Succinonitrile

Genetic toxicity: in vivo

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

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

yes (incl. QA statement)

Type of assay:

mammalian erythrocyte micronucleus test

Test material

Test material information

Constituent 1

Reference substance name:

Succinonitrile

EC Number:

203-783-9

EC Name:

Succinonitrile

Cas Number:

110-61-2

Molecular formula:

C4H4N2

IUPAC Name:

butanedinitrile

Details on test material:

- Chemical source: Aldrich Chemical
- Purity: 97% (according to label)

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: DSM Engineering Plastics B.V. lotnumber SN0620140520
- Expiration date of the lot/batch: 2016.07.01
- Purity test date: 99.93%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Store in a cool area (IO-20°C). Containers that have been opened must be filled with dry nitrogen for at least 1min and then sealed. Be careful not to import any water or impurities during the filling and sealing course.
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Easily soluble in cold water


FORM AS APPLIED IN THE TEST white waxy solid

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

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Remarks on result:

other: body weight decrease is observed in the lower dose group .

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.