Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes (incl. certificate)

Test animals

Species:
mouse
Strain:
ICR
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
- Vehicle(s)/solvent(s) used:water
- Justification for choice of solvent/vehicle: due to the good solubility of the solvent in water
- Concentration of test material in vehicle:
- Amount of vehicle (if gavage or dermal):
- Type and concentration of dispersant aid (if powder):
- Lot/batch no. (if required):
- Purity:

Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
negative

Applicant's summary and conclusion

Conclusions:
Conclusion. Under the conditions of this study, the results were negative, so the
study suggested that succinonitrile did not induce an increase of the incidence of
micronucleated PCE in mice.
Executive summary:

Introduction. This study was conducted to detect the possibility that Succinonitrile could induce the increase of the incidence of micronucleated polychromatic erythrocytes (PCE) in mice, in order to provide genotoxicity related data for the test item. The method was designed to be compatible with the requirements of OECD Guideline for the Testing of Chemicals, 474 “Mammalian Erythocyte Micronucleus Test” (2014).

Method. This study was conducted in ICR mice. All animals were SPF grade. According to the related information about the test item and the results of the preliminary test, in the micronucleus test, the animals were treated at 50, 25 and

12.5mg/kg.bw. Negative control (N G, Ultrapure water) group and positive control (Cyc10phOSphamide, CP, 50mg/kg) group were performed at the same time with the same method. All animals were randomly grouped based on body weight with 7 male animals in each group. Mice were administered the test item orally by gavage twice, with 24 hours interval between doses. All animals were sacrificed by cervical dislocation nearly 19 hours after the last administration. Bone marrow

from stemum was harvested. Bone marrow smear was prepared and analysed with microscope. The data were evaluated with t-test (two-tail) in Excel.

Results. During the test, a notable decrease in the body weights of the animals was found in 12.5mg/1cg.bw dose group as comparing with the concurrent NG approximate 24h after the first administration. The clinical observation results

showed that three mice were sluggish in the 50mg/kg.bw dose group after the first administration or the last administration, and one mouse had hematuria before being sacrificed.

The frequencies of micronucleated PCB were 1.2 +/-20.3%n in the NG group, 1.4 +/-0.2%o in the 12.5mg/kg.bw group, 1.3 +/-0.7% in the 25mg/kg.bw group, 1.6 +/-1.0% in the 50mg/kg.bw group and 24.4 +/-5.5%o in the CP group. No statistically significant difference (P>0.05) in the incidence of micronucleated PCE was observed in all

treated groups as compared with NG. At the same time, a statistically significant difference (P<0.01) in the incidence of micronucleated PCE was observed in the CP group as compared with NG. Furthermore, the PCE/RBC ratios in all treated

groups and positive control group were more than twenty percent of the ratio in NG.

Conclusion. Under the conditions of this study, the results were negative, so the study suggested that succinonitrile did not induce an increase of the incidence of micronucleated PCE in mice.