2,2'-dimethyl-2,2'-azodipropiononitrile

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test substance showed no genotoxicity in two bacterial gene reverse mutations tests with and without metabolic activation.

Additionally, the results of a chromosomal aberration test using cultured Chinese Hamster Lung (CHL/IU) cells were negative for genotoxicity.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only 4 strains used. Less positive controls.

Principles of method if other than guideline:

Method according to Ames, B.N. et al.: Mutat. Res. 31, 347-364

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

common name: Porofor N, Pt. 23091979

Target gene:

his

Species / strain / cell type:

other: Salmonella typhimurium TA98, TA100, TA1535, TA1537

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver microsomes

Test concentrations with justification for top dose:

20; 100; 500; 2,500; 12,500 ug/plate

Vehicle / solvent:

- DMSO for Porofor N, Trypaflavin and 2-aminoanthracene
- deion. water for Endoxan

Untreated negative controls:

other: vehicle control

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Endoxan (Cyclophosphamid); Trypaflavin; 2-Aminoanthracene.

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

at 12,500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Since precipitation of the test substance was observed at 12,500 µg/plate, this dose level could not be evaluated.

Conclusions:

Interpretation of results: negative

Based on the results of this study, the test substance Porofor N does not need to be classified according to EC/1272/2008 and 67/548/EEC.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1997

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

his, trp

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain / cell type:

S. typhimurium TA 97

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

Rat liver S9, induced with phenobarbital and 5,6-benzoflavone.

Test concentrations with justification for top dose:

0; 313; 625; 1250; 2500 and 5000 µg/plate.

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Species / strain:

S. typhimurium TA 97

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Precipitation observed at 1250 µg/plate (with metabolic activation) and 2,500 µg/plate (without metabolic activation).

Conclusions:

Interpretation of results: negative

Reference 3

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1997

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Qualifier:

according to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Species / strain / cell type:

other: Chinese hamster lung (CHL/IU) cells

Metabolic activation:

with and without

Metabolic activation system:

Rat liver, induced with phenobarbital and 5,6-benzoflavone.

Test concentrations with justification for top dose:

+/- S9 mix (short-term/continous treatment): 0; 0.4; 0.8; 1.6 mg/mL

Species / strain:

other: CHL/IU

Metabolic activation:

with and without

Genotoxicity:

negative

No signs of clastogenicity or polyploidy was found in the chinese hamster lung (CHL/IU) cells with or without metabolic activation.

Conclusions:

Interpretation of results: negative

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

The test substance showed no genotoxicity in a micronucleus test in mice.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Principles of method if other than guideline:

Acredine orange staining

GLP compliance:

not specified

Type of assay:

micronucleus assay

Species:

mouse

Strain:

other: ddY

Sex:

male

Route of administration:

oral: unspecified

Duration of treatment / exposure:

double oral administration

Remarks:

no data

Sex:

male

Genotoxicity:

negative

negative

The mice were given a double oral dose of the test substance. At both 24 and 48 h after treatment, bone marrow
smears were prepared. Administration of the test substance did not result in a significant increase in the frequency of micronucleated polychromatic erythrocytes.

Only abstract available; no further data.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Genetic toxicity in vitro

Ames test with and without metabolic activation with S9 mix prepared from liver homogenate of Aroclor 1254 pretreated male Sprague-Dawley rats was conducted. At the highest dose level, precipitation of the test substance was observed. The results were not assignable. Neither cytotoxicity nor mutagenicity was observed at doses up to 2500 µg/plate. Therefore, the test substance was considered to be not mutagenic in the Ames assay. (BASF, 1980)

Genetic toxicity in vivo

The mice were given a double oral dose of the test substance. At both 24 and 48 h after treatment, bone marrow smears were prepared. Administration of the test substance did not result in a significant increase in the frequency of micronucleated polychromatic erythrocytes. (Takenaka, 1993)

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No adverse findings on genotoxicity was observed in in vitro or in vivo studies. As a result the substance is not considered to be classified for mutagenicity under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No. 2017/776.