N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

only four tester strains TA98, TA100, TA1535, TA1537 used

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine

EC Number:

221-375-9

EC Name:

N,N'-bis(1,4-dimethylpentyl)-p-phenylenediamine

Cas Number:

3081-14-9

Molecular formula:

C20H36N2

IUPAC Name:

N1,N4-bis(5-methylhexan-2-yl)benzene-1,4-diamine

Details on test material:

Santoflex 77, purity: 100%

Method

Target gene:

ames assay

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

main experiment -S9: 0.01, 0.04, 0.2, 1.0, 3.0, 10 µg/plate; +S9: 0.2, 0.8, 1.0, 20, 60, 200 µg/plate

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Positive control substance:

other: -S9: 4-nitroquinoline-N-oxide, NaNO2, 9-aminoacridine; +S9: 2-acetylaminofluorene, benzo(a)pyrene, 2-aminoanthracene

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'. Remarks: TA98, TA100, TA1535, TA1537

Any other information on results incl. tables

Toxicity

A toxicity screen was conducted using test strain TA100 with and without S-9 Mix. In the toxicity screen the test sample

was toxic at levels of 10 µg/plate and above in the absence of S-9 Mix, and 200 µg/plate in the presence of S-9 Mix. A repeat toxicity test was performed using a maximum level of 10 µg/plate, to determine the lowest toxic concentration in the absence of S-9 Mix. In this repeat toxicity test, only the maximum level tested, 10 µg/plate, was toxic. The maximum levels tested in the plate incorporation tests were 200 µg/plate in the presence of S-9 Mix, and 10 µg/plate in the absence of S-9 Mix. These maximum levels tested, were also

toxic in the plate incorporation tests.

Results of the statistical analyses of plate incorporation assay

Results indicated that the test sample was not mutagenic. None of the strain/microsome combinations had three treatment levels with revertants/plate significantly elevated over control values (p<0.0l) or a significant positive dose response (p<0.01).

Conclusion

The test sample, Santoflex 77, was not mutagenic towards any of the Salmonella typhimurium test strains used (TA98, TA100,

TA1535 or TA1537) in the presence or absence of a rat liver homogenate mammalian metabolic activation system (S-9 Mix).

Applicant's summary and conclusion

Executive summary:

The mutagenic potential in bacteria of the test substance 77PD was evaluated in a GLP study (Monsanto Co. 1986). Here, the tester strains Salmonella typhimurium TA 98, TA 100, TA 1535, TA and 1537 were used. A dose range finding test was conducted using tester strain TA100 with and without metabolic activation. Toxicity was indicated at levels of 10 µg/plate and above without metabolic activation and 200 µg/plate with metabolic activation. A second dose range finding test was performed using a maximum level of 10µg/plate without metabolic activation. In this repeat toxicity test, only the maximum level tested, 10 µg/plate, was toxic. Based on these findings the maximum levels tested in the plate incorporation tests were 200µg/plate in presence of metabolic activation, and 10µg/plate in absence of metabolic activation. The maximum levels tested, were toxic in the plate incorporation assay. In this study no biologically relevant and dose dependent increases in revertants was observed in any of the tester strains evaluated with and without metabolic activation. The authors concluded that the test sample was not mutagenic towards any of the Salmonella typhimurium test strains used with and without metabolic activation.