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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21.09.-14.10.1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (GLP)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995
Reference Type:
secondary source
Title:
Unnamed
Year:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Details on test material:
- CAS number (as cited in study report): 1854-26-8
- Physical state: liquid
- Analytical purity: 73%
- Lot/batch No.: 682
- Storage condition of test material: at 5°C >= 21 d

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Fa. Mollegaard, Germany
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 20-27g
- Assigned to test groups randomly: no
- Housing: Macrolon Typ 3
- Diet (e.g. ad libitum): Altromin Nr . N 1326, ad libitum
- Water (e.g. ad libitum): drinking water
- Acclimation period: 4 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 55+-10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12 h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
3 days before application.
0.1 ml solution was applicated to 10 g body weight.
Frequency of treatment:
single application
Post exposure period:
24 h (additionally 48 h in the 2000 mg/kg treatment)
Doses / concentrations
Remarks:
Doses / Concentrations:
500, 1000, and 2000 mg/kg as 73 % solution in water
Basis:

No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s):
- Route of administration: oral
- Doses / concentrations: 20/80 mg/kg b.w. (24 hrs post exposure period)

Examinations

Tissues and cell types examined:
bone marrow of the femora; 2000 polychromatic erythrocytes per animal were studied for the presence of micronucleus.
Evaluation criteria:
Micronucleus
- are round, oval or crescent-shaped
- have a precise contour
Application of high doses of clastogenic substances can cause the appearence of several almond- or ring-shaped micronuclei.
- are uniformly coloured
- have a diameter of approximately 1/20 to 1/5 of an erythrocyt
- Es ist meistens nur ein Mikrokem vorhanden .
- Nach Behandlung mit hohen Dosen von Substanzen, die Chromosomenbrüche erzeugen, können
bei einigen Erythrozyten auch mehrere Mikrokeme auftreten, die auch mandelförmig oder ringförmig
sein können

Results and discussion

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

Any other information on results incl. tables

Substance Dose (mg/kg) Sex post exposure period (h) PCE with micronuclei total number of PCE Ratio PCE/NCE
vehicle solvent male 24 0.30 6.0 0.97
female 24 0.34 6.8 0.96
test substance 500 male 24 0.31 6.2 0.99
female 24 0.27 5.4 0.98
test substance 1000 male 24 0.36 7.2 1.02*
female 24 0.32 6.4 1.00
test substance 2000 male 24 0.24 4.8 0.95
female 24 0.26 5.2 0.97
test substance 2000 male 48 0.37 7.4 0.99
female 48 0.33 6.6 0.99
positive ctrl 80 male 24 2.01 40.2 0.69
female 24 1.90 38.2 0.69
positive ctrl 20 male 24 0.86 17.4 0.76
female 24 0.82 16.4 0.86
PCE = polychromatic erythrocyts (2000 were scored for micronuclei)
NCE = normochromatic erythrocyts
The NCE/PCE ratio (as an indicator of cytotoxicity) is based on the scoring of 1000 erythrocyts
* = significantly different from the control, but within historical control data (0.6 to 1.2)

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative

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