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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
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28.08. - 12.11.2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
GLP compliance:
yes (incl. certificate)
Type of assay:
mammalian germ cell cytogenetic assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Details on species / strain selection:
The rat is an which has been used for many years as suitable experimental in cytogenetic investigations.
Sex:
male/female
Details on test animals and environmental conditions:
Number of main animlas: 48 (24 males/24 females (nulliparous and non-pregnant))
Number of main animals per group: 6 and 6 females
Number of pretest animals: 2 and 2 females group
Age at start of acclimatization: 7 -10 weeks
Age at start of treatment pretest/ main study: 7-10 weeks/8-11 weeks
Body weight at start of acclimatization: 173.9-238.9 g
Body weight at start of treatment: 177.2-281.3 g
Acclimatization: Under laboratory conditions, after health examination.Only animals without any visible signs of illness will be used for the study.
Conditions: Air-conditioned with target for room temperature 22+/- 3°C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these occasionally occurred, following room These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automaticallylight cycle of 12 hours light and 12 hours dark. Music was played the light period.
Accomodation: Groups of three in Makrolon type-4 cages with wire. mesh top and Standard softwood bedding .
Diet: Pelleted Standard Kliba 3433, ad libitum
Water: tap water, ad libiitum


Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
Natrium chloratum 0.9 %
Details on exposure:
dose volume: 10 ml/kg bw
Duration of treatment / exposure:
24, 48 hours
Frequency of treatment:
single administration
Doses / concentrations
Dose / conc.:
50 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
Substance: CPA; Cyclophosphamide
Dissolved in: NaCl-solution (0.9%)
Dosing: 15 mg/kg bw
Route and frequency of administration: intraperitoneally, once
Volume adminstered: 10 ml/kg bw

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Negative controls validity:
valid
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
In conclusion, it be stated that the test described and the experimental conditions the test item did not induce chromosome mutations as determined by the chromosome aberration test with bone marrow cells of the rat.
Therefore, the test substance is considered to be non-mutagenic in this chromosome aberration assay in vivo.
Executive summary:

This study was  to investigate the potential of A130 to induce chromosome aberrations in bone marrow cells of the rat.

The test item was formulated in physiological (0.9 %) NaCl-solution. The volume asminstered intraperitoneally was 10 ml/kg body weight (b.w.). The animals were treated once. Twenty-four  or 48 h, respectively, after the treatment the bone marrow cells were collected for chromosome aberration analysis. Ten animals (5males, 5 females) per test group were evaluated for the occurrence of cytogenetic darnage. Per animal 100 well spread metaphases were scored for gaps, breaks, fragments, deletions, multiple aberrations, and chromosomal disintegrations.

The test item was investigated in this cytogenetic assay at a single dose of 50  mg/kg b.w..

The dose for the cytogenetic assay was determined in pre-experiments for toxicity . 50 mg/kg b.w. were estimated as to be close to the maximum tolerated dose.

As compared to the vehicle control a reduction of the mitotic indices could be observed after treatment with the test item, indicating that the test item was cytotoxic item at the indicated dose in the bone marrow.

No biologically relevant or statistically significant increase in the frequency of aberrant cells occurred after treatment with the test item as compared to the vehicle control.

An appropriate reference mutagen (cyclophosphamide) was used as positive control and showed a distinct and statistically  increase of induced aberration frequency.