Registration Dossier

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:
other information
Study period:
nov 1985-Aug 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: well reported GLP study, comparable to guideline

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ZK 74.804
- Batch No.: 6471

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
single administration
Frequency of treatment:
single administration
Post exposure period:
24, 48 or 72 h (negative control and treatment group)
24 h (positive control)
Doses / concentrations
Remarks:
Doses / Concentrations:
1.0, 2.5 or 5.0 g/kg
Basis:
nominal conc.
application volume: 40 ml/kg
No. of animals per sex per dose:
15-20
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
Erythrocytes; femur bone marrow smears were prepared and stained using May-Gruenwald and Giemsa solutions.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Vehicle controls valid:
yes
Positive controls valid:
yes

Any other information on results incl. tables

A slight but statistically significant increases of micronucleated polychromatic erythrocyte counts were seen at the low and high dose groups versus the concurrent negative control at the last sample time (72 h). However, this increase is biologically not relevant because the control values in males are unusually low (0.6 ± 0.6) compared to those of the first and second sample times (1.4± 1.1 and 1.4± 0.6) and moreover, there was no dose response relationship at all. Additionally, the biological fluctuation is also weIl characterized by the fact that the micronucleated normochromatic erythrocyte count in the high dose group at the last sample time was lower than in all vehicle controls and ZK 74.804 groups.

The positive control compound triaziquone proved to be toxic and gave the expected increase in the micronucleated polychromatic cell counts.

Applicant's summary and conclusion

Executive summary:

To investigate the potential of AD-Cyanhydrin (= ZK 74.804) to induce chromosome breakage or malfunction of the spindle apparatus an mouse micronucleus test was conducted. Male and female NMRI mice were treated once by gavage with 1.0, 2.5 or 5.0 g/kg body weight. Control animals were given the vehicle at 40 ml/kg in the same manner. Triaziquone (0.15 mg/kg; single i.p. treatment) served as positive control. Animals of the control and treatment groups were killed at intervals of 24, 48 and 72 hours after treatment. The positive control animals were killed 24 hours after treatment. Femur bone marrow smears were prepared and stained using May-Gruenwald and Giemsa solutions. The coded slides were examined for the presence of micronuclei in 1000 polychromatic and 1000 normochromatic erythrocytes and for the ratio of polychromatic to normochromatic erythrocytes. The micronucleated cell counts obtained with ZK 74.804 were comparable with the concurrent control values. No bone marrow depression was observed.

Therefore, AD-Cyanhydrin showed no mutagenic potential when administered by gavage up to 5 g/kg in the mouse micronucleus test.