they were sacrificed).

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because it was carried out in a method equivalent/similar to OECD TG 479 with modifications.