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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 18 April 1984 to 2 February 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted by a GLP accredited laboratory using a method similar to OECD 475 Testing Guideline and meets acceptable scientific standards

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
Intraperitoneal injection not recommended as it is not a relevant route of human exposure. No historical data.
GLP compliance:
yes (incl. QA statement)
Type of assay:
mammalian germ cell cytogenetic assay

Test material

Constituent 1
Reference substance name:
Distillates (petroleum), light catalytic cracked
EC Number:
265-060-4
EC Name:
Distillates (petroleum), light catalytic cracked
Cas Number:
64741-59-9
IUPAC Name:
64741-59-9
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Light catalytic cracked distillate (petroleum)
- Substance type: Hydrocarbons having carbon numbers predominantly in the range of C9 through C25. Also contains relatively large portion of bicyclic aromatic hydrocarbons
- Physical state: Light brown liquid
- Storage condition of test material: stored in the dark at room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratory
- Age at study initiation: 6-8 weeks
- Weight at study initiation: Male: 235-299g, Female: 150-204g
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: AAALAC-accredited facility
- Diet: ad libitum, certified laboratory rodent chow
- Water: ad libitum
- Acclimation period: 10-14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-27°C
- Humidity (%): 50±20%
- Photoperiod (hrs dark / hrs light): 12 hours dark, 12 hours light cycle

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
- Vehicle(s)/solvent(s) used: corn oil
- Concentration of test material in vehicle: 0.3, 1.0 and 3.0 g/kg
- Lot/batch no. (if required): B11B
Duration of treatment / exposure:
Immediate
Frequency of treatment:
Once
Post exposure period:
6, 24, 48 hours
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
3.0g/kg
Basis:
no data
Remarks:
Doses / Concentrations:
1.0g/kg
Basis:
no data
Remarks:
Doses / Concentrations:
0.3g/kg
Basis:
no data
No. of animals per sex per dose:
5
Control animals:
yes
yes, concurrent vehicle
Positive control(s):
- Substance: triethylenemelamine
- Route of administration: IP
- Doses / concentrations: 0.5mg/kg

Examinations

Tissues and cell types examined:
Bone marrow cells
Details of tissue and slide preparation:
colchine injected into bone marrow at 1mg/kg to all rats two-four hours prior to sacrifice. After sacrifice bone marrow was aspirated into a syringe of HBSS (Hank's balanced salt solution) and stored till samples had been collected from all animals. They were then washed and mixed with Carnoy's fixative before being air dried on a slide the following day. The dry slides were stained with 4% Giemsa Stain and permanently mounted. Two slides were prepared per rat.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Remarks:
no increase in number of cells with aberrations noted compared to vehicle control
Toxicity:
yes
Remarks:
Diarrhea, crusty eyes and noses observed in rats following a dose related correlation
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
RESULTS OF DEFINITIVE STUDY
- Types of structural aberrations for significant dose levels: Gaps; chromosome and chromatid breaks; fragments; EX, DIC and RG rearrangements; Severe cell damage
- Appropriateness of dose levels and route: Intraperitoneal injection not recommended as it is not a relevant route of human exposure.
- Statistical evaluation: Student's t test, chi-square analysis

Any other information on results incl. tables

Chromosomal damage in bone marrow of rats after treatment with API 83-08

Substance Concentration Time (hr) Total number of cells Incidence of Aberrations (%) Total number of aberrations Aberrationsfrom severelydamaged cells Aberrationsper cell
Evaluated With Aberrations Gaps Breaks Rearrangments
Corn Oil 5ml/kg 6 500  1 0.2 0 1 0 0 0.002
24 500  0 0 0 0 0 0 0
48 500  2 0.4 4 2 0 0 0.004
API 83-08 3.0mg/kg 6 500 0 0 1 0 0 0 0
24 500 1 0.2 0 1 0 0 0.002
48 500 0 0 4 0 0 0 0
1.0mg/kg 6 500 0 0 0 0 0 0 0
24 500 0 0 0 0 0 0 0
48 500 1 0.2 5 1 0 0 0.002
0.3mg/kg 6 500 0 0 0 0 0 0 0
24 500 0 0 1 0 0 0 0
48 500 0 0 4 0 0 0 0
TEM 0.5mg/kg 24 500 198 39.6 13 144 77 1250 2.942

Breaks include chromatid and chromosome breaks and fragments

Cells with more than 10 aberrations were counted as 10

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
The test item was considered to be non-mutagenic under the conditions of the test.
Executive summary:

The in vivo cytogenicity of the test substance was determined according to a method similar to the OECD Guideline for Testing of chemicals 475. Chromosome aberrations were evaluated in Sprague-Dawley rats after administration by intraperitoneal route.

The results were negative for acute cytogenotoxicity. The animals were exposed to 0.2, 0.67, or 2g/kg of the test item using corn oil as a vehicle for 6, 24 and 48 hours before the rat was sacrificed and the bone marrow removed. The incidence of cells with aberrations was not significantly increased when compared to the vehicle control. Triethylenemelamine was used as a positive control. Rats showed signs of lethargic behaviour, scruffy coat, blood around nose, disorientation and uncoordination, and death on a dose and time related correlation.

The test item was therefore evaluated as none genotoxic under the conditions of this assay.

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