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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:
1983
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
yes
Type of assay:
chromosome aberration assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Paraffin waxes and Hydrocarbon waxes, chloro
EC Number:
264-150-0
EC Name:
Paraffin waxes and Hydrocarbon waxes, chloro
Cas Number:
63449-39-8
Molecular formula:
C18H33Cl5 C18H30Cl8 C20H36Cl6 C20H33Cl9 C25H45Cl7 C25H42Cl10 C25H29C23 C30H53Cl9 C30H49Cl13 C30H35Cl27
IUPAC Name:
Paraffin waxes and Hydrocarbon waxes (C18 and longer), chloro
Details on test material:
C20-30; 70% Cl (solid)

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
vehicle of 1% carboxymethylcellulose in water
Details on exposure:
The CP treatment and 1% carboxymethylcellulose control animals were all dosed once daily by oral gavage for 5 days. The cyclophosphamide and saline control groups were dosed via i.p. 36 and 12 hours before scheduled sacrafice. Approximately 6 hours prior to sacrafice all animals were administered colchicine, 5 mg/kg, i.p. to arrest mitosis at C-metaphase.
Duration of treatment / exposure:
5 days
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
500, 1500, 5000 mg/kg /day
Basis:
actual ingested
No. of animals per sex per dose:
8
Control animals:
yes, concurrent vehicle
Positive control(s):
Cyclophosphamide (40 mg/kg), the positive control, was administered by i.p. injection to groups of 8 male Fischer 344 rats on days 5 and 6 of the study, 36 and 12 hours prior to scheduled termination, respectively . Control groups of 8 rats received i.p. injections of saline on the same schedule.

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
Femurs were dissected, bone marrow collected and slides of metaphase spreads were prepared. Up to 100 smears were examined from each rat receiving the test compound (less for positive controls).
Statistics:
Statistical evaluation of mutation frequencies was made by the method described by Kastenbaum and Bowman.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

No deaths occurred during the exposure period. Body weight gain was reduced in rats receiving 5000 mg/kg test material, compared to controls. No treatment related signs of toxicity were noted. No increases in the frequency of chromosomal abnormalities were observed in the treated groups when compared to the controls. The positive agent, cyclophosphamide, produced a highly statistically significant frequency of chromosomal aberrations per cell, with nearly 70% of all spreads examined appearing abnormal. The high frequency of chromosomal aberrations noted for the positive control group indicates the experimental system to be appropriate and sensitive. No specific evidence was presented to demonstrate that the test article reached the target organ at doses up to 5000 mg/kg po, the limit dose applied in the study design.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
No increases in the frequency of chromosomal abnormalities were observed in the treated groups when compared to the controls. The positive agent, cyclophosphamide, produced a highly statistically significant frequency of chromosomal aberrations per cell, with nearly 70% of all spreads examined appearing abnormal. The high frequency of chromosomal aberrations noted for the positive control group indicates the experimental system to be appropriate and sensitive. No specific evidence was presented to demonstrate that the test article reached the target organ at doses up to 5000 mg/kg po, the limit dose applied in the study design.
Executive summary:

No increases in the frequency of chromosomal abnormalities were observed in the treated groups when compared to the controls.